Does Seasonal Influenza Related Hospital Occupancy Surge Impact Hospital Staff Sickness Presenteeism and Productivity Costs?
Background-The workload of public hospital staff is heightened during seasonal influenza surges in hospitals serving densely populated cities. Such work environments may subject staff to increased risk of sickness presenteeism. Presenteeism is detrimental to nurses' health and may lead to downstream productivity loss, resulting in financial costs for hospital organizations. Aims-This study aims to quantify how seasonal influenza hospital occupancy surge impacts nurses' sickness presenteeism and related productivity costs in high-intensity inpatient metropolitan hospitals. Methods-Full-time nurses in three Hong Kong acute-care hospitals were surveyed. Generalized estimating equations (GEE) was applied to account for clustering in small number of hospitals. Results-A total of 71.3% of nurses reported two or more presenteeism events last year. A 6.8% increase in hospital inpatient occupancy rate was associated with an increase of 19% (1.19, 95% CI: 1.06-1.34) in nurse presenteeism. Presenteeism productivity loss costs between nurses working healthy (USD1983) and worked sick (USD 2008) were not significantly different, while sick leave costs were highest (USD 2703). Conclusion-Presenteeism prevalence is high amongst acute-care hospital nurses and workload increase during influenza flu surge significantly heightened nurse sickness presenteeism. Annual presenteeism productivity loss costs in this study of USD 24,096 were one of the highest reported worldwide. Productivity loss was also considerably high regardless of nurses' health states, pointing towards other potential risk factors at play. When scheduling nurses to tackle flu surge, managers may want to consider impaired productivity due to staff presenteeism. Further longitudinal research is essential in identifying management modifiable risk factors that impact nurse presenteeism and impairing downstream productivity loss.


Scale economies and total factor productivity growth on poultry egg farms in Benin: a stochastic frontier approach.
The study examines economies of scale and sources of total factor productivity growth on poultry farms producing table eggs in Benin Republic. We use panel data on commercial poultry farms from 2010 to 2018, and the flexible translog production functions to estimate a stochastic frontier and economies of scale. The results showed that there were significant economies of scale to be exploited, and the average productivity growth rate was decreasing of 5.09% over the study period. This deterioration was mainly because of the decline of technical efficiency growth rate (2.16%) and technology growth rate (2.67%). Although the returns to scale (1.31) were increasing, their effects on productivity during the study period were negative (-0.74%). As implications, policy makers may encourage the increasing of the "size" of poultry farms and act on the sources of productivity growth identified in this study to increase the productivity of commercial poultry farms to meet the demand of table egg in Benin.


Improvement of the Cu and Cd phytostabilization efficiency of perennial ryegrass through the inoculation of three metal-resistant PGPR strains.
To explore a novel strategy for the remediation of soils polluted with Cu and Cd, three strains of plant-growth-promoting rhizobacteria (PGPRs) isolated from contaminated mines and two grass species (perennial ryegrass and tall fescue) were selected in this study. The performance of PGPR strains in metal adsorption, maintaining promotion traits under stress, and ameliorating phytostabilization potential was evaluated. Cd2+ exerted a stronger deleterious effect on microbial growth than Cu2+, but the opposite occurred for grass seedlings. Adsorption experiment showed that the growing PGPR strains were able to immobilize maximum 79.49% Cu and 81.35% Cd owing to biosorption or bioaccumulation. The strains exhibited the ability to secrete indole-3-acetic acid (IAA) and dissolve phosphorus in the absence and presence of metals, and IAA production was even enhanced in the presence of low Cu2+ (5 mg L-1). However, the siderophore-producing ability of the isolates was strongly suppressed under Cu and Cd exposure. Ryegrass was further selected for pot experiments owing to its higher germination rate and tolerance under Cu and Cd stress than fescue. Pot-experiment results revealed that PGPR addition significantly increased the shoot and root biomasses of ryegrass by 11.49%-44.50% and 43.53%-90.29% in soil co-contaminated with 800 mg Cu kg-1 and 30 mg Cd kg-1, respectively. Metal uptake and translocation in inoculated ryegrass significantly decreased owing to the reduced diethylenetriamine pentaacetic acid-extractable metal content and increased residual metal-fraction percentage mediated by PGPR. Interestingly, stress mitigation was observed in these inoculated plants; in particular, their malondialdehyde content and superoxide dismutase activity were even significantly lower than those of ryegrass under normal conditions. Therefore, PGPR could be a promising option to enhance the phytostabilization efficiency of Cu and Cd in heavily polluted soils.


