Rapid development of an integrated remote programming platform for neuromodulation systems through the biodesign process.
Treating chronic symptoms for pain and movement disorders with neuromodulation therapies involves fine-tuning of programming parameters over several visits to achieve and maintain symptom relief. This, together with challenges in access to trained specialists, has led to a growing need for an integrated wireless remote care platform for neuromodulation devices. In March of 2021, we launched the first neuromodulation device with an integrated remote programming platform. Here, we summarize the biodesign steps taken to identify the unmet patient need, invent, implement, and test the new technology, and finally gain market approval for the remote care platform. Specifically, we illustrate how agile development aligned with the evolving regulatory requirements can enable patient-centric digital health technology in neuromodulation, such as the remote care platform. The three steps of the biodesign process applied for remote care platform development are: (1) Identify, (2) Invent, and (3) Implement. First, we identified the unmet patient needs through market research and voice-of-customer (VOC) process. Next, during the concept generation phase of the invention step, we integrated the results from the VOC into defining requirements for prototype development. Subsequently, in the concept screening phase, ten subjects with PD participated in a clinical pilot study aimed at characterizing the safety of the remote care prototype. Lastly, during the implementation step, lessons learned from the pilot experience were integrated into final product development as new features. Following final product development, we completed usability testing to validate the full remote care system and collected preliminary data from the limited market release experience. The VOC data, during prototype development, helped us identify thresholds for video quality and needs priorities for clinicians and patients. During the pilot study, one subject reported anticipated remote-care-related adverse events that were resolved without sequelae. For usability analysis following final product development, the failure rates for task completion for both user groups were about 1%. Lastly, during the initial 4 weeks of the limited market release experience, a total of 858 remote care sessions were conducted with a 93% success rate. Overall, we developed a remote care platform by adopting a user-centric approach. Although the system intended to address pre-COVID19 challenges associated with disease management, the unforeseen overlap of the study with the pandemic elevated the importance of such a system and an innovative development process enabled us to advance a patient-centric platform to gain regulatory approval and successfully launch the remote care platform to market.


Africa Centres for Disease Control and Prevention Is Closing Gaps in Disease Detection.
In 2017, the African Union established a new continent-wide public health agency, the Africa Centres for Disease Control and Prevention (Africa CDC). Many outbreaks are never detected in Africa, and among outbreaks that are detected, countries often respond slowly and ineffectively. To address these problems, Africa CDC is working to increase early detection and reporting, improve access to diagnostic tests, promote novel laboratory approaches, help establish national public health institutes, improve information exchange between health agencies, and enhance recording and reporting of acute public health events and vital statistics. The health security of Africa will be strengthened by this new public health agency's ability to build comprehensive, timely disease surveillance that rapidly detects and contains health threats.


The best-interests standard as threshold, ideal, and standard of reasonableness.
The best-interests standard is a widely used ethical, legal, and social basis for policy and decision-making involving children and other incompetent persons. It is under attack, however, as self-defeating, individualistic, unknowable, vague, dangerous, and open to abuse. The author defends this standard by identifying its employment, first, as a threshold for intervention and judgment (as in child abuse and neglect rulings), second, as an ideal to establish policies or prima facie duties, and, third, as a standard of reasonableness. Criticisms of the best-interests standard are reconsidered after clarifying these different meanings.


Pediatric Weight Management Interventions in Primary Care Settings: A Meta-Analysis.
Although the primary care setting has been recommended as an acceptable environment for pediatric overweight/obesity treatment, a quantitative analysis has not been conducted to determine the effectiveness of pediatric weight management interventions delivered in these settings. Therefore, the purpose of the current study was to conduct a meta-analysis of weight management interventions for youth in primary care settings. A literature search using PsycINFO and PubMed was conducted to identify articles published through October 2015. Eighteen studies (3,358 participants) met inclusion criteria; studies included a treatment and comparison group and targeted individuals or families for treatment. Study characteristics were coded, and study rigor of articles was assessed. The overall effect size for change in body mass index (BMI) in primary care weight management interventions compared to control groups was small but statistically significant (d = 0.26, 95% CI [.14, .38]). The number of treatment contacts, treatment months, and visits with a pediatrician emerged as significant moderators of outcome, such that BMI reduction was positively related to greater contact. In comparison to control conditions, weight management programs in primary care settings can be effective for BMI reduction, suggesting that primary care is a suitable setting for treatment of pediatric overweight/obesity. Additionally, treatments that were longer in duration, included more contacts (in person or phone), and included more contacts by a pediatrician had greater impact on BMI reduction. Future studies should continue to examine other aspects of acceptability and accessibility as well as demonstrate the effectiveness of interventions on improving psychosocial outcomes. (PsycINFO Database Record


Insulin receptor substrate (IRS)-1 and IRS-2 are tyrosine-phosphorylated and associated with phosphatidylinositol 3-kinase in response to brain-derived neurotrophic factor in cultured cerebral cortical neurons.
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophins, promotes differentiation and survival of various types of neurons in the central nervous system. BDNF binds to and activates the tyrosine kinase receptor, TrkB, initiating intracellular signaling and exerting its effects. Phosphatidylinositol 3-kinase (PI3-K), which has been implicated in promotion of neuronal survival by neurotrophic factors, is a component in the signaling pathway of BDNF. We examined how BDNF activates PI3-K in cultured cerebral cortical neurons. We found that insulin receptor substrate (IRS)-1 and -2 are involved in the BDNF signaling pathway that activates PI3-K. IRS-1 and -2 were tyrosine-phosphorylated and bound to PI3-K in response to BDNF. This BDNF-stimulated signaling via IRS-1 and -2 was inhibited by K-252a, an inhibitor of Trk tyrosine kinase. In addition, signaling via IRS-1 and -2 was markedly sustained as well as the BDNF-induced tyrosine phosphorylation of TrkB. On the other hand, we observed no association of PI3-K with TrkB in response to BDNF. These results indicate that the activation of TrkB by BDNF induces the activation of PI3-K via IRS-1 and -2 rather than by a direct interaction of TrkB with PI3-K in cultured cortical neurons.


Thrombolysis in patients with marked clinical fluctuations in neurologic status due to cerebral ischemia.
It is unclear whether thrombolysis benefits patients with fluctuating neurologic symptoms. To evaluate the clinical course of patients with acute stroke who presented with marked fluctuations in neurologic status and received thrombolytic therapy. Prospective analysis. London Health Science Centre University Hospital, London. Patients We prospectively identified patients who were treated with intravenous or intra-arterial recombinant tissue plasminogen activator between January 1, 2004, and January 1, 2006. For this analysis, we chose patients who had marked fluctuation in neurologic status at presentation and who received thrombolytic therapy. Main Outcome Measure Fluctuation of neurologic deficits, defined as a 4-point or greater increase or decrease in the National Institutes of Health Stroke Scale (NIHSS) score. Among 127 patients, 13 (10.2%) had clinical fluctuations. Patients with fluctuations presented with a lower NIHSS score (median, 7; interquartile range, 10-17) compared with patients without fluctuations (median, 12; interquartile range, 10-17) (P < .001). Fluctuation of symptoms or signs ceased after thrombolysis. At 24 hours after stroke, the median NIHSS score was 2 (range, 1-12). All patients had favorable neurologic and functional outcomes at 3 months after thrombolysis (modified Rankin scale score, 0-2). Thrombolysis may benefit patients with fluctuating symptoms or signs due to cerebral ischemia.


Experimental transmission of sleeping disease in one-year-old rainbow trout, Oncorhynchus mykiss (Walbaum), induced by sleeping disease virus.
Sleeping disease (SD) is a serious disease of rainbow trout, Oncorhynchus mykiss, reared in fresh water caused by sleeping disease virus (SDV). In this study a detailed clinical, histological, virological and serological description of the experimental reproduction of SD in 1-year-old rainbow trout exposed to SDV was carried out. Two hundred disease-free fish were intraperitoneally inoculated with a SDV isolate and 100 fish were inoculated with an uninfected cell culture lysate as a negative control. Infected and control fish were randomly removed at days 4, 7, 14, 21, 42 and 70 post-infection. Blood and tissues were collected for virus isolation, histopathological examination and serum neutralization. SDV was detected in serum, kidney and brain of infected fish from 4 to 21 days post-infection (dpi). Characteristic pathological lesions were observed in infected fish as early as 7 dpi. Lesions were first detected in exocrine pancreas and subsequently observed in heart and skeletal muscle. Neutralizing antibodies to SDV were detected in infected fish from 14 to 70 dpi. Infected fish displayed typical signs of SD 1-month pi and the mortality reached 18.7% within 44 days. This study experimentally reproduced all the pathognomonic features of natural outbreaks of SD in 1-year-old rainbow trout.


Coherent and incoherent scatterings for measurement of mandibular bone density and stable iodine content of tissue.
The aim of present study is to investigate the feasibility of gamma ray scattering for measurements of mandibular bone density and stable iodine content of tissue. Scattered spectra from solutions of K(2)HPO(4) in distilled water (a phantom simulating the mandibular bone) and KI in distilled water filled in a thin plastic vial (a phantom simulating the kinetics of thyroid iodine) are recorded for 59.54 and 145 keV incident gamma rays, respectively. A high-purity germanium detector is placed at various angular positions to record the scattered spectra originating from interactions of incident gamma rays with the phantom. The measured intensity ratio of coherent to incoherent scattered gamma rays, corrected for photo-peak efficiency of HPGe detector, absorption of gamma rays in air column present between phantom and detector, and self-absorption in the phantom, is found to be increasing linearly with increase in concentration of K(2)HPO(4) and KI in distilled water within experimental estimated error of <6%. The regression lines, obtained from experimental data for intensity ratio, provide the bone density and stable iodine contents of thyroid. The present non-destructive technique has the potential for a measure of mandibular bone density and stable iodine contents of thyroid.


