The internationalization of human microbiome research.
The human microbiome has now been linked with myriad diseases, yet most of this research has been conducted on American and European populations that make up only 1/6th of the world's population. With growing recognition that human microbiomes differ tremendously across global populations, it is especially important to understand how these compositional differences impact health outcomes. Recent advances in infectious disease and malnutrition research have demonstrated the potential for microbiome-based strategies to address the biggest challenges in global health. This review highlights major advances toward understanding microbiome diversity across the world and its contributions to disease, and outlines key questions, challenges, and opportunities to broaden the scope of and promote inclusivity within microbiome research.


Identification of the C-terminal activator domain in yeast heat shock factor: independent control of transient and sustained transcriptional activity.
In yeast, heat shock factor (HSF) is a trimer that binds DNA constitutively but only supports high levels of transcription upon heat shock. The C-terminal regions of HSF from Saccharomyces cerevisiae and Kluyveromyces lactis are unconserved yet both contain strong transactivators which are correctly regulated when substituted for each other. We have performed high resolution mapping of these activator domains which shows that in K.lactis HSF (KlHSF) activity can be located to a confined short domain, while in S.cerevisiae HSF (ScHSF) two separate regions are required for full activity. Alignment of the activator domains reveals similarity, as both overlap potential leucine zipper motifs (zipper C) with a distribution of hydrophobic residues similar to two highly conserved N-terminal domains which mediate HSF trimerization (zippers A and B). In higher eukaryotes a C-terminal leucine zipper is required to maintain HSF in a monomeric and non DNA-binding state under normal conditions and we therefore address the regulatory roles of the three leucine zipper motifs in KlHSF. Whilst the longest and most N-terminal of the trimer region zippers, A, is dispensable for regulation, mutation of a single leucine in zipper B makes HSF constitutively active. In contrast to the situation in higher eukaryotes disruption of zipper C has no observable regulatory effect and therefore, although an intramolecular contact between zippers B and C cannot be ruled out, such contact is not required for restraining the C-terminal activator domain. We furthermore find that deletions which abolish activator potential of the C-terminus render the host strain temperature sensitive. However, deletion of a double proline-glycine motif in the activator, whilst leaving HSF unable to respond to heat shock, does not cause temperature sensitivity. This result demonstrates that independent mechanisms control the transient and sustained activities of HSF.


Renal angiomyolipomas, cysts, and cancer in tuberous sclerosis complex.
Tuberous sclerosis is a multisystem syndrome characterized by neurological symptoms and tumors in multiple organs, including kidney, brain, skin, eyes, heart, and lung. The kidney and brain are the two most frequently affected organs in TSC, and renal disease is a leading cause of death in TSC patients. Three types of tumors occur in TSC kidneys: (1) angiomyolipomas, which are benign tumors composed of smooth muscle, fat, and vessels; (2) epithelial cysts; and (3) malignant tumors. This review focuses on the clinical, pathological, and molecular features of these tumors.


Effect of a medical food on body mass index and activities of daily living in patients with Alzheimer's disease: secondary analyses from a randomized, controlled trial.
To investigate the effect of a medical food (Souvenaid) on body mass index (BMI) and functional abilities in patients with mild Alzheimer's disease (AD). DESIGN/SETTING/PARTICIPANTS/INTERVENTION /MEASUREMENTS: These analyses were performed on data from a 12-week, double-blind, randomized, controlled, multicenter, proof-of-concept study with a similarly designed and exploratory 12-week extension period. Patients with mild AD (Mini-Mental State Examination score of 20-26) were randomized to receive either the active product or an iso-caloric control product. While primary outcomes included measures of cognition, the 23-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale was included as a secondary outcome. Both ADCS-ADL and BMI were assessed at baseline and Weeks 6, 12 and 24. Data were analyzed using a repeated-measures mixed model. Overall, data suggested an increased BMI in the active versus the control group at Week 24 (ITT: p = 0.07; PP: p = 0.03), but no treatment effect on ADCS-ADL was observed. However, baseline BMI was found to be a significant treatment effect modifier (ITT: p = 0.04; PP: p = 0.05), and an increase in ADCS-ADL was observed at Week 12 in patients with a 'low' baseline BMI (ITT: p = 0.02; PP: p = 0.04). These data indicate that baseline BMI significantly impacts the effect of Souvenaid on functional abilities. In addition, there was a suggestion that Souvenaid increased BMI.


Human chronotope status during short-term visual deprivation.
Measuring of an individual minute and individual decimeter by humans with open eyes and eyes closed for 1 min was evaluated. All chronotope parameters were highly individual, but the distribution of time and space measuring values was different. The individual decimeter and, to a lesser extent, chronotope individual decimeter were less in humans subjected to short-term visual deprivation than in subjects with open eyes. Variability of individual minute measuring by humans was less pronounced than the variability of individual decimeter measuring. These differences in variability were less pronounced in the chronotope measured units in subjects with open eyes and were not detected in subjects with short-term visual deprivation.


Optic flow in the natural habitats of zebrafish supports spatial biases in visual self-motion estimation.
Animals benefit from knowing if and how they are moving. Across the animal kingdom, sensory information in the form of optic flow over the visual field is used to estimate self-motion. However, different species exhibit strong spatial biases in how they use optic flow. Here, we show computationally that noisy natural environments favor visual systems that extract spatially biased samples of optic flow when estimating self-motion. The performance associated with these biases, however, depends on interactions between the environment and the animal's brain and behavior. Using the larval zebrafish as a model, we recorded natural optic flow associated with swimming trajectories in the animal's habitat with an omnidirectional camera mounted on a mechanical arm. An analysis of these flow fields suggests that lateral regions of the lower visual field are most informative about swimming speed. This pattern is consistent with the recent findings that zebrafish optomotor responses are preferentially driven by optic flow in the lateral lower visual field, which we extend with behavioral results from a high-resolution spherical arena. Spatial biases in optic-flow sampling are likely pervasive because they are an effective strategy for determining self-motion in noisy natural environments.


Feasibility of applying a single treatment plan for both fractions in PDR image guided brachytherapy in cervix cancer.
This study explores the feasibility of limiting dose optimisation to the first brachytherapy fraction (BT1) and applying the same plan for the second fraction (BT2). Seventy one consecutive patients were analysed. Pulsed dose rate (PDR) BT was initiated after about 4 weeks of external beam radiotherapy (EBRT). Thirty eight patients had only intracavitary applicator (IC), and 33 had combined IC with interstitial needles (IC/IS). The optimised BT1 plan was copied to BT2 images with no further optimisation (single plan scenario) and dose volume histogram (DVH) parameters were compared with those of full dose optimisation for every fraction (optimised plan scenario). 31/38 IC patients had similar applicator geometry in both fractions and mean DVH parameters were comparable between full optimisation and single plan. The mean HR CTV D90 in total EQD2 with optimisation was 94.5 Gy and with single plan scenario was 94.4 Gy (p=0.89). Organs at risk (OARs) planning aims were fulfilled with the single plan, although 5/31 patients would receive 3-10 Gy extra to the D(2cm(3)). The mean doses in total EQD2 for the D(2cm(3)) of the bladder, rectum, sigmoid and bowel were respectively 68.5, 61.0, 64.9 and 60.6 Gy for the optimised plan, and for the single plan scenario were 69.0, 61.3, 65.1 and 60.8 Gy respectively. The difference was statistically not significant. The standard deviation (SD) of the difference between the single plan and the optimised plan was 3.2 Gy for HR CTV and 2.9, 1.4, 1.2, 1.6 Gy for the bladder, rectum, sigmoid and bowel D(2cm(3)), respectively. Only 4/33 IC/IS patients had the same applicator geometry and single plan was therefore not feasible for the majority of these patients. For IC BT in small volume tumours (primarily stage IB-IIB) with mean HR CTV volume at BT1=24±12 cm(3), comparable mean DVH parameters resulted when applying a single plan, but with considerable variations in individual patients. Yet since in our population the applied target doses are high and the OARs doses are lower than the dose volume constraints these variations may not have considerable clinical consequences. Individual optimisation for each BT fraction is recommended when interstitial needles are used.


A Sex-Based Analysis From the RAIN-CARDIOGROUP VII Study (VeRy Thin Stents for Patients With Left MAIn or BifurcatioN in Real Life) on Left Main Stenting.
There is a lack of data on clinical outcomes of percutaneous coronary intervention (PCI) with ultrathin stents on unprotected left main (ULM) coronary artery comparing women and men. All patients treated with ULM-PCI with ultrathin stents (struts ≤81 μm) enrolled in the RAIN-CARDIOGROUP VII study were analyzed according to a sex-assessment evaluation. Major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, target-lesion revascularization [TLR], and stent thrombosis) was the primary endpoint, whereas single components of MACE were the secondary endpoints. Out of a cohort of 793 patients, a total of 172 women (21.7%) and 621 men (78.3%) were included. Compared with men, women were older and less frequently smokers, had more frequently a history of previous PCI, and presented more frequently with an acute coronary syndrome. Among women, ostial lesions were more prevalent and mean stent diameter was lower compared with men. After 13.4 months (range, 8.4-21.6 months), 32 women (18.6%) and 106 men (17.1%) experienced MACE (P=.64). Censoring follow-up data at 3 years, no differences were observed in MACE (16.9 vs 14.7 per 100•patient-years; log-rank P=.61) and their single components between women and men. At multivariate analysis, chronic kidney disease (hazard ratio [HR], 1.91: 95% confidence interval [CI], 1.23 to -2.95; P<.01) and acute coronary syndrome presentation (HR, 1.84; 95% CI, 1.22-2.77; P=.01) were independent predictors of MACE overall. Larger stent size (HR, 0.65; 95% CI, 0.48-0.89; P<.01) and longer dual-antiplatelet therapy duration (HR, 0.95; 95% CI, 0.90-0.99; P=.03) were associated with a reduced risk of MACE during the subsequent follow-up. Ultrathin stents offer low rates of MACE and TLR in the overall population without significant differences between sexes.