Changes in physical activity patterns from adolescence to young adulthood: the BELINDA study.
Physical activity (PA) is recognized as a marker of health. The aim was to investigate PA differences from adolescence to young adulthood. European adolescents included in the HELENA study were invited to participate in a follow-up study, 10 years later. The present study included 141 adults (25.0 ± 1.4 years) for whom valid accelerometer data were available in adolescence and adulthood. Changes in PA by sex, weight and maternal education level were explored with interactions. Time spent in sedentary activity, light PA (LPA) and moderate PA (MPA) increased by 39.1, 59.6 and 6.6 min/day, respectively, whereas the time spent in vigorous PA (VPA) decreased by 11.3 min/day compared with adolescent VPA (p < 0.05). Increases in MPA were greater on weekends compared with weekdays, but we found a greater decrease in VPA on weekdays compared with weekends. Moderate-to-vigorous PA (MVPA) decreased significantly on weekdays (-9.6 min/day; 95%CI, -15.9 to -3.4), while it increased on weekends (8.4 min/day; 95%CI, 1.9 to 14.8). Significant heterogeneity was found across sexes for VPA and MVPA, with a stronger decrease in VPA in males compared with females and a significant decrease in MVPA (-12.5 min/day; 95%CI, -20.4 to -4.5) in males but not in females (1.9 min/day; 95%CI, -5.5 to 9.2). No significant heterogeneity was found to be linked to maternal education level or weight, irrespective of PA level. Conclusion: Our data suggest that the transition from adolescence to young adulthood is a critical period for lifestyle PA habits. A decline in VPA and an increasingly sedentary time were observed. The observed changes are worrying and may increase the risk of developing adverse health consequences later in life. What is Known: • The transition from adolescence to adulthood is marked by many life changes affecting lifestyle habits. Most studies tracking physical activity from adolescence to adulthood were done using PA questionnaires, which is a subjective method. What is New: • Our study bring first data on objective changes in PA patterns between adolescence and young adulthood, taking account of BMI, sex and maternal educational level. Our results suggest that the transition from adolescence to young adulthood is a critical period for lifestyle PA habits, especially for time spent on sedentary activities.


A new highly polymorphic marker in the 5' untranslated region of HLA-F shows strong allelic association with haemochromatosis.
The 5' untranslated region of HLA-F contains a polypurine tract comprising repeats of tri- and hexa-nucleotide motifs. We have recently demonstrated that this polypurine tract is highly polymorphic by using the polymerase chain reaction. Here, we demonstrate that some of the alleles can be explained by a deletion of approximately 100 bp DNA and show that alleles of this novel, highly polymorphic locus are as strongly associated with haemochromatosis as HLA-A3 or D6S105-8. The observed frequency of heterozygosity at HLA-RF is extremely high (95%) and this locus has been found to be informative in pedigrees that are non-informative at HLA-A and D6S105. We also show an example of replication slippage at HLA-F in one pedigree.


Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan.
Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques, including an in-house-developed augmented whole-exome sequencing method (CoDE-seq) that enables simultaneous detection of whole-exome copy number variations (CNVs) and point mutations in coding regions. We identified 110 (49%) probands carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for nonsyndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of cases in the studied cohort are likely to have a discrete genetic cause, with 13% of these as a result of CNVs, demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible overlapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with a high prevalence of obesity provide unique, genetically enriched material in the quest of new genes/variants influencing energy balance.


