Swimming pools and fungi: An epidemiology survey in Polish indoor swimming facilities.
Environmental conditions for swimming facilities may support fungal growth and also may represent a biological risk for users. However, since previously published studies both cleaning procedures and sanitary regulations are likely to have been improved. The aim of the study was to examine whether attendance to public swimming pools was still a risk factor for fungal infection of the skin in Poland. We investigated the occurrence of mycotic species, in a sample from Polish swimming pools. Detection and identification of isolated species were achieved by cultural and morphological methods. Study revealed high incidence of yeast and yeast-like fungi. Candida spp. and Rhodotorula rubra were commonly detected, followed by Aspergillus spp. and Trichophyton mentagrophytes. Surprisingly, the prevalence of clinically important species isolated from swimming pool environments did not reflect prevalence of those species in Polish population. The present results are in agreement with previous research and support that swimming pools remain an important reservoir of clinically important fungi, yet the exposure associated with swimming pools may not be a major source of dermatophytic infection in Poland.


Distribution patterns of inorganic mercury and methylmercury in tissues of rice (Oryza sativa L.) plants and possible bioaccumulation pathways.
Whole rice plants (Oryza sativa L.) were collected at different typical mercury (Hg) contaminated sites during regular harvest periods to investigate the distribution of inorganic mercury (IHg) and methylmercury (MeHg) in tissues. The whole rice plants were divided into rice seed (brown rice), hull, root, stalk and leaf. Elevated IHg and MeHg concentrations were observed in rice plants cultivated in Hg mining area compared to those obtained from the control site, which attributed to the Hg contamination of soil compartments by the historical large-scale Hg mining/smelting and ongoing artisanal Hg smelting activities. Our observations showed that Hg in ambient air was the potential source of IHg to the above ground parts, whereas IHg concentrations in root were restricted to Hg concentrations in paddy soil. The rice seed has the highest ability to accumulate MeHg compared to the other tissues. MeHg in paddy soil is a potential source to tissues of rice plant. Our study suggested that newly deposited Hg is comparatively more easily methylated than old mercury in soil.


Modified timing characteristic of a scintillation detection system with photonic crystal structures.
It is intuitively expected that an enhanced light extraction of a scintillator can be easily achieved by photonic crystal structures. Here, we demonstrate a modified timing characteristic for a detection system induced by enhanced light extraction with photonic crystal structures. Such improvement is due to the enhanced light extraction which can be clearly proven by the independent measurements of the light output and the timing resolution. The present investigation is advantageous to promote the development of a scintillation detection system performance based on the time-of-flight measurement.


Increased use of injectable contraception in sub-Saharan Africa.
National surveys show a remarkable upsurge in the use of injectable contraceptives in east and South Africa, in contrast to central and West Africa and certain other regions. Data are analyzed here from 95 surveys conducted since 1980 in 38 sub-Saharan African countries, to determine past injectable trends in the context of alternative methods and to explore related issues. In eastern and southern countries injectable use has risen to about 15%-20% of married women, equaling about 40% of all contraceptive use, with some countries above that. Increases in total use have followed increases in injectable use; that and other evidence is clear that the injectable has not merely substituted for the use of pre-existing methods but has given a net increase to total use. Rural use patterns are not much different from urban ones; however the middle and higher wealth quintiles have especially moved toward injectable use. In west and central countries traditional methods are still paramount, with modern methods increasing slightly, but total use remains quite low there. So far no plateau has appeared in total injectable use, though one may be emerging in its share of all use as other methods also increase. Most use is supplied through the public sector, which raises long-term cost issues for health ministries and donors. Many sexually active, unmarried women use the method Discontinuation rates are quite high, and alternative methods need to be kept readily available.


Renaming "chemobrain".
A subset of breast cancer survivors are reporting cognitive impairment after cancer treatment, which has commonly been attributed to the receipt of chemotherapy and colloquially termed "chemobrain." For some, a fear of this side effect enters into their decision regarding therapy. Our review of the literature reveals that so-called "chemobrain" is complex and that factors other than chemotherapy may affect cognitive function, including the impact of surgery and anesthesia, hormonal therapy, menopause, anxiety, depression, fatigue, supportive care medications, genetic predisposition, comorbid medical conditions, or possibly paraneoplastic phenomenon. Studies to date have differed in their assessment and definition of cognitive impairment, thus, making comparisons between studies difficult. In addition, most studies have been limited by a small sample size, and there has been a general lack of focus on older patients despite their high concentration within the cancer population. Large, multicenter studies are needed to better understand the magnitude and mechanism of cognitive changes in cancer survivors and to assess the impact of cognitive changes on the patient's daily lives. We propose that the phenomenon commonly referred to as "chemobrain" would be more accurately labeled "cancer- or cancer-therapy-associated cognitive change."


The Pathogenicity of BPI-ANCA in a Patient With Systemic Vasculitis.
Objective: ANCA associated vasculitis (AAV) is characterized by systemic necrotizing vasculitis with the presence of ANCA. Although BPI-ANCA is one of the atypical ANCAs and is occasionally seen in patients with vasculitis, the pathogenicity of BPI-ANCA remains unclear. This study was performed to examine the pathogenic role of BPI-ANCA against neutrophils. Methods: A 76-year-old Japanese man showed BPI-ANCA positive systemic vasculitis with a medical history of Pseudomonas aeruginosa infection. BPI-ANCA IgGs were eluted from the patient serum using an immunoadsorbent column. In vitro experiment, healthy donor neutrophils were treated with BPI-AAV IgGs, MPO-AAV IgGs, healthy control IgGs under TNFα stimulation. After 3 h incubation, neutrophil extracellular trap (NET) was assessed by immunofluorescent imaging. To determine the pathogenicity of BPI-ANCA, TNFα-primed neutrophils were incubated with monoclonal BPI-ANCA in the presence or absence of recombinant BPI. Results: BPI-AAV IgGs-treated neutrophils showed NET formation with histone citrullination. Interestingly, the monoclonal BPI-ANCA did not induce NET, but the immune complexes (ICs) of recombinant BPI and BPI-ANCA induced TNFα-dependent NET formation with hypercitrullination. Furthermore, TNFα increased the expression of BPIs in neutrophils and the BPIs were translocated to cell surface. Conclusion: BPI-ANCA could affect neutrophils leading to NET formation and may play a role in the development of systemic vasculitis as pathogenic autoantibody.


Practical 12.5-Gb/s, 12.5-GHz spaced ultra-dense WDM PON.
We report a practical 12.5-Gb/s, 12.5-GHz-spaced ultra-dense wavelength-division-multiplexed passive optical network (UD-WDM PON). For the cost-effectiveness, we implement the downstream links by using electro-absorption modulated lasers (EMLs) in the 4-level pulse amplitude modulation (4PAM) format and PIN receivers, and the upstream links by using reflective semiconductor optical amplifiers (RSOAs) modulated in the quadrature phase-shift-keying (QPSK) format and low-cost self-homodyne receivers. To further enhance its cost-effectiveness, we also utilize an optical frequency comb generator, instead of a large number of wavelength-selected lasers, to provide the seed light for these colorless RSOAs. We optimize the operating conditions of the EMLs and RSOAs to maximize the power margins in the presence of the crosstalk arising from closely spaced neighboring channels and the inter-symbol interference (ISI) caused by the narrow passband of the cascaded arrayed-waveguide gratings (AWGs) as well as the limited modulation bandwidths of RSOAs. The experimental results show that we can secure the power margins of >2.5 dB for both upstream and downstream links of the proposed UD-WDM PON.


Heterogeneity of Rhizobium lipopolysaccharides.
The lipopolysaccharides ( LPSs ) from strains of Rhizobium leguminosarum, Rhizobium trifolii, and Rhizobium phaseoli were isolated and partially characterized by mild acid hydrolysis and by polyacrylamide gel electrophoresis. Mild acid hydrolysis results in a precipitate which can be removed by centrifugation or extraction with chloroform. The supernatant contains polysaccharides which, in general, are separated into two fractions ( LPS1 and LPS2 ) by Sephadex G-50 gel filtration chromatography. The higher-molecular-weight LPS1 fractions among the various Rhizobium strains are highly variable in composition and reflect the variability reported in the intact LPSs (R. W. Carlson and R. Lee, Plant Physiol. 71:223-228, 1983; Carlson et al., Plant Physiol. 62:912-917, 1978; Zevenhuizen et al., Arch. Microbiol. 125:1-8, 1980). The LPS1 fraction of R. leguminosarum 128C53 has a higher molecular weight than all other LPS1 fractions examined. All LPS2 fractions examined are oligosaccharides with a molecular weight of ca. 600. The major sugar component of all LPS2 oligosaccharides is uronic acid. The LPS2 compositions are similar for strains of R. leguminosarum and R. trifolii, but the LPS2 from R. phaseoli was different in that it contained glucose, a sugar not found in the other LPS2 fractions or found only in trace amounts. Polyacrylamide gel electrophoretic analysis shows that each LPS contains two banding regions, a higher-molecular-weight heterogeneous region often containing many bands and a lower-molecular-weight band. The lower-molecular-weight bands of all LPSs have the same electrophoretic mobility, which is greater than that of lysozyme. The banding pattern of the heterogeneous regions varies among the different Rhizobium strains. In the case of R. leguminosarum 128C53 LPS, the heterogeneous region of a higher molecular weight than is this region from all other Rhizobium strains examined and consists of many bands separated from one another by a small and apparently constant molecular weight interval. When the heterogeneous region of R. Leguminosarum 128C53 LPS was cut from the gel and analyzed, its composition was found to be that of the intact LPS, whereas the lower-molecular-weight band contains only sugars found in the LPS2 oligosaccharide. In the case of R. leguminosarum 128C63 and R. trifolii 0403 LPSs, the heterogeneous regions are similar and consist of several band s separated by a large-molecular-weight interval with a the major band of these heterogeneous regions having the lowest molecular weight with an electrophoretic mobility near that of beta-lactoglobulin. The heterogeneous region from R. phaseoli 127K14 consists of several bands with electrophoretic mobilities near that of beta-lactoglobulin, whereas this region from R. trifolii 162S7 shows a continuous staining region, indicating a great deal of heterogeneity. The results described in this paper are discussed with regard to the reported properties of Escherichia coli and Salmonella LPSs.