Radon and radioactivity at a town overlying Uranium ores in northern Greece.
Extensive measurements of (222)Rn in the town of Xanthi in N Greece show that the part of the town overlying granite deposits and the outcrop of a uranium ore has exceptionally high indoor radon levels, with monthly means up to 1500 Bq m(-3). A large number of houses (40%) in this part of the town exhibit radon levels above 200 Bq m(-3) while 11% of the houses had radon levels above 400 Bq m(-3). Substantial interannual variability as well as the highest in Europe winter/summer ratios (up to 12) were observed in this part of the town, which consist of traditional stone masonry buildings of the late 19th-early 20th century. Measurements of (238)U and (232)Th content of building materials from these houses as well as radionuclide measurements in different floors show that the high levels of indoor radon measured in these buildings are not due to high radon emanation rates from the building materials themselves but rather due to high radon flux from the soil because of the underlying geology, high radon penetration rates into the buildings from underground due to the lack of solid concrete foundations in these buildings, or a combination thereof. From the meteorological variables studied, highest correlation with indoor (222)Rn was found with temperature (r(2) = 0.65). An indoor radon prognostic regression model using temperature, pressure and precipitation as input was developed, that reproduced indoor radon with r(2) = 0.69. Hence, meteorology is the main driving factor of indoor radon, with temperature being the most important determinant. Preliminary flux measurements indicate that the soil-atmosphere (222)Rn flux should be in the range 150-250 Bq m(-2) h(-1), which is in the upper 10% of flux values for Europe.


Gadoxetate for direct tumor therapy and tracking with real-time MRI-guided stereotactic body radiation therapy of the liver.
SBRT is increasingly utilized in liver tumor treatment. MRI-guided RT allows for real-time MRI tracking during therapy. Liver tumors are often poorly visualized and most contrast agents are transient. Gadoxetate may allow for sustained tumor visualization. Here, we report on the first use of gadoxetate during real-time MRI-guided SBRT.


Do not attempt resuscitation decisions in a cancer centre: addressing difficult ethical and communication issues.
Talking to patients about 'Do Not Attempt Resuscitation' decisions is difficult for many doctors. Communication about 'Do Not Attempt Resuscitation' decisions should occur as part of a wider discussion of treatment goals at an earlier stage in the patient's illness. A doctor should not initiate any treatment, including cardio-pulmonary resuscitation if he/she does not believe it will benefit the patient. An ethical framework is offered which may be of practical help in clarifying decision-making.


Detection of infectious bursal disease virus by reverse transcription-polymerase chain reaction amplification of the virus segment A gene.
A reverse transcription-polymerase chain reaction (RT-PCR) amplification assay was developed to detect infectious bursal disease virus (IBDV) gene sequences in clinical samples, infected cell cultures and chicken embryos. Two pairs of primers were designed to amplify the 5'- and 3'-termini of segment A genes that partially code for the IBDV proteins VP2 and VP3, respectively. One primer pair specifies a 309-bp fragment, the other a 520-bp fragment. Direct RT-PCR analysis of 5 bursal samples of chickens derived from a suspected first outbreak of infectious bursal disease in New Zealand yielded the 309-bp and 520-bp by fragments. The identity of both amplified fragments was confirmed by restriction endonuclease analysis, chemiluminescence Southern blot hybridization and direct cycle sequencing. RT-PCR amplification of RNAs extracted from 4 out of 5 IBDV isolates propagated in Vero cells, chicken embryo fibroblasts and specific pathogen-free chicken embryos yielded IBDV-specific fragments of unpredicted small sizes.


Evaluation of fear, anxiety, and knowledge among dental providers during the COVID 19 pandemic.
COVID-19 has caused a global public health crisis with a major impact on the dental community. The unknown nature of the disease, close and prolonged contact between the patient and provider, aerosol-generating dental procedures in dental settings, guidelines that kept evolving are some of the factors that have alarmed the dental community. The purpose of this study was to evaluate the fear/anxiety among dental providers and assess the knowledge and related practice modification in a post-doctoral dental institution in Upstate New York. An online, anonymous, validated survey was sent to all dental faculty and trainees (n = 358) including general dentists and specialists from various departments between August and October 2020. Descriptive statistics and Chi-square goodness-of-fit test were performed. A total of 144 responded to the survey. It was reported that the majority of the dental providers (faculty (80%) and trainees (90%)) were afraid of getting infected with COVID-19 from the patient. Approximately 90% in both groups reported fear of carrying the infection home to their family and about reports of people dying. The majority of dental providers were well-versed with the Centers for Disease Control and Prevention guidelines. There was difference in knowledge about using N-95 and level 3 masks with face shields for various dental procedures. The study concluded that COVID-19 related fear/anxiety among dental providers was immediate and needed to be addressed.


Nudging low-medium income mothers towards healthy child options in an online restaurant scenario.
Helping mothers make the healthiest choices for their children when eating out can contribute to preventing the prevalence of childhood overweight and obesity, particularly in economically disadvantaged classes. Herein, we tested whether two different nudges (a default option and a social norm prompt) could guide low- and middle-income mothers towards healthier children's menu choices in a fictive restaurant setting and investigated the drivers of healthy child menu selection. A cross-sectional online survey was performed among 809 Italian mothers with children aged between 3 and 12 years, and a between-subjects design (control, nudge 1, and nudge 2) was applied. The findings revealed that both nudges had no significant effect on the number of healthy menu selections compared with the healthy choices made in the control condition. Furthermore, considering the entire sample, the results show that certain characteristics of a mother (e.g., authoritative parenting style) and child (younger age) duo increase the likelihood of the former selecting a healthy children's menu. Similarly, a positive correlation between the likelihood of choosing a healthy children's menu and the mother's involvement in the child's nutrition (meal preparation and weekly diet) was observed.


Parameter-specific modulation of the mismatch negativity to duration decrement and increment: evidence for asymmetric processes.
The mismatch negativity (MMN) component of event-related potentials (ERPs) reflects a change-detection process in the brain. The present study investigated whether stimulus parameters (sound type and duration) exert a differential influence on the MMN for a duration decrement and increment of an equal magnitude. Some asymmetries were reported in the previous studies; yet no systematical study has been conducted. ERPs were recorded from 16 healthy adults presented with repetitive standard sounds interspersed with duration changes (deviant sounds). In separate sequences, stimuli were vowels, music chord, sinusoid, or band-pass filtered white noise. The stimulus durations (standard/deviant) were either 200/120 ms or 400/240 ms for decrements, and vice versa for increments. The MMN for the increments was abolished in the 400/240 ms condition, whereas the MMN for decrements was significant irrespective of the sound duration. The amplitude of the increment MMN paralleled with the spectral complexity of the stimulus sound, whereas that of the decrement MMN was larger for natural sounds than artificial sounds. The observed interactions demonstrated asymmetries in the MMN for duration increment and decrement. The present findings suggest that the effects of stimulus parameters should be taken into account when comparing different studies, especially where clinical populations are involved, with one another.


Preincubation of pneumococci with beta-lactams alone or combined with levofloxacin prevents quinolone-induced resistance without increasing intracellular levels of levofloxacin.
Preincubation of pneumococci with sub-MIC concentrations of ceftriaxone (1/16x MIC), cefotaxime (1/8x MIC), and meropenem (1/4x MIC) alone or combined with levofloxacin (1/8x MIC) over 6 h prevents the emergence of levofloxacin-resistant mutants after 96 h of incubation but does not affect the intracellular accumulation of levofloxacin in two penicillin-resistant pneumococcal strains, suggesting a link between the mechanism of action of beta-lactams and the emergence of quinolone-induced resistance in pneumococci.


Gastrointestinal Langerhans cell histiocytosis with unifocal, single-system involvement in adults: Cases report and literature review.
Langerhans cell histiocytosis (LCH) is characterized by unifocal, multifocal single-system, or multi-system disease that occurs in all age groups, while it primarily attacks pediatric patients. Solitary gastrointestinal (GI) LCH in adults is exceedingly rare, so we aimed to investigate GI LCH in adults with unifocal single-system involvement and clarified the clinicopathologic characteristics of this disease. Two cases of solitary GI LCH in adults were presented, and the clinicopathologic features of this diagnosis in the literature were reviewed. The main diagnostic feature of LCH is the morphologic identification of the characteristic Langerhans cells with prominent nuclear grooves and abundant eosinophilic cytoplasm, accompanied by a variable number of lymphocytes, eosinophils, and plasma cells. The distinctive cells expressed S100, CD1a, and langerin (CD207) on immunohistochemistry. BRAF V600E mutations were detected in the two patients. Gastrointestinal Langerhans cell histiocytosis in adults with unifocal, single-system involvement is extremely rare. Most patients were asymptomatic and usually a small solitary polyp in GI tract can be observed under routine endoscopy. Although the overall prognosis of unifocal single-system LCH is favorable, long-term follow-up is still necessary to rule out systemic disease.


Staged upper and lower lip reanimation following facial palsy: Peer-reviewed, patient-rated and objective outcomes.
One approach to reanimating both upper and lower lips following facial palsy is through staged surgery: cross-face nerve grafting at stage I, free gracilis muscle transfer to levators at stage II and pedicled anterior belly of digastric muscle transfer (ABDMT) to depressors at stage III. The results of this approach were hitherto unquantified. This study retrospectively assessed peer-reviewed, patient-rated and objective outcomes following staged reanimation in adults between 2010 and 2020. Demographics, palsy characteristics and surgery details were recorded. Pre- and postoperative videos were rated by independent assessors using Terzis' aesthetic and symmetry scale. Photographs were analysed using Emotrics and patients completed the Glasgow Benefit Inventory (GBI) patient-rated outcome measure. Ten patients [mean age = 34 (SD = 12.48)] were eligible. All regained lip elevation and depression. All markers of symmetry improved after gracilis transfer. All markers were also improved after ABDMT except for lower lip height when smiling with teeth showing (p > 0.05). Five patients (50%) responded to the GBI (mean score = +39.44). No patients reported detriment from the reanimations. Mean Terzis' scores preoperatively and after stages II and III were 1.5, 2.26 and 2.39, respectively (p < 0.05). Nine patients underwent aesthetic refinements [lipofilling to lower lip notches (n = 5), debulking of gracilis bulk (n = 6), repositioning of muscle insertion (n = 5) and facelifts (n = 2)]. The outcomes were positive objectively and as judged by peers and patients themselves. Aesthetic refinements may also be required to enhance these results.