Mucosal expression of Ca and P transporters and claudins in the small intestine of broilers is altered by dietary Ca:P in a limestone particle size dependent manner.
High calcium (Ca) intake and fine limestone reduces precaecal phosphorus (P) absorption independently of P solubility in broilers. This study aimed to determine whether dietary total Ca: total P ratio (Ca:P) and limestone particle size (LPS) affect gene expression of P transporters in the small intestine. A total of 384 one-day-old Ross 308 male broiler chickens received diets low (0.50), medium (1.00) or high (1.75) in Ca:P containing either fine (160 μm) or coarse (1062 μm) limestone, in a 3×2 factorial arrangement. Expression of Ca- and P-related genes were determined using real-time quantitative PCR (RT-qPCR) in duodenum and jejunum. Increasing dietary Ca:P decreased duodenal calcium-sensing receptor (CaSR), calbindin-D28k (CaBP-D28k), plasma membrane Ca-ATPase 1 (PMCA1) and sodium-coupled P cotransporter type IIb (NaPi-IIb), but not transient receptor potential canonical 1 (TRPC1) mRNA. This effect was greater with fine limestone when Ca:P increased from low to medium, but greater with coarse limestone when increased from medium to high. A similar inhibitory effect was observed for jejunal CaBP-D28k expression where increasing dietary Ca:P and fine limestone decreased CaSR mRNA, while dietary Ca:P decreased TRPC1 mRNA only for coarse limestone. It also decreased jejunal NaPi-IIb mRNA irrespective of LPS. Dietary treatments did not affect jejunal PMCA1 mRNA expression or that of inorganic phosphate transporter 1 and 2 and xenotropic and polytropic retrovirus receptor 1 in both intestinal segments. Dietary Ca increase reduced mucosal claudin-2 mRNA in both segments, and jejunal zonula occludens-1 (ZO-1) mRNA only for coarse limestone. In conclusion, increasing dietary Ca:P reduced expression of duodenal P transporters (NaPi-IIb) in a LPS dependent manner, hence Ca induced reduction in intestinal P absorption is mediated by decreasing P transporters expression. Dietary Ca reduces Ca digestibility by downregulating mRNA expression of both Ca permeable claudin-2 and Ca transporters (CaBP-D28k, PMCA1).


Age differences in overlapping-task performance: evidence for efficient parallel processing in older adults.
Two psychological refractory period (PRP) experiments were conducted to examine overlapping processing in younger and older adults. A shape discrimination task (triangle or rectangle) for Task 1 (T1) and a lexical-decision task (word or nonword) for Task 2 (T2) were used. PRP effects, response time for T2 increasing as stimulus onset synchrony (SOA) decreased, were obtained for both age groups. The effect of word frequency on T2 was smaller at the short SOA than at the long SOA, reflecting slack effects, which were larger for older than younger adults in both experiments. These results suggest that older adults can perform lexical access of T2 in parallel with the processing of T1 at least as efficiently as younger adults.


Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia.
Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans and confirmed by meta-analysis of published linkage data. Systematic fine mapping using extended Icelandic pedigrees identified an associated haplotype in the gene neuregulin 1 (NRG1), also known as heuregulin, glial growth factor, NDF43 and ARIA. A 290 kb core at risk haplotype at the 5' end of the gene (HAP(ICE)), defined by five SNPs and two microsatellite polymorphisms was found to be associated with schizophrenia in the Icelandic and Scottish populations. A number of subsequent independent studies have attempted to replicate the association, and while some have been successful, the associated haplotype is not always HAP(ICE). Furthermore, no obviously functional or pathogenic variants have been identified, and the relationship between the gene and schizophrenia has remained inconclusive. To reconcile these conflicting findings and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 13 published population-based and family-based association studies up to November 2005. We analysed data from the SNP markers SNP8NRG241930, SNP8NRG243177, SNP8NRG221132 and SNP8NRG221533, and the microsatellite markers 478B14-848, 420M9-1395. Across these studies, strong positive association was found for all six polymorphisms. The haplotype analysis also showed significant association in the pooled international populations (OR=1.22, 95% CI 1.15-1.3, P=8 x 10(-10)). In Asian populations, the risk haplotype was focused around the two microsatellite markers, 478B14-848, 420M9-1395 (haplotype block B), and in Caucasian populations with the remaining four SNP markers (haplotype block A). This meta-analysis supports the involvement of NRG1 in the pathogenesis of schizophrenia, but with association between two different but adjacent haplotypes blocks in the Caucasian and Asian populations.


Isolation of protoplasts and vacuoles from storage tissue of red beet.
A fast and efficient method is described for the isolation of protoplasts and vacuoles from storage tissue of Beta vulgaris L. The viability of the isolated protoplasts is indicated by the development within a few hours of plasma strands with active cyclosis as well as by transport activity.The effect of aging of the tissue on the yield and on the properties of the protoplasts is examined. Adding 1 millimolar dithiothreitol to the water during the aging of the tissue prevents a change of the cell wall structure which otherwise reduces the protoplast yield within 2 days to zero. When protoplasts are isolated from tissue after different times of aging, they show an increase in transport activity which parallels that in the intact tissue.


Hysteresis in Mental Workload and Task Performance: The Influence of Demand Transitions and Task Prioritization.
We examine how transitions in task demand are manifested in mental workload and performance in a dual-task setting. Hysteresis has been defined as the ongoing influence of demand levels prior to a demand transition. Authors of previous studies predominantly examined hysteretic effects in terms of performance. However, little is known about the temporal development of hysteresis in mental workload. A simulated driving task was combined with an auditory memory task. Participants were instructed to prioritize driving or to prioritize both tasks equally. Three experimental conditions with low, high, and low task demands were constructed by manipulating the frequency of lane changing. Multiple measures of subjective mental workload were taken during experimental conditions. Contrary to our prediction, no hysteretic effects were found after the high- to low-demand transition. However, a hysteretic effect in mental workload was found within the high-demand condition, which degraded toward the end of the high condition. Priority instructions were not reflected in performance. Online assessment of both performance and mental workload demonstrates the transient nature of hysteretic effects. An explanation for the observed hysteretic effect in mental workload is offered in terms of effort regulation. An informed arrival at the scene is important in safety operations, but peaks in mental workload should be avoided to prevent buildup of fatigue. Therefore, communication technologies should incorporate the historical profile of task demand.


Effects of green light emitting diode light during incubation and dietary organic macro and trace minerals during rearing on tibia characteristics of broiler chickens at slaughter age.
This study was designed to evaluate the effects of green light emitting diode (LED) light during incubation and dietary organic macro and trace minerals during rearing on tibia morphological, biophysical, and mechanical characteristics of broiler chickens at slaughter age. The experiment was setup as a 2 × 2 × 2 factorial arrangement, with the following treatments: 1) light during incubation (green LED light or darkness), 2) macro mineral source during rearing (organic or inorganic Ca and P), and 3) trace mineral source during rearing (organic or inorganic Fe, Cu, Mn, Zn, and Se). A total of 2,400 eggs (Ross 308) were either incubated under green LED light (16L:8D) or in complete darkness. After hatch, a total of 864 male broiler chickens were reared until slaughter age (day 42) and provided with 1 of 4 diets, differing in macro and/or trace mineral source. During rearing, the experiment had a complete randomized block design with 9 replicate pens per treatment and 12 chickens per pen. At slaughter age (day 42), 2 chickens per replicate were randomly selected and tibia bones were obtained. Tibia weight, length, thickness, osseous volume, pore volume, total volume, mineral content, mineral density, ultimate strength, and stiffness were determined. Green LED light during incubation did not affect any of the tibia characteristics. Dietary organic macro minerals positively affected most of the tibia morphological, biophysical, and mechanical characteristics compared to the inorganic macro minerals, whereas trace mineral sources did not affect tibia characteristics. It can be concluded that dietary organic macro minerals Ca and P stimulated tibia characteristics, whereas green LED light during incubation and dietary trace minerals during rearing did not affect tibia characteristics, locomotion, or leg disorders.


[Cognitive behavior therapy for the treatment of alcoholism].
The cognitive-behavioral model for the treatment of alcoholism is mainly based on social learning and conditioning theories. Clinical applications emphasize behavioral changes with acquisition of new skills and avoidance strategies. Individual or group therapy is in the form of cognitive-behavioral psychoeducational modules which are designed to take account of the degree of neuropsychological impairment and adopt specific objectives in accordance with patient motivation.


[Adjustable action of pi-shen recipe on immune function in mice with L1210 ascites].
Proliferation of Con A stimulated splenic lymphocyte was examined by incorporation of 3H-thymidine. Fluorescence polarization of DPH labelled splenic lymphocyte and bone marrow cells was measured. Proliferation of Con A stimulated splenic lymphocyte in DBA inbred healthy mice was higher than that of L1210 mice but fluorescence polarization of DPH labelled splenic lymphocyte in same healthy mice was lower than that of L1210 mice. i.e. membranous lipid lymphocyte fluidity of lymphocyte in the healthy mice was smaller than that of L1210 mice. 9 days after administration of Pi-Shen recipe by tube stomach proliferation of Con A-lymphocyte in the healthy mice has been increased. The recipe adjusted splenic lymphocyte membrane lipid fluidity of L1210 mice to level of those in healthy mice. Effects of Pi-Shen recipe on lipid fluidity of bone marrow cell membrane of L1210 mice were almost similar to that in splenic lymphocytes. These studies suggest that the mechanism on adjustable role of Pi-Shen recipe on T-lymphocyte function related to lymphocyte membrane lipid fluidity.


One-year study of occupational human immunodeficiency virus postexposure prophylaxis.
A 12-month experience with human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) in a tertiary care center was evaluated for timeliness of treatment and adherence to treatment recommendations. Forty-six health care workers were started on HIV PEP. Risk status of the source patient, rather than type of exposure, was a significant determinant for both initiating and completing treatment. Of those exposed to HIV-positive sources, 79% completed the full 28 days of therapy. Only 22% of all health care workers who started PEP discontinued treatment because of adverse effects. Excluding three cases with significant delays in reporting and one in which treatment was controversial, the mean time from exposure to first dose of PEP was 1 hour and 46 minutes. The use of a defined treatment protocol, with supporting educational material and PEP medication immediately available, is an effective way of managing HIV exposures.


Mechanism of sulfate transport inhibition by cycloheximide in plant tissues.
Inhibition by cycloheximide of sulfate transport in both barley roots (Hordeum vulgare L.) and potato tuber (Solanum tuberosum L.) increases with increasing inhibitor concentration only to a limited extent, depending on the length of the tissue incubation with the inhibitor. In contrast to this, increasing concentrations of dinitrophenol have a rapid and total inhibitory effect on the active transport. Leucine transport in the same tissues is strongly inhibited by dinitrophenol but is not affected by cycloheximide, whereas incorporation into protein is mainly inhibited by cycloheximide. It appears that the mechanism of transport inhibition by cycloheximide in plant tissues consists in stopping new carrier synthesis and not in the disruption of energy flow. Sulfate carriers show comparable decay rates in barley roots and potato tuber, the mean life being shorter than that of the leucine carriers. These appear more stable in roots than in storage tissues.


