Rock-Hosted Subsurface Biofilms: Mineral Selectivity Drives Hotspots for Intraterrestrial Life.
The continental deep subsurface is likely the largest reservoir of biofilm-based microbial biomass on Earth, but the role of mineral selectivity in regulating its distribution and diversity is unclear. Minerals can produce hotspots for intraterrestrial life by locally enhancing biofilm biomass. Metabolic transformations of minerals by subsurface biofilms may occur widely with the potential to significantly impact subsurface biogeochemical cycles. However, the degree of impact depends upon the amount of biofilm biomass and its relationship to host rock mineralogy, estimates that are currently loosely constrained to non-existent. Here, we use in situ cultivation of biofilms on native rocks and coupled microscopy/spectroscopy to constrain mineral selectivity by biofilms in a deep continental subsurface setting: the Deep Mine Microbial Observatory (DeMMO). Through hotspot analysis and spatial modeling approaches we find that mineral distributions, particularly those putatively metabolized by microbes, indeed drive biofilm distribution at DeMMO, and that bioleaching of pyrite may be a volumetrically important process influencing fluid geochemistry at this site when considered at the kilometer scale. Given the ubiquity of iron-bearing minerals at this site and globally, and the amount of biomass they can support, we posit that rock-hosted biofilms likely contribute significantly to subsurface biogeochemical cycles. As more data becomes available, future efforts to estimate biomass in the continental subsurface should incorporate host rock mineralogy.


The antimicrobial activity of garlic and onion extracts.
Aqueous extracts of garlic (Allium sativum) and onion (Allium cepa) were tested for activity against Gram-positive organisms, Gram-negative organisms and fungi. A significant growth inhibition was shown by most of the organisms, tested at random. A quantitative assessment of the activity was carried out by determining the minimum bacteriostatic and bactericidal concentrations of the extracts against Gram-positive and Gram-negative organisms. Garlic extract showed greater activity as compared to the extract of onion. The activity of the garlic extract on the mouth flora of volunteers was then investigated. A mouth wash containing 10% garlic in quarter Ringer solution produced a drastic reduction in the number of oral bacteria.


Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating enterococcus faecalis infective endocarditis.
The aim of this study was to compare the effectiveness of the ampicillin plus ceftriaxone (AC) and ampicillin plus gentamicin (AG) combinations for treating Enterococcus faecalis infective endocarditis (EFIE). An observational, nonrandomized, comparative multicenter cohort study was conducted at 17 Spanish and 1 Italian hospitals. Consecutive adult patients diagnosed of EFIE were included. Outcome measurements were death during treatment and at 3 months of follow-up, adverse events requiring treatment withdrawal, treatment failure requiring a change of antimicrobials, and relapse. A larger percentage of AC-treated patients (n = 159) had previous chronic renal failure than AG-treated patients (n = 87) (33% vs 16%, P = .004), and AC patients had a higher incidence of cancer (18% vs 7%, P = .015), transplantation (6% vs 0%, P = .040), and healthcare-acquired infection (59% vs 40%, P = .006). Between AC and AG-treated EFIE patients, there were no differences in mortality while on antimicrobial treatment (22% vs 21%, P = .81) or at 3-month follow-up (8% vs 7%, P = .72), in treatment failure requiring a change in antimicrobials (1% vs 2%, P = .54), or in relapses (3% vs 4%, P = .67). However, interruption of antibiotic treatment due to adverse events was much more frequent in AG-treated patients than in those receiving AC (25% vs 1%, P < .001), mainly due to new renal failure (≥25% increase in baseline creatinine concentration; 23% vs 0%, P < .001). AC appears as effective as AG for treating EFIE patients and can be used with virtually no risk of renal failure and regardless of the high-level aminoglycoside resistance status of E. faecalis.


Mitogenic effects of propoxur on male rat bladder urothelium.
Propoxur produces bladder tumors in rats, but not other species. The hyperplastic and tumorigenic effects do not occur if urinary pH is lowered by administering propoxur in a semi-synthetic diet or co-administering it with ammonium chloride (NH4Cl). We fed propoxur at 8000 p.p.m. in Altromin 1321 diet to male Wistar rats for 4 weeks, with or without NH4Cl as 10,000 p.p.m. of the diet. The urine of rats fed control diet with or without propoxur had a relatively high urinary pH (approximately 8); the addition of NH4Cl lowered the urinary pH by approximately 0.5-1.0 units. There was no evidence of urinary calculi or amorphous precipitate nor was there an increase in microcrystals or formation of different crystals than occur in normal rat urine. Propoxur produced hyperplasia of the urothelium, as observed by light and scanning electron microscopy, and increased the labeling index for proliferating cell nuclear antigen. These effects were significantly inhibited by co-administration with NH4Cl. There was no evidence of urothelial necrosis. Thus, the hyperplasia appears to result from a direct mitogenic effect of propoxur or a metabolite on the urothelium, rather than from toxicity and consequent regeneration. Based on the present study and previous investigations, the urothelial effects of propoxur in the rat are dependent on high urinary pH and high administered doses, factors which need to be incorporated into any mechanistic model for the chemical and into any extrapolation to potential effects in humans.


Risk factors for physical disability upon release from multidrug therapy in new cases of leprosy at a referral center in Brazil.
The present study sought to investigate the risk factors for physical disability upon release from multidrug therapy (MDT) in new cases of leprosy, registered at a referral center in Brazil. This is a longitudinal and retrospective study that evaluated 260 patients. Multivariate analyses, using both the ordinal logistic regression, as well as the classification and regression tree (CART) algorithm were performed to determine the factors associated with physical disability upon release from treatment. The prevalence of disability did not differ significantly between diagnosis and release from treatment. Number of affected nerves and sensory impairment upon diagnosis were risk factors for disability at the end of MDT. The analysis using the CART algorithm resulted in the development of a clinical score to predict the risk of disability upon release from MDT. The decision tree may have a direct applicability in clinical practice for professionals dealing with leprosy, as it allows them to identify patients with a higher risk of physical disability through the use of simple and widely available clinical tests. This study also shows that the disability grade upon admission is the main risk factor for disability upon release from MDT. This result draws attention to the importance of early diagnosis in disability prevention.


Use of the Healthy Lifestyle Coaching Chatbot App to Promote Stair-Climbing Habits Among Office Workers: Exploratory Randomized Controlled Trial.
Lack of time for exercise is common among office workers given their busy lives. Because of occupational restrictions and difficulty in taking time off, it is necessary to suggest effective ways for workers to exercise regularly. Sustaining lifestyle habits that increase nonexercise activity in daily life can solve the issue of lack of exercise time. Healthy Lifestyle Coaching Chatbot is a messenger app based on the habit formation model that can be used as a tool to provide a health behavior intervention that emphasizes the importance of sustainability and involvement. This study aimed to assess the efficacy of the Healthy Lifestyle Coaching Chatbot intervention presented via a messenger app aimed at stair-climbing habit formation for office workers. From February 1, 2018, to April 30, 2018, a total of 106 people participated in the trial after online recruitment. Participants were randomly assigned to the intervention group (n=57) or the control group (n=49). The intervention group received cues and intrinsic and extrinsic rewards for the entire 12 weeks. However, the control group did not receive intrinsic rewards for the first 4 weeks and only received all rewards as in the intervention group from the fifth to twelfth week. The Self-Report Habit Index (SRHI) of participants was evaluated every week, and the level of physical activity was measured at the beginning and end of the trial. SPSS Statistics version 21 (IBM Corp) was used for statistical analysis. After 4 weeks of intervention without providing the intrinsic rewards in the control group, the change in SRHI scores was 13.54 (SD 14.99) in the intervention group and 6.42 (SD 9.42) in the control group, indicating a significant difference between the groups (P=.04). When all rewards were given to both groups, from the fifth to twelfth week, the change in SRHI scores of the intervention and control groups was comparable at 12.08 (SD 10.87) and 15.88 (SD 13.29), respectively (P=.21). However, the level of physical activity showed a significant difference between the groups after 12 weeks of intervention (P=.045). This study provides evidence that intrinsic rewards are important to enhance the sustainability and effectiveness of an intervention. The Healthy Lifestyle Coaching Chatbot program can be a cost-effective method for healthy habit formation. Clinical Research Information Service KCT0004009; https://tinyurl.com/w4oo7md.


Interference of HCV replication by cell penetrable human monoclonal scFv specific to NS5B polymerase.
A new class of hepatitis C virus (HCV)-targeted therapeutics that is safe, broadly effective and can cope with virus mutations is needed. The HCV's NS5B is highly conserved and different from human protein, and thus it is an attractive target for anti-HCV therapeutics development. In this study, NS5B bound-phage clones selected from a human single chain variable antibody fragment (scFv) phage display library were used to transform appropriate E. coli bacteria. Two scFv inhibiting HCV polymerase activity were selected. The scFvs were linked to a cell penetrating peptide to make cell penetrable scFvs. The transbodies reduced the HCV RNA and infectious virus particles released into the culture medium and inside hepatic cells transfected with a heterologous HCV replicon. They also rescued the innate immune response of the transfected cells. Phage mimotope search and homology modeling/molecular docking revealed the NS5B subdomains and residues bound by the scFvs. The scFv mimotopes matched residues of the NS5B, which are important for nucleolin binding during HCV replication, as well as residues that interconnect the fingers and thumb domains for forming a polymerase active groove. Both scFvs docked on several residues at the thumb armadillo-like fold that could be the polymerase interactive sites of other viral/host proteins for the formation of the replication complex and replication initiation. In conclusion, human transbodies that inhibited HCV RdRp activity and HCV replication and restored the host innate immune response were produced. They are potentially future interferon-free anti-HCV candidates, particularly in combination with other cognates that are specific to NS5B epitopes and other HCV enzymes.