Analysis of retest reliability for pregnant women undergoing cfDNA testing with a no-call result.
Determining the reasons for unreportable or no-call cell-free DNA (cfDNA) test results has been an ongoing issue, and a consensus on subsequent management is still lacking. This study aimed to explore potential factors related to no-call cfDNA test results and to discuss whether retest results are reliable. This was a retrospective study of women with singleton pregnancies undergoing cfDNA testing in 2021. Of the 9871 pregnant patients undergoing cfDNA testing, 111 had a no-call result, and their results were compared to those of 170 control patients. The no-call rate was 1.12% (111/9871), and the primary cause for no-call results was data fluctuation (88.29%, 98/111). Medical conditions were significantly more frequent in the no-call group than in the reportable results group (P < 0.001). After retesting, 107 (107/111, 96.40%) patients had a result, and the false-positive rate (FPR) of retesting was 10.09% (10.09%, 11/109). In addition, placental lesions were more frequent in the no-call group than in the reportable results group (P = 0.037), and 4 patients, all in the no-call group, experienced pregnancy loss. Pregnant women with medical conditions are more likely to have a no-call result. A retest is suggested for patients with a no-call result, but retests have a high FPR. In addition, pregnant women with a no-call result are at increased risk of adverse pregnancy outcomes. In conclusion, more attention should be given to pregnant women for whom a no-call cfDNA result is obtained.


Inequities in paid parental leave across industry and occupational class: Drivers and simulated policy remedies.
Paid family leave (PFL) has the potential to reduce persistent health disparities. This study aims to characterize differences in access to paid leave by industry sector and occupational class. The Bay Area Parental Leave Survey of Mothers included respondents 18 years of age or older who worked in the San Francisco Bay Area and gave birth from 2016 to 2017. Using linear probability models, we examined differences in five separate measures of PFL by industry sector and occupational class. We extended our regression analysis to simulate the full pay equivalent (FPE) weeks of leave that would have been taken under hypothetical scenarios of increased uptake and wage replacement rates. Our study included 806 women in private for-profit or non-profit jobs. In fully adjusted models, blue-collar workers were 10.9% less likely to take 12 weeks of paid parental leave versus white-collar workers (95% CI: -25.9, 4.1). Respondents were 19.2% less likely receive 100% of their regular pay if they worked in education and health services (-29.1, -9.3) and 17.0% less likely if they worked in leisure and hospitality (-29.5, -4.4) versus respondents in professional and financial services. Respondents in leisure and hospitality reported 1.6 fewer FPE weeks of leave versus respondents in professional and financial services (-2.73, -0.42) and blue-collar respondents reported an average of 1.5 fewer FPE weeks versus white-collar workers (-2.66, -0.42). In our simulation analysis, when we manipulated rates of uptake for paid leave, the disparities in FPE by industry sector and occupational class were eliminated. We observed substantial inequities in access to paid leave by industry sector and occupational class. These findings underscore the potential importance of universal PFL programs with universal benefits to reduce clear inequities that persist within the labor market today.


Occurrence of the insecticide fipronil and its degradates in indoor dust from South, Central, and North China.
No known data are available regarding the occurrence of fipronil (FP) in indoor dust in China, despite the fact that it is an emerging insecticide that is used extensively. In this study, FP and its derivatives (FPs), including fipronil sulfone (FP-SFO), fipronil sulfide, fipronil desulfinyl, and fipronil amide, were determined in indoor dust samples (n = 436) collected from three different cities in China between 2016 and 2019, namely Shenzhen (February and September 2019), Wuhan (October 2016, October 2018, and August 2019), and Taiyuan (October 2016), located in south, central, and north China, respectively. FP and FP-SFO were the major target analytes detected in all dust samples, accounting for approximately 68.6-90.1% of the cumulative concentration of FPs (ΣFPs). The ΣFPs values for the dust samples ranged from not detected (ND) to 33.6 μg/g (median ± median absolute deviation [MAD]: 7.12 ± 6.44 ng/g), with a detection frequency of 95.6%. The median value of the ΣFPs of the dust samples collected from Shenzhen (22.6 ± 15.6 ng/g) was higher than that found in the dust samples collected in Taiyuan 2016 (1.87 ± 1.65 ng/g) and Wuhan (6.43 ± 5.62 ng/g). Significantly higher ΣFPs were observed in the dust samples collected in urban areas than in the rural areas of Taiyuan and Wuhan. Furthermore, an increasing trend of FP (from 2016 to 2018) in the rural areas of Wuhan, and a seasonal variation (summer > autumn) in FP, FP-SFO, and ΣFPs in the dust samples from urban areas of Wuhan were observed. The estimated daily intake of FPs via dust ingestion for people in Shenzhen was approximately 12 times higher than in Taiyuan based on the samples analyzed. This is the first study to describe the occurrence and spatiotemporal variations of FPs in indoor dust in China.


A computer simulation of the growth of a tumour in vitro.
This paper presents a computer model which simulates the growth of an in vitro tumour assumed to be a spheroid. Growth of the tumour is primarily affected by inward diffusion of ambient nutrients and outward diffusion of catabolites which tend to inhibit mitosis of living cells within this colony. In its final stages, the tumour consists of a necrotic core surrounded by a series of concentric shells which are comprised of non-proliferating and partially proliferating cells. Beyond this, an outermost shell of freely proliferating cells is in contact with the ambient medium which contains essential nutrients. The main purpose of this study is the qualitative study of the growth behaviour when various input parameters are altered. As noted in the final discussion, the main import of the paper is the observation that under certain conditions the initial monotonic growth of the tumour may give way to a series of temporary regressions alternating with growth periods. This behaviour eventually dampers out to yield a steady state situation when the amount of cell proliferation is exactly balanced by the decomposition of cells in the necrotic core.


Decreased apparent diffusion coefficient in the placentas of monochorionic twins with selective intrauterine growth restriction.
The apparent diffusion coefficient (ADC) was associated with the onset of intrauterine growth restriction in singleton pregnancies. However, the correlation of ADC with selective intrauterine growth restriction (sIUGR) of monochorionic (MC) twin pregnancies remained unknown. In this study, we aimed to evaluate the association of ADC with sIUGR in MC twin pregnancies by exploring diffusion weighted MR imaging (DWI). Fifty-one MC twin pregnancies, consisting 19 cases of sIUGR and 32 cases without sIUGR, were re-analyzed by DWI. ADCs were quantitated from two regions of interest, surrounding the insertion of the umbilical cord of placenta for each twin. A rADC (ADClarger twin/ADCsmaller twin) in each placenta was also evaluated. Then ADCs and rADCs were compared between cases with and without sIUGR. The ADC in cases with sIUGR was significantly decreased compared with cases without sIUGR (1.846 × 103 vs 2.471 × 103 mm2/s, p < 0.001). The rADC in cases with sIUGR was significantly increased (1.346 vs 1.053, p < 0.001). The ADC decreases and the rADC increases in the placentas of MC twins with sIUGR, suggesting that diffusion in the placenta is restricted in pregnancies with sIUGR.


Evaluation of the analgesic effect of Echium amoenum Fisch & C.A. Mey. extract in mice: possible mechanism involved.
Echium amoenum Fisch & C.A. Mey. has been used in Iranian traditional medicine as demulcent and analgesic in common cold from long ago. In this investigation, the analgesic effect of the methanolic extract of the petals of this plant on male albino mice was evaluated by formalin and hot-plate test. The methanolic percolated extract with different doses 5, 10, 20 and 30 mg/kg were injected intraperitoneally to mice. The results showed that the dose of 10 mg/kg of extract had the highest analgesia in formalin (P<0.05) and hot-plate test (P<0.01) compared to the control group. The analgesic effect of extract was lower than morphine 2.5 mg/kg and ASA 300 mg/kg in the chronic phase of pain in formalin test (P<0.05) and in hot-plate test too (P<0.05). Pretreatment of animal with naloxone 4 mg/kg, s.c. 5 min before extract, decreased the analgesia induced by extract in hot-plate and acute phase of formalin tests; therefore, the opioid receptor may be involved at least partly in the analgesic effect of Echium amoenum extract. The results suggested that Echium amoenum extract has a suitable analgesic effect and further studies are required to evaluate these effects and the potential of the plant.


Bayesian confidence intervals for the difference between variances of delta-lognormal distributions.
Unnatural rainfall fluctuation can result in such severe natural phenomena as drought and floods. This variability not only occurs in areas with unusual natural features such as land formations and drainage but can also be due to human intervention. Since rainfall data often contain zero values, evaluating rainfall change is an important undertaking, which can be estimated via the confidence intervals for the difference between delta-lognormal variances using the highest posterior density-based reference (HPD-ref) and probability-matching (HPD-pm) priors. Simulation results indicate that HPD-pm performances were better than other methods in terms of coverage rates and relative average lengths for the difference in delta-lognormal variances, even with a large difference in variances. To illustrate the efficacy of our proposed methods, we applied them to daily rainfall data sets for the lower and upper regions of northern Thailand.


Thrombolytic and newer mechanical device treatment for acute ischemic stroke.
For 8 years, only intravenous tissue plasminogen activator was approved by the US FDA for acute stroke treatment. The US FDA has now cleared the Merci Retriever (Concentric Medical, Inc.), a corkscrew-like device attached to a catheter, for the removal of clots causing ischemic strokes. Since the clearance was based on nonrandomized treatment trials, practitioners must scrutinize available data describing effects of the device on recanalization of the vessel, outcomes and important adverse events, such as symptomatic intracranial hemorrhage. This article reviews the study findings that are likely to contribute to current treatment decisions.


Cues for perceived pitch register.
The aim of this experiment was to assess empirically listeners' behaviour in characterising pitch contours with the label pitch register. The motivation for this assessment was initiated by the conflicting use of the term register in speech science and intonology. The findings reported here indicate that pitch register would more appropriately be associated with the position of the low pitch targets and the mean value of the tonal contour. In addition, the importance of the reference frequency (the lowest F(0) of a speaker) and the distance between H and L targets have been found to be weaker than previously assumed.


Correction to: Estimated expenditures for hip fractures using merged healthcare insurance data for individuals aged ≥ 75 years and long-term care insurance claims data in Japan.
The article Estimated expenditures for hip fractures using merged healthcare insurance data for individuals aged ≥ 75 years and long-term care insurance claims data in Japan.