Comparison of two skin imaging analysis instruments: The VISIA® from Canfield vs the ANTERA 3D® CS from Miravex.
The skin imaging analysis instruments are widely used to record and measure the surface and subsurface skin conditions. The main aim of this study is to reveal the differences and correlations in measuring wrinkle, skin texture, coloration/evenness, vascular features, and pore between two commercially available instruments. Twenty-eight subjects were enrolled in the study. A 2*2 cm cardboard was used to make sure the two instruments analyze the same area. Pictures were taken and analyzed by the VISIA® from Canfield and the ANTERA 3D® CS from Miravex, in sequence. The spot, ultraviolet spot, brown spot, red area, texture values measured with VISIA® were positively correlated with age, while the pore and wrinkle values showed no significance. The wrinkle, texture, melanin, hemoglobin, pore index, pore volume values measured with ANTERA 3D® had a significantly positive correlation with age. The spot, brown spot values from VISIA® were positively correlated with the melanin value from ANTERA 3D® . Texture value measured with the two instruments revealed positive linear correlation. Strong correlation was found between the red area value from VISIA® and the hemoglobin value from ANTERA 3D® . Ultraviolet spot from VISIA® showed no linear correlation with the melanin value from ANTERA 3D® . Neither of the wrinkle and pore measured with the two instruments showed linear correlation. ANTERA 3D® relies on multidirectional illumination obtained by LEDs of different wavelengths from different directions which make it advanced at the qualitative evaluation of various dermatologic conditions. Compared with VISIA® , ANTERA 3D® is more sensitive in the assessment of wrinkle and it may also be available to evaluate the aging-related enlarged pore.


Comparative antihypertensive effectiveness of once-daily mibefradil and diltiazem CD. Mibefradil Hypertension Study Group.
This multicenter, double-masked, randomized, forced-titration, parallel-group trial was designed to determine whether we could confirm the results of a previous trial that demonstrated a significantly greater antihypertensive effect for mibefradil compared with diltiazem CD. Two hundred thirty-nine patients with uncomplicated mild-to-moderate essential hypertension and a baseline sitting diastolic blood pressure (SDBP) between 95 and 114 mm Hg were randomized to receive once-daily treatment with mibefradil 50 mg (n = 119) or diltiazem CD 180 mg (n = 120). After 4 weeks of treatment, all patients underwent forced titration to mibefradil 100 mg or diltiazem CD 360 mg for an additional 8 weeks. After 12 weeks of active treatment, the mean reduction from baseline in trough SDBP was significantly greater with mibefradil than with diltiazem CD (-14.3 +/- 6.6 mm Hg vs -11.7 +/- 7.4 mm Hg, respectively). In addition, significantly more patients receiving mibefradil had a decrease in SDBP > or = 10 mm Hg or a decrease to < or = 90 mm Hg by week 12 than did patients receiving diltiazem CD (82% vs 72%, respectively). The tolerability of mibefradil and diltiazem CD were comparable, with similar percentages of patients in both groups reporting at least one adverse event (21% vs 22%, respectively) that was considered to be at least remotely related to the study drug. The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 100 mg is significantly more effective than diltiazem CD 360 mg in lowering both diastolic and systolic blood pressure. Both drugs are well tolerated.


Attention UW-Net: A fully connected model for automatic segmentation and annotation of chest X-ray.
Automatic segmentation and annotation of medical image plays a critical role in scientific research and the medical care community. Automatic segmentation and annotation not only increase the efficiency of clinical workflow, but also prevent overburdening of radiologists. The objective of this work is to improve the accuracy and give a probabilistic map for automatic annotation from small data set to reduce the use of tedious and prone to error manual annotations from chest X-rays. In this paper, we have proposed an attention UW-Net, which introduces an intermediate layer acting as a bridge between the encoder and decoder pathways. The intermediate layer is a series of fully connected convolutional layers generated from the upsampling of the final encoder layer connected to the corresponding up sampled and down sampled blocks via skip-connections. The intermediate layer is further connected to the decoder pathway using a downsampling layer. The proposed attention UW-Net is giving a very good performance, achieving an average F1-score of 95.7%, 80.9%, 81.0% and 77.6% for lung (large), heart (medium), trachea (small), and collarbone (small) object segmentations, respectively. The attention UW-Net outperforms not only in comparison to U-Net and its variations but also with respect to other standard recent automatic and semi-automatic segmentation/annotation models. An ablation study was also performed to find the best suited high-performing architecture. The uniformity in prediction accuracy of segmentation masks for all kinds of segmentation masks (large, medium, and small lesions) makes this model best for automatic annotation of organs.