Overexpression of miR169o, an Overlapping MicroRNA in Response to Both Nitrogen Limitation and Bacterial Infection, Promotes Nitrogen Use Efficiency and Susceptibility to Bacterial Blight in Rice.
Limiting nitrogen (N) supply contributes to improved resistance to bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) in susceptible rice (Oryza sativa). To understand the regulatory roles of microRNAs (miRNAs) in this phenomenon, 63 differentially expressed overlapping miRNAs in response to Xoo infection and N limitation stress in rice were identified through deep RNA sequencing and stem-loop quantitative real-time PCR. Among these, miR169o was further assessed as a typical overlapping miRNA through the overexpression of the miR169o primary gene. Osa-miR169o-OX plants were taller, and had more biomass accumulation with significantly increased nitrate and total amino acid contents in roots than the wild type (WT). Transcript level assays showed that under different N supply conditions, miR169o oppositely regulated NRT2, and this is reduced under normal N supply conditions but remarkably induced under N-limiting stress. On the other hand, osa-miR169o-OX plants also displayed increased disease lesion lengths and reduced transcriptional levels of defense gene (PR1b, PR10a, PR10b and PAL) compared with the WT after inoculation with Xoo. In addition, miR169o impeded Xoo-mediated NRT transcription. Therefore, the overlapping miR169o contributes to increase N use efficiency and negatively regulates the resistance to BB in rice. Consistently, transient expression of NF-YA genes in rice protoplasts promoted the transcripts of PR genes and NRT2 genes, while it reduced the transcripts of NRT1 genes. Our results provide novel and additional insights into the co ordinated regulatory mechanisms of cross-talk between Xoo infection and N deficiency responses in rice.


Use and abuse of systemic corticosteroid therapy.
Steroid-responsive acute dermatoses should be treated with a single morning dose of prednisone for approximately 2 weeks. It is necessary to "taper" a short course of oral prednisone given by this method. Chronic dermatoses should be treated whenever possible with prednisone used in the morning and on alternate days. This method is effective, is free of most side effects, and suppresses the HPA axis minimally. There are few real advantages in using intramuscular corticosteroids. TAC is an unusually strong suppressor of the HPA axis. For chronic dermatoses, a less suppressive preparation might best be chosen if the physician feels that the intramuscular route is the most reasonable one. In any event TAC should never be used more often than every two months. Finally, the time-course of HPA recovery following short courses of steroids is presently unknown. Nonetheless, some astute critics of steroid metabolism have felt obliged to advise us that individuals who have received from 1 to 4 weeks of suppressive steroid treatment should be suspect as to the integrity of their HPA axis in stressful situations for up to one year. The withdrawal from, as well as the use of, systemic corticosteroids requires a creative and critical physician.


Unraveling the Metabolic Derangements Occurring in Non-infarcted Areas of Pig Hearts With Chronic Heart Failure.
Objective: After myocardial infarction (MI), the non-infarcted left ventricle (LV) ensures appropriate contractile function of the heart. Metabolic disturbance in this region greatly exacerbates post-MI heart failure (HF) pathology. This study aimed to provide a comprehensive understanding of the metabolic derangements occurring in the non-infarcted LV that could trigger cardiovascular deterioration. Methods and Results: We used a pig model that progressed into chronic HF over 3 months following MI induction. Integrated gene and metabolite signatures revealed region-specific perturbations in amino acid- and lipid metabolism, insulin signaling and, oxidative stress response. Remote LV, in particular, showed impaired glutamine and arginine metabolism, altered synthesis of lipids, glucose metabolism disorder, and increased insulin resistance. LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation in the remote zone and were found differentially expressed also in the myocardium of patients with ischemic and/or dilated cardiomyopathy. In addition, a simultaneous significant decrease in arginine levels and altered PRCP, PTPN1, and ARF6 expression suggest alterations in vascular function in remote area. Conclusions: This study unravels an array of dysregulated genes and metabolites putatively involved in maladaptive metabolic and vascular remodeling in the non-infarcted myocardium and may contribute to the development of more precise therapies to mitigate progression of chronic HF post-MI.


Streamlining cutaneous melanomas in young women of the Belgian Mosan region.
Sporadic cutaneous melanoma (SCM) has shown a dramatic increase in incidence in Caucasian populations over the past few decades. A particular epidemiological increase was reported in women during their childbearing age. In the Belgian Mosan region, a progressive unremitting increase in SCM incidence was noticed in young women for the past 35 years. The vast majority of these SCMs were of the superficial type without any obvious relationship with a large number of melanocytic nevi or with signs of frequent and intense sunlight exposures as disclosed by the extent in the mosaic subclinical melanoderma. A series of investigations pointed to a possible relationship linking the development of some SCM to the women hormonal status including the effect of hormonal disruptors. These aspects remain, however, unsettled and controversial. It is possible to differentiate and clearly quantify the SCM shape, size, scalloped border, and variegated pigmentation using computerized morphometry as well as fractal and multifractal methods.


Correcting for strong eddy current induced B0 modulation enables two-spoke RF pulse design with parallel transmission: demonstration at 9.4T in the human brain.
Successful implementation of homogeneous slice-selective RF excitation in the human brain at 9.4T using 16-channel parallel transmission (pTX) is demonstrated. A novel three-step pulse design method incorporating fast real-time measurement of eddy current induced B0 variations as well as correction of resulting phase errors during excitation is described. To demonstrate the utility of the proposed method, phantom and in-vivo experiments targeting a uniform excitation in an axial slice were conducted using two-spoke pTX pulses. Even with the pre-emphasis activated, eddy current induced B0 variations with peak-to-peak values greater than 4 kHz were observed on our system during the rapid switches of slice selective gradients. This large B0 variation, when not corrected, resulted in drastically degraded excitation fidelity with the coefficient of variation (CV) of the flip angle calculated for the region of interest being large (~ 12% in the phantom and ~ 35% in the brain). By comparison, excitation fidelity was effectively restored, and satisfactory flip angle uniformity was achieved when using the proposed method, with the CV value reduced to ~ 3% in the phantom and ~ 8% in the brain. Additionally, experimental results were in good agreement with the numerical predictions obtained from Bloch simulations. Slice-selective flip angle homogenization in the human brain at 9.4T using 16-channel 3D spoke pTX pulses is achievable despite of large eddy current induced excitation phase errors; correcting for the latter was critical in this success.


Small-Molecule PROTACS: New Approaches to Protein Degradation.
The current inhibitor-based approach to therapeutics has inherent limitations owing to its occupancy-based model: 1) there is a need to maintain high systemic exposure to ensure sufficient in vivo inhibition, 2) high in vivo concentrations bring potential for off-target side effects, and 3) there is a need to bind to an active site, thus limiting the drug target space. As an alternative, induced protein degradation lacks these limitations. Based on an event-driven model, this approach offers a novel catalytic mechanism to irreversibly inhibit protein function by targeting protein destruction through recruitment to the cellular quality control machinery. Prior protein degrading strategies have lacked therapeutic potential. However, recent reports of small-molecule-based proteolysis-targeting chimeras (PROTACs) have demonstrated that this technology can effectively decrease the cellular levels of several protein classes.


[Effect of low-frequency ultrasound on the course of the wound process].
By the methods of clinical and morphological investigations as well as by measurements of the wound medium pH it was established that the application of low-frequency ultrasound for the treatment of purulent wounds accelerated necrolysis, decreased bacterial contamination of the wound, normalised the microcirculation system, activated the macrophagal reaction, increased the proliferative and synthetic activity of fibroblasts, collagen fibrillogenesis and contributed to a sharp shortening of the hydratation phase which resulted in the earlier closing of the wound.


Postantibiotic effects of imipenem, norfloxacin, and amikacin in vitro and in vivo.
The postantibiotic effects (PAEs) of imipenem and norfloxacin were tested against Staphylococcus aureus, Streptococcus (Enterococcus) faecalis, Escherichia coli, and Pseudomonas aeruginosa. Amikacin was tested against the same bacteria except Streptococcus faecalis. For in vitro tests, a viable count-washing method was used, and for in vivo tests, the thread technique in normal mice was used. All three drugs produced PAEs of 1.1 to 3.8 h in vitro and 1.4 to 4.3 h in vivo against the pathogens tested. In vitro and in vivo results correlated well. The PAE had a significantly (P less than 0.01 to 0.001) longer duration in vivo than in vitro, but the PAE of imipenem on Staphylococcus aureus was longer in vitro. The PAE was not due to residual antibiotics at the site of infection, and no PAE was obtained if at any time the antibiotic concentration at the infection site reached the MIC for the pathogen tested. The results indicate that the presence of a PAE may enable antibiotics to be given more intermittently without a loss of efficacy and that the PAE can only be induced if the level of the antibiotic exceeds the MIC for the pathogen in question for at least several minutes.