On the validity of the Symptom Check List-90 (SCL90): a comparison of diagnostic self-ratings in general practice patients and 'normals', based on the Hebrew version.
The short clinical diagnostic self-rating scale for emotional and somatic concerns--Symptom Check List--90 (SCL-90)--was translated into everyday Hebrew and tested on 131 subjects for: 1. Construct validity, using item analysis. 2. Discriminating validity on a gradient of general practice patients and 'normal' controls. The Hebrew SCL-90 was found to retain its validity and to be easily administered and scored in non-treatment situations. It was also used as a tool for generating and substantiating hypotheses on psychosomatic and psychosocial interrelationships.


Initial experience of a deep learning application for the differentiation of Kikuchi-Fujimoto's disease from tuberculous lymphadenitis on neck CECT.
Neck contrast-enhanced CT (CECT) is a routine tool used to evaluate patients with cervical lymphadenopathy. This study aimed to evaluate the ability of convolutional neural networks (CNNs) to classify Kikuchi-Fujimoto's disease (KD) and cervical tuberculous lymphadenitis (CTL) on neck CECT in patients with benign cervical lymphadenopathy. A retrospective analysis of consecutive patients with biopsy-confirmed KD and CTL in a single center, from January 2012 to June 2020 was performed. This study included 198 patients of whom 125 patients (mean age, 25.1 years ± 8.7, 31 men) had KD and 73 patients (mean age, 41.0 years ± 16.8, 34 men) had CTL. A neuroradiologist manually labelled the enlarged lymph nodes on the CECT images. Using these labels as the reference standard, a CNNs was developed to classify the findings as KD or CTL. The CT images were divided into training (70%), validation (10%), and test (20%) subsets. As a supervised augmentation method, the Cut&Remain method was applied to improve performance. The best area under the receiver operating characteristic curve for classifying KD from CTL for the test set was 0.91. This study shows that the differentiation of KD from CTL on neck CECT using a CNNs is feasible with high diagnostic performance.


MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic cells is sufficient for control of Leishmania major.
Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)-dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II-positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)gamma-producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Abeta(b), expression is restricted to CD11b+ and CD8alpha+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II-negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNgamma. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8alpha+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection.


Nucleotide sequence alignment of hdcA from Gram-positive bacteria.
The decarboxylation of histidine -carried out mainly by some gram-positive bacteria- yields the toxic dietary biogenic amine histamine (Ladero et al. 2010 〈10.2174/157340110791233256〉 [1], Linares et al. 2016 〈http://dx.doi.org/10.1016/j.foodchem.2015.11.013〉〉 [2]). The reaction is catalyzed by a pyruvoyl-dependent histidine decarboxylase (Linares et al. 2011 〈10.1080/10408398.2011.582813〉 [3]), which is encoded by the gene hdcA. In order to locate conserved regions in the hdcA gene of Gram-positive bacteria, this article provides a nucleotide sequence alignment of all the hdcA sequences from Gram-positive bacteria present in databases. For further utility and discussion, see 〈http://dx.doi.org/ 10.1016/j.foodcont.2015.11.035〉〉 [4].


Hypoxia exacerbates cardiomyocyte injury via upregulation of Wnt3a and inhibition of Sirt3.
Ischemic injury is a major cause of several cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy, and ventricular remodeling. Using an in vitro hypoxia model to mimic ischemia, we found that hypoxia stimulated Wnt3a expression. A mechanistic study showed that hypoxia-inducible factor 1α (HIF-1α) was directly recruited to the Wnt3a promoter. Wnt3a overexpression significantly decreased cell viability, promoted the generation of apoptotic cells, and enhanced hypoxia-induced injury in neonatal rat cardiomyocytes. This was partially through the upregulation of Caspase-3 mRNA levels and cleaved PARP-1 protein levels. In addition, we observed that Wnt3a exacerbated hypoxia-induced mitochondrial dysfunction and cytosolic release of cytochrome C. Furthermore, we found that Sirt3, a mitochondrial NAD+-dependent deacetylase that modulates mitochondrial metabolism and homeostasis, was negatively regulated by Wnt3a. Conversely, Sirt3 overexpression repressed Wnt3a expression and ameliorated the hypoxia-induced mitochondrial dysfunction. Overall, our findings suggest that the hypoxia-Wnt3a-Sirt3 regulatory axis might be a potential target for cell protection in cardiac ischemia and hypoxia.


The ubiquitin-proteasome pathway is necessary for maintenance of the postmitotic status of neurons.
The ubiquitin-proteasome pathway (UPP) has been implicated in the regulation of a number of key cellular processes in mammalian cells, including the cell cycle and apoptosis. Furthermore, defects in the UPP have been implicated in neurodegenerative disorders such as Parkinson's disease (PD), as mutations in the ubiquitin ligase Parkin underlie a familial form of parkinsonism and ubiquitinated inclusions are a defining hallmark of PD pathology. To functionally dissect molecular components of the UPP in postmitotic neurons, we used RNA interference to knock down genes that encode genetically characterized components of the UPP. Here, we show that knockdown of two such components, the ubiquitin ligase scaffolding protein Cullin-1 (Cul-1) and the proteasome-associated deubiquitinating protein Pad-1, lead to cell cycle reactivation and apoptosis in subsets of postmitotic neurons. Furthermore, knockdown of Cul-1 appears to specifically affect the dopaminergic population. These data support the hypothesis that the UPP normally functions to regulate cell-cycle reentry in postmitotic neurons and further implicate this pathway in dopamine neuron degeneration.


Age-dependence of susceptibility to single and repeated deltamethrin exposure in pyrethroid-resistant Aedes aegypti strains.
Monitoring insecticide resistance is crucial in disease-transmitting mosquitoes to allow assessment of viable candidate insecticides to use for control and to provide indication of changes in resistance. Insecticide resistance bioassays are typically performed on young female mosquitoes, yet disease is transmitted by older females, which may also have encountered insecticide multiple times during their adult life. If insecticide mortality rates increase with age directly, or indirectly via cumulative toxicity from repeated exposure, the strategy of testing young mosquitoes as the least susceptible cohort would be supported. We tested three hypotheses via examination of how age and cumulative exposure impact mortality rates to the pyrethroid deltamethrin in strains of Aedes aegypti from Jeddah, Saudi Arabia and the Cayman Islands, which show differences in resistance mechanisms. Females of different ages (5, 7, 10 and 14 days-old) were exposed using WHO tube assays to either a single dose of insecticide, or in a second experiment females (initially 5 days-old) were exposed daily over 10 days. Age only increased mortality in the Jeddah strain at 14 days-old and had no impact on the Cayman strain. This is consistent with greater impact linked to metabolic resistance in the Jeddah strain, though results from qPCR of four candidate genes, failed to provide evidence for a candidate underpinning an age-dependent change in resistance. With repeated exposure, mortality rates of surviving females decreased to very low levels, suggesting that surviving older cohorts of females may exhibit substantially lower susceptibility than young females in single exposure assays. Our results indicate that testing young females with a single insecticide exposure should capture minimum susceptibility for the majority of the population, but a small fraction of older females may prove particularly unresponsive to pyrethroid-based control measures.


Treatment of acute hepatic porphyria with hematin.
The efficacy of hematin has been evaluated in eight patients with acute intermittent porphyria: six with acute attacks and two with chronic subacute symptoms. Hematin suppressed the chemical signs of porphyria in all patients and the symptoms in those with acute attacks. The clinical response to hematin occurred uniformly on the third or fourth day of treatment, suggesting that a stereotypic response to this form of therapy can be defined. Hematin had no effect on chronic subacute symptoms. The indications for hematin therapy, its rationale and the details of its administration are reviewed.


Incidence and cause of hypertension during adrenal radiofrequency ablation.
To evaluate the incidence and cause of hypertension prospectively during adrenal radiofrequency ablation (RFA). For this study, approved by our institutional review board, written informed consent was obtained from all patients. Patients who received RFA for adrenal tumors (adrenal ablation) and other abdominal tumors (nonadrenal ablation) were included in this prospective study. Blood pressure was monitored during RFA. Serum adrenal hormone levels including epinephrine, norepinephrine, dopamine, and cortisol levels were measured before and during RFA. The respective incidences of procedural hypertension (systolic blood pressure >200 mmHg) of the two patient groups were compared. Factors correlating with procedural systolic blood pressure were evaluated by regression analysis. Nine patients underwent adrenal RFA and another 9 patients liver (n = 5) and renal (n = 4) RFA. Asymptomatic procedural hypertension that returned to the baseline by injecting calcium blocker was found in 7 (38.9%) of 18 patients. The incidence of procedural hypertension was significantly higher in the adrenal ablation group (66.7%, 6/9) than in the nonadrenal ablation group (11.1%, 1/9, P < 0.0498). Procedural systolic blood pressure was significantly correlated with serum epinephrine (R (2) = 0.68, P < 0.0001) and norepinephrine (R (2) = 0.72, P < 0.0001) levels during RFA. The other adrenal hormones did not show correlation with procedural systolic blood pressure. Hypertension occurs frequently during adrenal RFA because of the release of catecholamine.


Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces.
There is a great demand for precisely quantitating the expression of genes of interest in synthetic and systems biotechnology as new and fascinating insights into the genetics of streptomycetes have come to light. Here, we developed, for the first time to our knowledge, a quantitative method based on flow cytometry and a superfolder green fluorescent protein (sfGFP) at single-cell resolution in Streptomyces. Single cells of filamentous bacteria were obtained by releasing the protoplasts from the mycelium, and the dead cells could be distinguished from the viable ones by propidium iodide (PI) staining. With this sophisticated quantitative method, some 200 native or synthetic promoters and 200 ribosomal binding sites (RBSs) were characterized in a high-throughput format. Furthermore, an insulator (RiboJ) was recruited to eliminate the interference between promoters and RBSs and improve the modularity of regulatory elements. Seven synthetic promoters with gradient strength were successfully applied in a proof-of-principle approach to activate and overproduce the cryptic lycopene in a predictable manner in Streptomyces avermitilis. Our work therefore presents a quantitative strategy and universal synthetic modular regulatory elements, which will facilitate the functional optimization of gene clusters and the drug discovery process in Streptomyces.