Stability of Acetazolamide, Baclofen, Dipyridamole, Mebeverine Hydrochloride, Propylthiouracil, Quinidine Sulfate, and Topiramate Oral Suspensions in SyrSpend SF PH4.
The objective of this study was to evaluate the stability of 7 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): acetazolamide 25.0 mg/mL, baclofen 10.0 mg/mL, dipyridamole 10.0 mg/mL, mebeverine hydrochloride 10.0 mg/mL, propylthiouracil 5.0 mg/mL, quinidine sulfate 10.0 mg/mL, and topiramate 5.0 mg/mL. All suspensions were stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by measuring the percentage recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredient quantification was performed by ultraviolet (UV) high-performance liquid chromatography, via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredient + vehicle) was at least 90 days for all suspensions with regards to both temperatures. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.


Restorative dental treatments of abraded canine teeth in a Sumatran tiger (Panthera tigris sumatrae).
A Sumatran tiger had developed severely abraded canine teeth by biting on cage-bars. This resulted in weakening and marked sensitivity of the teeth. Indications for, techniques of and complications of restorative dental treatments are described. The outcome of different restorative dental treatments indicates that endodontic treatment should be carried out first if the fracture of a weakened tooth is anticipated. To improve retention, the acid-etch technique is preferred in combination with macroretentive preparations. In this case, amalgam was used successfully in combination with composite resin to restore function to a canine tooth with a large distal defect.


A macromolecular approach to excitation phenomena: mechanical and thermal changes in nerve during excitation.
(1) Nerve fibers and cells were shown to swell when they develop action potentials. Both in the squid giant axon and in the garfish olfactory nerve, the peak of swelling coincides with the peak of the action potential recorded from the site of mechanical recording. Substitution of univalent cations for the bivalent cations (Ca) bound to multi-anion sites in the membrane macromolecules is considered to be at the base of the phenomenon of swelling. (2) Measurements of heat production by the garfish olfactory nerve indicate that the rate of temperature rise is maximal at the peak of the action potential. Since heat production lasts for the entire depolarizing phase of the action potential, the "condenser theory" of heat production is abandoned. Again, substitution of the bound bivalent cations in the membrane macromolecules with univalent cations is regarded as the origin of nerve heat. (3) The two stable states of the nerve membrane, which are readily demonstrable in TEA-treated or internally perfused squid giant axons, are shown to represent bivalent cation-rich and univalent cation-rich states of the nerve membrane. (4) A physicochemical theory is described that explains macromolecular transitions between two stable states. The mechanism of nerve excitation is explained on a physicochemical basis. (5) The importance of the role played by water molecules in the process of nerve excitation is emphasized.


microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus.
Kaposi's sarcoma (KS) is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL). In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs). The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA) expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.


Cutaneous larva migrans with parts of the larva in the epidermis.
Creeping eruption is usually caused by hookworms, most commonly Ancylostoma braziliensis and Ancylostoma caninum. Because lesions of cutaneous larva migrans have a typical clinical appearance, they are rarely biopsied. Specimens usually show spongiotic dermatitis with spongiotic vesicles containing neutrophils and eosinophils and a mixed-cell dermal infiltrate with numerous eosinophils. We report a case with parts of the larva migrans in the epidermis on histologic examination.


Intralabyrinthine schwannomas: a new surgical treatment.
To define a new surgical option, with lower morbidity, for the treatment of intralabyrinthine schwannomas. Retrospective case review. Tertiary referral centers. Eight patients affected by an intralabyrinthine schwannoma, with or without extension to the internal auditory canal, that underwent surgery with a transcanal transpromontorial approach, were included in the study. The average age at presentation was 47 years. Patients' characteristics, symptoms, tumor features, and surgical results were analyzed. All patients were diagnosed and evaluated pre-operatively with high-resolution, gadolinium-enhanced MRI and CT scan of the temporal bone, and underwent surgery via either transcanal transpromontorial endoscopic approach (TTEA) or enlarged transcanal transpromontorial endoscopic approach (ETTA). Hearing function was evaluated with the Hearing Classification System according to the Committee on Hearing and Equilibrium Guidelines. Facial nerve function was evaluated using the House-Brackmann grading system (HB). In six patients out of eight, a TTEA was performed, whereas, due to the extension of the pathology to the cerebellopontine angle, two patients underwent an ETTA. The mean follow-up period was 15.5 months (range 1-69). No intra-operative and post-operative major complications were observed. Post-operative facial nerve function was normal in seven out of eight patients (grade I HB). One patient presented a grade II HB. The endoscopic approach to cochlear schwannoma represents a good treatment option for patients and should be preferred to other more invasive surgical techniques when indicated, to reduce complications, hospitalization, and offer to patients the chance to eradicate the disease, thus avoiding the stress of a long-life radiological follow-up. 4.


[Comparison of different moxibustion techniques in clinical treatment of diseases based on data mining].
To explore the specific efficacy of different moxibustion techniques in treatment of common diseases and clinical indications, and compare the specificity in clinical indications and efficacy among different moxibustion techniques so as to guide clinical practice better. The modern computerization and data mining technology were adopted to set up moxibustion literature database. The relevant literature of moxibustion techniques in recent 60 years were collected, screened, examined, extracted and analyzed statistically so as to explore the advantages of different moxibustion techniques in clinical treatment. (1) Of 2,516 literature, moxa stick, moxe cone and moxa device were used in the highest frequency in internal medicine department, for 730 times, 278 times and 102 times respectively. The warm needling technique was used in the highest frequency, for 70 times in the surgical department. (2) In the dermatology department, the curative rate with moxa cone was the highest, 75%. In the ear-nose-throat department, the warm needing technique and moxa device achieved the highest curative rate, 49% for both of them. In the internal medicine department and surgical department, the curative rate of warm needling technique was 53% and 58% respectively. In the gynecology department, the curative rate of moxa device was the highest, 59%. In the pediatrics department, the curative rate of moxa cone was the highest, 80%. (3) The numbers of priority disorders, frequency ≥20 times: 24 kinds of disease for moxa stick, five kinds of disease for moxa cone, 2 kinds of disease for warm needling technqiue and one disorder for moxa device. Facial paralysis, diarrhea, lumbar and leg pain and elbow and knee swelling pain were of the highest priority, treated with these 4 moxibustion techniques, with a certain of literature research values. (4) The warm needling technique achieved the better efficacy on elbow and knee swelling pain, lumbar and leg pain and diarrhea compared with the other three techniques and the curative rate was higher. The moxa device tecnique achieved the higher curative rate for facial paralysis compared with the other three techniques. Through the comparison of application frequency, curative rate, clinical application frequency in disorders and the efficacy of priority disorders in the treatment with different moxibustion techniques, it is found that moxa stick, moxa cone and moxa device are simple in manipulation, safe and effective. Hence, they can be extensively used in the treatment of common disorders in every department in clinic. The warm needling technique acts on the body by the co-work of needling and warming stimulation of mugwort. It achieves the particular effect on the disorders with complicated etiologies compared with the other three techniques. It can be chosen in priority for the disorders caused by blockage in meridian and collateral and stagnation of qi and blood.