The effects of proteasomal inhibition on synaptic proteostasis.
Synaptic function crucially depends on uninterrupted synthesis and degradation of synaptic proteins. While much has been learned on synaptic protein synthesis, little is known on the routes by which synaptic proteins are degraded. Here we systematically studied how inhibition of the ubiquitin-proteasome system (UPS) affects the degradation rates of thousands of neuronal and synaptic proteins. We identified a group of proteins, including several proteins related to glutamate receptor trafficking, whose degradation rates were significantly slowed by UPS inhibition. Unexpectedly, however, degradation rates of most synaptic proteins were not significantly affected. Interestingly, many of the differential effects of UPS inhibition were readily explained by a quantitative framework that considered known metabolic turnover rates for the same proteins. In contrast to the limited effects on protein degradation, UPS inhibition profoundly and preferentially suppressed the synthesis of a large number of synaptic proteins. Our findings point to the importance of the UPS in the degradation of certain synaptic proteins, yet indicate that under basal conditions most synaptic proteins might be degraded through alternative pathways.


Protein tyrosine phosphorylation under capacitating conditions in porcine fresh spermatozoa and sperm cryopreserved with and without alpha tocopherol.
The aim of this study was to evaluate the capacitation behaviour of fresh and alpha-tocopherol frozen spermatozoa. Spermatozoa frozen with or without alpha-tocopherol and fresh semen were incubated under capacitating conditions. Aliquots were collected at 0, 15, 30, 45, 60, 90, 120 and 180 min of incubation time. Parameters of semen quality were evaluated by optical microscopy and capacitation was determined by the epifluorescence chlortetracycline technique. Protein tyrosine phosphorylation was examined by Western immunoblotting. Motility, viability and intact spermatozoa were higher (P < 0.05) in fresh semen compared with frozen samples. These parameters significantly decreased, in every treatment, throughout the incubation time. Fresh semen showed a progressive increase in capacitated spermatozoa, reaching 25 +/- 3% at 180 min. Cryopreserved semen had a fast increase at the beginning of incubation time (28 +/- 5% at 45 min and 28 +/- 3% at 30 min for samples with or without alpha-tocopherol, respectively). The amount of an MW 32 kDa tyrosine-phosphorilated protein, associated with capacitation, increased throughout incubation for fresh semen and spermatozoa cryopreserved with alpha-tocopherol. The supplementation with alpha-tocopherol preserved sperm plasma membrane, reflected not only in the acrosome integrity but also in a greater efficiency of energy production.


180° turn while walking: characterization and comparisons between subjects with and without stroke.
[Purpose] Limitations in performing the 180°-turning increase the risk of falls and disabilities in stroke patients. The aim of this study was to characterize and compare the 180°-turning between people with and without stroke, considering the direction towards which they turned. [Subjects and Methods] Fourteen subjects with stroke and 14 matched healthy controls performed the 180°-turning twice while walking: towards the self-selected, and the opposite directions. The turning performances were recorded using three video cameras. The videos were randomly analyzed by a single examiner, who characterized the turning, while considering the time required to complete the task, the number of steps, balance, and turning type. Friedman Tests and ANOVA (2 × 2) were used to compare the groups and turning direction factors (turning towards the self-selected versus opposite sides, and towards the paretic/non-dominant versus non-paretic/dominant sides). [Results] No interaction between the groups and turning directions, and no significant differences between the turning directions were found. However, significant differences were found between the groups for all variables used to characterize the turning performance, except for the type of turning. [Conclusion] Stroke subjects demonstrated poor performance on the 180°-turning, regardless of the turning direction. Duration, number of steps, and balance loss indicated difficulties in turn performance.


Visible light photocatalytic H₂-production activity of CuS/ZnS porous nanosheets based on photoinduced interfacial charge transfer.
Visible light photocatalytic H(2) production through water splitting is of great importance for its potential application in converting solar energy into chemical energy. In this study, a novel visible-light-driven photocatalyst was designed based on photoinduced interfacial charge transfer (IFCT) through surface modification of ZnS porous nanosheets by CuS. CuS/ZnS porous nanosheet photocatalysts were prepared by a simple hydrothermal and cation exchange reaction between preformed ZnS(en)(0.5) nanosheets and Cu(NO(3))(2). Even without a Pt cocatalyst, the as-prepared CuS/ZnS porous nanosheets reach a high H(2)-production rate of 4147 μmol h(-1) g(-1) at CuS loading content of 2 mol % and an apparent quantum efficiency of 20% at 420 nm. This high visible light photocatalytic H(2)-production activity is due to the IFCT from the valence band of ZnS to CuS, which causes the reduction of partial CuS to Cu(2)S and thus enhances H(2)-production activity. This work not only shows a possibility for substituting low-cost CuS for noble metals in the photocatalytic H(2) production but also for the first time exhibits a facile method for enhancing H(2)-production activity by photoinduced IFCT.


Linear ultrasonic motor for absolute gravimeter.
Thanks to their compactness and suitability for vacuum applications, linear ultrasonic motors are considered as substitutes for classical electromagnetic motors as driving elements in absolute gravimeters. Still, their application is prevented by relatively low power output. To overcome this limitation and provide better stability, a V-type linear ultrasonic motor with a new clamping method is proposed for a gravimeter. In this paper, a mechanical model of stators with flexible clamping components is suggested, according to a design criterion for clamps of linear ultrasonic motors. After that, an effect of tangential and normal rigidity of the clamping components on mechanical output is studied. It is followed by discussion of a new clamping method with sufficient tangential rigidity and a capability to facilitate pre-load. Additionally, a prototype of the motor with the proposed clamping method was fabricated and the performance tests in vertical direction were implemented. Experimental results show that the suggested motor has structural stability and high dynamic performance, such as no-load speed of 1.4m/s and maximal thrust of 43N, meeting the requirements for absolute gravimeters.


Resistance to erythroleukemia in immunodeficient xid- CBA/N mice with susceptibility after immune stimulation.
CBA/N (xid-) mice failed to develop erythroleukemia when inoculated with an NB-tropic, anemia-causing Friend virus stock (FVA), while Fv-2ss mouse strains succumbed rapidly to the characteristic Friend disease, even after a virus dose 30-fold lower than that given to CBA/N mice. Immunization with bacterial antigens or with spleen cell allografts prior to FVA inoculation rendered CBA/N mice highly susceptible to FVA. Transplantation studies confirmed that non-immunized CBA/N mice were able to both support erythroleukemic cells and permit erythroleukemic transformation, thus arguing against host defense mechanisms as a cause of resistance. On the basis of early erythroid progenitor cell sensitivity to hydroxyurea in vivo, the CBA/N strain appeared to have the FVA sensitive genotype (Fv-2ss). These results imply that CBA/N mice are not intrinsically resistant to FVA and that an as yet unknown type of immunological activity, evoked both by various immunizations and allogeneic transplantation, is required for Friend leukemogenesis in this immunodeficient inbred strain. These findings further suggest that the erythroid target cells transformed by Friend viruses are influenced by immunological activity.


The genetic history of Mayotte and Madagascar cattle breeds mirrors the complex pattern of human exchanges in Western Indian Ocean.
Despite their central economic and cultural role, the origin of cattle populations living in Indian Ocean islands still remains poorly documented. Here, we unravel the demographic and adaptive histories of the extant Zebus from the Mayotte and Madagascar islands using high-density SNP genotyping data. We found that these populations are very closely related and both display a predominant indicine ancestry. They diverged in the 16th century at the arrival of European people who transformed the trade network in the area. Their common ancestral cattle population originates from an admixture between an admixed African zebu population and an Indian zebu that occurred around the 12th century at the time of the earliest contacts between human African populations of the Swahili corridor and Austronesian people from Southeast Asia in Comoros and Madagascar. A steep increase in the estimated population sizes from the beginning of the 16th to the 17th century coincides with the expansion of the cattle trade. By carrying out genome scans for recent selection in the two cattle populations from Mayotte and Madagascar, we identified sets of candidate genes involved in biological functions (cancer, skin structure, and UV-protection, nervous system and behavior, organ development, metabolism, and immune response) broadly representative of the physiological adaptation to tropical conditions. Overall, the origin of the cattle populations from Western Indian Ocean islands mirrors the complex history of human migrations and trade in this area.


Identification of immunogenic cell wall-associated proteins of Streptococcus suis serotype 2.
Streptococcus suis serotype 2 (SS2) is a porcine and human pathogen with adhesive and invasive properties. The absence of suitable vaccine or virulent marker can be the bottleneck to control SS2 infection. An immunoproteome-based approach was developed to identify candidate antigens of SS2 for vaccine development. Hyperimmune sera, convalescent sera, and control sera were analyzed for reactivity by Western Blot against SS2 cell wall-associated proteins (WAPs) separated by 2-DE. A total of 34 proteins were identified by immunoproteomic analysis, of which 15 were recognized by both hyperimmune sera and convalescent sera, including most WAPs currently characterized as SS2 vaccine candidate antigens: muramidase-released protein (MRP), surface protein SP1 (Sao), and glyceraldehyde-3-phosphate dehydrogenase (GapdH). The novel immunogenic proteins may be developed as alternative antigens for further study of SS2 vaccine and diagnostics.


Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1.
RALGDS is a 115 kDa protein which was identified by its ability to enhance guanine nucleotide exchange for the ras family member ral. It also binds to activated ras and rap1, and appears to function as part of a signalling complex in downstream events following rap1 activation. Here we report the identification of full-length cDNA clones for human RALGDS, isolated from a brain cDNA library. The predicted protein has strong sequence homology to rat and murine isoforms of RALGDS in the N- and C-terminal regions, but an internal region (aa 250-380) shows relatively high divergence with only 42% identical amino acid residues. The human RALGDS gene is contained within a 30 kb region of 9q34, approximately 200 kb proximal to the ABO gene, within the current critical region for the tuberous sclerosis gene TSC1. Partial genomic structure was determined; it consists of at least 11 exons. Based upon analysis of Southern blots from 110 TSC patients, genomic DNA SSCP analysis, and RT-PCR analysis which demonstrated RNA expression of both alleles in patients from 9q34-linked TSC families using intragenic polymorphisms, we conclude that RALGDS is not likely to be TSC1.