Abatement of paraquat contaminated water using solar assisted heterogeneous photo-Fenton like treatment with iron-containing industrial wastes as catalysts.
Owing to the tremendous increase of chemicals for agricultural practices, the quality of water has degraded significantly and requires inevitable attention. With this in mind, present work aims at treating Paraquat (PQ) contaminated water using Fe containing industrial waste as a catalyst via photo-Fenton treatment. Utilizing the industrially generated Fe rich waste by-products i.e., Fly ash (FA), Foundry sand (FS), Red mud (RM), and Blast sand (BS) as catalysts marks the novelty of the work since this idea of using waste for treating waste serves the dual purpose of environment remediation:first by treating wastewater and second by resolving the issue of solid waste disposal. In the present study, 25 mg/L PQ was subjected to both UV and solar radiations in the presence of FeSO4, FA, FS, RM, and BS as catalysts. The presence of Fe in the catalysts was verified using analytical techniques namely FTIR, FESEM-EDX, and their XRD was also analyzed. The system was further optimized for various parameters and results indicated maximum PQ degradation under UV radiations was attained in the order FeSO4 (73%) > BS (65%) > FS (46%) > RM (37%) > FA (14%) within 60 min which significantly increased with introduction of solar radiations to 83% for Fe salt and 76% for BS justifying the potential of using waste for treating waste. Further, to enhance the real-life utilization of industrial waste, Fe2O3/BS heterojunction (Fe-BS) was synthesized which along with leading to 88% degradation of PQ, also showed 82% COD removal indicating that the catalyst not only degrades the pollutant but also converts it into a lower toxic form. Further, the intermediates formed during the process were analyzed using LCMS.


Pattern of chromosomal localization of the Hoppel transposable element family in the Drosophila melanogaster subgroup.
We have isolated a Hoppel-like transposon from heterochromatin of the second chromosome of Drosophila melanogaster and used a conserved DNA sequence between the different elements of this family to determine their distribution in both mitotic and polytene chromosomes. The hybridization pattern of polytene chromosomes extends throughout the entire chromocentre, as well as a substantial portion of the fourth chromosome. Analysis of different wild-type strains of D. melanogaster shows variation in euchromatic insertion sites, although most insertions are found near the chromocentre. The positions and the number of heterochromatic clusters of Hoppel on mitotic chromosomes are conserved among the several strains analysed. Accurate mapping of this element was achieved by in situ hybridization on D. melanogaster mitotic chromosomes that had previously been banded with Hoechst 33258. To evaluate the evolutionary stability of this pattern, different species were analysed by in situ hybridization and Southern blotting. We conclude that Hoppel has a conserved distribution in mitotic heterochromatin within the D. melanogaster subgroup, established around 5 million years ago. The overall conservation of heterochormatic organization supports the notion that heterochormatin does perform important structural and functional roles.


Pseudoprogression in glioblastoma patients: the impact of extent of resection.
Pseudoprogression (psPD) is a radiation-induced toxicity that has substantial neurological consequence in glioblastoma (GBM) patients. MGMT promoter methylation has been shown to be an important prognostic factor of psPD, but the significance of extent of resection (EOR) remains unclear. We performed a retrospective analysis on newly diagnosed GBM patients with assessable MGMT promoter status who underwent the Stupp protocol. EOR was grouped into gross total resection (GTR), subtotal resection (STR), partial resection (PR) and stereotactic biopsy. Contrast enhancing lesion enlargement was classified as psPD or non-psPD. Among a total of 101 patients, GTR, STR, PR and stereotactic biopsy was performed in 57 (56.4%), 34 (33.7%), 9 (8.9%) and 1 patient (1%), respectively. Follow-up imaging at the end of Stupp protocol classified 45 patients (44.6%) as psPD and 56 (55.4%) as non-psPD. psPD was observed in 24 (61.5%) of 39 patients with methylated MGMT promoter and 21 (33.9%) of 62 patients with unmethylated MGMT promoter (p < 0.01). psPD was documented in 17 (29.8%), 19 (55.9%), 8 (88.9%) and 1 (100%) patient with GTR, STR, PR and stereotactic biopsy (p < 0.01), respectively. On multivariate analysis MGMT promoter status (OR 3.36, 95% CI 1.36-8.34) and EOR (OR 4.12, 95% CI 1.71-9.91) were independent predictors of psPD. A Cox proportional hazards model showed that MGMT status (HR 2.51, p < 0.01) and EOR (HR 2.99, p < 0.01) significantly influenced survival. MGMT status and EOR have a significant impact on psPD. GTR can reduce the side effects of psPD and prolong survival.


Modulatory and plastic effects of kinins on spinal cord networks.
Inflammatory kinins are released following spinal cord injury or neurotrauma. The effects of these kinins on ongoing locomotor activity of central pattern generator networks are unknown. In the present study, kinins were shown to have short- and long-term effects on motor networks. The short-term effects included direct depolarization of interneurons and motoneurons in the ventral horn accompanied by modulation of transient receptor potential vanilloid 1-sensitive nociceptors in the dorsal horn. Over the long-term, we observed a bradykinin-mediated effect on promoting plasticity in the spinal cord. In a model of spinal cord injury, we observed an increase in microglia numbers in both the dorsal and ventral horn and, in a microglia cell culture model, we observed bradykinin-induced expression of glial-derived neurotrophic factor. The expression and function of inflammatory mediators in the developing spinal cord remain poorly characterized. We discovered novel, short and long-term roles for the inflammatory nonapeptide bradykinin (BK) and its receptor bradykinin receptor B2 (B2R) in the neuromodulation of developing sensorimotor networks following a spinal cord injury (SCI), suggesting that BK participates in an excitotoxic cascade. Functional expression of B2R was confirmed by a transient disruptive action of BK on fictive locomotion generated by a combination of NMDA, 5-HT and dopamine. The role of BK in the dorsal horn nociceptive afferents was tested using spinal cord attached to one-hind-limb (HL) preparations. In the HL preparations, BK at a subthreshold concentration induced transient disruption of fictive locomotion only in the presence of: (1) noxious heat applied to the hind paw and (2) the heat sensing ion channel transient receptor potential vanilloid 1 (TRPV1), known to be restricted to nociceptors in the superficial dorsal horn. BK directly depolarized motoneurons and ascending interneurons in the ventrolateral funiculus. We found a key mechanism for BK in promoting long-term plasticity within the spinal cord. Using a model of neonatal SCI and a microglial cell culture model, we examined the role of BK in inducing activation of microglia and expression of glial-derived neurotrophic factor (GDNF). In the neonatal SCI model, we observed an increase in microglia numbers and increased GDNF expression restricted to microglia. In the microglia cell culture model, we observed a BK-induced increased expression of GDNF via B2R, suggesting a novel mechanism for BK spinal-mediated plasticity.


Repeat hepatectomy versus percutaneous ablation for recurrent hepatocellular carcinoma: emphasis on the impact of early or late recurrence.
Recurrent hepatocellular carcinoma (rHCC) patients with early recurrence usually suffer a poorer prognosis than those with late recurrence. We aimed to compare the treatment efficacy of repeat hepatectomy (RH) and percutaneous ablation (PA) in early-stage rHCC patients with early or late recurrence. This retrospective study enrolled 268 patients diagnosed with early-stage rHCC who received RH and PA. Overall survival (OS) and repeat recurrence-free survival (rRFS) were compared using log-rank analysis. Propensity score matching (PSM) was used to reduce the confounding bias. Among the 268 patients with early-stage rHCC, 79 underwent RH and 189 underwent PA. Early (n = 174) and late (n = 94) recurrence was defined as recurrence within and after 2 years following initial hepatectomy, respectively. For patients with early recurrence, RH and PA provided similar 5-year OS (71.5% versus 74.4%, P = 0.87) and rRFS rates (24.7% versus 24.9%, P = 0.73). For patients with late recurrence, RH resulted in comparable 5-year OS (73.1% versus 86.1%, P = 0.62) and rRFS rates (36.6% versus 27.8%, P = 0.34) as PA. After PSM, RH continued to share similar 5-year OS and rRFS rates with PA in patients with early recurrence, and comparable efficacy of RH and PA was also observed in patients with late recurrence. RH can offer comparable OS and rRFS rates as PA for early-stage rHCC patients, regardless of whether they experience early or late recurrence. Therefore, both RH and PA are feasible treatment options for early-stage rHCC patients.


Reversible H2 addition across a nickel-borane unit as a promising strategy for catalysis.
We report the synthesis and characterization of a series of nickel complexes of the chelating diphosphine-borane ligands ArB(o-Ph(2)PC(6)H(4))(2) ([(Ar)DPB(Ph)]; Ar = Ph, Mes). The [(Ar)DPB(Ph)] framework supports pseudo-tetrahedral nickel complexes featuring η(2)-B,C coordination from the ligand backbone. For the B-phenyl derivative, the THF adduct [(Ph)DPB(Ph)]Ni(THF) has been characterized by X-ray diffraction and features a very short interaction between nickel and the η(2)-B,C ligand. For the B-mesityl derivative, the reduced nickel complex [(Mes)DPB(Ph)]Ni is isolated as a pseudo-three-coordinate "naked" species that undergoes reversible, nearly thermoneutral oxidative addition of dihydrogen to give a borohydrido-hydride complex of nickel(II) which has been characterized in solution by multinuclear NMR. Furthermore, [(Mes)DPB(Ph)]Ni is an efficient catalyst for the hydrogenation of olefin substrates under mild conditions.


E-consultation for medications to treat opioid use disorders: a pilot study.
An electronic consultation to provide expert guidance on medications to treat opioid use disorders [MOUD] was piloted. Medical record review of the first 100 unique patients receiving consultation with 6-month follow-up. Descriptive statistics, chi-square, and Fisher's exact tests of significance were calculated as appropriate. Most consultation requests originated from inpatient psychiatry (66%). Patients (67%) and consultants (33%) preferred buprenorphine/naloxone most often (p < 0.0001). Half of the patients received MOUD prior to discharge. Three quarters of the half who kept their first outpatient appointments received the recommended treatment (p < 0.0001). At 6 months, four patients died and four others overdosed only. Type of MOUD was not associated with either overdose or death, but those who overdosed used cannabis, sedative-hypnotics, or stimulants (all, p < 0 .05). Guidance for MOUD offered via e-consultation may have increased outpatient treatment engagement following inpatient treatment.