Hyperattenuated Lesions on Immediate Non-contrast CT After Endovascular Therapy Predict Intracranial Hemorrhage in Patients With Acute Ischemic Stroke: A Retrospective Propensity Matched Study.
Background and Purpose: This study aimed to analyze the association between hyperattenuated lesions (HALs) and postoperative intracranial hemorrhage (IH) and predict perioperative IH through quantitative analysis of HALs in acute ischemic stroke (AIS) with anterior large vessel occlusion (LVO) after endovascular therapy (ET). Materials and Methods: This retrospective, propensity-matched study enrolled AIS who received ET from a single-center registry study between August 2017 and May 2020. The enrolled patients were divided into two groups: IH and non-IH, by follow-up postoperative CT. The occurrences of HALs on immediate CT after ET were also recorded. The association between IH and HALs after propensity score matching (PSM) was determined by binary logistic regression models. The receiver operating characteristic (ROC) curve was used to determine the predictive value of the highest CT Hounsfield units (HU) value on immediate CT. Results: Initially, 1,418 patients who underwent digital subtraction angiography were reviewed and 114 AIS patients with immediate postoperative CT and follow-up CT after ET were enrolled. Forty-nine out of the 114 patients developed IH after therapy. After PSM analysis, patients with IH were more likely to have HALs on immediate CT (Odds Ratio, OR 11.9, P = 0.002, and 95% CI: 2.485-57.284). For 80 patients with HALs, ROC analysis of the highest CT value in the HALs territory showed that the cut-off value was 97 HU, the sensitivity was 70.21%, and the specificity was 81.82%. Conclusions: Patients with HALs after ET are more likely to have perioperative IH. The highest CT value in the HALs area might be used to predict IH.


Prokaryotic Expression of α-13 Giardin Gene and Its Intracellular Localization in Giardia lamblia.
To study prokaryotic expression and subcellular localization of α-13 giardin in Giardia lamblia trophozoites, α-13 giardin gene was amplified and cloned into prokaryotic expression vector pET-28a(+). The positive recombinant plasmid was transformed into E. coli BL21(DE3) for expression by using IPTG and autoinduction expression system (ZYM-5052). The target protein was validated by SDS-PAGE and Western blotting and purified by Ni-NTA Resin. Rabbits were immunized with purified fusion proteins for preparation of polyclonal antibody; then the intracellular location of α-13 giardin was determined by fluorescence immunoassay. The results showed that the length of α-13 giardin gene was 1038 bp, encoding a polypeptide of 345 amino acids. The expressed product was a fusion protein with about 40 kDa largely present in soluble form. The target protein accounted for 21.0% of total proteins after being induced with IPTG, while it accounted for 28.8% with ZYM-5052. The anti-α13-giardin polyclonal antibody possessed good antigenic specificity as well as excellent binding activity with recombinant α-13 giardin. Immunofluorescence assays revealed that α-13 giardin was localized in the cytoplasm of G. lamblia trophozoite, suggesting that it is a cytoplasm-associated protein. The present study may lay a foundation for further functional research on α-13 giardin of G. lamblia.


Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats.
Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.


Atopic Dermatitis, Depression, and Suicidality.
Atopic dermatitis (AD) is a common disease associated with an underappreciated increased risk of depression and suicidality. Current literature investigates associated risk factors, including severity of disease, age, sex, and atopic comorbidities, which may help identify patients with AD at high risk for depression or suicidality. Increasing severity of AD and female sex are associated with an increased risk for both depression and suicidality, while increasing age is associated with an increased risk for depression only. Further research is required to validate the studies supporting these reported associations with a particular emphasis on suicidality and AD due to lack of information. The use of these risk factors may assist in the creation of simple screening tools to screen for psychiatric comorbidity in patients with AD.


An optimized protocol for DNA extraction from wheat seeds and Loop-Mediated Isothermal Amplification (LAMP) to detect Fusarium graminearum contamination of wheat grain.
A simple, rapid, and efficient method for isolating genomic DNA from germinated seeds of wheat that is free from polysaccharides and polyphenols is reported. DNA was extracted, treated with RNase, measured and tested for completeness using agarose gel electrophoresis. DNA purification from wheat grains yielded abundant, amplifiable DNA with yields typically between 100 and 200 ng DNA/mg. The effectiveness and reliability of the method was tested by assessing quantity and quality of the isolated DNA using three PCR-based markers. Inter-simple sequence repeats (ISSRs) were used to assess the genetic diversity between different wheat varieties. Specific PCR primer pair Tox5-1/Tox5-2 and a loop-mediated isothermal amplification (LAMP) procedure were used to detect genomic DNA of Fusarium graminearum in contaminated wheat seeds. In this method there is no need to use liquid nitrogen for crushing germinated seedlings. The protocol takes approximately one hour to prepare high quality DNA. In combination with the LAMP assay it is a fast and cost-effective alternative to traditional diagnostic methods for the early detection of toxigenic fusaria in cereals.


IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma.
Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (P<0.001) had a significantly higher frequency of rhinosinusitis, as compared to those with the minor alleles of these two single nucleotide polymorphisms. AIA patients with the GG genotype had a higher peripheral eosinophil count (P=0.025) and a higher serum eotaxin-1 level (P=0.044), as compared to patients with the AA genotype IL-13 Arg110Gln (110G>A). These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.


Silencing of the Il2 gene transcription is regulated by epigenetic changes in anergic T cells.
Anergy is induced in T cells as a consequence of a partial or suboptimal stimulation. Anergic T cells become unresponsive and fail to proliferate and produce cytokines. We had previously shown that in anergic CD4(+) T cells, Ikaros participates in the transcriptional repression of the Il2 gene by recruiting histone deacetylases that cause core histone deacetylation at the Il2 promoter. Here we show that deacetylation at the Il2 promoter is the initial step in a process that leads to the stable silencing of the Il2 gene transcription in anergic T cells. We have found that anergy-induced deacetylation of the Il2 promoter permits binding of the histone methyl-transferase Suv39H1, which trimethylates lysine-9 of histone H3 (Me3H3-K9). Furthermore, the establishment of the Me3H3-K9 mark allows the recruitment of the heterochromatin protein HP1, allowing the silenced Il2 loci to reposition close to heterochromatin-rich regions. Our results indicate that silencing of Il2 transcription in anergic T cells is attained through a series of epigenetic changes that involve the establishment of repressive marks and the subsequent nuclear repositioning of the Il2 loci, which become juxtaposed to transcriptionally silent regions. This mechanism may account for the stable nature of the inhibition of IL-2 production in anergic cells.


[Transaxial tomography in the study of myocardial perfusion with thallium-201].
Stress and redistribution thallium-201 myocardial imaging using a transaxial single emission computed tomographic system has been applied to the diagnosis of coronary artery disease. Data sampling was performed along a limited 180 degree arc, obtaining 32 images in a continuous mode, at a rate of 20 seconds per image. The production of perfusion defects in patients was stimulated by exercise testing or by dipyridamole infusion. No significant differences existed when both tests were compared (p less than 0.01). Normal and abnormal patterns including the different pathophysiological alterations of myocardial ischemia were defined in three tomographic planes using this methodology. Patients with coronary disease are separated from patients without coronary disease with high probability (84%). Transaxial SPECT (single photon emission computerized tomography) provides a significant increment in sensitivity and specificity in relation to planar scintigraphy in the detection of myocardial infarction (91 and 100%, respectively); residual ischemia postinfarction (96 and 97%, respectively), and significant coronary artery disease (91 and 97%, respectively).


Clinical and microbiological characteristics of nocardiosis: A 5-year single-center study in Crete, Greece.
Nocardiosis is a rare disease affecting both immunocompromised and immunocompetent hosts, presented in various clinical forms ranging from localized to disseminated infection. Aim of the present study was to investigate the clinical and microbiological characteristics of nocardiosis, antimicrobial resistance profiles, treatment, and outcomes of Nocardia infection over the last 5 years at our institution. The medical records and microbiological data of patients affected by nocardiosis and treated at the university hospital of Heraklion, Crete, Greece, between 2018 and 2022, were retrospectively analyzed. The isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and through sequencing of 16S rRNA. Antimicrobial susceptibility for 17 agents was determined by E-test and results were interpreted according to CLSI guidelines. Among the 28 Nocardia isolates, eight species were identified, with Nocardia brasiliensis being the most prevalent (32.1%), followed by Nocardia otitidiscaviarum (25%), and Nocardia farcinica (14.3%). Skin and soft tissue infections were the most common presentations, noted in 13 (50%) patients, followed by pulmonary infection presented in 10 (38.5%) patients. Fifteen patients (57.7%) had at least one underlying disease, and 11 (42.3%) were on immunosuppressive or long-term corticosteroid treatment. Susceptibility rates of linezolid, tigecycline, amikacin, trimethoprim-sulfamethoxazole, moxifloxacin, and imipenem were 100, 100, 96.4, 92.9, 82.1, and 42.9%, respectively. The 26 patients in this study were treated with various antibiotics. Mortality rate was 3.8%, and the patient who died had disseminated infection. Since epidemiology and antimicrobial susceptibility are evolving, continuous surveillance is mandatory in order to initiate appropriate treatment in a timely manner.


Using the arts and humanities to support learning about loss, suffering and death.
In this article, the benefits of using the arts and humanities as teaching and learning strategies are explored. Their contribution to undergraduate nursing curricula, as a means of promoting a deeper understanding of the experiences of loss, suffering and death, cannot be undervalued. They need to be present equally alongside the physical and social sciences in nursing curricula. More than ever, is the need for all undergraduate nursing students to participate in self-reflection of these experiences, in order that they may meet the needs of their patients and families adequately, in a range of healthcare settings.