Preparation of a New Solid-Phase Microextraction Fiber Based on Molecularly Imprinted Polymers for Monitoring of Phenobarbital in Urine Samples.
A simple solid-phase microextraction technique using molecularly imprinted polymers (MIP-SPME) was prepared to monitor phenobarbital in urine samples. In this technique, the fiber was prepared via insertion of the modified stainless-steel wire in the reaction solution including 3-aminopropyltriethoxysilane and tetraethyl orthosilicate in the presence of an acidic catalyst (acetic acid). The fabricated MIP-SPME fiber was utilized to selectively extract phenobarbital from urine samples and prepare it for detection through high-performance liquid chromatography with ultraviolet detection. The synthesized MIPs were characterized by several techniques such as Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, and thermal gravimetric analysis. The effects of various influencing factors on the extraction yield of phenobarbital were considered and optimized. The conditions that yielded the maximum extraction efficiency were as follows: pH of 5, 25 min extraction time, 500 rpm stirring rate, 15 min desorption time and using methanol as elution solvent. Within the range of concentrations of 0.02 to 100 μg mL-1, the method had linear characteristics, with a suitable coefficient of determination (0.9983). We determined limits of detection and limits of quantification to be 9.88 and 32.9 ng mL-1, respectively. The repeatability and reproducibility of the prepared fibers were 4.6 and 6.5%, respectively.


Spatially Filtered Multilevel Analysis on Spatial Determinants for Malaria Occurrence in Korea.
Since its re-emergence in 1993, the spatial patterns of malaria outbreaks in South Korea have drastically changed. It is well known that complicated interactions between humans, nature, and socio-economic factors lead to a spatial dependency of vivax malaria occurrences. This study investigates the spatial factors determining malaria occurrences in order to understand and control malaria risks in Korea. A multilevel model is applied to simultaneously analyze the variables in different spatial scales, and eigenvector spatial filtering is used to explain the spatial autocorrelation in the malaria occurrence data. The results show that housing costs, average age, rice paddy field ratio, and distance from the demilitarized zone (DMZ) are significant on the level-1 spatial scale; health budget per capita and military base area ratio are significant on the level-2 spatial scale. The results show that the spatially filtered multilevel model provides better analysis results in handling spatial issues.


Closed extensor tendon rupture caused by Kienböck disease: a case report.
Kienböck disease, a rare disease that can cause chronic pain and motor dysfunction, occurs due to avascular necrosis of the lunate bone, which leads to dislocation of the carpal bone. Among various other etiologies, Kienböck disease can cause closed tendon rupture of the finger. In this report, we introduce a case of total rupture of the second extensor digitorum communis and the extensor indicis proprius tendons caused by undiagnosed Kienböck disease in an elderly female patient.


Childhood Respiratory Conditions: Lower Respiratory Tract Infection.
Bronchiolitis, a lower respiratory tract infection, commonly affects infants and children younger than 2 years. Respiratory syncytial virus is the most common cause. Nasal congestion, rhinorrhea, and mild fever occur in the first 1 to 3 days. Symptoms worsen for several days to include wheezing and other lower respiratory tract signs, and then resolve over days to weeks. However, some children develop hypoxemia and/or respiratory distress and require hospitalization. The diagnosis is clinical, based on the history and physical examination findings. Routine chest x-rays and blood tests are not recommended. Management is supportive, including nasal suctioning, oxygen (in cases of hypoxemia), and hydration. Use of bronchodilators (ie, albuterol, epinephrine) and systemic corticosteroids is not recommended in infants and children ages 1 to 23 months. Pneumonia, another common infection in infants and children, typically is caused by viruses or bacteria. The diagnosis is clinical, and chest x-rays and blood cultures are not required for patients well enough to be treated as outpatients. Antibiotics are not routinely required for preschool-aged children (ie, younger than 5 years) with pneumonia because most have viral infections. For immunized school-aged children with mild to moderate pneumonia suspected to be of bacterial origin, amoxicillin is recommended. In school-aged children, if atypical pathogens (eg, Mycoplasma) are suspected, a macrolide antibiotic should be prescribed.


Serum folate levels among women attending family planning clinics--Georgia, 2000.
Since 1998, serum folate levels have increased nationally after mandatory fortification of cereal grain products with folic acid. Whether serum folate levels have increased among all women has not been well-studied. Identifying characteristics of women with lower serum folate levels would also be helpful in designing educational campaigns. Data for this report were collected during January 2000-January 2001. During 2000, blood samples were collected from 1,059 women aged 18-45 years who attended six family planning clinics in Georgia and analyzed for serum folate levels. This sample included women aged 18-25 years (60%), black women (41%), and women who had a high school education or less (49%). The median serum folate level (8.9 ng/mL) among this population was lower than the median of women of childbearing age (13.0 ng/mL) who participated in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). In logistic regression analysis, women who were black (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.48, 3.96), who smoked (OR = 2.1; 95% CI = 1.26, 3.43), or who used Depo-Provera contraceptive injection (manufactured by Pharmacia Corporation, Peapack, New Jersey) (OR = 2.3; 95% CI = 1.15, 4.62) were more likely to be ranked in the lowest quartile (< or = 62 ng/mL) of serum folate concentrations when compared with the highest quartile (> 12.4 ng/mL). Women who consumed cereal regularly (OR = 0.4; 95% CI = 0.26, 0.62) or folic acid supplements (OR = 0.2; 95% CI = 0.09, 0.30) were the least likely to be in the lowest serum folate quartile. This study indicates that certain women are at greater risk for having lower serum folate levels, including women who are black, smokers, Depo-Provera users, and those less likely to eat cereal regularly or to take folic acid supplements. In Georgia, these data are useful in defining target populations (e.g., black women and smokers) for folic acid education campaigns because public health officials can develop contextually appropriate messages and outreach approaches for targeting women for folic acid interventions. Ongoing surveillance of serum folate status among women can guide future intervention efforts.


[Recent perceptions on the development, assembly and function of the immune system].
The immune system developed through many stages during evolution. It is fascinating that none of the diverse defense mechanisms vanished in such a long period of nearly 3.5 billion years. They still function in the integrated immune system. The barrier system can be compared to the immune system. The immune system itself is subdivided in antigen-independent, paraspecific (primitive immune system) and antigen specific (specific immune system), restricted immune reactions. The role and use of the phylogenetically older, paraspecific mechanisms, that will react immediately after antigen exposure, are discussed in detail. The immune system is not autonomous. It is closely linked to the hormonal, circulatory, metabolic and nervous systems. Its function is comparable to a sensory organ. Psychoneuroimmunology as a new discipline is mentioned. Immunity and paramunity are not seen as opposing phenomena but are linked in their functions. The terminology of immunology is discussed.


[Influence of pressure on cricoid on insertion ProSeal laryngeal mask airway and ventilation function].
To assess the influence of cricoid pressure (CP) on insertion and ventilation function of ProSeal laryngeal mask airway (PLMA). Fifty adult patients with American Society of Anesthesiologists (ASA) physical status category I, scheduled for elective plastic surgery were studied. After induction of intravenous anesthesia, the PLMA was inserted using an introducer under CP and the intracuff pressure was set to 60 cm H(2)O (1 cm H(2)O=0.098 kPa) with the introducer in place. The content degree of lung ventilation, airway seal pressure and anatomic position of the cuff were assessed. Then CP was temporary terminated, the PLMA was further advanced to the ideal position and the intracuff pressure was readjusted to 60 cm H(2)O. The above-mentioned assessments were re-performed, and the expiratory tidal volume and peak inspiratory pressure during positive-pressure ventilation (PPV) with and without CP were recorded. The gastric tube placement through the PLMA was observed, anatomical position of the drain tube was also scored by fiberoptic examination. After the PLMA was further advanced to the ideal position under temporary termination of CP, lung ventilation content degree (good: acceptable=50:14 cases), airway seal pressure [(27+/-7) cm H(2)O vs. (21+/-7) cm H(2)O] and fiberoptic score of anatomical position of cuff were significantly improved compared with those after PLMA insertion under CP (P<0.05). The expiratory tidal volume during PPV was not significantly different between with and without CP, but the peak inspiratory pressure increased from (14+/-2) cm H(2)O without CP to (28+/-5) cm H(2)O with CP, and there was statistically significant difference (P<0.05). In all patients, gastric tube placement through the PLMA was successful with single attempt and correct anatomical position of the drain tube was confirmed by fiberoptic examination. The CP can impede the insertion of PLMA into the ideal position. The PLMA is still able to be advanced to the ideal position with a special introducer under temporary termination of CP. After the PLMA is advanced to the ideal position, the CP produces a significant increase in the peak inspiratory pressure during PPV.


A near-infrared fluorescent long-chain fatty acid toward optical imaging of cardiac metabolism in living mice.
Non-invasive fatty acid (FA) metabolic imaging is crucial for the evaluation of cardiac function in the heart. Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are widely employed for cardiac metabolic imaging both in pre-clinical and clinical studies. Although SPECT and PET enable highly sensitive cardiac metabolic imaging, there are several disadvantages such as the high cost of instruments and radioactive tracer synthesis. In contrast, near-infrared (NIR) optical imaging using fluorescent FAs provides a simple and useful platform for in vivo imaging of cardiac metabolism. In this work, we synthesized a NIR fluorescence labelled long-chain fatty acid (LCFA) for real-time imaging of cardiac metabolism in vivo. A NIR fluorescence labelled LCFA was designed as an analogue of β-methyl [123I] iodophenyl-pentanedecanoic acid (123I-BMIPP), which is widely used for the diagnosis of heart diseases in clinical practice. As a NIR fluorescent label, we used an Alexa 680 fluorophore that emits over 700 nm. By conjugation of Alexa 680 to Amino-BMPP (15-(4-(3-aminopropyl)phenyl)-3-methylpentadecanoic acid), we prepared a NIR fluorescent BMIPP analogue, Alexa680-BMPP. NIR fluorescence imaging showed that Alexa680-BMPP is taken up by the mouse heart tissue after intravenous injection, showing that Alexa680-BMPP can act as a fluorescent LCFA analogue. Among Alexa680 conjugated FA analogues including short and middle chain NIR fluorescent FAs, Alexa680-BMPP was most efficiently taken up by heart tissues. For fasted and fed mice, the difference in the degree of the uptake of Alexa680-BMPP in their heart tissues was clearly observed by in vivo and ex vivo NIR fluorescence imaging. Herein, we present the synthesis of a NIR fluorescent LCFA, Alexa680-BMPP, and its capability for real-time optical imaging of cardiac metabolism in living mice.