Nox enzymes in immune cells.
The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase of phagocytes is a multi-component electron transferase that uses cytoplasmic NADPH to convert molecular oxygen to superoxide anion, consequently delivering reactive oxygen species to the site of invading microorganisms. Together with soluble factors and other phagocyte-derived agents, the resultant toxic species kill and degrade the ingested microbe. Flavocytochrome b (558), a heterodimeric protein composed of gp91 phox and p22 phox, is the membrane component of the NADPH oxidase and was previously thought to be uniquely expressed in phagocytes. Based on structural homology with gp91 phox, recent studies have defined a family of NADPH oxidase proteins (Nox) that is widely distributed throughout the plant and animal kingdoms and in many tissues in multicellular organisms. The goals of this review are to review features of the phagocyte NADPH oxidase that serve as a paradigm for exploiting oxidants for host defense, and to discuss contributions of other Nox proteins to innate immunity.


Leber's Hereditary Optic Neuropathy (LHON) with 14484/ND6 mutation in a North African patient.
We report the clinical and genetic study of a Leber's Hereditary Optic Neuropathy (LHON) patient of North African origin harboring the 14484/ND6 mutation of mtDNA. For over a year we followed the ophthalmological course of this 24-year-old male with LHON treated with idebenone and vitamin B12. Serum lactate after effort was evaluated before, during and after therapy. Muscle biopsy was obtained for morphological study. Homo/heteroplasmy of 14484/ND6 mutation was studied in different tissues. Recovery of visual acuity was documented 6 months after onset and 3 months after therapy was established. Baseline serum lactate was elevated but normalized after 3.5 months of therapy. Muscle biopsy demonstrated only a few fibers with a slightly increased subsarcolemmal SDH activity. Genetic analysis showed homoplasmic 14484/ND6 mutation in all tissues investigated. The clinical phenotype of LHON/14484 in this patient closely resembles that commonly found in European patients. Even if LHON/14484 patients are reported to have a better prognosis for visual recovery, it is possible that the evolution of visual recovery in this patient could have been influenced by therapy as suggested by changes in serum lactate levels. Bioenergetic impairment of skeletal muscle was documented by lactate levels and muscle morphology. The 14484/ND6 mutation behaves as a primary mutation regardless of mtDNA population-specific backgrounds.


Emotion expression and regulation in three cultures: Chinese, Japanese, and American preschoolers' reactions to disappointment.
There are strong cultural norms for how emotions are expressed, yet little is known about cultural variations in preschoolers' outward displays and regulation of disappointment. Chinese, Japanese, and American preschoolers' (N = 150) displays of emotion to an undesired gift were coded across both social and nonsocial contexts in a "disappointing gift" paradigm. Generalized estimating equations revealed that, regardless of culture, when children received a disappointing gift, they showed more positive expressions of emotion ("fake smile") in social contexts (in the presence of unfamiliar and familiar examiners) relative to when they were alone, suggesting that preschool-aged children are able to mask their disappointment with positive displays. However, children's emotion expressions varied across both cultures and contexts. American children were more positively and negatively expressive than Japanese children and were more negatively expressive than Chinese children. Chinese and Japanese preschoolers verbally reported more negative emotions but showed more neutral expressions than American preschoolers when receiving the disappointing gift. In addition, across different contexts of the task, there were subtle differences in how Chinese and Japanese children regulated their emotional expressions, with Chinese children showing similar levels of neutral expressions (e.g., "poker face") across different contexts in the task. Thus, our findings highlight the importance of understanding cultural meanings and practices underlying emotion development during early childhood.


NAMPT inhibition relieves intestinal inflammation by regulating macrophage activation in experimental necrotizing enterocolitis.
Nicotinamide phosphoribosyl transferase (NAMPT) is associated with various NAD+ -consuming enzymatic reactions. The precise role in intestinal mucosal immunity in necrotizing enterocolitis (NEC) is not well defined. Here, we examined whether NAMPT inhibition by the highly specific inhibitor FK866 could alleviate intestinal inflammation during the pathogenesis of NEC. In the present study, we showed that NAMPT expression was upregulated in the human terminal ileum of human infants with NEC. FK866 administration attenuated M1 macrophage polarization and relieved the symptoms of experimental NEC pups. FK866 inhibited intercellular NAD+ levels, macrophage M1 polarization, and the expression of NAD+ -dependent enzymes, such as poly (ADP ribose) polymerase 1 (PARP1) and Sirt6. Consistently, the capacity of macrophages to phagocytose zymosan particles, as well as antibacterial activity, were impaired by FK866, whereas NMN supplementation to restore NAD+ levels reversed the changes in phagocytosis and antibacterial activity. In conclusion, FK866 reduced intestinal macrophage infiltration and skewed macrophage polarization, which is implicated in intestinal mucosal immunity, thereby promoting the survival of NEC pups.


Attenuation of low dose phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in rats by cimetidine.
Cimetidine, a substituted imidazole, is an inhibitor of hepatic cytochrome P-450-mediated drug metabolism in rats and humans. We investigated the effect of cimetidine on phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in the rat. Phenobarbital induction of aminopyrine N-demethylase was log-linear in the range of 1-6 mg/kg/day and the ED50 was approximately 3 mg/kg/day. Cimetidine 75 mg/kg (four times a day) attenuated the induction of aminopyrine N-demethylase activity by 58% in low dose (3 mg/kg/day) but not in high dose (40 mg/kg/day) phenobarbital treated rats. This result could not be explained by residual inhibition of enzyme activity by cimetidine and suggests that cimetidine affects the induction of hepatic cytochrome P-450 by low dose phenobarbital.


Fast and accurate object detector for autonomous driving based on improved YOLOv5.
Autonomous driving is an important branch of artificial intelligence, and real-time and accurate object detection is key to ensuring the safe and stable operation of autonomous vehicles. To this end, this paper proposes a fast and accurate object detector for autonomous driving based on improved YOLOv5. First, the YOLOv5 algorithm is improved by using structural re-parameterization (Rep), enhancing the accuracy and speed of the model through training-inference decoupling. Additionally, the neural architecture search method is introduced to cut redundant branches in the multi-branch re-parameterization module during the training phase, which ameliorates the training efficiency and accuracy. Finally, a small object detection layer is added to the network and the coordinate attention mechanism is added to all detection layers to improve the recognition rate of the model for small vehicles and pedestrians. The experimental results show that the detection accuracy of the proposed method on the KITTI dataset reaches 96.1%, and the FPS reaches 202, which is superior to many current mainstream algorithms and effectively improves the accuracy and real-time performance of unmanned driving object detection.


Dynamical excitation of the tropical Pacific Ocean and ENSO variability by Little Ice Age cooling.
Tropical Pacific Ocean dynamics during the Medieval Climate Anomaly (MCA) and the Little Ice Age (LIA) are poorly characterized due to a lack of evidence from the eastern equatorial Pacific. We reconstructed sea surface temperature, El Niño-Southern Oscillation (ENSO) activity, and the tropical Pacific zonal gradient for the past millennium from Galápagos ocean sediments. We document a mid-millennium shift (MMS) in ocean-atmosphere circulation around 1500-1650 CE, from a state with dampened ENSO and strong zonal gradient to one with amplified ENSO and weak gradient. The MMS coincided with the deepest LIA cooling and was probably caused by a southward shift of the intertropical convergence zone. The peak of the MCA (900-1150 CE) was a warm period in the eastern Pacific, contradicting the paradigm of a persistent La Niña pattern.


Dermal exposure to toluene diisocyanate and respiratory cancer risk.
Human exposure to toluene diisocyanate (TDI) occurs mainly through inhalation of vapors in occupational settings where TDI is produced or used, but dermal exposure to TDI is also possible during some operations. Because of a recent epidemiology study reporting a possible association with lung cancer risk in workers with potential dermal exposure to TDI, we evaluated the evidence from epidemiological, toxicological, and toxicokinetic studies to assess whether it is likely that dermal exposure to TDI can cause human respiratory cancers. We found that the reported associations with respiratory cancers in the epidemiology studies do not support TDI as a causal factor, as there are other explanations that are more likely than causation, such as confounding by smoking and low socioeconomic status. Experimental animal and genotoxicity studies indicate that the carcinogenic potential of TDI depends on its conversion to toluene diamine (TDA), and there is no evidence of systemic availability of TDA after dermal or inhalation exposure to TDI. Also, systemic uptake of TDI is very low after dermal exposure, and any absorbed TDI is more likely to react with biomolecules on or below the skin surface than to form TDA. Even if some TDA formation occurred after dermal exposure to TDI, TDA does not induce respiratory tract tumors in experimental animals after either dermal or oral exposure. We conclude that the available evidence indicates that dermal TDI exposure does not cause respiratory cancers in humans.


Differential molecular regulation of processing and membrane expression of Type-I BMP receptors: implications for signaling.
The Type-I bone morphogenetic protein receptors (BMPRs), BMPR1A and BMPR1B, present the highest sequence homology among BMPRs, suggestive of functional similitude. However, sequence elements within their extracellular domain, such as signal sequence or N-glycosylation motifs, may result in differential regulation of biosynthetic processing and trafficking and in alterations to receptor function. We show that (i) BMPR1A and the ubiquitous isoform of BMPR1B differed in mode of translocation into the endoplasmic reticulum; and (ii) BMPR1A was N-glycosylated while BMPR1B was not, resulting in greater efficiency of processing and plasma membrane expression of BMPR1A. We further demonstrated the importance of BMPR1A expression and glycosylation in ES-2 ovarian cancer cells, where (i) CRISPR/Cas9-mediated knockout of BMPR1A abrogated BMP2-induced Smad1/5/8 phosphorylation and reduced proliferation of ES-2 cells and (ii) inhibition of N-glycosylation by site-directed mutagenesis, or by tunicamycin or 2-deoxy-D-glucose treatments, reduced biosynthetic processing and plasma membrane expression of BMPR1A and BMP2-induced Smad1/5/8 phosphorylation.


B-cell responses to male-specific antigen(s) in mice.
It has been found that B-cell responses to male-specific antigen(s) can be clearly demonstrated by reversed plaque assays. Female mice injected with syngeneic male spleen cells showed significant increases (greater than 100 X in some strains) in the number of immunoglobulin-secreting cells in lymph nodes draining the injection site. There was a variation in B-cell responsiveness between strains and this correlated only partially with previously reported T-cell responsiveness to the H-Y antigen. C57BL (H-2b) mice were among the most responsive, while CBA (H-2k), (CBA X C57BL)F1, and BALB/c (H-2d) were all much less responsive. These results apparently open up a new approach to the investigation of B-cell responses to male-specific antigen(s).