More or Less Unnatural: Semantic Similarity Shapes the Learnability and Cross-Linguistic Distribution of Unnatural Syncretism in Morphological Paradigms.
Morphological systems often reuse the same forms in different functions, creating what is known as syncretism. While syncretism varies greatly, certain cross-linguistic tendencies are apparent. Patterns where all syncretic forms share a morphological feature value (e.g., first person, or plural number) are most common cross-linguistically, and this preference is mirrored in results from learning experiments. While this suggests a general bias towards natural (featurally homogeneous) over unnatural (featurally heterogeneous) patterns, little is yet known about gradients in learnability and distributions of different kinds of unnatural patterns. In this paper we assess apparent cross-linguistic asymmetries between different types of unnatural patterns in person-number verbal agreement paradigms and test their learnability in an artificial language learning experiment. We find that the cross-linguistic recurrence of unnatural patterns of syncretism in person-number paradigms is proportional to the amount of shared feature values (i.e., semantic similarity) amongst the syncretic forms. Our experimental results further suggest that the learnability of syncretic patterns also mirrors the paradigm's degree of feature-value similarity. We propose that this gradient in learnability reflects a general bias towards similarity-based structure in morphological learning, which previous literature has shown to play a crucial role in word learning as well as in category and concept learning more generally. Rather than a dichotomous natural/unnatural distinction, our results thus support a more nuanced view of (un)naturalness in morphological paradigms and suggest that a preference for similarity-based structure during language learning might shape the worldwide transmission and typological distribution of patterns of syncretism.


Family experiences of antenatal counselling of spina bifida: a systematic review.
To describe families' experiences of antenatal counselling of spina bifida. Systematic review. MEDLINE, CINAHL, PsycINFO and Embase databases were searched using a combination of Medical Subject Headings and text/abstract terms. Case reports, survey results and qualitative interview data were included. The quality of research was evaluated using the Critical Appraisal Skills Programme checklist. 8 papers were included. Families described shock and grief at diagnosis, with some immediately offered termination of pregnancy (TOP) even though they knew little about the condition. Positive and negative aspects of care were found. Teams that were gentle, kind and empathetic, who did not use jargon, and highlighted positive and negative aspects of the baby's life were seen favourably. Callous language, and overly negative or incorrect counselling was not, particularly if there was pressure to agree to TOP. Families based their decisions on how they would cope, the effect on siblings and the baby's likely quality of life. Prenatal surgery was viewed positively. The views of families who chose TOP, were happy with their care, partners, families, and the LGBTQ+ community were under-represented in the literature. Unlike other conditions where limited data on outcome exist or the spectrum is genuinely broad, the outcomes of children with spina bifida is well described. Poor aspects of antenatal counselling were described frequently by families, and further work is needed to capture the full spectrum of views on antenatal counselling, how it can be improved, and what training and resources healthcare professionals need to perform it better.


Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity.
Polyphenols present in foods and supplements may contribute to human health by preventing cardiovascular diseases and cancer. Drug-food or drug-herb interactions have recently come into focus but, except for some phytochemicals, few components of food or herbs participate in such interactions. In this study, we systematically evaluated the inhibitory effects of 60 polyphenols and related compounds on human cytochrome P450 (CYP) 3A4 and CYP2C9 activity by in vitro assay to investigate whether some polyphenols induce drug interactions. In addition, the kinetics of potent CYP inhibitors was investigated by Lineweaver-Burk plot analysis. Three coumarins and 12 flavonoids significantly suppressed CYP3A4 or CYP2C9 activities. Lineweaver-Burk plot analysis indicated that apigenin and its dimer amentoflavone and imperatorin displayed a mixed type of inhibition on CYP3A4 or CYP2C9. Among the inhibitors, amentoflavone was the most potent inhibitor of CYP3A4 and CYP2C9 activities with IC(50) values of 0.07 and 0.03 microM, respectively. The K(i) value of amentoflavone was significantly lower than that of the CYP2C9 inhibition positive control sulfaphenazole. These findings suggest that some dietary polyphenols may have the potential to inhibit the metabolism of clinical drugs.


Interaction of adeno-associated virus Rep78 with p53: implications in growth inhibition.
Adeno-associated virus (AAV) is a nonpathogenic, single-stranded DNA virus belonging to the parvoviridae family. Onco-suppressive properties of AAV against adenovirus, a DNA tumor virus, have been well documented. Rep78, a major regulatory protein of AAV, is believed to be responsible for its antioncogenic properties. Most DNA tumor viruses disturb the cell cycle pathways by essentially abrogating the functions of p53. Here we present evidence that AAV acts as an antiproliferative agent against adenovirus by protecting the adenoviral-mediated degradation of p53 as confirmed by both Western blot analysis and immunoprecipitation analysis with anti-p53 antibody. Coimmunoprecipitation experiments revealed that the AAV Rep78 is physically bound to p53 in vivo. Furthermore, the binding of purified p53 to the AAV Rep78 affinity column confirms their interaction. These results document for the first time that the antiproliferative effects of AAV against adenovirus are mediated, at least in part, by the interaction of AAV Rep78 with p53.


Racial/ethnic discrimination and tobacco and cannabis use outcomes among US adults.
Racial/ethnic discrimination (hereafter, discrimination) is associated with use of individual tobacco and cannabis products. However, we know little about how discrimination affects dual/polytobacco and cannabis use and associated use disorders. We used cross-sectional data on adults (18+) from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (n = 35,744). We defined past-year discrimination as a summary scale (range: 0-24) based on six scenarios. We created a mutually exclusive six-category use variable: noncurrent, individual tobacco and noncannabis, individual tobacco and cannabis, individual cannabis and nontobacco, dual/polytobacco and noncannabis, and dual/polytobacco and cannabis based on past 30-day tobacco use of four products (i.e., cigarettes, electronic nicotine delivery systems, other combustibles (cigars, pipe), smokeless tobacco) and cannabis use. We also examined past-year tobacco use disorder (TUD) and cannabis use disorder (CUD) as a four-level variable: no disorders, TUD only, CUD only, and TUD and CUD. We estimated associations between discrimination and each outcome using adjusted multinomial logistic regression and assessed effect modification by stratifying adjusted models by race/ethnicity (i.e., Hispanic, non-Hispanic (NH) White, NH Black, and another race/ethnicity). Experiencing more discrimination was associated with each outcome but was most strongly associated with dual/polytobacco and cannabis use (OR: 1.13, 95 % CI: 1.07-1.19) and joint TUD and CUD (OR: 1.16, 95 % CI: 1.12-1.20). Models stratified by race/ethnicity showed that discrimination was associated with dual/polytobacco and cannabis only among NH White adults, and with joint TUD and CUD only among NH Black and NH White adults. Discrimination was associated with tobacco and cannabis use outcomes among multiple adult racial/ethnic populations, but associations were more profound for NH White and NH Black adults than adults from other racial/ethnic populations.


Prospective vaccine prepared from a new mutant of Toxoplasma gondii for use in cats.
Kittens are the principal disseminators of Toxoplasma gondii. They can shed greater than 10(8) oocysts in the feces after initial infection with bradyzoites in tissue cysts. Thereafter, most kittens develop protective immunity and do not shed oocysts again if they are reinfected. Bradyzoites of a T gondii mutant, designated T-263, were used to vaccinate kittens. Their use did not result in oocyst shedding, but successfully prevented 84% (31/37) of the kittens from shedding oocysts when challenge exposed with a normal isolate of T gondii. Vaccination of outdoor-roaming cats and kittens would be a useful public health measure to prevent transmission of toxoplasmosis near homes, on farms, and in zoos. It is anticipated that several years will be required for a lyophilized bradyzoite vaccine to be ready for licensing and possible commercial availability.


Prehospital emergency services screening and referral to reduce falls in community-dwelling older adults: a systematic review.
Falls represent an increasing source of geriatric morbidity and mortality. Prehospital emergency services may be uniquely suited to screen and refer subsets of high-risk older adults to fall prevention programmes. This systematic review assesses the effectiveness of such screening and referral programmes. We searched PubMed, Embase, CINAHL, Web of Science, Scopus, the Cochrane Library and OTseeker for English-language peer-reviewed randomised trials, non-randomised trials and cohort studies evaluating prehospital fall risk screening and referral programmes for community-dwelling adults ≥60 years of age. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary outcomes included the risk and rate of falling. Secondary outcomes included successful follow-up to address fall risks and adverse events. From 6187 unique records, 6 studies were included. Screening varied from using semistructured risk assessments to recording chief complaints. All studies were at high risk of bias. One unblinded trial of a multifactorial fall prevention programme demonstrated a 14.3% (95% CI 6.1% to 22.5%) absolute reduction in annual fall risk and a relative fall incidence of 0.45 (95% CI 0.35 to 0.58). The probability of successful follow-up varied from 9.8% to 81.0%. No studies demonstrated any attributable adverse events. No high-quality evidence demonstrates that prehospital services reduce falls in community-dwelling older adults. Screening by prehospital personnel using semistructured risk assessments appears feasible, but it is unclear whether this is superior to referral based on fall-related chief complaints. PROSPERO 2012:CRD42012002782.


Whole-genome sequencing of nine esophageal adenocarcinoma cell lines.
Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines-ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4-all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC.


Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer.
Despite decades of study, the molecular mechanisms and selectivity of the biomolecular components of honeybee (Apis mellifera) venom as anticancer agents remain largely unknown. Here, we demonstrate that honeybee venom and its major component melittin potently induce cell death, particularly in the aggressive triple-negative and HER2-enriched breast cancer subtypes. Honeybee venom and melittin suppress the activation of EGFR and HER2 by interfering with the phosphorylation of these receptors in the plasma membrane of breast carcinoma cells. Mutational studies reveal that a positively charged C-terminal melittin sequence mediates plasma membrane interaction and anticancer activity. Engineering of an RGD motif further enhances targeting of melittin to malignant cells with minimal toxicity to normal cells. Lastly, administration of melittin enhances the effect of docetaxel in suppressing breast tumor growth in an allograft model. Our work unveils a molecular mechanism underpinning the anticancer selectivity of melittin, and outlines treatment strategies to target aggressive breast cancers.


Incretins: a new treatment option for type 2 diabetes?
This article describes how the discovery of a protein almost 100 years ago led to a clinical treatment for type 2 diabetes. Food intake, but also stimulation of the sympathetic nervous system (for example physical exercise), stimulates the secretion of glucagon-like-peptide-1 (GLP-1), derived from the glucagon precursor proglucagon in the small intestine. GLP-1 stimulates the production and secretion of insulin, the release of somatostatin, glucose utilisation by increasing insulin sensitivity and in animal studies also beta-cell function and expansion (proliferation). It inhibits glucagon release, gastric emptying, appetite and food intake via the central nervous system and in animal experiments also apoptosis of beta-cells. Since GLP-1 has to be administered parenterally and its half-life is short, a long-acting GLP-1 receptor agonist (exenatide) and a long-acting GLP-1 analogue (liraglutide) have been developed as well as an inhibitor of DPP-IV (the enzyme that breaks down endogenous GLP-1). Clinical studies with exenatide and liraglutide as monotherapy show a significant increase in the postprandial insulin concentration as well as a smaller increase in the postprandial glucose values. Adding these drugs to standard oral glucose-lowering medication shows improvement in glucose and insulin concentrations and HbA1c compared with adding placebo. The effect of exenatide on HbA1c is the same as adding a long-acting insulin analogue (glargine), but the increase in weight after adding insulin is not seen after exenatide, where even a small decrease in weight is found. This is an important advantage, because most type 2 patients are already obese. Whether less beta-cell apoptosis and maintenance of beta-cell function occurs, as has been shown in animal studies, has to be awaited. Clinical studies with the oral DPPIV inhibitors sitagliptin and vildagliptin show promising results, but are only published as abstracts at scientific meetings.


Dynamics of swimming bacteria: transition to directional order at high concentration.
At high cell concentrations, bacterial suspensions are known to develop a state of collective swimming (the "zooming bionematic phase," or ZBN) characterized by transient, recurring regions of coordinated motion greatly exceeding the size of individual cells. Recent theoretical studies of semidilute suspensions have suggested that long-range hydrodynamic interactions between swimming cells are responsible for long-wavelength instabilities that lead to these patterns, while models appropriate for higher concentrations have suggested that steric interactions between elongated cells play an important role in the self-organization. Using particle imaging velocimetry in well-defined microgeometries, we examine the statistical properties of the transition to the ZBN in suspensions of Bacillus subtilis, with particular emphasis on the distribution of cell swimming speeds and its correlation with orientational order. This analysis reveals a nonmonotonic relationship between mean cell swimming speed and cell concentration, with a minimum occurring near the transition to the ZBN. Regions of high orientational order in the ZBN phase have locally high swimming speeds, while orientationally disordered regions have lower speeds. A model for steric interactions in concentrated suspensions and previous observations on the kinetics of flagellar rebundling associated with changes in swimming direction are used to explain this observation. The necessity of incorporating steric effects on cell swimming in theoretical models is emphasized.


Atrophy subtypes in prodromal Alzheimer's disease are associated with cognitive decline.
Alzheimer's disease is a heterogeneous disorder. Understanding the biological basis for this heterogeneity is key for developing personalized medicine. We identified atrophy subtypes in Alzheimer's disease dementia and tested whether these subtypes are already present in prodromal Alzheimer's disease and could explain interindividual differences in cognitive decline. First we retrospectively identified atrophy subtypes from structural MRI with a data-driven cluster analysis in three datasets of patients with Alzheimer's disease dementia: discovery data (dataset 1: n = 299, age = 67 ± 8, 50% female), and two independent external validation datasets (dataset 2: n = 181, age = 66 ± 7, 52% female; dataset 3: n = 227, age = 74 ± 8, 44% female). Subtypes were compared on clinical, cognitive and biological characteristics. Next, we classified prodromal Alzheimer's disease participants (n = 603, age = 72 ± 8, 43% female) according to the best matching subtype to their atrophy pattern, and we tested whether subtypes showed cognitive decline in specific domains. In all Alzheimer's disease dementia datasets we consistently identified four atrophy subtypes: (i) medial-temporal predominant atrophy with worst memory and language function, older age, lowest CSF tau levels and highest amount of vascular lesions; (ii) parieto-occipital atrophy with poor executive/attention and visuospatial functioning and high CSF tau; (iii) mild atrophy with best cognitive performance, young age, but highest CSF tau levels; and (iv) diffuse cortical atrophy with intermediate clinical, cognitive and biological features. Prodromal Alzheimer's disease participants classified into one of these subtypes showed similar subtype characteristics at baseline as Alzheimer's disease dementia subtypes. Compared across subtypes in prodromal Alzheimer's disease, the medial-temporal subtype showed fastest decline in memory and language over time; the parieto-occipital subtype declined fastest on executive/attention domain; the diffuse subtype in visuospatial functioning; and the mild subtype showed intermediate decline in all domains. Robust atrophy subtypes exist in Alzheimer's disease with distinct clinical and biological disease expression. Here we observe that these subtypes can already be detected in prodromal Alzheimer's disease, and that these may inform on expected trajectories of cognitive decline.


The Use of 2 e-Learning Modalities for Diabetes Education Using Facebook in 2 Cities of Argentina During the COVID-19 Pandemic: Qualitative Study.
The COVID-19 pandemic and the confinement that was implemented in Argentina generated a need to implement innovative tools for the strengthening of diabetes care. Diabetes self-management education (DSME) is a core element of diabetes care; however, because of COVID-19 restrictions, in-person diabetes educational activities were suspended. Social networks have played an instrumental role in this context to provide DSME in 2 cities of Argentina and help persons with diabetes in their daily self-management. The aim of this study is to evaluate 2 diabetes education modalities (synchronous and asynchronous) using the social media platform Facebook through the content of posts on diabetes educational sessions in 2 cities of Argentina during the COVID-19 pandemic. In this qualitative study, we explored 2 modalities of e-learning (synchronous and asynchronous) for diabetes education that used the Facebook pages of public health institutions in Chaco and La Rioja, Argentina, in the context of confinement. Social media metrics and the content of the messages posted by users were analyzed. A total of 332 messages were analyzed. We found that in the asynchronous modality, there was a higher number of visualizations, while in the synchronous modality, there were more posts and interactions between educators and users. We also observed that the number of views increased when primary care clinics were incorporated as disseminators, sharing educational videos from the sessions via social media. Positive aspects were observed in the posts, consisting of messages of thanks and, to a lesser extent, reaffirmations, reflections or personal experiences, and consultations related to the subject treated. Another relevant finding was that the educator/moderator role had a greater presence in the synchronous modality, where posts were based on motivation for participation, help to resolve connectivity problems, and answers to specific user queries. Our findings show positive contributions of an educational intervention for diabetes care using the social media platform Facebook in the context of the COVID-19 pandemic. Although each modality (synchronous vs asynchronous) could have differential and particular advantages, we believe that these strategies have potential to be replicated and adapted to other contexts. However, more documented experiences are needed to explore their sustainability and long-term impact from the users' perspective.


Mouse spleen lymphoblasts generated in vitro. Their replication and differentiation in vitro.
Mouse spleen lymphoblasts induced with lipopolysaccharide and fetal calf serum were obtained in high yield and purity in their first proliferative cell cycle by floatation in dense bovine plasma albumin columns (3). The blasts were maintained in vitro for 3 more days. The cultures were examined in bulk on each day, and in addition, those cells in S phase initially were tagged with [(3)H]thymidine and followed continuously in vitro. Grain count dilution data indicated that most blasts divided but twice over a 2- to 3-day interval in vitro. [(3)H]Thymidine pulse radiolabeling and flow microfluorometry suggested that at least 50-70 percent of the proliferating blasts withdrew from proliferative activity after 2-3 days of culture. Morphologic studies demonstrated that lymphoblasts persisted as such for 1-2 days in vitro and then matured into typical plasma cells. Many of the blastprogeny had small nuclei and considerable basophilic cytoplasm on Giemsa-stained cell smears; abundant rough endoplasmic reticulum by electron microscopy; and readily detectable cytoplasmic Ig by immunocytochemistry. Reversion of blasts to small lymphocytes could not be detected; however, some blasts persisted even after 3 days of culture. The viability of the cultured lymphoblast was followed by initially tagging the cells with [(3)H]thymidine as well as several other techniques. Little cell death was documented during the first day of culture. The number of labeled progeny increased twofold whereas the grain count halved. But 40- 50 percent of the cell-associated label was lost during each of the second and third days, and fewer labeled progeny than predicted by grain count dilution were identified. The culture medium could not be implicated in this loss of lymphoblast progeny, and we suggest that the maturation of the lymphoblast to a short-lived plasma cell was responsible. Therefore mitogen-stimulated B blasts seem to mature into typical plasma cells after just two cycles of cell division. The plasma cells resemble those produced in situ during an immune response in their cytologic features, withdrawal from active proliferative activity, and short life-span.