Fasted and fed small bowel motility patterns at cine-MRI in chronic intestinal pseudo-obstruction.
Chronic intestinal pseudo-obstruction (CIPO) is a severe intestinal motility disorder of which the pathophysiology is largely unknown. This study aimed at gaining insight in fasted and fed small bowel motility in CIPO patients using cine-MRI with caloric stimulation. Eight adult patients with manometrically confirmed CIPO were prospectively included. Patients underwent a cine-MRI protocol after an overnight fast, comprising fasting-state scans and scans after ingestion of a meal (Nutridrink, 300 kcal). Small bowel motility was quantified resulting in a motility score in arbitrary units (AU) and visually assessed by three radiologists. Findings were compared with those in 16 healthy volunteers. Motility scores (median, IQR) in CIPO patients were 0.21 (0.15-0.30) in the fasting state and 0.23 (0.15-0.27) directly postprandially. In healthy volunteers, corresponding motility scores were 0.15 (0.13-0.18) and 0.22 (0.19-0.25), respectively. The postprandial change in motility score was +1% (-19 to +21%) in CIPO and +39% (+23 to +50%) in healthy volunteers (p = 0.001*). Visual analysis revealed increased small bowel contractility in four, normal in two, and decreased in two CIPO patients. Surprisingly, we found hyperactive small bowel motility in half of the CIPO patients, suggestive of uncoordinated motility. A wide variation in motility patterns was observed, both higher, lower, and comparable contractility compared with healthy subjects. No clear postprandial activation was seen in patients. Cine-MRI helps to gain insight in this complex disease and can potentially impact treatment decisions in the future.


Influence of CHIEF pathway genes on gene expression: a pathway approach to functionality.
Candidate pathway approaches in disease association studies often utilize a tagSNP approach to capture genetic variation. In this paper we assess gene expression patterns with SNPs in genes in the CHIEF pathway to help determine their potential functionality. Quantitative real-time RT-PCR was run to determine gene expression of 13 genes in normal colon tissue samples from 82 individuals. TagSNP genotype data were obtained from a GoldenGate Illumina multiplex bead array platform. Age, sex, and genetic ancestry adjusted general linear models were used to estimate beta coefficients and p values. Genetic variation in mTOR (1 SNP), NFKB1 (4 SNPs), PRKAG2 (3 SNPs), and TSC2 (1 SNP) significantly influenced their expression. After adjustment for multiple comparisons several associations between pathway genes and expression of other genes were significant. These included AKT1 rs1130214 associated with expression of PDK1; NFκB1 rs13117745 and rs4648110 with STK11 expression; PRKAG2 rs6965771 with expression of NFκB1, PIK3CA, and RPS6KB2; RPS6KB1 rs80711475 with STK11 expression; STK11 rs741765 with PIK3CA and PRKAG2 expression; and TSC2 rs3087631 with AKT1, IkBκB, NFκB1, PDK1, PIK3CA, PRKAG2, and PTEN expression. The higher levels of differential expression were noted for TSC2 rs3087631 (percent difference ranges from 108% to 198% across genes). Many of these SNPs and genes also were associated with colon and rectal cancer risk. Our results suggest that pathway genes may regulate expression of other genes in the pathway. The convergence of these genes in several biological pathways involved in cancer further supports their importance to the carcinogenic process.


A reverse method for diversity introduction of benzimidazole to synthesize H(+)/K(+)-ATP enzyme inhibitors.
A series of 2-[(2-pyridylmethyl)sulfinyl]benzimidazole derivatives were synthesized via a solution phase synthetic route using a reversal method of diversity introduction. Using this synthetic strategy, we obtained two key intermediates (4-A and 4-B) simultaneously, which allows us to introduce diversity points onto the benzimidazole part of the final product under reliable reaction conditions to identify potent H(+)/K(+)-ATP enzyme inhibitors. Compound 14l (IC(50)=1.6×10(-5)M) was comparable with H(+)/K(+)-ATP enzyme inhibitor in vitro.


New Benzenoid Derivatives and Other Constituents from Lawsonia inermis with Inhibitory Activity against NO Production.
Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (4-14). The structures of three new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4-6, 13 and 14 were evaluated for inhibition of nitric oxide production in LPS-stimulated product of nitrite in RAW 264.7 cells with IC50 values of 6.12, 16.43, 18.98, 9.30, 9.30 and 14.90 μg/mL, respectively.