A causal variant rs3769823 in 2q33.1 involved in apoptosis pathway leading to a decreased risk of non-small cell lung cancer.
Although our previous genome-wide association study (GWAS) has identified chromosome 2q33.1 as a susceptibility locus for non-small cell lung cancer (NSCLC), the causal variants remain unclear. The aims of this study were to identify the causal variants in 2q33.1 and to explore their biological functions in NSCLC. CCK-8, colony formation, EdU incorporation, Transwell, and quantitative real-time polymerase chain reaction assays were applied to examine variant function. The tumor xenograft model was used to examine variant function in vivo. Caspase-8 activity assays, flow cytometry analysis, and co-immunoprecipitation assays were used to explore the molecular mechanism. The missense variant rs3769823 (A > G), which caused the substitution of lysine with arginine at amino acid 14 in caspase-8 (caspase-8K14R), was identified as a potential causal candidate in 2q33.1. Compared with the wild type caspase-8 (caspase-8WT) group, the caspase-8K14R group had higher expression of caspase-8 and cleaved caspase-8. Caspase-8K14R inhibited the proliferation and metastasis of human lung cancer cell lines in vitro. Moreover, caspase-8K14R repressed lung cancer cell growth in vivo. Mechanistically, caspase-8K14R was more sensitive than caspase-8WT to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and showed higher binding of caspase-8 and FADD. These results suggested that rs3769823 is the causal variant in chromosome 2q33.1 and is involved in an apoptosis pathway, leading to a decreased risk of NSCLC.


H/D exchange kinetics: experimental evidence for formation of different b fragment ion conformers/isomers during the gas-phase peptide sequencing.
Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) combined with H/D exchange reactions was utilized to explore the existence of different b(5)(+) and b(4)(+) fragment ion conformers/isomers of hexapeptide WHWLQL in the gas phase. Distinct H/D exchange trends for protonated WHWLQL ([M + H](+)) and its b(5)(+) and b(4)(+) fragment ions (with ND(3)) were observed. Isolated (12)C(all) isotopomers of both b(5)(+) and b(4)(+) fragment ions yielded bimodal distributions of H/D exchanged product ions. The H/D exchange reaction kinetics also confirmed that b(5)(+) and b(4)(+) fragment ions exist as combination of slow-exchanging ("s") and fast-exchanging ("f") species. The calculated rate constant for the first labile hydrogen exchange of [M + H](+) (k([M + H](+)) = 3.80 +/- 0.7 x 10(-10) cm(3) mol(-1) s(-1)) was approximately 30 and approximately 5 times greater than those for the "s" and "f" species of b(5)(+), respectively. Data from H/D exchange of isolated "s" species at longer ND(3) reaction times confirmed the existence of different conformers or isomers for b(5)(+) fragment ions. The sustained off-resonance irradiation collision-activated dissociation (SORI-CAD) of WHWLQL combined with the H/D exchange reactions indicate that "s" and "f" species of b(5)(+) and b(4)(+) fragment ions can be produced in the ICR cell as well as the ESI source. The significance of these observations for detailed understanding of protein sequencing and ion fragmentation pathways is discussed.


Optimal Threshold of Homeostasis Model Assessment of Insulin Resistance to Identify Metabolic Syndrome in a Chinese Population Aged 45 Years or Younger.
Metabolic syndrome (MetS) is regarded as a major risk factor for diabetes mellitus and cardiovascular disease (CVD). The optimal threshold of the homeostasis model assessment of insulin resistance (HOMA-IR) has been established for predicting MetS in diverse populations and for different ages. This study assessed the serum HOMA-IR level in a healthy Chinese population aged ≤45 years to determine its relationship with metabolic abnormalities. Cross-sectional study data were collected from health checkup records of Chinese adults aged ≥18 years between 2013 and 2016 at Xiamen Chang Gung Hospital. Participants completed a standardized questionnaire, which was followed by a health examination and blood sample collection. Exclusion criteria were as follows: history of known CVDs; liver, kidney, or endocrine diseases or recent acute illness; hypertension; hyperlipidemia; and pregnancy or lactation. The clinical and laboratory characteristics of 5954 men and 4185 women were analyzed. Significant differences were observed in all assessed variables (all P < 0.05). The optimal cutoff point of HOMA-IR for predicting MetS was 1.7 in men and 1.78 in women. We aimed to determine the optimal cutoff point of HOMA-IR for predicting MetS in a healthy Chinese population aged ≤45 years. The findings of this study would provide an evidence-based threshold for evaluating metabolic syndromes and further implementing primary prevention programs, such as lifestyle changes in the target population.


Response of osteoblastic cells to titanium submitted to three different surface treatments.
In the complex process of bone formation at the implant-tissue interface, surface properties are relevant factors modulating osteoblastic function. In this study, commercially pure titanium (cp Ti) samples were prepared with different surface characteristics using chemical attack with a sulfuric acid/hydrochloric acid based solution (treatment A); chemical attack plus anodic oxidation using phosphoric acid (treatment B); and chemical attack plus thermal oxidation followed by immersion in a sodium fluoride solution (treatment C). The samples were characterized by scanning electron microscopy (SEM), contact profilometry and contact angle. The biological performance of the prepared surfaces was evaluated using mice osteoblastic cell cultures for up to 21 days. Cells seeded on the different titanium samples showed similar behavior during cell attachment and spreading. However, cellular proliferation and differentiation were higher for samples submitted to treatments A and C (p < or = 0.05; n = 3), which were less rough and showed surface free energy with smaller polar components.


A nested case-control study of influenza vaccination was a cost-effective alternative to a full cohort analysis.
In the absence of trial results that are applicable to the target population, nested case-control studies might be an alternative to full-cohort analysis. We compared relative and absolute estimates of associations in an influenza vaccine study using both designs. Data from elderly persons enrolled during six consecutive influenza seasons were used (147,551 person-periods). The endpoints "hospitalization for pneumonia or influenza" (P&I) or "death" were used combined and separately to define three types of cases. Controls for the case-control samples were randomly selected from the remainder of the total cohort at different ratios (1:1 to 1:4). Logistic regression analysis was used to assess adjusted vaccine effectiveness (VE). Sampling fractions were used to determine the number needed to treat to prevent one outcome. Receiver-operator-curve analysis was conducted to estimate the area under the curve (AUC) as a measure of discriminative capacity of the prognostic model. In all, 978 P and I hospitalizations and 1,339 deaths were observed. The adjusted estimates of relative estimates (VE, AUC) and their corresponding 95% confidence intervals were virtually the same using both study designs, notably when the case-control ratio was high (1:4). A nested case-control design can provide valid and precise estimates of associations and is a cost-effective alternative for full-cohort analysis.


Identification of a splice site mutation in the cystathionine beta-synthase gene resulting in variable and novel splicing defects of pre-mRNA.
We used single-strand conformational polymorphism and direct nucleotide sequencing to identify a novel mutation in the cystathionine beta-synthase (CBS) gene of two siblings with homocystinuria. Both patients are heterozygous carriers of the G919A transition and the novel mutation which involves a G-to-A transition in the intron 12 splice donor site. Reverse transcription of RNA harvested from transformed lymphocytes followed by PCR showed a normal size product along with two shorter products involving the deletion of either exon 12 alone or both exons 11 and 12. To our knowledge, the skipping of more than one exon through a single base substitution at a splice-donor site has not been previously reported. The normal size splice product was found to have either a G or an A at nucleotide position 919, indicating that normal size mRNA was produced by both alleles.


Management of advanced juvenile granulosa cell tumor of the ovary.
Juvenile granulosa cell tumor of the ovary occurs most frequently in young women and children. Ten percent of cases present during pregnancy. The majority of tumors are in FIGO Stage I and have a favorable prognosis. The prognosis of higher stage tumors, however, is generally less favorable. We report the long-term, disease-free survival of a patient with FIGO Stage III juvenile granulosa cell tumor of the ovary. We believe this to be the first report of a successful pregnancy following "MAC" chemotherapy for this particular malignancy.


Patient counselling service with the use of pictograms as the example of pharmacist intervention to improving compliance and medicine safety.
Pharmaceutical pictograms have been designed to help communicate medication instructions to patients. Pictograms used within a patient counseling service can significantly improve medication compliance and adherence. The study aimed to assess the improvement of adherence to therapy with the use of pictogram intervention in comparison to standard pharmacy practice in community pharmacies. Pictograms informing about the proper way of using metoprolol prolonged release tablets were designed to be used on the packages of the drug in community pharmacies. Pharmacies belonging to a pharmacy practice-based research network were randomly assigned to a group using pictograms when dispensing the drug or one following their normal practice. At the first visit, all patients answered a structured questionnaire about their medication behavior in the preceding 7 days. The same questions were asked 4 weeks later to follow-up treatment adherence change and compare patients from pictogram group and standard practice group. Descriptive statistics was used to analyze the data, and the McNemar test was used to compare categorical data at baseline and follow-up. Of a total of 253 patients screened, 117 and 104 patients completed the study in the standard practice and pictogram groups, respectively. The use of pictograms significantly improved medication adherence in the following areas: not omitting doses (p < 0.0001), not crushing tablets (p = 0.004), number of tablets/day (p = 0.49), and time of use (p = 0.001), compared to the standard practice group. Our results suggest that pictograms are effective in conveying messages about the proper way of using medications, and they increase treatment adherence, in comparison to standard dispensing practice.


Acquired partial auricular defect rehabilitation aided by four-part mold technique and spectrophotometer.
Patients with auricular defects benefit greatly by an ear prosthesis. However, during the fabrication of auricular prosthesis, difficulties can be faced in obtaining a satisfactory outcome, such as tearing of the prosthesis, fracture of the mold and poor color matching. An 18 year old male lost part of his left auricle in an assault and battery because of which the patient was suffering from adverse psychosocial impact. Surgical reconstruction was ruled out because of patient's desire and financial constraints. Partial auricular prosthesis using four part mold technique and spectrophotometer was fabricated leading to a desirable outcome. Four part mold technique prevented fracture of mold and made retrieval of prosthesis easier. Spectrophotometer reduced the duration of patient visit and the artistic skill required for colour matching in tral and error method.