1199G>A and 2677G>T/A polymorphisms of ABCB1 independently affect tacrolimus concentration in hepatic tissue after liver transplantation.
Tacrolimus is an immunosuppressive drug widely used in hepatic transplantation to avoid graft rejection. Its pharmacokinetics is characterized by a large interindividual variability requiring the use of therapeutic drug monitoring in daily clinical practice. Some genetic polymorphisms in biotransformation enzymes or transporter proteins, such as CYP3A5 and P-glycoprotein (ABCB1), in donors and/or recipients, appear as important determinants of the Tac blood pharmacokinetics. A recent study has shown that Tac hepatic tissue concentrations vary greatly among patients and are well correlated with graft outcome. The aim of our study was to investigate the effect of genetic polymorphisms in biotransformation enzymes (CYP3A5 and CYP3A7) or in their regulatory protein pregnane X receptor as well as in transporter proteins (ABCB1 and OATP-C) on Tac pharmacokinetics in liver transplant patients and more specifically on Tac hepatic concentrations. One hundred and fifty liver donors were genotyped for 13 different polymorphisms. Tac blood and hepatic concentrations were compared according to hepatic genotypes. We confirmed that Tac dose requirement (on the basis of blood therapeutic drug monitoring) was higher among patients expressing hepatic CYP3A5 (at least one CYP3A5*1 allele) compared with patients who did not (CYP3A5*3/*3). Hepatic expression of CYP3A5, however, did not seem to influence Tac hepatic concentrations. In contrast, ABCB1 genetic polymorphisms significantly influenced Tac hepatic concentrations, whereas their impact on blood concentrations seemed negligible. Among these ABCB1 polymorphisms, the 1199G>A and 2677G>T/A single nucleotide polymorphisms seemed to reduce the activity of P-gp on Tac. As Tac hepatic concentrations have been significantly related to the graft outcome, it might be interesting, in the future, to genotype donors for ABCB1 polymorphisms to better individualize the Tac immunosuppressive therapy in hepatic transplantation.


Facile fabrication of sponge-like porous micropillar arrays via an electrochemical process.
A large variety of synthetic methods have been developed for hierarchically porous materials by which the performance of a wide range of applications can be dramatically enhanced. Herein, hierarchically porous micropillar arrays are demonstrated by employing electrochemical etching to silicon micropillars. The approach relies on the steering of current flow through the three-dimensional silicon-electrolyte interface to enable nanopores to grow on the entire surface of the micropillars, simultaneously. The pores grow perpendicular to the surface of the micropillars, whereas the pore diameter and porosity vary depending on the locations of the surfaces. The finite element analysis shows that the spatial variation of the pore diameter and porosity is determined by the distribution of current density. Further, the thickness of the porous layer can be tuned by etching time so that sponge-like porous structures are conveniently obtained by regulating the etching time. In addition to the effect of current density flowing through the etched surfaces, the growth of pores also depends on the crystal orientations of the etched surfaces. The etching results on square micropillar arrays and microgroove arrays show that the growth direction and rate of nanopores inside the microstructure also depend on the exposed crystal planes. The facile characteristics of the fabrication method can serve as an effective route for a wide range of applications of porous materials with enhanced capabilities.


Neck pain.
Six conditions cause most of the neck pain complaints seen by primary care physicians: cervical muscle strain or sprain, torticollis, acceleration injury, myofascial pain dysfunction syndrome, and cervical osteoarthritis or rheumatoid arthritis. Most of them can be diagnosed and treated by the primary care physician. Of the more unusual causes, one should not miss a clinical fracture; a herniated cervical disc, spinal cord compression from a disc, or epidural tumor; infection of the disc or the vertebral body; subluxation of the vertebral bodies; or pain referred from the chest or mediastinal structures. MRI offers new opportunity for early diagnosis of myelopathy owing to OA or RA, vertebral osteomyelitis, and metastatic involvement of cervical vertebrae.


Awareness of genetic testing for children with autism spectrum disorder among caregivers in an autism support group.
Recent discoveries have improved our understanding of the complex genetic mechanisms underlying autism spectrum disorder (ASD). Despite current guidelines, genetic testing for children with ASD is largely underutilized. This has been attributed to a lack of public awareness regarding genetic testing. The role that autism support groups play in this awareness has not been previously described. A web-based survey was developed and distributed through a community support group to assess the awareness and utilization of genetic testing among caregivers for children with ASD. A total of 138 caregivers responded in total. Only 53.6% were aware that genetic testing exists for ASD. Genetic testing was completed in 17.4% of respondents. Rates of awareness were similar across demographic factors including race, family income, education level, and urban, suburban, or rural residence. This supports low awareness as a key factor in the underutilization of genetic testing for ASD, even among members in an organized autism support group. Targeting public awareness through these organizations may be a promising approach for improving the utilization of genetic testing in ASD.


Formation of close-packed nanoparticle chains.
The self-assembly of CoPt(3) particles (diameter 6 nm) into low-dimensional ordered arrays results from phase separation in a hexane solution containing nanoparticles, hexadecylamine, and water. The evaporation of hexane from the thin film of solution initiates the formation of a water layer on the solid substrate. Subsequent dewetting of this water layer leads to the formation of water droplets. The nanoparticles follow the motion of the contact line of the dewetting water layer and thus assemble into ordered arrays at the periphery of the water droplets.


Research of Eliminating the Day-Boundary Discontinuities in GNSS Carrier Phase Time Transfer through Network Processing.
Time and frequency transfer through global navigation satellite system (GNSS) precise point positioning (PPP) based on carrier-phase measurements has been widely used for clock comparisons in national timing laboratories. However, the time jumps up to one nanosecond at the day boundary epochs of adjacent daily batches lead to discontinuities in the time transfer results. Therefore, it is a major obstacle to achieve continuous carrier phase time transfer. The day-boundary discontinuities have been studied for many years, and they are believed to be caused by the long-term pseudorange noise during estimation of the clock offset in the daily batches and are nearly in accordance with a Gaussian curve. Several methods of eliminating the day-boundary discontinuity were proposed during the past fifteen years, such as shift and overlapping, longer batch processing, clock handover, and ambiguity stacking. Some errors and new noise limit the use of such methods in the long-term clock stability comparison. One of the effective methods is phase ambiguity fixing resolution in zero-differenced PPP, which is based on the precise products of wide-lane satellite bias (WSB) provided by the new international GNSS Service (IGS) Analysis Center of Centre National d'Etudes Spatiales (CNES) and Collecte Localisation Satellites (CLS). However, it is not suitable for new GNSS, such as the Beidou Satellite System (BDS), GALILEO, and QZSS. For overcoming the drawbacks above, Multi-GNSS Experiment (MGEX) observation data of 10 whole days from MJD 58624 to 58633have been network processed by batch least square resolution. These observations come from several ground receivers located in different national timing laboratories. Code and carrier phase ionosphere-free measurements of GPS and BDS satellites are used, and the time transfer results from network processing are compared with PPP results provided by Bureau International des Poids et Mesures (BIPM) and used for international atomic time (TAI) computation (TAIPPP) and universal time coordination (UTC). It is shown that the time offsets of three different time links are almost continuous and the day-boundary discontinuities are sharply eliminated by network processing, although a little extent of day-boundary discontinuities still exist in the results of UTC(USNO)-UTC(PTB). The accuracy of time transfer has been significantly improved, and the frequency stability of UTC(NTSC)-UTC(PTB) can be up to 6.8 × 10-15 on average time of more than one day. Thus, it is suitable for continuous multi-GNSS time transfer, especially for long-term clock stability comparison.


Evaluation of selected oral cavity microbiota--risk factors of management complications in patients with masticatory system disorders.
The retrospective analysis of data on oral cavity clinical status in relation to microbiota species composition is presented. The research regards patients of different age, with and without congenital malformation, pretreatment assessed for occurrence of pathological changes in the masticatory system. Samples of the swabs collected from each patient (from dental plaque, periodontium and dental pockets) were used for identification of oral protozoans in wet slides and stained preparations; additionally, transmission electron microscope examination was performed. The material was used for in vitro cultures to identify bacteria strains. Clinically, intensity of tissue deteriorations was higher in patients with a congenital disease. Alive Trichomonas tenax and Entamoeba gingivalis, species with confirmed pathogenic impact on oral cavity and neighboring structures, were detected with higher prevalence in older patients. Enterococci, Staphylococcus aureus, various Enterobacteriaceae were more frequently detected in patients with somatic and mental retardations; in mouths of those patients, Klebsiella pneumonia and Pseudomonas aeruginosa opportunistic strains occurred. Masticatory system abnormalities favor colonization of oral cavity by exogenous species and dissemination of infections, especially dangerous for patients with congenital diseases. Oral microbiota assessment and preventive measures may be helpful to avoid subsequent peri-surgery complications.