Antipathogenic properties and applications of low-dimensional materials.
A major health concern of the 21st century is the rise of multi-drug resistant pathogenic microbial species. Recent technological advancements have led to considerable opportunities for low-dimensional materials (LDMs) as potential next-generation antimicrobials. LDMs have demonstrated antimicrobial behaviour towards a variety of pathogenic bacterial and fungal cells, due to their unique physicochemical properties. This review provides a critical assessment of current LDMs that have exhibited antimicrobial behaviour and their mechanism of action. Future design considerations and constraints in deploying LDMs for antimicrobial applications are discussed. It is envisioned that this review will guide future design parameters for LDM-based antimicrobial applications.


Depletion of antigen-presenting cells by clodronate liposomes reverses the psoriatic skin phenotype in KC-Tie2 mice.
There is ongoing debate regarding the initiation of psoriatic plaque as primarily arising from an anomaly in epidermal keratinocytes (KCs) or from abnormalities in immunocytes that secondarily activate otherwise normal KCs. In mice engineered to overexpress the angiopoietin receptor Tie2 in KCs, skin spontaneously develops the characteristic clinical, histological and immune cell phenotypes of psoriasis which can be reversed with either transgene repression or ciclosporin administration, suggesting key roles for both KCs and T cells in mediating the skin disease in this murine model. To determine if antigen-presenting cells (APCs) and macrophages alone are sufficient to sustain psoriasiform inflammation in the KC-Tie2 murine model of psoriasis. Clodronate liposomes were intradermally injected into involved dorsal skin of KC-Tie2 or control animals once a week for 6weeks and acanthosis, angiogenesis, immune cell infiltration and cytokine production were quantitated using immunohistochemistry and interactive image analyses, enzyme-linked immunosorbent assay (ELISAs) and quantitative real-time polymerase chain reaction (qRT-PCR). Clodronate liposome injection eliminated CD11c+, F4/80+ and CD11b+ cells in the skin and returned CD8+ T-cell numbers to control mouse levels. APC depletion in KC-Tie2 mouse skin resulted in resolution of the acanthotic skin phenotype, decreased dermal angiogenesis, and a return to control mouse levels for interleukin (IL)-1α, IL-6, IL-23 and tumour necrosis factor (TNF)-α expression and modest reductions in interferon-γ and IL-17. These findings suggest a critical role for APCs and myeloid cell-derived IL-23 and TNF-α and underscore the importance of Th1 and Th17 T cells in maintaining the psoriasiform skin phenotype in the KC-Tie2 mouse model.


[Anesthesia and Angelman syndrome].
Angelman syndrome (AS) is a rare neurodevelopmental disorder with an incidence of 1:10,000-1:40,000 caused by deficient genetic imprinting in the chromosomal segment 15q11-q13. Experimental data suggest that the gamma-aminobutyric acid A (GABA(A)) receptor as well as the N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors may be affected by this condition. The first description of the syndrome goes back to 1965 when the British pediatrician Harry Angelman (1915-1996) recognized similar clinical features in three children. Angelman's description of puppet children was changed to happy puppet syndrome 2 years later before this euphemistic denotation was replaced by the concept Angelman syndrome over the years. Angelman syndrome is characterized by ataxia, jerky movements especially hand flapping, a seizure disorder with a characteristic electroencephalogram (EEG), severe learning difficulties, a happy disposition, lack of verbal communication and dysmorphic facial features. Most hospitalizations are caused by epilepsy and the most common indications for surgical procedures are in dental medicine. The first anesthesiology case report to be published dates back to 2001. A total of 13 cases have now been published and in 11 cases the age was registered (mean age 11.6 years, standard deviation 11.7 and 2 outliers aged 27 and 40 years). In this paper, the published case reports are contrasted with 15 cases of anesthesia in 6 patients with AS who underwent surgery during 14 years of routine operations at a Berlin anesthesiology clinic (mean age 15.9 years, standard deviation 4.2 with no outliers). Besides neurosurgical and orthopedic operations most were dental interventions. Summarized, these cases of anesthesia and the results of the published case reports allow the formulation of guidelines for administration of anesthesia in AS cases but do not permit conclusions on which method of anesthesia is the safest for AS patients. For the preoperative consultation and anesthetization, communication with the patients requires the aid of parents or other relatives. Water and reflecting surfaces may be used to gain contact with AS patients. Patients with AS feel pain like any other person although they are frequently smiling and laughing and this has to be considered especially in major surgery (e.g. scoliosis surgery). The most important life-threatening complication is bradycardia due to vagal hypertonia which can lead to asystole with delayed response to atropine. None of the Berlin patients had severe bradycardia but the complication has to be taken into consideration. The use of drugs to ensure complete reversal of neuromuscular relaxation should be avoided because anticholinergic agents could cause bradycardia. The use of sugammadex in cases of AS has not been tested. To avoid elevation of the vagal tone, the indications for laparascopy have to be considered very carefully. There is no evidence that any drug or hypnotic may be more appropriate or advantageous. Balanced anesthesia and total intravenous anesthesia are possible but the duration of drug effect has to be taken into account. If ketamine is used the side-effects of the drug (psychomimetic reactions, muscular rigidity) should be prevented by the consistent administration of propofol, midazolam or thiopental. Usually AS patients are agitated so that regional anesthesia techniques are difficult to administer. If regional anesthesia does have considerable advantages over general anesthesia in a particular case, peripheral regional anesthesia should be preferred, especially because scoliosis is often present. There is no evidence that AS patients cause more intubation problems but because of facial dysmorphia accurate evaluation is needed in advance. This is even more important for older AS patients because the dysmorphia tends to accelerate during the course of life. Although epilepsy is the primary feature of AS, not every EEG alteration indicates the presence of epilepsy. The advantage in using neuromonitoring for measuring the depth of anesthesia is limited. Administration of anticonvulsants must be continued if they were used preoperatively.