Nanoparticles in plant extracts: influence of drugs on the formation of nanoparticles and precipitates in black tea infusions.
The influence of the neuroleptics fluphenazine and promethazine on the formation of nanoparticles in aqueous tea infusions was investigated using photon correlation spectroscopy. Formation of nanoparticles and of precipitates was observed in decaffeinated tea and caffeine-containing tea. The amount of drug in the nanoparticle fraction was determined at different starting concentrations using high-performance liquid chromatography. In the case of fluphenazine, between 8 and 30% are assigned to the nanoparticles fraction, in the case of promethazine between 30 and 56%. The concentration of free active principle is reduced by about 99% for fluphenazine or by about 90% for promethazine. A loss of pharmacological activity of the neuroleptics is probable. The addition of promethazine to infusions of caffeine containing tea resulted in the formation of nanoparticles with a small size distribution; their mean size was comparable to the diameter of nanoparticles in pure tea infusions. In the case of fluphenazine the mean particle size grew with increasing concentration. Adding promethazine to infusions of decaffeinated tea resulted in the formation of nanoparticles with a broad size distribution. Two different size classes were formed after addition of fluphenazine. Caffeine and neuroleptics both take part in the formation of nanoparticles in caffeine containing tea. The particles were visualized using scanning electron microscopy. Molecular modelling calculations were performed to investigate probable geometries between neuroleptics and thearubigins.


Ceramide activates a mitochondrial p38 mitogen-activated protein kinase: a potential mechanism for loss of mitochondrial transmembrane potential and apoptosis.
This study examined the impact of ceramide, an intracellular mediator of apoptosis, on the mitochondria to test the hypothesis that ceramide utilized p38 MAPK in the mitochondria to alter mitochondrial potential and induce apoptosis. The capacity of ceramide to adversely affect mitochondria was demonstrated by the significant loss of mitochondrial potential (DeltaPsim), indicated by a J-aggregate fluorescent probe, after embryonic chick cardiomyocytes were treated with the cell permeable ceramide analogue C2-ceramide. p38 MAPK was identified in the mitochondrial fraction of the cell and p38 MAPK phosphorylation in this mitochondrial fraction of the cell occurred with ceramide treatment. In addition, SAPK phosphorylation and a decrease in ERK phosphorylation occurred in whole cell lysates after ceramide treatment. The p38 MAPK inhibitor SB 202190 but not the MEK inhibitor PD 98059 significantly inhibited ceramide-induced apoptosis and loss of DeltaPsim. These data suggest that p38 MAPK is present in the mitochondria and its activation by ceramide indicates local signaling more directly coupled to the mitochondrial pathway in apoptosis.


The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank.
To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR). Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n = 94 206 and n = 27 777, respectively), macular inner retinal OCT measurements (n = 36 274 and n = 9991, respectively), and glaucoma status (n = 86 803 and n = 23 556, respectively). We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma. Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status. In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by +0.57 μm (P < 0.001) and +0.42 μm (P = 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of +0.08 mmHg (P = 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome. Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Enzymatic oligomerization and polymerization of arylamines: state of the art and perspectives.
The literature concerning the oxidative oligomerization and polymerization of various arylamines, e.g., aniline, substituted anilines, aminonaphthalene and its derivatives, catalyzed by oxidoreductases, such as laccases and peroxidases, in aqueous, organic, and mixed aqueous organic monophasic or biphasic media, is reviewed. An overview of template-free as well as template-assisted enzymatic syntheses of oligomers and polymers of arylamines is given. Special attention is paid to mechanistic aspects of these biocatalytic processes. Because of the nontoxicity of oxidoreductases and their high catalytic efficiency, as well as high selectivity of enzymatic oligomerizations/polymerizations under mild conditions-using mainly water as a solvent and often resulting in minimal byproduct formation-enzymatic oligomerizations and polymerizations of arylamines are environmentally friendly and significantly contribute to a "green" chemistry of conducting and redox-active oligomers and polymers. Current and potential future applications of enzymatic polymerization processes and enzymatically synthesized oligo/polyarylamines are discussed.


Correspondence of increased debrisoquine 4-monooxygenase activity with seizure-susceptibility in Mongolian gerbils.
Four drug-metabolizing activities in Wistar rat and Mongolian gerbil liver microsomes were investigated to clarify the biochemical basis of convulsions. No significant associations were observed between the susceptibility to the tonic-clonic seizures in Mongolian gerbils and the drug-metabolizing enzymatic activities of p-nitroanisole O-demethylase, aminopyrine demethylase and benzo[a]pyrene-3-monooxygenase. However, a significant association was observed with the debrisoquine 4-monooxygenase (cytochrome P-450db1-linked monooxygenase system) activity, which is known to metabolize exogenous and endogenous parkinsonism-inducing neurotoxins such as MPTP and TIQ, and to activate carcinogens during the detoxication of xenobiotics. The mean activity of debrisoquine 4-monooxygenase in the seizure-sensitive group (male, 380; female, 350 pmol/h/mg protein) remained significantly higher (about 4-5 times) than that in the seizure-resistant group (male, 90; female, 80 pmol/h/mg protein). More Mongolian gerbils were extensive metabolizers of debrisoquine in the seizure-sensitive group than in the seizure-resistant group. These results suggest a possibility that the cytochrome P-450db1-linked monooxygenase system may activate the potential neurotoxins which are associated with tonic-clonic seizures in the Mongolian gerbil.


Surface tension properties of surfactant.
Surface tension area relations from pulmonary surfactants (natural, lipid extract, synthetic) are obtained with a leak-free captive bubble of controllable size. One of the most sensitive parameters to consider is the area change required to achieve minimum surface tension. For synthetic surfactant, this change can be minimized by increasing the cycling speed of the films. Film area reduction at minimum surface tension causes collapse and decreased surface activity for all surfactants investigated. To avoid film collapse, positive end-expiratory pressure becomes important during surfactant replacement therapy.


Determination of pharmaceutically related compounds by suppressed ion chromatography: II. Interactions of analytes with the suppressor.
For the hyphenation of ion chromatography to nebulising detectors or mass spectrometry, suppression of the non-volatile ionic eluent to water is a required step. However, suppression of weakly acidic or weakly basic organic analytes can potentially lead to losses of analytes during suppression resulting from precipitation, hydrophobic adsorption onto the suppressor, or permeation of the analyte through the suppressor membranes. This study investigates the interactions between the suppressor and weak organic acid analytes, including pharmaceutically related compounds, for eluents containing organic solvent. Correlations were observed between analyte recovery rates after electrolytic suppression and the eluent composition, the suppression conditions, and the physico-chemical properties of the analytes. These results suggest that hydrophobic adsorption interactions occur in the electrolytic suppressor and that these interactions are ameliorated by the addition to the eluent of high levels of organic solvents, especially acetonitrile. Use of eluents containing 80% acetonitrile resulted in very low losses of analyte during suppression. Recovery experiments conducted in various compartments of the electrolytic suppressor showed that some analytes permeated through the suppressor membrane into the regenerant chambers, but this could be prevented by adding organic solvent to the regenerant solution. It was also noted that analyte losses increased with ageing of the electrolytic suppressors. Chemical suppression avoids some of the analyte losses observed with an electrolytic suppressor, but when used under the correct conditions, electrolytic suppressors gave close to equivalent performance to chemical suppressors.


Green and sustainable fabrication of a durable superhydrophobic cotton fabric with self-cleaning properties.
The use of more toxic reagents in the finishing of superhydrophobic cotton fabrics is one of the main factors that limit the application of the fabrics. Therefore, a green and sustainable method for preparing superhydrophobic cotton fabrics is urgently needed. In this study, a cotton fabric was etched with phytic acid (PA), which can be extracted from plants, effectively improving the surface roughness of the fabric. Subsequently, the treated fabric was coated with epoxidized soybean oil (ESO)-derived thermosets and then covered with stearic acid (STA). The finished cotton fabric exhibited excellent superhydrophobic properties, with a water contact angle of 156.3°. The superhydrophobic coatings of the finished cotton fabric endowed the fabric with excellent self-cleaning properties, irrespective of the liquid pollutant or solid dust. In addition, the inherent properties of the finished fabric were largely retained after the modification. Therefore, the finished cotton fabric with excellent self-cleaning properties has great potential for applications in the household and clothing fields.


Expression of interleukin-16 in sciatic nerves, spinal roots and spinal cords of experimental autoimmune neuritis rats.
Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain-Barré Syndrome. In this study, we studied the spatiotemporal expression of interleukin-16 (IL-16) in the nervous system of EAN rats and pharmacological effects of minocycline on IL-16 expressions in EAN rats. In sciatic nerves and dorsal/ventral roots of EAN rats, IL-16+ cells, identified as macrophages and T cells, were mainly found to concentrate around blood vessels. However, in spinal cords, IL-16+ microglial cells were mainly found in lumbar dorsal horns. Massive IL-16+ cell accumulation in sciatic nerves and spinal roots was temporally correlated with severity of neurological signs of EAN. Furthermore, a strong correlation of IL-16+ cell accumulation with local demyelination in perivascular areas of sciatic nerves, and significant reduction of IL-16+ cell numbers in sciatic nerves and spinal cords by minocycline suggested a pathological contribution of IL-16+ cells in EAN. Taken together, robust IL-16+ cell accumulation in the nervous system and its temporal correlation with severity of neurological signs in EAN might suggest a pathological role of IL-16 in EAN, which makes IL-16 a potential pharmacological target.