Thermal denaturation: a method to rank slow binding, high-affinity P38alpha MAP kinase inhibitors.
It has been reported that the diaryl urea class of p38alpha inhibitors binds to p38 map kinase with both high affinity and slow binding kinetics (Pargellis et al. Nat. Struct. Biol. 2002, 9, 268-272). The slow binding kinetics of this class of inhibitors is believed to be the result of binding to an allosteric pocket adjacent to the p38alpha active site. The use of traditional kinetic and equilibrium methods to measure the binding affinity of this class of compounds has created many challenges for determination of structure-activity relationships (SAR). The thermal denaturation method provides a means of measuring high-affinity interactions. In this paper, the method of thermal denaturation will be described as it has been applied to the diaryl urea class of p38 map kinase inhibitors.


Smoking: a disease prevention issue.
Smoking cessation plays a major role in preventing disease. Self-efficacy has a demonstrated effect on successful smoking cessation. An intervention plan is outlined in which self-efficacy is used to increase the effectiveness of a smoking cessation program.


[Origin of three symbols in medicine and surgery].
Humans use many ways to communicate with fellow humans. Symbols have been one of these ways. Shamans probably used these in the beginning and adopted other distinctive symbols as they were introduced. The origin, the reason and use of three symbols in medicine and surgery are discussed. Some symbols currently remain the same and others have been modified or have disappeared. The oldest of these three symbols is the staff of Aesculapius, related to the Greek god of medicine and health. Since the 19th century, in some countries the symbol of the medical profession has become the caduceus, but the staff is the natural symbol. The second symbol is the barber pole that was created at the beginning of the Middle Ages. This was the means to locate the office and shop of a barber/surgeon in towns, cities and battlefields. On the other hand, the surgeon made use of the emblem of the union, trade or fraternity to which he belonged, accompanied by the bowl for bloodletting. The third symbol is the wearing of long and short robes that distinguished graduate surgeons from a medical school and the so-called barber/surgeons. Symbols facilitate the manner in which to identify the origin or trade of many working people. Some symbols currently remain and others have either been modified or are obsolete, losing their relationship with surgery and medicine.


Central Role for Dermal Fibroblasts in Skin Model Protection against Candida albicans.
The fungal pathogen Candida albicans colonizes basically all human epithelial surfaces, including the skin. Under certain conditions, such as immunosuppression, invasion of the epithelia occurs. Not much is known about defense mechanisms against C. albicans in subepithelial layers such as the dermis. Using immune cell-supplemented 3D skin models we defined a new role for fibroblasts in the dermis and identified a minimal set of cell types for skin protection against C. albicans invasion. Dual RNA sequencing of individual host cell populations and C. albicans revealed that dermal invasion is directly impeded by dermal fibroblasts. They are able to integrate signals from the pathogen and CD4+ T cells and shift toward an antimicrobial phenotype with broad specificity that is dependent on Toll-like receptor 2 and interleukin 1β. These results highlight a central function of dermal fibroblasts for skin protection, opening new possibilities for treatment of infectious diseases.


The Influence of an Active Glove Arm in Softball Pitching: A Biomechanical Evaluation.
The purpose of this study was to determine whether glove arm kinematics during a windmill softball pitch impact pelvic and trunk kinematics as well as pitching arm shoulder kinetics. Thirty-Nine college softball pitchers (20.0±1.4 yrs.; 174.7±6.1 cm; 82.0±13.0 kg; 10.7±2.7 yrs. of experience) threw 3 pitches to a catcher while kinematic and kinetic data were collected. Pearson product moment correlations were run, and significant correlations found with glove arm kinematics, occurring before pelvis kinematics, trunk kinematics, and shoulder kinetics, were then put through a linear regression to identify whether there was any potential cause and effect. Results revealed that glove arm elbow flexion during phase 1 significantly predicted normalized shoulder rotation moment during phase 4 (t=2.60, p=0.013). Additionally, glove arm shoulder horizontal abduction during phase 1 significantly predicted normalized shoulder moment in phase 3 (t=- 2.40, p=0.021) and pelvic angular velocity during phase 3 (t=- 3.20, p=0.003). In conclusion, an active glove arm was predictive of a more efficient kinetic chain later in the windmill pitching motion and could possibly play a role in preventing injury by lessening pitching shoulder joint loads.


[Physical performance of older adults living in rural areas at sea level and at high altitude in Peru].
Living at high altitudes requires the inhabitants to adapt biologically and socially to the environment. The objective of this study was to determine the difference in physical performance (PP) in rural populations at sea level and at high altitude. A cross-sectional study was conducted in rural communities in Ancash, Peru, located at 3.345 meters above sea level (m.a.s.l.) and also in communities located in coastal areas at 6m.a.s.l. PP was measured by the Short Physical Performance Battery (SPPB) and other associated factors. Adjusted prevalence ratios (aPR) were calculated. A total of 130 older adults were assessed in the high altitude communities and 129 on the coast. The median age was 71.4 years, and 55.6% were female. Low physical performance (SPPB ≤ 6) was 10.0% at high altitude and 19.4% on the coast (p<0.05). Factors associated with low physical performance were residing at the coast (aPR: 2.10, 95% CI 1.02 to 4.33), self-reported poor health (aPR: 2.48, 95% CI 1.21 -5.08), hypertension (aPR: 1.73, 95% CI 1.01 to 2.98), and age (aPR: 1.04, 95% CI 1.01 to 1.07), while being a farmer (aPR: 0.49, 95% CI 0.25 to 0.97), and being independent (aPR: 0.37, 95% CI 0,20-, 072) were found to be protective factors. It was also found that the inhabitants of the coast have a mean of 0.86 points lower total SPPB than the high altitude ones (p=0.004). There is an association between altitude of residence and PP in older adults. The prevalence of a low PP in older adults in rural areas at sea level is twice as high compared to those living in high altitude rural communities.


Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: together we grow.
The aim of this study is to compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in identifying recurrence in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition. A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax, and SUVmean from the PET images; rCBV from perfusion; and ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0, 1, and 2 representing discordance, < 50% and > 50% concordance respectively. There were 35 cases of recurrence and 13 cases of post-treatment changes without recurrence. The highest area under curve (AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases. Amino acid PET had the highest diagnostic accuracy in identifying recurrence in post-treatment gliomas. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.


Applying MAPPs Assays to Assess Drug Immunogenicity.
Immunogenicity against biotherapeutic proteins (BPs) and the potential outcome for the patient are difficult to predict. In vitro assays that can help to assess the immunogenic potential of BPs are not yet used routinely during drug development. MAPPs (MHC-associated peptide proteomics) is one of the assays best characterized regarding its value for immunogenicity potential assessment. This review is focusing on recent studies that have employed human HLA class II-MAPPs assays to rank biotherapeutic candidates, investigate clinical immunogenicity, and understand mechanistic root causes of immunogenicity. Advantages and challenges of the technology are discussed as well as the different areas of application.


Constructing land-use maps of the Netherlands in 2030.
The National Environmental Assessment Agency of the RIVM in the Netherlands is obliged to report on future trends in the environment and nature every 4 years. The last report, Nature Outlook 2, evaluated the effects of four alternative socio-economic and demographic scenarios on nature and the landscape. Spatially detailed land-use maps are needed to assess effects on nature and landscape. The objective of the study presented here was how to create spatially detailed land-use maps of the Netherlands in 2030 using the Environment Explorer, a Cellular Automata-based land-use model to construct land-use maps from four scenarios. One of these is discussed in great detail to show how the maps were constructed from the various scenario elements, story lines and additional data and assumptions on national, regional and local land-use developments. It was the first time in the history of our outlooks that consistent, spatially detailed land-use maps of the Netherlands for 2030 were constructed from national economic and demographic scenarios. Each map represents a direct reflection of model input and assumptions. The maps do not show the most probable developments in the Netherlands but describe the possible change in land use if Dutch society were to develop according to one of the four scenarios. The large (societal) uncertainties are reflected in the total set of future land-use maps. The application of a land-use model such as the Environment Explorer ensures that all relevant aspects of a scenario, i.e. economic and demographic developments, zoning policies and urban growth, are integrated systematically into one consistent framework.


Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population.
Diabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease. This was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004-2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry. A total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8-8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05). Diabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.


Invited review: Helping dairy farmers to improve economic performance utilizing data-driving decision support tools.
The objective of this review paper is to describe the development and application of a suite of more than 40 computerized dairy farm decision support tools contained at the University of Wisconsin-Madison (UW) Dairy Management website http://DairyMGT.info. These data-driven decision support tools are aimed to help dairy farmers improve their decision-making, environmental stewardship and economic performance. Dairy farm systems are highly dynamic in which changing market conditions and prices, evolving policies and environmental restrictions together with every time more variable climate conditions determine performance. Dairy farm systems are also highly integrated with heavily interrelated components such as the dairy herd, soils, crops, weather and management. Under these premises, it is critical to evaluate a dairy farm following a dynamic integrated system approach. For this approach, it is crucial to use meaningful data records, which are every time more available. These data records should be used within decision support tools for optimal decision-making and economic performance. Decision support tools in the UW-Dairy Management website (http://DairyMGT.info) had been developed using combination and adaptation of multiple methods together with empirical techniques always with the primary goal for these tools to be: (1) highly user-friendly, (2) using the latest software and computer technologies, (3) farm and user specific, (4) grounded on the best scientific information available, (5) remaining relevant throughout time and (6) providing fast, concrete and simple answers to complex farmers' questions. DairyMGT.info is a translational innovative research website in various areas of dairy farm management that include nutrition, reproduction, calf and heifer management, replacement, price risk and environment. This paper discusses the development and application of 20 selected (http://DairyMGT.info) decision support tools.