Acute Care Pediatric Nurse Practitioners as Leaders: Perceptions, Self-Identity, and Role Congruity.
This study aimed to gain an understanding of practicing acute care pediatric nurse practitioners' (AC-PNPs') perceptions of themselves as leaders in both clinical and professional contexts. This qualitative study was conducted at a midwestern quaternary care children's hospital. Cultural domain analysis, semistructured interviews, and free listing techniques were employed to identify areas of consensus and variation among a convenience sample of AC-PNPs. Findings demonstrated the AC-PNPs have a limited self-view of leadership. Nurse practitioners need additional leadership capacity and capability building during graduate education, the transition to practice, and throughout their careers.


Mark Mattson Q&A Interview.
In an interview with Neuron, Mark Mattson discusses his scientific and personal journey, from racing horses to heading a laboratory at NIH. Mattson reflects on a wide-ranging career that has included fundamental findings in developmental neuroscience and bringing intermittent fasting to the forefront of neurodegeneration research.


Familial thoracic aortic dilatations and dissections: a case control study.
Evidence suggesting that genetic factors contribute to the development of common disorders can be obtained by demonstrating familial aggregation of the disease. This study investigated whether thoracic aortic dilations and dissections aggregate in families by comparing the prevalence of thoracic aortic aneurysms, thoracic aortic dissections, and sudden death in first-degree relatives of patients referred for thoracic aortic surgery. Families were ascertained through 158 nonsyndromic patients referred for surgical correction of either thoracic aortic aneurysms or dissections (probands) and their 843 first-degree relatives. A control group of 547 first-degree relatives was derived from 114 proband spouses. Groups were examined for statistical differences in the prevalence of thoracic aneurysms, thoracic aortic dissections, abdominal aortic aneurysms, sudden death, and myocardial infarctions. First-degree relatives of probands demonstrated a higher prevalence of thoracic aortic aneurysms and sudden death when compared with the control group. Relative risks of thoracic aortic aneurysm development in proband fathers, brothers, and sisters were 1.8, 10.9, and 1.8, respectively. A pattern of inheritance of the thoracic aortic aneurysms could not be determined. This study indicates proband first-degree relatives are at higher risk of thoracic aortic aneurysms and sudden death compared with a control group. This study supports the role of genetic factors in the cause of thoracic aortic aneurysms and provides important information for identifying individuals at risk.


Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals.
Incensole acetate (IA), a constituent of Boswellia resin ('frankincense'), was previously demonstrated to exhibit an antidepressive-like effect in the Forced Swim Test (FST) in mice following single dose administration (50 mg/kg). Here, we show that acute administration of considerably lower dose (10 mg/kg) IA to selectively bred mice, showing prominent submissive behavior, exerted significant antidepressant-like effects in the FST. Furthermore, chronic administration of 1 or 5 mg/kg per day of IA for three consecutive weeks dose- and time-dependently reduced the submissiveness of the mice in the Dominant-Submissive Relationship test, developed to screen the chronic effect of antidepressants. This behavioral effect was concomitant to reduced serum corticosterone levels, dose-dependent down-regulation of corticotropin releasing factor and up-regulation of brain derived neurotrophic factor transcripts IV and VI expression in the hippocampus. These data suggest that IA modulates the hypothalamic-pituitary-adrenal (HPA) axis and influences hippocampal gene expression, leading to beneficial behavioral effects supporting its potential as a novel treatment of depressive-like disorders.