Descemet's membrane substrate from human donor lens anterior capsule.
To study the potential use of human donor anterior lens capsule as a Descemet's membrane substrate. Anterior lens capsules were recovered from the lenses of 30 cornea donors. Human corneal endothelial cells were recovered from the remaining corneal sclera rims of 15 donor corneas used for penetrating keratoplasty. Samples were sorted into three groups. Group 1 consisted of 10 samples in which the endothelial cells were allowed to grow on anterior lens capsules. In Group 2 human corneal endothelial cells grew on a collagen membrane and in Group 3 on polystyrene culture plates. Cell density, morphology and adherence of the cell-capsule complex were evaluated at 1, 4, 7 and 14days with a phase-contrast microscope, a scanning electron microscope and by histology. Cell viability was quantified by a microscopic live-dead assay. Expression of zonula occludens-1, Na(+) /K(+) -adenosine triphosphatase, tissue transglutaminase and vimentin were investigated by immunohistochemistry. A mean diameter of 10.05±0.13mm of anterior capsule was obtained as a substrate for cell culture. Endothelial cell density of Group 1 was measured at 2455.4±283.8cells/mm(2) , which was also comparable with the cell density of the control group. Cell viability was 95% or superior in all groups and multiple cellular interconnections developed between growing cells. Immunohistochemical analysis demonstrated strongly positive staining for all investigated proteins. Electron microscopy confirmed the adherence and monolayer growth of the endothelial cells. Human donor anterior lens capsule might therefore be a potential scaffold for the ex vivo expansion of human corneal endothelial cells.


Combination of cytologic evaluation and quantitative digital cytometry is reliable in detecting recurrent disease in patients with urinary diversions.
Detecting recurrent bladder carcinoma early is important because it is a multifocal disease that may affect the bladder mucosa, ureters, urethra, and renal pelvis and is associated with high morbidity and mortality rates. However, specimens from patients who have undergone cystectomy with urinary diversion can be difficult to interpret by cytologic evaluation because they often contain degenerated epithelial cells, histiocytes, acute inflammatory cells, bacteria, and cellular debris. In this retrospective study, the reliability of quantitative digital cytometry (QDC) in conjunction with cytologic evaluation in detecting recurrent disease was determined in these patients. In all, 116 specimens were identified from the cytology files from 83 patients who had undergone radical cystectomy with urinary diversion for bladder carcinoma at the study institution between 2002 and 2005; all specimens underwent cytologic evaluation and 105 underwent QDC. Two cytospin slides were prepared for cytologic evaluation and 1 for QDC. At least 100 of the most atypical cells were interactively digitized and evaluated for ploidy, the percentage of proliferating cells, and the percentage of cells with a DNA content greater than 5c. Based on these parameters, the DNA histograms were grouped by pattern: diploid, abnormal diploid, tetraploid, and aneuploid. The cytologic evaluation and QDC results were compared with the clinical follow-up data. In all, 103 specimens were negative for recurrent disease or had atypical cells on cytologic examination and were found to have diploid or abnormal diploid patterns on QDC. None of these cases had clinical evidence of upper urinary tract disease at the time the first specimen was obtained. However, recurrent urothelial carcinoma was found in subsequent conduit specimens from 2 patients. Thirteen specimens from 9 patients were suspicious or positive for malignancy by cytology. Five of these patients had an upper urinary tract recurrence and their specimens were found to be abnormal on cytologic evaluation and QDC, with 15% of cells with a DNA content greater than 5c. Combined cytologic evaluation and QDC is a reliable method of detecting recurrent disease in patients with urinary diversions and can be used to regularly monitor these high-risk patients.


Cardiovascular and perceptual stress of female basketball referees during women's International matches.
The current aims were to determine body composition (BC), and heart rate (HR) and rating of perceived effort (RPE) responses by female basketball referees during elite international competition. Pre-competition, BC via skinfolds was assessed in 10 referees (38 ± 3 yr) who officiated 11 matches. Referees' HR and exercise intensity (based upon maximum HR, HRmax) was recorded during each quarter of each match and RPE assessed post- match. Differences between quarters were examined via repeated measures ANOVA while correlations between RPE, HR, BC and experience were also considered. The average match HR was 86.2±5.0 HRmax with this being significantly lower during the 4th quarter compared to the 1st (p = 0.18) and 2nd quarters (p = 0.001), and significantly lower during the 3rd compared to the 2nd quarter (p = 0.005). The average post-match RPE was 12.5 ± 1.6 with significant inverse correlations identified between post-match RPE and exercise intensity (average HR, %HRmax). Significant correlations were identified between the average match HR and BC (0.608, p = 0.016), and experience (-0.653, p = 0.008). The current investigation has demonstrated that elite female basketball referees experience significant cardiovascular and perceptual stress during international matches that may be influenced by referee experience and BC. These unique characteristics may aid in referee preparation for elite competition.


Caffeine-inhibited DNA repair in 7-bromomethylbenz (a)-anthracene-treated Chinease hamster cells: formation of breaks in parental DNA and inhibition of ligation of nascent DNA as a mechanism for enhancement of lethality and chromosome damage.
The cytotoxic and clastogenic effects of 7-bromomethylbenz(a)anthracene (7-BMBA) are potentiated by post-treatment incubation of cells in the presence of an non-toxic concentration of caffeine. Under these conditions caffeine inhibits the rate of ligation of newly-synthesised DNA and induces breaks in the template strand of DNA. It is proposed that endonucleolytic attack occurs at the site of lesions in the template strand of DNA and that a later step(s) of excision-repair is (are) inhibited by the presence of caffeine-induced 'gap' in the nascent DNA opposite these lesions.


Olefination reactions of phosphorus-stabilized carbon nucleophiles.
A range of phosphorus-stabilized carbon nucleophiles have been employed for alkene synthesis with high chemo-, regio-, and stereoselectivity. The Wittig, Horner-Wadsworth-Emmons, Horner-Wittig, and Evans-Akiba reactions utilize phosphonium-, phosphonate-, phosphine oxide-, and pentacoordinated phosphorane-stabilized carbanions as nucleophiles, respectively, to undergo olefination with aldehydes or ketones, and each of these transformations has its own advantages and limitations. Modifying the structures of these nucleophiles along with optimizing reaction conditions results in the formation of a wide variety of polysubstituted alkenes in a highly stereoselective manner. The olefination of imines with phosphonium ylides has recently emerged as a useful approach to tune the stereoselectivity for alkene synthesis. This review focuses on recent advances in the stereoselective olefination of phosphorus-stabilized carbon nucleophiles.


Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study.
Congenital dysplasia of the hip is an abnormal seating of the femoral head in the acetabulum, mainly caused by shallow acetabulum and lax joint capsule. Genetic factors play a considerable role in the pathogenesis of congenital dysplasia of the hip. The gene growth differentiate factor 5 (GDF5) has been implicated in skeletal development and joint morphogenesis in humans and mice. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of GDF5 (rs143383) was reported to be associated with osteoarthritis susceptibility. As a key regulator in morphogenesis of skeletal components and soft tissues in and around the joints, GDF5 may be involved in the aetiology and pathogenesis of congenital dysplasia of the hip. Our objective is to evaluate if the GDF5 SNP is associated with congenital dysplasia of the hip in people of Han Chinese origin. The GDF5 SNP was genotyped in 338 children with congenital dysplasia of the hip and 622 control subjects. The SNP was significantly associated with congenital dysplasia of the hip (p = 0.0037; odds ration (OR) = 1.40; 95% confidence interval (CI) = 1.11 to 1.75). A significant difference was detected in female samples when stratified by gender (p = 0.0053; OR = 1.46; 95% CI = 1.21 to 1.91), and in hip dislocation when stratified by severity (p = 0.0078; OR = 1.43; 95% CI = 1.11 to 1.85). Our results indicate that GDF5 is important in the aetiology of congenital dysplasia of the hip. To the authors' knowledge this is the first time that a definite association with the congenital dysplasia of the hip susceptibility has been detected.


Symptom outcomes in endoscopic sinus surgery: a systematic review of measurement methods.
To determine the type and prevalence of measurement methods used to analyze symptom outcomes after endoscopic sinus surgery (ESS). Data were derived from PubMed, MEDLINE, EMBASE, Web of Science, Cochrane databases, Google Scholar, and manual searches. All English-language studies consisting of more than 10 adult patients from January 1980 to December 2006 reporting ESS symptom outcome results were reviewed. Studies of radical surgery and studies involving patients with significant comorbidities were excluded. The ESS symptom outcome results of 29,333 patients were reported in 204 studies. Symptom outcome was determined by survey instruments in 47 (23.0%) studies and individual symptom scoring in 63 (31%) studies. Of 18 validated instruments used, almost two thirds of studies that reported results by survey measures used the following three instruments: Chronic Sinusitis Survey (12 studies), Sinonasal Outcome Test-20 (11 studies), and Medical Outcomes study 36-Item Short-Form Health Survey (10 studies). The percentages of studies that reported specific results of the 1997 American Academy of Otolaryngology-Head Neck Surgery Rhinosinusitis Task Force (RSTF) chronic rhinosinusitis symptom criteria varied as follows: facial pain/pressure, 35%; facial congestion/fullness, 10%; nasal obstruction/blockage, 42%; nasal discharge/purulence/discolored postnasal discharge, 47%; hyposmia/anosmia, 35%; fever, 2%; halitosis, 4%; fatigue, 11%; dental pain, 3%; cough, 10%; and ear pain/pressure/fullness, 6%. ESS symptom outcome is assessed inconsistently by numerous measures. Individual report- ing of all RSTF chronic rhinosinusitis symptom criteria, as recommended by the RSTF and by subsequent consensus conferences, is rarely noted. Many RSTF symptom criteria are seldom studied.


Disruption of Magnetic Compass Orientation in Migratory Birds by Radiofrequency Electromagnetic Fields.
The radical-pair mechanism has been put forward as the basis of the magnetic compass sense of migratory birds. Some of the strongest supporting evidence has come from behavioral experiments in which birds exposed to weak time-dependent magnetic fields lose their ability to orient in the geomagnetic field. However, conflicting results and skepticism about the requirement for abnormally long quantum coherence lifetimes have cast a shroud of uncertainty over these potentially pivotal studies. Using a recently developed computational approach, we explore the effects of various radiofrequency magnetic fields on biologically plausible radicals within the theoretical framework of radical-pair magnetoreception. We conclude that the current model of radical-pair magnetoreception is unable to explain the findings of the reported behavioral experiments. Assuming that an unknown mechanism amplifies the predicted effects, we suggest experimental conditions that have the potential to distinguish convincingly between the two distinct families of radical pairs currently postulated as magnetic compass sensors. We end by making recommendations for experimental protocols that we hope will increase the chance that future experiments can be independently replicated.