The effect of telephone social support and education on adaptation to breast cancer during the year following diagnosis.
To find the most effective methods of providing social support for women diagnosed with breast cancer by testing the effectiveness of a telephone social support and education intervention to promote emotional and interpersonal adaptation to breast cancer. Multisite, two-group experimental study with repeated measures. Arkansas and New Jersey. The Arkansas sample consisted of 106 women who entered the study two to four weeks postsurgery for nonmetastatic breast cancer and were randomly assigned to an experimental or control group. The comparison group consisted of 91 women from New Jersey who had participated in a previously completed study that used the same interventions and found that telephone support resulted in more positive, statistically significant adaptation to the disease. The experimental group received 13 months of telephone social support and education. Both groups received educational materials via a mailed resource kit. The Profile of Mood States; Visual Analogue Scale-Worry; Relationship Change Scale; University of California, Los Angeles, Loneliness Scale-Version 3; and the modified Symptom Distress Scale provided data regarding the variables of interest. Data analysis included descriptive statistics, t tests, and multivariate analysis of variance with repeated measures. Mood, worry, relationships with significant others, loneliness, and symptoms. Data analysis showed no significant differences between groups, and both improved on some of the outcomes. Significant time-by-location interaction effects were found when comparing the Arkansas and New Jersey samples, thereby supporting the need to consider regional differences when developing interventions. The mailed educational resource kit alone appeared to be as effective as the telephone social support provided by oncology nurses in conjunction with the mailed resource kit. Mailed educational resource kits may be the most efficient and cost-effective way to provide educational support to newly diagnosed patients with breast cancer, but their effect may differ according to region.


Flame speed and self-similar propagation of expanding turbulent premixed flames.
In this Letter we present turbulent flame speeds and their scaling from experimental measurements on constant-pressure, unity Lewis number expanding turbulent flames, propagating in nearly homogeneous isotropic turbulence in a dual-chamber, fan-stirred vessel. It is found that the normalized turbulent flame speed as a function of the average radius scales as a turbulent Reynolds number to the one-half power, where the average radius is the length scale and the thermal diffusivity is the transport property, thus showing self-similar propagation. Utilizing this dependence it is found that the turbulent flame speeds from the present expanding flames and those from the Bunsen geometry in the literature can be unified by a turbulent Reynolds number based on flame length scales using recent theoretical results obtained by spectral closure of the transformed G equation.


Three faces of node importance in network epidemiology: Exact results for small graphs.
We investigate three aspects of the importance of nodes with respect to susceptible-infectious-removed (SIR) disease dynamics: influence maximization (the expected outbreak size given a set of seed nodes), the effect of vaccination (how much deleting nodes would reduce the expected outbreak size), and sentinel surveillance (how early an outbreak could be detected with sensors at a set of nodes). We calculate the exact expressions of these quantities, as functions of the SIR parameters, for all connected graphs of three to seven nodes. We obtain the smallest graphs where the optimal node sets are not overlapping. We find that (i) node separation is more important than centrality for more than one active node, (ii) vaccination and influence maximization are the most different aspects of importance, and (iii) the three aspects are more similar when the infection rate is low.


Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus.
Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, "collapsing" glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and "collapsing" glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group.


Stable transformation of Sorghum bicolor protoplasts with chimeric neomycin phosphotransferase II and β-glucuronidase genes.
Parameters influencing the stable transformation of Sorghum bicolor protoplasts with a chimeric neomycin phosphotransferase II (NPT II) gene by electroporation were investigated. The mean number of kanamycin-resistant calli produced increased in direct proportion to the concentration of DNA used for transformation. Linearization of the plasmid doubled the mean number of kanamycin-resistant calli produced, while the addition of carrier DNA had no effect. The copy number (1-4) of integrated genes was low compared with that frequently reported for PEG-mediated transformation. Two strategies for transforming protoplasts with a nonselectable, β-glucuronidase (GUS) gene were compared. One utilized a plasmid containing a CaMV 35S-NPT II gene covalently linked to a CaMV 35S-GUS gene, and the other strategy utilized the two genes on separate plasmids. DNA from all 77 kanamycin-resistant calli analyzed contained restriction fragments hybridizing to the NPT II probe; approximately 70% of the clones from all transformation treatments contained a 1.7-kb EcoRI/HindIII restriction fragment corresponding to the full-length gene. Of the kanamycin-resistant calli, 38-63% (depending on the transformation treatment) contained GUS-hybridizing fragments, and 8-19% contained the full-length gene. The addition of NPT II and GUS genes on a single plasmid or on separate plasmids did not appear to lead to an appreciable difference in the frequency of cointegration of these genes, although an increased proportion of the plasmid bearing the nonselectable (GUS) gene appeared to favor its cointegration.


Structural insights into the regulation of cohesion establishment by Wpl1.
Correct segregation of duplicated chromosomes to daughter cells during mitosis requires the action of the cohesin complex. This tripartite ring-shaped molecule is involved in holding replicated sister chromatids together from S phase until anaphase onset. Establishment of stable cohesion involves acetylation of the Smc3 component of cohesin during replication by the Eco1 acetyltransferase. This has been proposed to antagonise the activity of another member of the cohesin complex, Wpl1. Here, we describe the X-ray structure of the conserved Wapl domain, and demonstrate that it binds the ATPase head of the Smc3 protein. We present data that suggest that Wpl1 may be involved in regulating the ATPase activity of cohesin, and that this may be subject to the acetylation state of Smc3. In addition, we present a structure of the Wapl domain bound to a functionally relevant segment of the Smc3 ATPase.


Sculptured 3D twister superlattices embedded with tunable vortex spirals.
We present diverse reconfigurable complex 3D twister vortex superlattice structures in a large area embedded with tunable vortex spirals as well as dark rings, threaded by vortex helices. We demonstrate these tunable complex chiral vortex superlattices by the superposition of relatively phase engineered plane waves. The generated complex 3D twister lattice vortex structures are computationally as well as experimentally analyzed using various tools to verify the presence of phase singularities. Our observation indicates the application-specific flexibility of our approach to tailor the transverse superlattice spatial irradiance profile of these longitudinally whirling vortex-cluster units and dark rings.


Polystyrene Pocket Lithography: Sculpting Plastic with Light.
Tissue-culture-ware polystyrene is the gold standard for in vitro cell culture. While microengineering techniques can create advanced cell microenvironments in polystyrene, they require specialized equipment and reagents, which hinder their accessibility for most biological researchers. An economical and easily accessible method is developed and validated for fabricating microstructures directly in polystyrene with sizes approaching subcellular dimensions while requiring minimal processing time. The process involves deep ultraviolet irradiation through a shadow mask or ink pattern using inexpensive, handheld devices followed by selective chemical development with common reagents to generate micropatterns with depths/heights between 5 and 10 µm, which can be used to guide cell behavior. The remarkable straightforwardness of the process enables this class of microengineering techniques to be broadly accessible to diverse research communities.


Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle actin filaments during myofibroblast differentiation.
Myofibroblasts are implicated in pathological stromal responses associated with lung fibrosis. One prominent phenotypic marker of fully differentiated myofibroblasts is the polymerized, thick cytoplasmic filaments containing newly synthesized α-smooth muscle actin (α-SMA). These α-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of α-SMA-containing filaments have not been defined. This study demonstrates a critical role for neuronal Wiskott-Aldrich syndrome protein (N-WASP) in regulating the formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-β1 (TGF-β1) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-β1-induced formation of α-SMA-containing cytoplasmic filaments in primary human lung fibroblasts. In addition, we demonstrate that actin-related protein (Arp) 2/3 complex is downstream of N-WASP and mediates the maturation of α-SMA-containing cytoplasmic filaments. Together, this study supports a critical role of N-WASP in integrating FAK and Arp2/3 signaling to mediate formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation.


Mitochondrial Dysfunction in Skeletal Muscle Pathologies.
Several molecular mechanisms are involved in the regulation of skeletal muscle function. Among them, mitochondrial activity can be identified. The mitochondria is an important and essential organelle in the skeletal muscle that is involved in metabolic regulation and ATP production, which are two key elements of muscle contractibility and plasticity. Thus, in this review, we present the critical and recent antecedents regarding the mechanisms through which mitochondrial dysfunction can be involved in the generation and development of skeletal muscle pathologies, its contribution to detrimental functioning in skeletal muscle and its crosstalk with other typical signaling pathways related to muscle diseases. In addition, an update on the development of new strategies with therapeutic potential to inhibit the deleterious impact of mitochondrial dysfunction in skeletal muscle is discussed.


Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC with electrospray ionization tandem mass spectrometry.
Clinical presentation and disease severity in disorders of purine and pyrimidine metabolism vary considerably. We present a method that allows comprehensive, sensitive, and specific diagnosis of the entire spectrum of abnormalities in purine and pyrimidine metabolism in 1 analytical run. We used reversed-phase HPLC electrospray ionization tandem mass spectrometry to investigate 24 metabolites of purine and pyrimidine metabolism in urine samples from healthy persons and from patients with confirmed diagnoses of inherited metabolic disorders. Urine samples were filtered and diluted to a creatinine concentration of 0.5 mmol/L. Stable-isotope-labeled internal standards were used for quantification. The metabolites were analyzed by multiple-reaction monitoring in positive and negative ionization modes. Total time of analysis was 20 min. Recovery (n = 8) of a compound after addition of a known concentration was 85%-133%. The mean intraday variation (n = 10) was 12%. The interday variation (n = 7) was < or =17%. Age-related reference intervals were established for each compound. Analysis of patient urine samples revealed major differences in tandem mass spectrometry profiles compared with those of control samples. Twelve deficiencies were reliably detected: hypoxanthine guanine phosphoribosyl transferase, xanthine dehydrogenase, purine nucleoside phosphorylase, adenylosuccinate lyase, uridine monophosphate synthase, adenosine deaminase, adenine phosphoribosyl transferase, molybdenum cofactor, thymidine phosphorylase, dihydropyrimidine dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase. This method enables reliable detection of 13 defects in purine and pyrimidine metabolism in a single analytical run.


QSAR studies on HIV-1 protease inhibitors using non-linearly transformed descriptors.
Human Immunodeficiency Virus (HIV)-1 protease is one of the key targets for Acquired Immunodeficiency Syndrome (AIDS). A large number of inhibitors are being designed for this target with the focus towards interactions with backbone atoms to combat drug resistance. In the present study, we have developed QSAR models for 99 inhibitors which include P₁/P₁' and P₂/P₂' substituents with diverse scaffolds. In the present work, HIV-1 protease inhibitors dataset with tanimoto similarity of 0.7 were compiled from The Binding Database (Binding DB). Multiple linear regression analysis was performed to compute the relationship between 2D and 3D structure descriptors and binding affinity. Untransformed and non-linearly transformed descriptors were used for the QSAR model development. Transformation of descriptors resulted in better QSAR model (r²=0.77) compared to the model developed using untransformed descriptors (r²=0.74). Molecular connectivity, cosmic bond angle energy and charged based descriptor were reported as a priori properties in the prediction of binding affinity. The developed models were validated using an external test set and r² test values of 0.73 and 0.72 were obtained. Models developed in this study have potential application in the prediction of binding affinity for the newly synthesized compounds.


Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma.
Between January 1988 and June 1990, seven previously untreated patients with histologically confirmed and clinically staged IIIa invasive thymoma (IT) were enrolled in a prospective, single treatment arm study of neoadjuvant chemotherapy (NC) followed by surgery and postoperative radiation therapy (4600 to 6000 cGy). The NC included three cycles of cisplatin (75 mg/m2 on day 1), epirubicin (100 mg/m2 on day 1), and etoposide (120 mg/m2 on days 1, 3, and 5), every 3 weeks. All patients showed a partial response (greater than 50%) and underwent complete (n = 4) or incomplete (gross [n = 1] or microscopic [n = 2] residual tumor) surgical resection. Histologic examination was negative for two completely resected patients. Projected 2-year survival was 80%; all patients but one currently are alive and disease-free. This approach appeared to be feasible and may be a new therapeutic choice in the management of IT, but its use on a regular basis should be reserved until a larger number of patients and longer follow-up are available.


Evolution of the parasitic wasp subfamily Rogadinae (Braconidae): phylogeny and evolution of lepidopteran host ranges and mummy characteristics.
The braconid subfamily Rogadinae is a large, cosmopolitan group of endoparasitoid wasps characterised by 'mummifying' their lepidopteran host larvae, from which the adult subsequently emerges. Rogadines attack a variety of both macro- and microlepidopteran taxa, although the speciose genus Aleiodes almost exclusively attacks macrolepidopterans. Here, we investigate the phylogenetic history of the Rogadinae, revise their higher-level classification and assess the evolution of their host ranges and mummy types. We also assess the divergence times within the subfamily and discuss the reasons for the extraordinary evolutionary diversification of Aleiodes. Our Bayesian analyses weakly support the monophyly of the subfamily. A clade comprising all Aleiodes species and some other taxa is not nested within the tribe Rogadini as previously supposed, but instead is recovered as sister to the Yeliconini, with the remaining Rogadini genera being recovered as sister to the Stiropiini. The Rogadinae is estimated to have originated during the mid to late Eocene, 36.1-51.62 MYA. Molecular dating gives a more recent origin for the Aleiodes clade (17.98-41.76 MYA) compared to the origins proposed for two of its principal lepidopteran host groups (Noctuidae: 60.7-113.4 MYA; Geometridae 48-62 MYA). The Bayesian ancestral reconstruction of the emergence habits from the mummified hosts weakly recovered an anterior emergence as the ancestral condition for the subfamily. Producing a hard mummy has evolved at various times independently, though most of the species with this biology belong to the Aleiodes clade. Based on our results, we erect the tribe Aleiodini nov. to include Aleiodes and Heterogamus stat. rev. Cordylorhogas, Pholichora and Hemigyroneuron are synonymised with Aleiodes. The molecular dating of clades and the ancestral reconstruction of host ranges support the hypothesis that radiation within Aleiodes s. s. was due to host recruitment leading to host range expansion followed by speciation, and not to parasitoid-host coevolution. Within the Rogadinae, variation in the site of emergence from the mummified host probably evolved as a consequence of the mummy's site and mode of formation, and the extent of mummy tanning/hardness to the degree of protection needed in relation to the cost of providing it.


A Survey of Health Sciences Faculty Practices and Attitudes Regarding the Peer Feedback Component of Team-Based Learning.
Peer feedback, an essential component of team-based learning (TBL), fosters accountability among team members. Effective utilization can be advantageous for both students and faculty, although there may be many implementation challenges. Our study objectives were to (1) identify current practices of peer feedback in TBL, (2) identify curricular assessment related to peer feedback, and (3) identify challenges with peer feedback in TBL. A survey link was sent via medical and TBL web boards. The survey asked for both quantitative and qualitative information regarding the peer feedback process. Quantitative results were analyzed using SPSS®. NVivo® was used to identify and code themes in open-ended responses. Both investigators reviewed and agreed upon themes. Sixty-one TBL users in health professions completed the survey. Multiple health professions were represented with medicine and pharmacy being the most common. Information on current practices showed a wide variety of implementation. Curricular alignment was common. Time and training were the most common challenges and difficulties. Meaningful feedback should be considered an important curricular outcome. Specific learning objectives and appropriate assessment strategies should be developed to meet the mission of the program. Students must receive guidance from faculty members on how to improve their skills in providing effective feedback. Overall, faculty saw peer evaluation as valuable. However, the time commitment, lack of student training, and student attitudes make implementation difficult. Future research should focus on best practices to streamline the TBL feedback process and on student training regarding how to provide effective feedback.


Media multitasking as an avoidance coping strategy against emotionally negative stimuli.
Background and Objectives: Emotion regulation refers to the way individuals manage and regulate their own emotions in response to negative emotional experiences. This study investigated whether media multitasking serves as an avoidance coping strategy for managing emotionally stressful events. Design and Methods: Using a correlational design, 140 participants completed self-report measures of media multitasking and emotion regulation, and cognitive measures assessing attentional bias for emotionally negative stimuli. Results: Media multitasking was associated with difficulties in accepting emotional responses for participants who showed an attentional bias away from anxiety words, and for participants with poorer inhibitory control over such words. Further, there was a strong association between media multitasking and reduced interference from anxiety words for participants with stronger inhibitory control over such words in the emotional Stroop task. Conclusions: Results support the idea that media multitasking is linked to difficulty dealing with emotionally negative stimuli and serves as an avoidance coping strategy where one deliberately directs attention away from negative stimuli to prevent their further processing. The findings have real-life implications for managing anxiety and depression, as media multitasking may be used as a maladaptive coping strategy that further increases these negative moods.


On mind wandering, attention, brain networks, and meditation.
Human attention selectively focuses on aspects of experience that are threatening, pleasant, or novel. The physical threats of the ancient times have largely been replaced by chronic psychological worries and hurts. The mind gets drawn to these worries and hurts, mostly in the domain of the past and future, leading to mind wandering. In the brain, a network of neurons called the default mode network has been associated with mind wandering. Abnormal activity in the default mode network may predispose to depression, anxiety, attention deficit, and posttraumatic stress disorder. Several studies show that meditation can reverse some of these abnormalities, producing salutary functional and structural changes in the brain. This narrative review presents a mechanistic understanding of meditation in the context of recent advances in neurosciences about mind wandering, attention, and the brain networks.


[Clinical effectiveness of carbenicillin in suppurative inflammatory processes of varying localization].
The study on sensitivity of clinical strains of the causative agents of purulent infections to carbenicillin showed that 34.6% of the staphylococcal strains, 48.1% of the E. coli strains and 40.3% of the Proteus strains were sensitive to the antibiotic. The strains of Ps. aeruginosa were characterized by moderate sensitivity to carbenicillin. The MTC for most of the isolates ranged within 25-128 microgram/ml. High therapeutic efficacy of carbenicillin in treatment of cases with purulent inflammatory processes of various localization was shown. Positive results were obtained in 82.5% of the adults and 76.2% of the premature infants treated with carbenicillin. A satisfactory therapeutic effect was observed in the cases with sepsis, diffuse purulent peritonitis and abscessing pneumonia treated with carbenicillin in combination with gentamicin.