Compliance to FDA's elimination of free tobacco product sampling at vape shops.
The 2016 FDA's "Deeming Rule" prohibited free samples of vaping products. The purpose of this study was to investigate compliance with or adaptation to this newly established FDA policy. Vape shops were recruited in Southern California between November 2017 and December 2018. Data collectors interviewed 121 vape shop employees who responded to questions pertaining to the sampling protocol at their shop. Nicotine levels used for sampling were also assessed for consideration of future policy adoption. Only 7.4% of shops were non-compliant to federal sampling rules. The remaining shops either: 1) charged a fee for samples (58.7%); 2) deducted the fee from the final purchase price (5.8%); or 3) eliminated product sampling (28.1%). Of the shops that charged for sampling (including membership fees), 94.4% initiated a minimal cost protocol (≤$1) for sampling. Half (50.0%) the shops that allowed sampling offered nicotine-containing samples. There was high compliance (92.6%) to the change in policy among vape shops. However, minimal modification of sampling protocol was observed due in part to the lack of specificity on parameters of compliance, which lessened the potential impact of the policy. To further protect consumers, policymakers must develop unambiguous and comprehensive policies to achieve intended results and true compliance. At minimum, future tobacco product sampling policies should consider standardized pricing; alternatively, total elimination of tobacco product sampling is suggested.


Impact of calcineurin inhibitors on rat glioma cells viability.
Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells. Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration. CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.


"Mental maps": Between memorial transcription and symbolic projection.
"The mental map" is a concept that has been used and defined in numerous ways. The cognitive map, and the concept map-also known as the "heuristic" or "mind" map-are the two distinct contextual meanings covered by the term mental map in the present article. In the mental map domain, the first major field of study is geography, spatial cognition, and neurophysiology and it aims to understand how the route taken by a subject (or a set of subjects) in space leads to memorization and internal representation(s). In general, the externalization of these representations takes the form of drawings, positioning in a graph, or oral/textual narratives, but it is primarily reflected as a behavior in space that can be recorded as tracking items. A second field of study, one which is geared more toward exploratory and combinatorial uses, is the concept (also heuristic or mind) map which consists in organizing notions, concepts, and information in the form of tree graphs or graphs that can be used to produce diagrams and flowcharts. The aim is projective, for clarification and discovery purposes or for data organization and visualization. To date, very few studies in the literature have examined the similar, overlapping and oppositional features in what is broadly referred to as "representation(s) of space" and "space(s) of representation." How can we better apprehend the complex notion of "mental map?" The question of memorial transcription? Of "symbolic projection?" Can we identify meeting points between these two polarities and, if possible, a continuum? Through the notion of cognitive graph, recent advances in the understanding of brain mechanisms enable us to approach the distinctions between cognitive map and conceptual map as an articulated and continuous whole.


Bifidobacterium longum W11: Uniqueness and individual or combined clinical use in association with rifaximin.
Strains belonging to bifidobacteria have been documented as being helpful in adults with intestinal dysbiosis conditions, like those related to irritable bowel syndrome (IBS). This review aims to present the most relevant evidence regarding the efficacy of Bifidobacterium longum W11, a Bifidobacterium used in clinical settings for conditions such as IBS and inflammatory bowel disease. The following electronic databases were systematically searched up to August 2020: MEDLINE (via PubMed), EMBASE, Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and Clinicaltrials.gov. Data arising from pooled analysis, 7 in vitro/pharmacological studies, 7 clinical trials including 1 randomized, double-blind and placebo-controlled, showed that the probiotic strain B. longum W11 has been extensively studied for its efficacy in subjects with IBS with constipation, leading to a significant reduction in symptoms. In particular, its role in alleviating constipation was also confirmed in subjects for whom a low-calorie weight-loss diet led to the slowing down of gut motility. The probiotic characteristics of B. longum W11 were further demonstrated in the treatment of minimal hepatic encephalopathy and hepatic disease. The most remarkable trait of B. longum W11 is its non-transmissible antibiotic resistance, due to a nucleotide polymorphism mutation in the rpoB gene, making it resistant to antibiotics of the rifampicin group, including rifaximin. The co-administration of B. longum W11 and rifaximin in patients with symptomatic uncomplicated diverticular disease brought about a further significant improvement in the clinical condition compared to patients treated with rifaximin alone. B. longum W11 is a probiotic which could synergize with rifaximin as an adjuvant to antibiotic treatment. Taken altogether these findings demonstrate the clinical role of the strain W11 both in some functional and in some inflammatory bowel diseases.