Structural and optical properties of a radio frequency magnetron-sputtered ZnO thin film with different growth angles.
This study introduces optical properties of a columnar structured zinc oxide [ZnO] antireflection coating for solar cells. We obtained ZnO films of columnar structure on glass substrates using a specially designed radio frequency magnetron sputtering system with different growth angles. Field-emission scanning electron microscopy was utilized to check the growth angles of the ZnO films which were controlled at 0°, 15°, and 30°. The film thickness was fixed at 100 nm to get a constant experiment condition. Grain sizes of the ZnO films were measured by X-ray diffraction. A UV-visible spectrometer was used to measure the transmittance and reflectance of the ZnO film columnar structures as a function of the growth angles.


A rationally designed fluorescence turn-on probe for the gold(III) ion.
A latent fluorophore (1) was rationally designed to give rise to strong fluorescence through a selective gold ion-mediated hydroarylation reaction by a catalytic amount of the gold(III) ion. It is a highly selective and sensitive fluorescence turn-on probe for gold(III) ions and is operative even in protic solvents.


Water Kefir and Derived Pasteurized Beverages Modulate Gut Microbiota, Intestinal Permeability and Cytokine Production In Vitro.
Fermentation is an ancient food preservation process, and fermented products have been traditionally consumed in different cultures worldwide over the years. The interplay between human gut microbiota, diet and host health is widely recognized. Diet is one of the main factors modulating gut microbiota potentially with beneficial effects on human health. Fermented dairy products have received much attention, but other sources of probiotic delivery through food received far less attention. In this research, a combination of in vitro tools mimicking colonic fermentation and the intestinal epithelium have been applied to study the effect of different pasteurized and non-pasteurized water kefir products on gut microbiota, epithelial barrier function and immunomodulation. Water kefir increased beneficial short-chain fatty acid production at the microbial level, reduced detrimental proteolytic fermentation compounds and increased Bifidobacterium genus abundance. The observed benefits are enhanced by pasteurization. Pasteurized products also had a significant effect at the host level, improving inflammation-induced intestinal epithelial barrier disruption and increasing IL-10 and IL-1β compared to the control condition. Our data support the potential health benefits of water kefir and demonstrate that pasteurization, performed to prolong shelf life and stability of the product, also enhanced these benefits.


The impact of email recruitment on our understanding of college smoking.
Email recruitment is growing in popularity; however, this convenience sampling method may yield very different results from prior convenience sampling methods. Participants in the current study were 825 undergraduate students, 446 recruited through a campus wide email and 379 recruited through Introductory Psychology courses, who completed an on-line survey on smoking and health. Outcomes varied significantly by group. Introductory Psychology students reported higher smoker self-concept, more pros of smoking, and were more likely to view smoking as a method of negative affect reduction. The current study suggests that recruitment method can bias our understanding of smoking behaviors among college students.


Regioselective, stereoselective, and conformationally controlled synthesis of (η4-tetraarylcyclobutadiene)(η5-carbomethoxycyclopentadienyl)cobalt metallocenes.
The Friedel-Crafts reaction of (η(4)-tetraphenylcyclobutadiene)(η(5)-carbomethoxycyclopentadienyl)cobalt with acid chlorides/aluminum chloride resulted exclusively in para-phenyl acylation. Both monoacylated (1.1 equiv of RCOCl/AlCl(3)) and tetraacylated products (>4 equiv of RCOCl/AlCl(3)) were synthesized. Reaction of PhCC(o-RC(6)H(4)) (R = Me, i-Pr) with Na(C(5)H(4)CO(2)Me) and CoCl(PPh(3))(3) gave predominantly (η(4)-1,3-diaryl-2,4-diphenylcyclobutadiene)(η(5)-carbomethoxycyclopentadienyl)cobalt metallocenes (1,3-[trans] vs 1,2-[cis] selectivity up to 6:1). Conformational control of Friedel-Crafts reactions on the major isomers gave exclusively para-acylation of the unsubstituted phenyl groups.


Complex interactions of Tyrp1 in the eye.
To use a systems genetics approach to construct and analyze co-expression networks that are causally linked to mutations in a key pigementation gene, tyrosinase-related protein 1 (Tyrp1), that is associated both with oculocutaneous albinism type 3 (OCA3) in humans and with glaucoma in mice. Gene expression patterns were measured in whole eyes of a large family of BXD recombinant inbred (RI) mice derived from parental lines that encode for wildtype (C57BL/6J) and mutant (DBA/2J) Tyrp1. Protein levels of Tyrp1 were measured in whole eyes and isolated irides. Bioinformatics analyses were performed on the expression data along with our archived sequence data. Separate data sets were generated which were comprised of strains that harbor either wildtype or mutant Tyrp1 and each was mined individually to identify gene networks that covary significantly with each isoform of Tyrp1. Ontology trees and network graphs were generated to probe essential function and statistical significance of covariation. Genes with strong covariance in wildtype mice were assembled into genome-wide heatmaps for cohorts carrying either wildtype or mutant Tyrp1. Single nucleotide polymorphism (SNP) analysis verified the presence of the Tyrp1b mutation in the Tyrp1 gene. Message levels were greater in BXD strains with the mutant Tyrp1. Interval mapping of these BXD mice revealed a strong expression quantitative trait locus (eQTL) on Chr 4 at the location of the gene itself. Composite mapping revealed a suggestive eQTL on Chr 9 at the location of myosin-Va (Myo5a), mutations in which are known as dilute. Enriched biologic processes associated with wildtype Tyrp1 included pigmentation, melanin biosynthetic process, and mesenchymal cell development, while associations with the mutant gene included categories of neural crest cell development, protein metabolic processes and glycoprotein metabolic processes. Genome-wide heatmaps revealed strong candidate cis-eQTLs on Chr 4 at Tyrp1 and on Chr 9 at Myo5a in all mice. In the wildtype data set, Tyrp1 was an upstream regulator of six pigmentation and two mesenchyme genes. In addition, five genes, including Tyrp1, were at least partially regulated by Myo5a. Analyses of the strains harboring the mutant gene revealed significant loss of correlation to traditional genes and gain of correlation to genes with little or no functional relationship. These findings indicate that the Tyrp1(b) mutation modifies the pathways and gene networks in which Tyrp1 functions. Our results also indicate direct and indirect regulatory control of Tyrp1 and other pigmentation and mesenchymal genes by Myo5a. Lastly, we find that the mutations reduce the ability of Tyrp1 to regulate expression of other genes that participate in pigmentation metabolism.


Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy.
Despite aggressive multi-modality treatment with surgery, radiation and chemotherapies, malignant glioma inevitably recurs and has dismal survival rates. Recent progress in immunotherapy has led to a resurgence of interest, and immunotherapies are being investigated for treatment of glioma. However, the unique brain anatomy and a highly immunosuppressive glioma microenvironment pose significant challenges to achieving efficacy. Thus, there is a critical need for assessment of next-generation immunotherapies for glioma. In this study, we have investigated the efficacy of the nanoparticle platform technology based on plant-derived Cowpea mosaic virus like particles (empty CPMV or eCPMV) to instigate a potent immune response against intracranial glioma. CPMV immunotherapy has been shown to efficiently reverse the immunosuppressive tumor microenvironments in pre-clinical murine models of dermal melanoma and metastatic melanoma, metastatic breast cancer, intraperitoneal ovarian cancer and in canine patients with oral melanoma. In the present study, we demonstrate that in situ administration of CPMV immunotherapy in the setting of glioma can effectively recruit unique subset of effector innate and adaptive immune cells to the brain parenchyma while reducing immune suppressive cellular population, leading to regression of intracranial glioma. The in situ CPMV nanoparticle vaccine offers a potent yet safe and localized immunotherapy for intracranial glioma.


Extensive RNA editing and possible double-stranded structures determining editing sites in the atpB transcripts of hornwort chloroplasts.
Three nonsense codons and an unusual initiation codon were located within the putative coding region of the atpB gene of chloroplast DNA of the hornwort Anthoceros formosae. Nucleotide sequencing of cDNA prepared from transcripts revealed extensive RNA editing. The unusual initiation codon ACG was changed to AUG and three nonsense codons were converted into sense codons. In total 15 C residues of the genomic DNA were replaced by U residues in the mRNA sequences, while 14 U residues were replaced by C residues. This is the highest number of editing events for a chloroplast mRNA reported so far. Partial editing was also shown in a cDNA clone where 23 sites were edited but six sites remained unedited, representing the existence of premature mRNA. The expected two-dimensional structure of the mRNA shows the existence of a sequence complementary to every editing site, which can produce continuous base pairing longer than 5 bp, suggesting that mispairing in the double strand is the site determinant for RNA editing in Anthoceros chloroplasts. Comparison of the cDNA sequence with other chloroplast genes suggests that the mechanism arose in the first land plants and has been reduced during evolution.


Using quantitative redox proteomics to dissect the yeast redoxome.
To understand and eventually predict the effects of changing redox conditions and oxidant levels on the physiology of an organism, it is essential to gain knowledge about its redoxome: the proteins whose activities are controlled by the oxidation status of their cysteine thiols. Here, we applied the quantitative redox proteomic method OxICAT to Saccharomyces cerevisiae and determined the in vivo thiol oxidation status of almost 300 different yeast proteins distributed among various cellular compartments. We found that a substantial number of cytosolic and mitochondrial proteins are partially oxidized during exponential growth. Our results suggest that prevailing redox conditions constantly control central cellular pathways by fine-tuning oxidation status and hence activity of these proteins. Treatment with sublethal H(2)O(2) concentrations caused a subset of 41 proteins to undergo substantial thiol modifications, thereby affecting a variety of different cellular pathways, many of which are directly or indirectly involved in increasing oxidative stress resistance. Classification of the identified protein thiols according to their steady-state oxidation levels and sensitivity to peroxide treatment revealed that redox sensitivity of protein thiols does not predict peroxide sensitivity. Our studies provide experimental evidence that the ability of protein thiols to react to changing peroxide levels is likely governed by both thermodynamic and kinetic parameters, making predicting thiol modifications challenging and de novo identification of peroxide sensitive protein thiols indispensable.