Ribosome synthesis in Tetrahymena pyriformis.
The cellular site of synthesis of ribosomal RNA in Tetrahymena pyriformis was studied by analyzing the purified nuclear and cytoplasmic RNA from cells pulse labeled with uridine-(3)H. The results of studies using zonal centrifugation in sucrose density gradients show that the ribosomal RNA is synthesized in the nucleus as a large precursor molecule sedimenting at 35S. The 35S molecule undergoes rapid transformation through two main nuclear intermediates, sedimenting at about 30S and 26S. The smaller ribosomal RNA (17S) appears first in the cytoplasm and it seems to be absent from the nucleus. The apparent delay in the appearance of the larger ribosomal RNA (26S) in the cytoplasm is due to the presence of a larger pool of its precursors in the nucleus as indicated by pulse-chase experiments. The newly synthesized ribosomal RNA's appear in the cytoplasm as discrete 60S and 45S ribonucleoprotein particles, before their incorporation into the polysomes.


Combination doxorubicin and interferon-α therapy stimulates immunogenicity of murine pancreatic cancer Panc02 cells via up-regulation of NKG2D ligands and MHC class I.
Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-α (IFN-α) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-α (IFN-α) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-α (IFN-α) on the ligands of NK and T cells was assessed by flow cytometry. The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-α (IFN-α) may be a potential strategy for treating pancreatic adenocarcinoma.


Eversion technique for distal mucosal proctectomy in ulcerative colitis: a preliminary report.
A technique is described for assisting the performance of distal mucosal proctectomy in ulcerative colitis by peranal eversion of the lower rectum. The ease, accuracy and expedition of the mucosal excision have been impressive. In 9 of 16 patients having this procedure as part of an ileo-anal anastomosis (with a pelvic ileal reservoir) the functional results seemed to be similar to those obtained in 14 patients submitted to the same operation but with an endocavitary technique of rectal mucosectomy.


Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach.
To differentiate effects of lovastatin on low density lipoprotein (LDL) receptor activity from effects on LDL metabolic properties, LDL apolipoprotein B (apoB) turnover was studied in eight hyperlipidemic subjects during baseline and lovastatin treatment, in the latter case with LDL tracers isolated during both baseline (CLDL) and drug treatment (Rx-LDL) conditions. Lovastatin (40 mg/day) significantly lowered total plasma and LDL cholesterol levels (27% and 25%, respectively) as well as plasma triglyceride levels (30%). Using contemporaneous tracers (C-LDL before and Rx-LDL during treatment), lovastatin caused a modest increase in LDL fractional catabolic rate (FCR) (0.410+/-0.113 vs. 0.339+/-0.108 pools/day, P < 0.04 by paired t). The increase in LDL tracer FCR was higher when C-LDL tracer isolated during the untreated period was injected during lovastatin treatment (0.496+/-0.177 vs. 0.339+/-0.108 pools/day, P < 0.02). These in vivo studies in humans were confirmed by injecting LDL tracers from two patients into five guinea pigs. The C-LDL tracer was cleared consistently faster than the Rx-LDL tracer (0.082+/-0.018 vs. 0.057+/-0.015 pools/h, P< 0.001). The results demonstrate three important outcomes of lovastatin treatment in these subjects: LDL receptor activity increased by 49% (P < 0.02); LDL apoB production rate decreased by 17% (P < 0.03), and LDL particle in vivo affinity for the LDL receptor decreased by 15% (P < 0.01). The decrease in LDL particle affinity partially negated the expected effect of increased LDL receptors on LDL clearance. The present study provides an explanation for earlier observations by several investigators using contemporaneous tracers that treatment with HMG-CoA reductase inhibitors resulted in only modest increases in low density lipoprotein functional catabolic rate.


Comparative evaluation of Raman spectroscopy at different wavelengths for extremophile exemplars.
Raman spectra have been obtained for extremophiles from several geological environments; selected examples have been taken from hot and cold deserts comprising psychrophiles, thermophiles and halophiles. The purpose of this study is the assessment of the effect of the wavelength of the laser excitation on the ability to determine unique information from the Raman spectra about the specificity of detection of biomolecules produced as a result of the survival strategies adopted by organisms in extreme terrestrial environments. It was concluded that whereas FT-Raman spectroscopy at 1064 nm gave good quality results the time required to record the data was relatively large compared with other wavelengths of excitation but that better access to the CH stretching region for organic molecules was given. Shorter wavelength excitation of biomolecules in the blue-green regions of the visible spectrum using a conventional dispersive spectrometer was more rapid but very dependent upon the type of chemical compound being studied; most relevant biomolecules fluoresced at these wavelengths but carotenoids exhibited a resonance effect which resulted in an improved detection capability. Minerals and geological materials, in contrast, were best studied at these visible wavelengths. In general, the best compromise system for the excitation of the Raman spectra of both geological and biological materials was provided using a 785 nm laser coupled with a dispersive spectrometer, especially for accessing the 1800-200 cm(-1) wavenumber shift region where much of the definitive analytical information resides. This work will have conclusions relevant to the use of miniaturised Raman spectrometers for the detection of biomolecules in extraterrestrial planetary exploration.


A rat model manifesting methanol-induced visual dysfunction suitable for both acute and long-term exposure studies.
A toxic dose of methanol can induce visual dysfunction and metabolic acidosis in humans. However, the methanol dose range capable of inducing such toxicities and the mechanism(s) of visual dysfunction are not clearly understood. Nonprimate laboratory animals do not develop the characteristic human methanol toxicities even after a lethal dose. In the present study, we investigated whether visual dysfunction can be induced by methanol in a folate-reduced (FR) rat model which accumulates formate. Methanol was administered to rats by either the oral or inhalation route. The latencies of P1 and N1 peaks of flash-evoked potentials were significantly increased in methanol-challenged FR rats (3.5 g/kg, po), indicating that methanol administration caused an adverse effect in the retinogeniculocortical visual pathway. Effects on retinal function were then assessed by evaluating the electroretinogram (ERG). A dose-related reduction in b-wave amplitude of the ERG was manifested following oral methanol administration (1.5 to 2.5 g/kg). The b-wave amplitude reduction was also manifested in FR rats exposed to methanol vapors (2000 ppm, a concentration which was nontoxic in monkeys). These observations were consistent with reported human methanol toxicity cases. Thus, our data suggest that the FR rat model could serve as a valuable human surrogate for studying mechanisms of methanol-induced visual dysfunction and providing reliable toxicity data on the visual system under various exposure scenarios.


Techniques for acute stroke intervention.
Stroke or cerebrovascular accident is the second most common cause of death in Western countries. Although stroke is a treatable disease, the majority of patients do not receive intravenous thrombolysis or catheter-based therapy. The lack of treatment is multifactorial. Several treatments have been studied. Research and development in the area of acute stroke treatment are ongoing.


A New Strategy Involving the Use of Peptides and Graphene Oxide for Fluorescence Turn-on Detection of Proteins.
The detection of proteins is of great biological significance as disease biomarkers in early diagnosis, prognosis tracking and therapeutic evaluation. Thus, we developed a simple, sensitive and universal protein-sensing platform based on peptide and graphene oxide (GO). The design consists of a fluorophore (TAMRA, TAM), a peptide containing eight arginines and peptide ligand that could recognize the target protein, and GO used as a quencher. To demonstrate the feasible use of the sensor for target detection, Bcl-xL was evaluated as the model target. The sensor was proved to be sensitive and applied for the detection of the target proteins in buffer, 2% serum and living cells.


Isolation and characterization of a novel human gene, VANGL1, as a therapeutic target for hepatocellular carcinoma.
Through analysis of genome-wide expression profiles, we have been attempting to isolate novel molecular targets for diagnosis, treatment and prevention of hepatocellular carcinoma (HCC). Among the genes that a cDNA microarray showed to be commonly transactivated in HCCs, we identified a novel human homologue of the Drosophila Van Gogh/Strabismus gene and termed it VANGL1 [Vang (Van Gogh, Drosophila)-like 1]. This gene, which encoded a transcript with an open reading frame of 1,572 bp, was expressed specifically in testis and ovary among 16 adult normal tissues examined. Transfection of antisense S-oligonucleotides, but not of sense S-oligonucleotides, into hepatoma cells suppressed expression of VANGL1 and subsequent growth of these cells was inhibited to a marked degree. The findings suggest that VANGL1 might serve as a diagnostic marker for HCC as well as a potential molecular target for development of novel therapeutic drugs.