Isotopic Composition of Lead and Strontium from Ascension and Gough Islands.
Isotopic composition of lead and strontium has been determined in a series of rock samples from two islands on the Mid-Atlantic Ridge. Both interand intra-island variations exist in the abundance of radiogenic isotopes of both elements. Lead from basalt of Ascension Island has a Pb(206)-Pb(204) ratio of 19.5, while the corresponding ratio at Gough Island is only 18.4. The Pb(208)-Pb(204) ratios from the two islands do not differ. Conversely, strontium from basalt of Ascension Island is less radiogenic than that from Gough Island basalts. The trachytes of both islands have lead and strontium that is more radiogenic than that found in the basalts. The inter-island differences indicate the existence of regional variations in the uranium-lead and rubidium-strontium ratios of the upper mantle source of these rocks and show that isotope compositions are a means for investigating chemical heterogeneities in the mantle.


Stream water hydrochemistry as an indicator of carbon flow paths in Finnish peatland catchments during a spring snowmelt event.
Extreme hydrological events are known to contribute significantly to total annual carbon export, the largest of which in Arctic and boreal catchments is spring snowmelt. Whilst previous work has quantified the export of carbon during snowmelt, the source of the carbon remains unclear. Here we use cation hydrochemistry to trace the primary flowpaths which govern the export of carbon during the snowmelt period; specifically we aim to examine the importance of snowpack meltwater to catchment carbon export. The study was carried out in two forested peatland (drained and undrained) catchments in Eastern Finland. Both catchments were characterised by base-poor stream water chemistry, with cation concentrations generally decreasing in response to increasing discharge. Streamflow during the snowmelt period was best described as a mixture of three sources: pre-event water, snowpack meltwater and a third dilute component we attribute to the upper snow layer which was chemically similar to recent precipitation. Over the study period, pre-event water contributed 32% and 43% of the total stream runoff in Välipuro (undrained) and Suopuro (drained), respectively. The results also suggest a greater near-surface throughflow component in Suopuro, the drained catchment, prior to snowmelt. CO(2) and DOC concentrations correlated positively with cation concentrations in both catchments indicating a common, peat/groundwater flowpath. CH(4) concentrations were significantly higher in the drained catchment and appeared to be transported in near-surface throughflow. Meltwater from the snowpack represented an important source of stream water CO(2) in both catchments, contributing up to 49% of total downstream CO(2) export during the study period. We conclude that the snowpack represents a potentially important, and often overlooked, transient carbon store in boreal snow-covered catchments.


Experimental demonstration of critical coupling of whispering gallery mode cavities on a Bloch surface wave platform.
We experimentally demonstrate critical coupling of whispering gallery mode (WGM) disk resonators implemented on a Bloch surface wave platform using scanning near-field optical microscopy. The studied structure is a 60 nm thick TiO2 WGM disk cavity (radius of 100 μm) operating within the C-band telecommunication wavelength. An extinction ratio of 26 dB and a quality factor of 2200 are measured. Such a high extinction ratio verifies the critical coupling of the WGM resonator. This result paves the way to planar optical signal processing devices based on the proposed geometry, for which a critical coupling condition is a guarantee of optimum performance.


The recurrence of the melanotic neuroectodermal tumour of infancy: an unusual presentation of a rare tumour.
The melanotic neuroectodermal tumour of infancy (MNTI), also known as melanotic progonoma, is a rare neoplasm derived from neural crest cells. Although it is fundamentally benign, the tumour may present a locally aggressive behaviour, characterised by a rapid progression and a destructive invasion of adjacent structures, hence causing deformities. Unfortunately, perhaps due to the low incidence of this type of tumour, the published cases in the literature do not characterise the factors that imply the malignant or recurrent behaviour of the disease, nor the therapy to conduct these cases. Here, we report a rare case of a recurrent benign MNTI, approached unusually with a favourable outcome.


Targeted GSH-exhausting and hydroxyl radical self-producing manganese-silica nanomissiles for MRI guided ferroptotic cancer therapy.
Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese-oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.


On the relationship between cell cycle analysis with ergodic principles and age-structured cell population models.
Cyclic processes, in particular the cell cycle, are of great importance in cell biology. Continued improvement in cell population analysis methods like fluorescence microscopy, flow cytometry, CyTOF or single-cell omics made mathematical methods based on ergodic principles a powerful tool in studying these processes. In this paper, we establish the relationship between cell cycle analysis with ergodic principles and age structured population models. To this end, we describe the progression of a single cell through the cell cycle by a stochastic differential equation on a one dimensional manifold in the high dimensional dataspace of cell cycle markers. Given the assumption that the cell population is in a steady state, we derive transformation rules which transform the number density on the manifold to the steady state number density of age structured population models. Our theory facilitates the study of cell cycle dependent processes including local molecular events, cell death and cell division from high dimensional "snapshot" data. Ergodic analysis can in general be applied to every process that exhibits a steady state distribution. By combining ergodic analysis with age structured population models we furthermore provide the theoretic basis for extensions of ergodic principles to distribution that deviate from their steady state.


Rethinking Antillothrix: the mandible and its implications.
A mandible of the Hispaniolan primate Antillothrix bernensis, virtually complete and providing the only definitive evidence of the species' lower dentition, has been discovered in a submerged Dominican Republic cave. The new specimen enables a more certain assessment of the species' phylogenetic position than previously possible. It belongs to the same individual as the nearly complete young adult cranium and postrcranial elements found earlier at the same site. Of the extinct Caribbean platyrrhines, the jaw compares well with partial mandibles representing Xenothrix mcgregori, from Jamaica. Among living platyrrhines, it closely resembles Callicebus and Aotus, as documented in a biometric analysis employing three-dimensional geometric morphometrics of Callicebus, Aotus, Pithecia, Chiropotes, Cacajao, Cebus, and Saimiri. The jaw falls within the morphological variability of Callicebus and Aotus in this three-dimensional analysis, is otherwise most similar to Pithecia, and is distinct from cebines. Lower molars resemble the Haitian primate, Insulacebus, a genus known by a full dentition and gnathic fragments with a pattern of derived features also present in Xenothrix. Considering the available craniodental and postcranial evidence, we conclude that Antillothrix is not properly classified as cebid but rather is best grouped with Pitheciidae, an idea long central to discussions of the phylogenetic affinities of the Greater Antillean primates. Since Antillothrix and Insulacebus are more primitive anatomically than the highly modified Xenothrix, it is tempting to surmise that the origins of the latter involved a vicariance or dispersal event via Hispaniola isolating it on Jamaica.


[Changes in the provision of psychiatric services at a psychiatric district hospital].
Changes in the provision of psychiatric services within the last decennials are probably best understood if the impact of national socialism on clinical psychiatry is regarded. Many psychiatrists took part in the "Aktion T4" the organised killing of their patients, at least they did not resist campaigns directed to killing or sterilisation patients. After WW II, a period of silence and acceptance of inhuman circumstances in the large mental state hospitals appeared, when in the sixties a new generation of psychiatrists was no longer willing to continue the traditional system of mental health care delivery. The Expert Commission on Mental Health Care reported a comprehensive agenda on reformation of service delivery in 1975, which was influential in the development of alternative structures of psychiatric services. Most mental state hospitals reduced their capacities and parallel to this process smaller units, devoted to principles of community psychiatry, associated to general hospitals were created. Overall, the number of hospital driven beds decreased at about 33 %, but in the large hospitals at two thirds within the last 25 years in Baden-Wurttemberg. This process of deinstitutionalization was accompanied by the development of structures for community care, internal reorganization and modernization, and important steps in budget development, which lead to better treatment opportunities for all kinds of psychiatric institutions. The concrete and historical reality of these circumstances and changes, and possible future directions are exemplified for the psychiatric hospital in Weinsberg.


Interplay of dFOXO and two ETS-family transcription factors determines lifespan in Drosophila melanogaster.
Forkhead box O (FoxO) transcription factors (TFs) are key drivers of complex transcriptional programmes that determine animal lifespan. FoxOs regulate a number of other TFs, but how these TFs in turn might mediate the anti-ageing programmes orchestrated by FoxOs in vivo is unclear. Here, we identify an E-twenty six (ETS)-family transcriptional repressor, Anterior open (Aop), as regulated by the single Drosophila melanogaster FoxO (dFOXO) in the adult gut. AOP, the functional orthologue of the human Etv6/Tel protein, binds numerous genomic sites also occupied by dFOXO and counteracts the activity of an ETS activator, Pointed (Pnt), to prevent the lifespan-shortening effects of co-activation of dFOXO and PNT. This detrimental synergistic effect of dFOXO and PNT appears to stem from a mis-regulation of lipid metabolism. At the same time, AOP activity in another fly organ, the fat body, has further beneficial roles, regulating genes in common with dfoxo, such as the secreted, non-sensory, odorant binding protein (Obp99b), and robustly extending lifespan. Our study reveals a complex interplay between evolutionarily conserved ETS factors and dFOXO, the functional significance of which may extend well beyond animal lifespan.


[Study of energy migration between native forms of chlorophyll at -196 degrees C by the method of sensitized fluorescence].
Mathematical decomposition of fluorescence spectra of chloroplasts and cells measured under monochromatic excitation in the regions of absorption maxima of the main native forms allowed the authors to calculate the efficiency of energy migration between forms. It is shown that 80--100% of absorbed quanta flow to the Chl 738/708 form (bean) in photosystem 1, whereas in photosystem 2, the Chl 695/690 and Chl 703/698 forms are terminal energy acceptors. Efficient backward energy transfer between the Chl 680/676 and Chl 686/682 forms and the existence of energy migration pathways passing one or two steps of the energy stairway formed by the energy levels of the chlorophyll forms are found. It is shown that chlorphyll b is not an intermediate link in the process of energy transfer from carotenoids to chlorophyll a. The intrinsic fluoresence quantum yields of the native forms are calculated.


Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia.
We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations. Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups. Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05). Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation.


The effect of the menstrual cycle on dichotic listening.
The purpose of this study was to determine the effect of the menstrual cycle on responses to a dichotic listening task. It was hypothesized that participants would exhibit a stronger right ear advantage during the menstrual cycle days when estrogen levels are at their peak. It was also hypothesized that the women not taking oral contraceptives would exhibit greater variations in ear advantage over the course of their menstrual cycle than those taking oral contraceptives. Finally, it was hypothesized that the error response rates would remain similar across different listening conditions and over the menstrual cycle. The participants were 30 women who took oral contraceptives and 15 who did not. They completed nine listening sessions comprised of three dichotic listening tasks: forced-left, forced-right, and open. The data were analyzed using a mixed effects models. The participants exhibited a reduction in right ear responses on the days that corresponded to when the level of estrogen would begin to increase. This response was different from what had been hypothesized. The analysis also indicated no response differences between the two groups of women. In addition, the women exhibited fewer errors over the course of the sessions, implying that they adapted to the task. The results indicate that the women's hormone fluctuation across the menstrual cycle affected their responses to the forced-left, cognitive control, task only.


Insights into the Management of Overactive Bladder with Transdermal Oxybutynin: A Practical Review.
Overactive bladder (OAB), clinically defined as urinary urgency, with or without incontinence, generally accompanied by an increase in urinary frequency and nocturia, after any local disease or metabolic disorder that would explain these symptoms have been ruled out, is a highly prevalent condition that affects millions of men and women worldwide. Not only can the symptoms of OAB be very bothersome, but OAB can have significant detrimental effects on many aspects of individuals' lives, representing a particularly impactful health burden to quality of life and productivity. Besides a wide range of conservative treatments, the clinical efficacy of which remains an open issue, antimuscarinics are the mainstay of pharmacotherapy for this condition but anticholinergic troublesome side effects like dry mouth, and the patient's perception of lack of efficacy and poor adherence, are common reasons of abandonment of treatment. An alternative to oral administration treatment, with a lower incidence of dry mouth and other anticholinergic adverse effects, might be attractive to patients and a real treatment option for physicians. Delivery of oxybutynin directly through the skin with oxybutynin transdermal (OXY-TDS) avoids the first-pass hepatic metabolism that occurs with orally administered oxybutynin and prevents the appearance of anticholinergic adverse events. OXY-TDS being equally effective than oral treatment improves adherence, persistence, and patient satisfaction. The aim of this review is to focus on evidence available of the use of OXY-TDS in the management of patients with OAB, and to help clinicians in the challenges involved in the treatment options for patients with this condition.


Displaying radiologic images on personal computers: image storage and compression--Part 2.
This is part 2 of our article on image storage and compression, the third article of our series for radiologists and imaging scientists on displaying, manipulating, and analyzing radiologic images on personal computers. Image compression is classified as lossless (nondestructive) or lossy (destructive). Common lossless compression algorithms include variable-length bit codes (Huffman codes and variants), dictionary-based compression (Lempel-Ziv variants), and arithmetic coding. Huffman codes and the Lempel-Ziv-Welch (LZW) algorithm are commonly used for image compression. All of these compression methods are enhanced if the image has been transformed into a differential image based on a differential pulse-code modulation (DPCM) algorithm. The LZW compression after the DPCM image transformation performed the best on our example images, and performed almost as well as the best of the three commercial compression programs tested. Lossy compression techniques are capable of much higher data compression, but reduced image quality and compression artifacts may be noticeable. Lossy compression is comprised of three steps: transformation, quantization, and coding. Two commonly used transformation methods are the discrete cosine transformation and discrete wavelet transformation. In both methods, most of the image information is contained in a relatively few of the transformation coefficients. The quantization step reduces many of the lower order coefficients to 0, which greatly improves the efficiency of the coding (compression) step. In fractal-based image compression, image patterns are stored as equations that can be reconstructed at different levels of resolution.


Incidence of cancer in children aged 0-14 years in Taiwan, 1996-2010.
Studies have found lower risk of childhood cancer among Asian children. We aim to characterize the recent incidence and incidence-trend of childhood cancer in Taiwan after the National Health Insurance program was launched in March 1995. Data were extracted from the Taiwan Cancer Registry, a population-based database established in 1979. Cases diagnosed at age 0-14 from 1996 to 2010 were analyzed and categorized according to the International Classification of Childhood Cancer, Third Edition (ICCC-3). In total, 8032 childhood cancer cases were included, with a microscopic verification rate of 93.9%. The overall age-standardized rate (ASR) of incidence adjusted to the 2000 World Standard Population is 125.0 cases/million, with a male-to-female ratio of 1.3. The top five cancer types (ICCC-3 subgroup[s]; ASR per million) are acute lymphoblastic leukemia (Ia, 30.3), acute myeloid leukemia (Ib; 9.4), non-Hodgkin lymphoma (IIb,c,e, 9.0), extracranial germ cell tumor (Xb,c; 8.3), and neuroblastoma (IVa; 7.8). The median age of diagnosis was 6 years for both genders. During the study period, the ASR of childhood cancer has been increasing at a rate of 1.2% per year (95% confidence interval, 0.6-1.7%). In contrast to Western countries, China, Japan, and Taiwan have lower incidence of childhood cancer; however, Taiwan's incidence rates of childhood germ cell tumors and hepatic tumors are higher. In conclusion, this population-based study reveals that the incidence rate of childhood cancer in Taiwan is rising consistently. The high incidence of germ cell tumors warrants further investigation.


Associations of Mitochondrial Deoxyribonucleic Acid Polymorphisms With Behçet's Disease in the Korean Population.
This study aims to examine the possible associations of mitochondrial single nucleotide polymorphisms (SNPs) and Behçet's disease (BD) in a larger patient group. Whole blood or buffy coat was collected from 98 BD patients (31 males, 67 females; mean age 48±2.8 years; range 20 to 60 years) from four university hospitals located in the Chung-Cheong district of the Republic of Korea, and 196 age- and sex-matched healthy controls (HCs) (62 males, 134 females; mean age 46.91±12.90 years; range 20 to 68 years) from Konyang University Hospital. Twenty targeted mitochondrial deoxyribonucleic acids (DNAs) were genotyped and compared using the revised Cambridge Reference Sequence. Chi square and Fisher's exact tests were used to analyze association of mitochondrial DNA SNPs with BD susceptibility and its clinical characteristics. There were no differences for m.248A>G, m.304C>A, m.709G>A, m.3010G>A, m.3970C>T, m.4883C>T, m.5178C>A, m.6392T>C, m.6962G>A, m.10310G>A, m.10609T>C, m.12406G>A, m.12882C>T, m.13928G>C, m.14668C>T, m.16129G>A, and m16304T> between patient and HC groups. However, m.16182A>C and m.16183A>C were more frequently observed in the patient group than the HC group (22 [22.4%] vs. 24 [12.2%], p=0.061 and 32 [32.7%] vs. 42 [21.4%], p=0.092) but without statistical significance. m.4883C>T and m.5178C>A were associated with posterior location of oral ulcers (p=0.025 for each) and m.16183A>C was associated with deep oral ulcers (p=0.001), while m.16189T>C was associated with deep oral ulcers and thrombosis (p=0.042, 0.048, respectively). m.16182A>C and m.16183A>C may be associated with BD in the Korean population.


Implementing Brief Mindfulness-Based Interventions to Reduce Compassion Fatigue.
Nurses in surgical-trauma units are susceptible to compassion fatigue due to work-related stressors. Mitigating and preventing compassion fatigue are critical to supporting the health and well-being of surgical-trauma nurses. During the COVID-19 pandemic, a surgical-trauma unit was converted to a designated COVID-19 unit. Nurses verbalized feelings of burnout and stress during the pandemic and did not have a mechanism to cope with work-related stress. This project evaluated the impact of brief mindfulness-based interventions on compassion fatigue. From February 2021 to March 2022, mindfulness champions led 5 minutes of mindfulness-based interventions, including meditation, deep breathing, and self-compassion exercises, during shift huddles. The Professional Quality of Life, version 5, questionnaire was used to evaluate preintervention and postintervention burnout, secondary traumatic stress, and compassion satisfaction. Paired-sample t tests were used to evaluate the results. Twenty-nine of 34 nurses responded (85% response rate) with matched preintervention and postintervention questionnaires. All subscale scores showed significant improvement after intervention. The mean burnout subscale score decreased by 9.35% (P = .003), mean secondary traumatic stress subscale score decreased by 11.89% (P = .005), and mean compassion satisfaction subscale score increased by 6.44% (P = .03) after intervention. After implementing brief mindfulness-based interventions in shift huddles, nurses reported reductions in elements of compassion fatigue (burnout and secondary traumatic stress). Nurses reported that adding brief mindfulness-based interventions to shift huddles helped them cope with work-related stress. Brief mindfulness-based interventions can improve nurses' compassion satisfaction while reducing compassion fatigue measurements.