Both strands of siRNA have potential to guide posttranscriptional gene silencing in mammalian cells.
Despite the widespread application of RNA interference (RNAi) as a research tool for diverse purposes, the key step of strand selection of siRNAs during the formation of RNA-induced silencing complex (RISC) remains poorly understood. Here, using siRNAs targeted to the complementary region of Survivin and the effector protease receptor 1 (EPR-1), we show that both strands of the siRNA duplex can find their target mRNA and are equally eligible for assembly into Argonaute 2 (Ago2) of RISC in HEK293 cells. Transfection of the synthetic siRNA duplexes with different thermodynamic profiles or short hairpin RNA (shRNA) vectors that generate double-stranded RNAs (dsRNAs), permitting processing specifically from either the 5' or 3' end of the incipient siRNA, results in the degradation of the respective target mRNAs of either strand of the siRNA duplex with comparable efficiencies. Thus, while most RNAi reactions may follow the thermodynamic asymmetry rule in strand selection, our study suggests an exceptional mode for certain siRNAs in which both strands of the duplex are competent in sponsoring RNAi, and implies additional factors that might dictate the RNAi targets.


Resolution of malignant biliary obstruction using endoscopic ultrasound-guided transmural drainage in a patient with unresectable pancreatic carcinoma complicated by a large cyst.
Highlight In this report of a rare case of obstructive jaundice caused by dilatation of cancerous gland ducts associated with advanced pancreatic cancer, Ryozawa and colleagues describe their method of endoscopic ultrasound-guided transmural drainage with a lumen-apposing metal stent as a novel treatment option for malignant biliary obstruction.


The homeodomain protein hmbx-1 maintains asymmetric gene expression in adult C. elegans olfactory neurons.
Differentiated neurons balance the need to maintain a stable identity with their flexible responses to dynamic environmental inputs. Here we characterize these opposing influences on gene expression in Caenorhabditis elegans olfactory neurons. Using transcriptional reporters that are expressed differentially in two olfactory neurons, AWC(ON) and AWC(OFF), we identify mutations that affect the long-term maintenance of appropriate chemoreceptor expression. A newly identified gene from this screen, the conserved transcription factor hmbx-1, stabilizes AWC gene expression in adult animals through dosage-sensitive interactions with its transcriptional targets. The late action of hmbx-1 complements the early role of the transcriptional repressor gene nsy-7: Both repress expression of multiple AWC(OFF) genes in AWC(ON) neurons, but they act at different developmental stages. Environmental signals are superimposed onto this stable cell identity through at least two different transcriptional pathways that regulate individual chemoreceptor genes: a cGMP pathway regulated by sensory activity, and a daf-7 (TGF-beta)/daf-3 (SMAD repressor) pathway regulated by specific components of the density-dependent C. elegans dauer pheromone.


Changes in platelet glycoprotein receptors after smoking--a flow cytometric study.
Cigarette smoking is accepted to be one of the major factors which increase the risk of coronary artery disease, peripheral vascular disease and stroke. A number of studies have been carried out on the acute and chronic effects of tobacco smoking on platelet activation. An enhancing effect of high nicotine cigarette smoking on platelet aggregation has been reported. Since platelet receptors are involved in the final stage of platelet aggregation, the intention of this study was to investigate platelet receptors in acute and chronic smokers before and after smoking. Nineteen chronic smokers, 18 acute smokers and 18 healthy non-smoking controls were included in the present study. Platelet aggregation was carried out using ristocetin, adenosine diphosphate (ADP) and collagen both before and after smoking in acute and chronic smokers. Flow cytometric studies of platelets were carried out utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated platelets, FITC-labelled anti-GP IIb/IIa antibody, FITC-labelled anti-GP Ib/IX antibody and FITC-labelled P-selectin antibody. The intensity of fluorescence was graded into three groups and expressed in arbitrary units. The interesting data generated in the present work is that in vivo platelet activation occurs immediately after smoking a cigarette which is detected by using FITC-labelled anti-human fibrinogen antibody binding to platelet and by P-selectin expression. It is also quite evident from the present study that a significant number of circulating platelets are in the activated state in chronic smokers. Therefore this study suggests that smoking-induced platelet activation may be an important contributory mechanism for acute coronary events in smokers.


Computational analysis of thoracic multidetector row HRCT for segmentation and quantification of small airway air trapping and emphysema in obstructive pulmonary disease.
Obstructive pulmonary disease phenotypes are related to variable combinations of emphysema and small-airway disease, the latter manifested as air trapping (AT) on imaging. The investigators propose a method to extract AT information quantitatively from thoracic multi-detector row high-resolution computed tomography (HRCT), validated by pulmonary function testing (PFT) correlation. Seventeen patients with obstructive pulmonary disease who underwent HRCT and PFT within a 3-day interval were retrospectively identified. Thin-section volumetric HRCT in inspiration and expiration was registered and analyzed using custom-made software. Nonaerated regions of lung were segmented through exclusion of voxels > -50 Hounsfield units (HU); emphysematous areas were segmented as voxels < -950 HU on inspiratory images. Small-airway AT volume (ATV) was segmented as regions of lung voxels whose attenuation values increased by less than a specified change threshold (set from 5 to 300 HU in 25-HU increments) between inspiration and expiration. Inspiratory and expiratory total segmented lung volumes, emphysema volume (EV), and ATV for each threshold were subsequently calculated and correlated with PFT parameters. A strong positive correlation was obtained between total segmented lung volume in inspiration and total lung capacity (r = 0.83). A strong negative correlation (r = -0.80) was obtained between EV and the ratio between forced expiratory volume in 1 second and forced vital capacity. Stronger negative correlation with forced expiratory volume in 1 second/forced vital capacity (r = -0.85) was demonstrated when ATV (threshold, 50 HU) was added to EV, indicating improved quantification of total AT to predict obstructive disease severity. A moderately strong positive correlation between ATV and residual volume was observed, with a maximum r value of 0.72 (threshold, 25 HU), greater than that between EV and residual volume (r = 0.58). The benefit of ATV quantification was greater in a subgroup of patients with negligible emphysema compared to patients with moderate to severe emphysema. Small-airway AT segmentation in conjunction with emphysema segmentation through computer-assisted methodologies may provide better correlations with key PFT parameters, suggesting that the quantification of emphysema-related and small airway-related components of AT from thoracic HRCT has great potential to elucidate phenotypic differences in patients with chronic obstructive pulmonary disease.


Immunosurgical approach to the treatment of malignant melanoma using 2,4-dinitrochlorobenzene (DNCB).
Non-specific local immunotherapy using 2,4-dinitrochlorobenzene (DNCB) was combined with additional excision of the primary melanoma. The treatment was completed by elective nodal dissection in cases of high risk invasive lesions. DNCB was also given in cases with advanced disease for the control of cutaneous lesions and disseminated metastases, respectively. Histological changes of regressed skin nodules and ways of DNCB administration are described. Comparison between surgery alone and the immunosurgical treatment was considered inappropriate at the present time due to limited number of cases.


Telomere-interactive agents affect proliferation rates and induce chromosomal destabilization in sea urchin embryos.
Cationic porphyrins, which interact with guanine quadruplex (G4) telomeric folds, inhibit telomerase activity in human tumor cells. In this study, we have further examined effects of porphyrins and other telomere- and telomerase-interactive agents on proliferation rates and chromosome stability in a novel in vivo model, developing sea urchin embryos. We studied two porphyrins: (i) TMPyP4, a potent telomerase inhibitor; and (ii) TMPyP2, an isomer of TMPyP4 and an inefficient telomerase inhibitor, azidothymine (AZT), the reverse transcriptase inhibitor, antisense phosphorothioate oligonucleotide to telomerase RNA (TAG6) and a control scrambled sequence (ODN). TMPyP4, AZT and TAG6 (but not TMPyP2 or ODN) decreased the rates of cell proliferation and increased the percentage of cells trapped in mitosis. Nuclear localization of TAG6, but not of ODN, was demonstrated with 5'-fluoresceinated analogs of TAG6 and ODN. Formation of elongated chromosomes incapable of separating in anaphase, induced by TMPyP4, AZT and TAG6, closely resembled phenotypes resulting from telomerase template mutation or dominant negative TRF2 allele. Our data suggest that G4-interactive agents exert their antiproliferative effects via chromosomal destabilization and warrant their further development as valuable anticancer tools.


NeMo: Network Module identification in Cytoscape.
As the size of the known human interactome grows, biologists increasingly rely on computational tools to identify patterns that represent protein complexes and pathways. Previous studies have shown that densely connected network components frequently correspond to community structure and functionally related modules. In this work, we present a novel method to identify densely connected and bipartite network modules based on a log odds score for shared neighbours. To evaluate the performance of our method (NeMo), we compare it to other widely used tools for community detection including kMetis, MCODE, and spectral clustering. We test these methods on a collection of synthetically constructed networks and the set of MIPS human complexes. We apply our method to the CXC chemokine pathway and find a high scoring functional module of 12 disconnected phospholipase isoforms. We present a novel method that combines a unique neighbour-sharing score with hierarchical agglomerative clustering to identify diverse network communities. The approach is unique in that we identify both dense network and dense bipartite network structures in a single approach. Our results suggest that the performance of NeMo is better than or competitive with leading approaches on both real and synthetic datasets. We minimize model complexity and generalization error in the Bayesian spirit by integrating out nuisance parameters. An implementation of our method is freely available for download as a plugin to Cytoscape through our website and through Cytoscape itself.


Parent and carer experiences of health care professionals' communication about childhood obesity: a qualitative systematic review protocol.
The objective of the systematic review is to identify, critically appraise, and synthesize the best available qualitative evidence on parent and carer experiences of health care professionals' communication about childhood obesity. Parents and carers play a key role in a child's environment and healthy development, which is why they can find it confronting to discuss their child's weight. This review will provide an insight into the experiences of parents and carers with health care professionals' communication about their child's overweight or obesity. This qualitative review will consider participants who are parents and carers with a child with overweight or obesity (birth to 12 years). The phenomenon of interest is parents' and carers' lived experiences of childhood obesity communication from a health care professional, and the context is health care settings. Communication includes verbal or written communication about a child's obesity from health care professionals received by a parent or carer. The proposed review will systematically search the following databases: MEDLINE (EBSCO), CINAHL (EBSCO), PsycINFO (Ovid), Scopus, LILACS, and the Finnish health sciences database MEDIC. ProQuest Dissertations and Theses (ProQuest) will be searched for unpublished articles. A manual search will supplement the database searches. The quality of included studies will be assessed independently by 2 reviewers, and the qualitative data will be extracted from papers by 2 independent reviewers using the standardized JBI data extraction tool. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis meta-aggregation will be used. PROSPERO CRD42022297709.