Asymmetric Hydrogenation of In Situ Generated Isochromenylium Intermediates by Copper/Ruthenium Tandem Catalysis.
The first asymmetric hydrogenation of in situ generated isochromenylium derivatives is enabled by tandem catalysis with a binary system consisting of Cu(OTf)2 and a chiral cationic ruthenium-diamine complex. A range of chiral 1H-isochromenes were obtained in high yields with good to excellent enantioselectivity. These chiral 1H-isochromenes could be easily transformed into isochromanes, which represent an important structural motif in natural products and biologically active compounds. The chiral induction was rationalized by density functional theory calculations.


Assessment of open source software for CBCT in detecting additional mental foramina.
The purpose of this study was to evaluate which post-processing imaging protocol would be better to analyze the additional mental foramen (AMF) in preoperative planning with cone-beam computed tomography (CBCT) exams, and to test reproducibility of measurements, using open source software (OsiriX). The software was used to detect the cases of AMF from among 58 exams for dental implant planning in edentulous mandible areas-three cases were found. The case images were submitted to qualitative analysis using 2D orthogonal MPR, 3D-MPR and 3D volume rendering protocols by two oral and maxillofacial radiologists. Quantitative analysis used the 3D-MPR protocol; the closed polygon tool measured the mental foramen (MF) and the AMF areas; the length tool measured the distance between foramina. The measurements were performed independently by the examiners, at two different times. Intra- and interexaminer agreement was assessed using the intraclass correlation coefficient. The panoramic view did not show the MF and the AMF clearly. The AMF could be detected in the parasagittal view. 2D Orthogonal MPR was effective to observe the AMF in some cases. The 3D-MPR and 3D view protocols were the most effective to locate and analyze the AMF. In conclusion, a 3D view improves visualization when anatomical points are not clearly visible. 3D-MPR was considered a more effective post-processing imaging protocol to observe foramina relationships. The high reproducibility of measurements for anatomical MF variations was established using specific tools featured in open source software for CBCT. OsiriX is realistic and recommended for preoperative planning.


Paving the way for new research strategies in mental disorders. First part: the recurring crisis of psychiatry.
Psychiatry is going through a deep crisis, both as a scientific discipline as a medical speciality. In the present paper we consider in length what we consider to be the three aspects that could explain the situation: the recurring disappointment in classification; the persistence of dualistic perspectives in research; and third, the continuing of a localizacionism inadequate to explain normal and pathological behaviour. Psychiatry lacks a definition of mental disorder that covers all situations, there are difficulties in drawing a precise distinction between normality and psychopathology, and the majority of these "diagnostic" categories are not validated by biological criteria. Furthermore, there is still a debate on the nature of the symptoms of mental disorders, a confusion classification and diagnosis and a preoccupation with the growing inflation of diagnostic categories. Dualism is at the core of psychopathology, simply because Cartesian dualism led to the development of modern science, but the price paid includes the split-up of mental and physical phenomena and illnesses and of psychiatry and the rest of medicine. Localizationism, that is, the approach to brain function considering that particular pychological functions are carried out by particular brain areas or centers, helps to understand many clinical and psychological phenomena, but have largely fild in explaining the nature of most mental disorders. In a second part of this article we provide some strategies that could help to go beyond the present impasse.


Comment on "Quasirelativistic theory equivalent to fully relativistic theory" [J. Chem. Phys. 123, 241102 (2005)].
The connection between the exact quasirelativistic approach developed in the title reference [W. Kutzelnigg and W. Liu, J. Chem. Phys. 123, 241102 (2005)] and the method of elimination of the small component in matrix form developed previously by Dyall is explicitly worked out. An equation that links Hermitian and non-Hermitian formulations of the exact quasirelativistic theory is derived. Besides establishing a kinship between the existing formulations, the proposed equation can be employed for the derivation of new formulations of the exact quasirelativistic theory.


Identification of potent, selective, and metabolically stable peptide antagonists to the calcitonin gene-related peptide (CGRP) receptor.
Calcitonin gene-related peptide (CGRP) is a 37-residue neuropeptide that can be converted to a CGRP(1) receptor antagonist by the truncation of its first seven residues. CGRP(8-37), 1, has a CGRP(1) receptor K(i) = 3.2 nM but is rapidly degraded in human plasma (t(1/2) = 20 min). As part of an effort to identify a prolonged in vivo circulating CGRP peptide antagonist, we found that the substitution of multiple residues in the CGRP peptide increased CGRP(1) receptor affinity >50-fold. Ac-Trp-[Arg(24),Lys(25),Asp(31),Pro(34),Phe(35)]CGRP(8-37)-NH(2), 5 (K(i) = 0.06 nM) had the highest CGRP(1) receptor affinity. Using complimentary in vitro and in vivo metabolic studies, we iteratively identified degradation sites and prepared high affinity analogues with significantly improved plasma stability. Ac-Trp-[Cit(11,18),hArg(24),Lys(25),2-Nal(27,37),Asp(31),Oic(29,34),Phe(35)]CGRP(8-37)-NH(2), 32 (K(i) = 3.3 nM), had significantly increased (>100-fold) stability over 1 or 5, with a cynomolgus monkey and human in vitro plasma half-life of 38 and 68 h, respectively.


The Active Ageing-concept translated to the residential long-term care.
Active Ageing (AA), as described by the WHO (Active Ageing: a policy framework. World Health Organisation, Geneva 5), is an important concept in gerontology. Since the AA-concept has not been examined in the context of residential long-term care facilities, our study addresses this gap by describing the determinants of AA within this setting. A qualitative study with semi-structured focus groups, followed by a thematic analysis, was conducted. Through purposive sampling, four focus groups of either residents of long-term care facilities (n = 8), children of residents (n = 8), community-dwelling older people (n = 8) and gerontologists (n = 6) were formed. The thematic analysis yielded nine determinants of AA. Seven correspond to those identified by the WHO: Culture, Behaviour, Psychological Factors, Physical Environment, Social Environment, Economic Characteristics and Health and Social Care. Two new determinants were identified: Meaningful Leisure and Participation. The determinant Participation is seen as crucial to AA in residential care. This study points to a more extensive set of determinants of AA than those identified by the WHO (Active Ageing: a policy framework. World Health Organisation, Geneva 5). Staff of long-term care facilities can make use of these determinants to promote AA in their residents.


On the adequacy of static analysis warnings with respect to code smell prediction.
Code smells are poor implementation choices that developers apply while evolving source code and that affect program maintainability. Multiple automated code smell detectors have been proposed: while most of them relied on heuristics applied over software metrics, a recent trend concerns the definition of machine learning techniques. However, machine learning-based code smell detectors still suffer from low accuracy: one of the causes is the lack of adequate features to feed machine learners. In this paper, we face this issue by investigating the role of static analysis warnings generated by three state-of-the-art tools to be used as features of machine learning models for the detection of seven code smell types. We conduct a three-step study in which we (1) verify the relation between static analysis warnings and code smells and the potential predictive power of these warnings; (2) build code smell prediction models exploiting and combining the most relevant features coming from the first analysis; (3) compare and combine the performance of the best code smell prediction model with the one achieved by a state of the art approach. The results reveal the low performance of the models exploiting static analysis warnings alone, while we observe significant improvements when combining the warnings with additional code metrics. Nonetheless, we still find that the best model does not perform better than a random model, hence leaving open the challenges related to the definition of ad-hoc features for code smell prediction.


Five tumors over six years in eighth decade of life.
Over a period of six years in the eighth decade of his life, a gentleman in our care (referred to as GH) developed five primary malignancies without any known etiological connection. There is little epidemiologic data for patients presenting with more than three primary malignancies. In reviewing some of the latest literature about the characteristics and risk factors of developing the malignancies that GH presented with, we find that aspects of GH's medical history often disagree with this information. We also calculated the probability of the occurrence of GH's specific tumors and find his case is indeed rare. We conclude at this point in time that unknown host or environmental factors may have played a role in this unusual presentation of malignancies. With great interest we continue to follow-up with GH to monitor his health.


Enhanced plasmon coupling of partly embedded gold nanospheres with surrounding silicon.
Gold nanospheres (AuNSs) were partly embedded into silicon through metal-assisted chemical etching, producing multiple-dimensional coupling of the plasmon resonances with the induced image charges in the surrounding medium. Rich plasmonic features of such coupling system were revealed by single particle dark-field scattering spectra, characterizing by two splitted multipolar resonances at short wavelength region and a mixed dipolar resonance extending to infrared region. Numerical electrodynamic calculations indicated that the multipolar modes arise from the in-plane and out-of-plane quadrupolar resonances, which are excited by the horizontal and verticle electric field components, respectively, of the incident light owing to the enhanced coupling interaction. As the embedding depth increases, the degree of symmetry breaking in such nanoparticles/substrate system changes, resulting in significantly modified optical response, which supplies a new way to modulate the optical properties of plasmonic nanoparticles.