[Clinical characteristics of alternating hemiplegia of childhood in 13 patients].
To summarize the clinical characteristics of alternating hemiplegia of childhood (AHC). The clinical data of 13 children with AHC were analyzed. Cranial MRI, EEG, analysis of serum amino acids and urinary organic acids, measurement of plasma lactate and pyruvate levels were done in all patients. Other laboratory examinations such as magnetic resonance angio-imaging (MRA), digital subtraction arteriography (DSA) and Video-EEG were also performed in some patients. Of the 13 patients, 12 were male, and 1 was female. The age of onset was from 2 days to 55 months (average 13.1 months). The initial symptoms were abnormal ocular movements (AOMs) consisting of ocular deviation, gaze or nystagmus in 2 cases, AOMs and dystonic posturing in 9 cases, hemiplegia in 2 cases. All patients had recurrent alternating hemiplegic episodes. The hemiplegic attacks lasted from a few minutes to 10 days. The occurrence of the attacks ranged from 8 times daily to one time every 2 months. In 10 patients the abnormal eye movements or dystonic posturing, at times, recurred intermittently during the hemiplegic attack. Choreoathetosis was present in 2 cases. Ataxia was present in 1 case; 7 patients also had the episodes of quadriplegia. During the episodes of quadriplegia, dysarthria or aphasia was present in 4 cases, dyspnea and dysphagia was present in 2 cases, respectively. Sleep could relieve both weakness and associated paroxysmal symptoms. Mental retardation was present in 9 cases, seizures in 3 cases. Except for EEG or Video-EEG was abnormal in 3 patients, other laboratory investigations were normal in all patients. Twelve patients received flunarizine therapy. Flunarizine reduced the severity, duration, or frequency of hemiplegic attacks in 8 patients. The results suggest that AHC is characterized by frequent episodes of alternating hemiplegia with extrapyramidal symptoms and mental retardation, flunarizine is effective in treating some AHC patients.


The evolutionary history of Saccharomyces species inferred from completed mitochondrial genomes and revision in the 'yeast mitochondrial genetic code'.
The yeast Saccharomyces are widely used to test ecological and evolutionary hypotheses. A large number of nuclear genomic DNA sequences are available, but mitochondrial genomic data are insufficient. We completed mitochondrial DNA (mtDNA) sequencing from Illumina MiSeq reads for all Saccharomyces species. All are circularly mapped molecules decreasing in size with phylogenetic distance from Saccharomyces cerevisiae but with similar gene content including regulatory and selfish elements like origins of replication, introns, free-standing open reading frames or GC clusters. Their most profound feature is species-specific alteration in gene order. The genetic code slightly differs from well-established yeast mitochondrial code as GUG is used rarely as the translation start and CGA and CGC code for arginine. The multilocus phylogeny, inferred from mtDNA, does not correlate with the trees derived from nuclear genes. mtDNA data demonstrate that Saccharomyces cariocanus should be assigned as a separate species and Saccharomyces bayanus CBS 380T should not be considered as a distinct species due to mtDNA nearly identical to Saccharomyces uvarum mtDNA. Apparently, comparison of mtDNAs should not be neglected in genomic studies as it is an important tool to understand the origin and evolutionary history of some yeast species.


[Incidence rates of cerebral palsy, severe mental and motor retardation, and Down syndrome in the city of Kokubunji in suburban Tokyo].
We investigated the incidence rates of cerebral palsy, severe mental and motor retardation, and Down syndrome in the City of Kokubunji in suburban Tokyo with a total population of about 100,000. The number of liveborn babies during 1985-1989 was 5,475. The number of children with cerebral palsy (CP) was 11 and the incidence rate was 2.01/1,000, which was equal to the rates in reports from several countries and was higher than those of the previous reports from Japan. Two out of 10 patients with CP had mild motor handicaps and were expected to "outgrow" their handicaps. The number of children with "severe mental and motor retardation" (SMMR) was 6 and the incidence rate was 1.10/1,000. Prenatal brain damage played a major role in the pathogenesis of CP and SMMR. The number of children with Down syndrome (DS) was 11 and the incidence rate was 2.01/1,000 which was higher than the previous rates. Incidence rates of CP, SMMR, and DS still remain high and further strategy to prevent pediatric neurological diseases is necessary.


Optimum immunotherapy method according to PD-L1 expression in advanced lung cancer: a network meta-analysis.
Aim: To compare the survival of advanced lung cancer patients treated with immune checkpoint inhibitors in different PD-L1 expression. Methods: We performed a network meta-analysis based on 25 trials involving 12,224 patients with different PD-L1 expression levels. Results: The results showed platinum-based chemotherapy plus pembrolizumab or nivolumab and ipilimumab was associated with the best survival rates for patients with <1% PD-L1 expression, while only platinum-based chemotherapy plus pembrolizumab produced better survival than chemotherapy in patients with 1-49% PD-L1 expression. As for patients with ≥50% PD-L1 expression, platinum-based chemotherapy plus pembrolizumab/atezolizumab and pembrolizumab/cemiplimab monotherapy were associated with better survival than chemotherapy. Conclusion: These results provide reference for selecting the optimum immunotherapy method based on the expression of PD-L1 in patients with advanced lung cancer.


Efficacy of a teaching intervention on nurses' knowledge regarding diabetes.
The absence of a diabetic nurse educator and continuing education opportunities regarding diabetes management was the impetus for one staff nurse's research. Subjects' (N = 72) current knowledge about diabetes mellitus was tested before and after a peer-developed diabetes management presentation. Results reflected a need for improving diabetes knowledge. The teaching intervention positively influenced postintervention scores (p =.000).


Short-term financial outcomes of pilon fractures.
Fractures of the distal tibia are potentially devastating injuries fraught with many complications and poor outcomes, including financial hardships. The purpose of this study was to examine the financial outcomes in the short term of pilon fractures. Sixty patients who sustained pilon fractures were prospectively assessed on financial criteria and injury characteristics. This included various scores and also introduced a financial data sheet and outcome form. Twenty-five patients met inclusion/exclusion criteria and were available for follow-up. The mean age was 46.3 +/- 12.0 years (19-61 years), with a mean follow-up of 11.8 +/- 4.8 months (6-20 months). Only 7 patients (29.2%) returned to work at latest follow-up. Seven of 19 patients (36.8%) reported selling possessions to meet financial obligations, and 8 of 19 patients (42.1%) used social assistance programs. All 4 white-collar workers returned to work whereas only 3 (14.3%) of 21 blue-collar workers had returned to work at last follow-up (P = .001). Five (62.5%) of 8 patients who had graduated from college returned to work, but only 2 (14.3%) of 14 patients who did not attend college returned to work (P = .01). Because there are no widely used measures of financial status change in the literature, we have introduced some in this article including preinjury financial preparedness and postinjury strategies to fulfill financial obligations. These may be useful in evaluating outcomes and counseling patients. In addition, we have again demonstrated that there is a significantly higher return to work outcome in white collar jobs and higher education.


Coming therapies: abacavir.
Abacavir is a nucleoside analogue reverse transcriptase inhibitor (NRTI). It has a good oral availability and penetrates the CNS. The metabolism of abacavir is not dependent on cytochrome P450 thus avoiding significant drug-drug interactions. It has an antiviral potency comparable to that of protease inhibitors (PIs) or to dual nucleoside combinations. In addition, evidence has shown that it is effective in decreasing viral load and increasing CD4 count in HIV-infected patients, especially NRTI-naïve patients. Abacavir has an acceptable tolerability profile, although hypersensitivity reactions lead to discontinuation of therapy in approximately 3% of patients. Abacavir has a potential role in first- and second-line combination regimens and as part of a PI-sparing regimen.


The effect of PAMAM G6 dendrimers on the structure of lipid vesicles.
Dendrimers are polymers with unique properties that make them promising in a variety of applications such as potential drug and gene delivery systems. PAMAM dendrimers, in particular, have been widely investigated and are efficiently translocated into the cell. The mechanism of translocation, however, is still unknown. Recently it was proposed that PAMAM dendrimers are able to open holes in lipid bilayers by stealing lipid from the bilayer and forming "dendrisomes". The present work intends to contribute in the clarification of this question: why are dendrimers able to translocate into the cell? We create simple models for cell membranes by using small lipid vesicles that present a single lipid phase at physiologically relevant conditions. We then follow the effect that dendrimers have on the structure of the vesicles by using a combination of various techniques: dynamic light scattering, cryo-TEM and small angle X-ray scattering. We discuss our results with respect to the previous findings and reflect on their possible implications for real translocation in living cells.


Real-time fluorescence tracking of gene delivery via multifunctional nanocomposites.
Fluorescence imaging of transduced cells and tissues is valuable in the development of gene vectors and the evaluation of gene therapy efficacy. We report here the simple and rational design of multifunctional nanocomposites (NCs) for simultaneous gene delivery and fluorescence tracking based on ZnS:Mn(2+) quantum dots (QDs) and positively charged polymer coating. The positively charged imidazole in the as-synthesized amphiphilic copolymer can be used for gene loading via electrostatic interaction. While the introduced poly(ethylene glycol) (PEG) can be used to reduce the binding of plasma proteins to nanovectors and minimize clearance by the reticuloendothelial system after intravenous administration. Most importantly, these multifunctional nanovectors showed much lower cellular toxicity than the commercial polyethylenimine (PEI) transfection vectors. On the basis of the red fluorescence of QDs, we can real-time track the gene delivery in cells, and the transfection efficacy of pDNA encoding enhanced green fluorescence protein (pEGFP) was monitored via the green fluorescence of the GFP expressed by the pDNA delivered into the nuclei. Fluorescence imaging analysis confirmed that the QDs-based nanovectors delivered pDNA into HepG2 cells efficiently. These new insights and capabilities pave a new way toward nanocomposite engineering for fluorescence imaging tracking of gene therapy.