Brachytherapy in cancer cervix: Time to move ahead from point A?
Brachytherapy forms an integral part of the radiation therapy in cancer cervix. The dose prescription for intracavitary brachytherapy (ICBT) in cancer cervix is based on Tod and Meredith's point A and has been in practice since 1938. This was proposed at a time when accessibility to imaging technology and dose computation facilities was limited. The concept has been in practice worldwide for more than half a century and has been the fulcrum of all ICBT treatments, strategies and outcome measures. The method is simple and can be adapted by all centres practicing ICBT in cancer cervix. However, with the widespread availability of imaging techniques, clinical use of different dose-rates, availability of a host of applicators fabricated with image compatible materials, radiobiological implications of dose equivalence and its impact on tumour and organs at risk; more and more weight is being laid down on individualised image based brachytherapy. Thus, computed tomography, magnetic-resonance imaging and even positron emission computerized tomography along with brachytherapy treatment planning system are being increasingly adopted with promising outcomes. The present article reviews the evolution of dose prescription concepts in ICBT in cancer cervix and brings forward the need for image based brachytherapy to evaluate clinical outcomes. As is evident, a gradual transition from "point" based brachytherapy to "profile" based image guided brachytherapy is gaining widespread acceptance for dose prescription, reporting and outcome evaluation in the clinical practice of ICBT in cancer cervix.


Clinical classification of recurrent laryngeal nerve palsy.
The application of intraoperative neurophysiological monitoring (IONM) has been accepted to avoid injury of a recurrent laryngeal nerve (RLN). Loss of the neuromonitoring signal indicates nerve injury and is subdivided into segmental type and global type nerve paralysis. This study aimed to determine the course of vocal cord function recovery after definitive loss of signal (LOS) types. This retrospective study included 1,442 patients (with 2,752 nerves at risk) who had thyroidectomies between January 2018 and December 2021. Preoperative and postoperative vocal cord functions were evaluated by laryngoscopic examination. LOS occurred in 168 of 1,442 (11.7%) patients and 171 of 2,748 (6.2%) nerves at risk during surgery. Of LOS nerves of benign tumors, 74.2% showed global type. In cancer cases, segmental paralysis was more common, accounting for 51.3% of LOS nerves. Of nerves with segmental LOS in cancer patients, 55.3% needed partial layer resection for RLN invasion. Intraoperative recovery was seen in 9 of 62 nerves (14.5%) with segmental LOS and 32 of 109 (29.4%) nerves with global type LOS. The vocal cord palsy rate on postoperative days (PODs) 2-3 was lower after global type nerve paralysis (63.6%) than after segmental loss (84.9%). At 6 months postoperatively, the rate of vocal cord paralysis in benign tumors was not significantly different between segmental type and global type (P=0.586). However, cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively (rate of nerve palsy: segmental 40.0% vs. global 3.4%) (P<0.001). The intraoperative recovery rate and early nerve recovery rate are significantly higher for patients with global LOS than for patients with segmental LOS. Cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively.


Application of spline wavelet transformation to the analysis of extended energy-loss fine structure.
We propose a new analysis method of the extended energy-loss fine structure (EXELFS), applying the multi-resolution analysis (MRA) in the wavelet transformation. We select the cardinal spline wavelet where the rank-4 cardinal spline function is used as a scaling function to construct the mother wavelet. In contrast with the conventional analysis method, the present method is efficient in filtering out the high-frequency noise and low-frequency components introduced by the numerical analysis process without distorting the original signal components, which promises quantitative analyses with less uncertainties.


Assembly of a tetrathiafulvalene-anthracene dyad on the surfaces of gold nanoparticles: tuning the excited-state properties of the anthracene unit in the dyad.
Due to the unique features of the tetrathiafulvalene (TTF) unit, such as the electron-donating ability and presence of methylthio groups, dyad 1 can be assembled on the surfaces of gold nanoparticles, as indicated by absorption, electrochemical, and fluorescent-spectral studies. Dyad 1 can also be disassembled by the addition of thiols. Assembly of dyad 1 on the surfaces of gold nanoparticles leads to the formation of a triad (A1-D-A2), which in turn modulates the photoinduced electron-transfer process within dyad 1. Accordingly, the fluorescence intensity of dyad 1, after assembly with gold nanoparticles, increases, and the fluorescence lifetime is prolonged. Furthermore, the assembly of dyad 1 on gold nanoparticles facilitates photodimerization of the anthracene units of dyad 1. Both fluorescence and photodimerization are associated with the excited-state behavior of the anthracene unit, thus it may be concluded that the excited-state properties of the anthracene unit can be tuned upon complexation with gold nanoparticles.


IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma.
Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.


Diarrhetic shellfish poisoning, Washington, USA, 2011.
Diarrhetic shellfish poisoning is a gastrointestinal illness caused by consumption of bivalves contaminated with dinophysistoxins. We report an illness cluster in the United States in which toxins were confirmed in shellfish from a commercial harvest area, leading to product recall. Ongoing surveillance is needed to prevent similar illness outbreaks.


Upgraded IR beamline at UVSOR.
BL6A1, a far-infrared (FIR) beamline at UVSOR, originally built in 1986, has been recently upgraded. The upgrade included the introduction of a second FT-IR spectrometer, making it possible to cover the entire FIR-IR range (3-10000 cm(-1)) in one sequence of measurements, without having to open the sample chamber; the beamline has become a more convenient and powerful experimental station than before. The upgrade is also expected to enable such experiments as IR studies of molecules adsorbed on solid surfaces, and time-resolved IR spectroscopies. This paper describes the characteristics of the upgraded BL6A1.


[Central Slice Theorem-based Relationship between 1D-NPS Obtained by the Slit Method and 2D-NPS for CT Images].
The method using a numerical slit (slit method) is used commonly to obtain the one-dimensional (1D) noise power spectrum (NPS) in computed tomography. However, the relationship between the 1D-NPS obtained by the slit method and the original two-dimensional (2D) NPS derived by the 2D Fourier transformation has not been elucidated clearly. The purpose of this study was to clarify their relationship based on the well-known central slice theorem (projection slice theorem) and validate it using computer simulation analysis. With the application of the central slice theorem, we described that the 1D-NPS obtained by the slit method was equal to the central slice (profile) in the 2D-NPS when we set the slit length to the maximum (i.e. the matrix size of the noise image). To verify this, we generated computer-simulated noise images with the known 2D-NPS (true 2D-NPS). From those images, we obtained the 1D-NPS that was obtained by the slit method and compared it with the central slice in the true 2D-NPS. When we set the slit length to the maximum, the 1D-NPS obtained by the slit method showed good agreement with the central slice in the true 2D-NPS. We clarified the relationship between the 1D-NPS obtained by the slit method and the 2D-NPS using a theoretical approach and the computer simulation. We had to maximize the slit length to achieve the accurate measurement of the 1D-NPS using the slit method.


Reversible pH Responsive Bovine Serum Albumin Hydrogel Sponge Nanolayer.
A pH dependent reversible sponge like behavior of a bovine serum albumin (BSA) nanolayer adsorbed at the gold-saline interface is revealed by quartz crystal microbalance with dissipation (QCM-D), atomic force microscope (AFM) and contact angle measurements. During the saline rinsing cycles, the BSA layer adsorbs water molecules at pH 7.0 and releases them at pH 4.5. The phenomenon remains constant and reproducible upon multiple rinsing cycles. The BSA layer thickness also increases upon rinsing with saline at pH 7.0 and reverses back to its original thickness at pH 4.5. Varying ionic strength with water further desorbs more water molecules from the BSA layer, which decreases its mass and thickness. However, upon both pH and ionic strength changes, all the BSA molecules remain adsorbed irreversibly at the gold interface and only the sorption of water molecules occurs. The study aims at engineering high efficiency pH-responsive biodiagnostics and drug delivery systems.


Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys.
In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates. CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology. In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity.


Dentin Erosion: Method Validation and Efficacy of Fluoride Protection.
The aging population experiences more gingival recession and root exposure which increases the opportunity for dentin erosion. This study tested the use of transverse microradiography (TMR) methods to assess dentin erosion and the interaction between fluoride and citric acid on the amount of erosion in the dentin samples. In a 4 × 3 interaction experimental design, four fluoride concentrations (0.00, 25.0, 50.0, and 100.0 mg/L) and three citric acid concentrations (0.0, 0.25, and 1.00%) were combined to form 12 experimental solutions. Forty-eight dentin samples were placed in the experimental solutions for 1 and 4 h and the amount of surface lost was determined by TMR methods. The resolution of the TMR method was 0.9 μm per pixel with a 0.1% and a 5% confidence interval of ±4.2 μm. Dentin erosion increased with the concentration of citric acid and time, the erosion decreased when concentration of fluoride was increased. Effects due to fluoride and citric acid concentrations individually, and their interaction on the amount of erosion observed was statistically significant (p < 0.0001). This study found that TMR methods are appropriate and that 25.0 mg/L was the optimal fluoride concentration to protect dentin from a 1.00% citric acid challenge.