A rapid LC-MS/MS method for simultaneous determination of berberine and irbesartan in rat plasma: Application to the drug-drug pharmacokinetic interaction study after oral administration in rats.
A sensitive, reproducible, and specific liquid chromatography tandem mass spectrometry method was developed and validated to simultaneously determine the concentration of berberine (BBR) and irbesartan in Sprague-Dawley rat plasma, and applied to study the pharmacokinetic drug-drug interaction (DDI) between BBR and irbesartan in rats. In this method, diphenhydramine was used as the internal standard, and the liquid-liquid extraction method using ethyl acetate as the extraction agent was used for sample preparation. After extraction, the prepared samples were run on an Agilent Welchrom C18 column with the mobile phase consisting of methanol-acetonitrile-water solution with 0.5% formic acid (45:50:5, v/v/v) at a flow rate of 0.8 mL·min-1 . The analytes BBR, irbesartan, and diphenhydramine (IS) were detected using multiple reactions monitoring mode, with the ion transitions being m/z 336.1 → m/z 320.0, m/z 429.1 → m/z 206.9, and m/z 256.2 → m/z 167.0, respectively. In the rats' plasma, BBR had good linearity in the range of 0.5-100 ng·mL-1 with the lower limit of quantitation of 0.5 ng·mL-1 , and the accuracy, intra-day, and inter-day precision were less than 12.33%. Irbesartan had good linearity in the range of 20-1200 ng·mL-1 with the lower limit of quantification of 20 ng·mL-1 , and the accuracy, intra-day, and inter-day precision were less than 13.55%. The validated method was verified to meet the determination requirements of biological samples. It was the first time to study the pharmacokinetics of DDI between BBR and irbesartan successfully, which would be necessary and beneficial to explore the clinical safety and efficacy of the combination of BBR and irbesartan in the treatment of diabetic nephropathy.


Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations.
Mucosal melanoma is a rare malignancy; however, the reported incidence rate of mucosal melanoma is higher in Asians than in Caucasians. Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with a poor prognosis due to distant metastasis. Systemic therapy with BRAF inhibitor and MEK inhibitor is one of the standards of care for cutaneous melanoma patients with BRAF V600 mutations. However, no molecular targeted therapy for patients with mucosal melanoma has been established. Relatively few studies have described the genetic mutations associated with mucosal melanoma because of its low frequency. Furthermore, to the best of our knowledge, the genetic mutations among Japanese patients have not been reported. Therefore, in the current study, we evaluated the genetic and clinicopathological characteristics of patients with SNMM. A total of 18 tissue samples obtained from patients with SNMM were analyzed for genetic mutations based on targeted next-generation sequencing to investigate the driver of tumorigenesis and/or candidate genes for predicting clinical outcomes in SNMM. We also performed immunohistochemistry for patients identified with CTNNB1 mutations. Eight of the 18 (44 %) patients had genetic mutations. The most frequent mutation was NRAS (6/18, 33 %), followed by CTNNB1 (2/18, 11 %) and BRAF (1/18, 5.6 %). One patient had both NRAS and CTNNB1 mutations. Clinical outcomes did not differ significantly between those with and without genetic mutations. NRAS mutations were associated with relatively higher T classification and worse survival rates, although the differences were not significant. The nuclear translocation of β-catenin was detected in both tumors with CTNNB1 mutations. The amino acid change in the BRAF mutation was K601R in exon 15. In the current study, no BRAF V600 mutations were detected. Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.


DNA conformation and chromatin organization of a d(CA/GT)30 sequence cloned in SV40 minichromosomes.
The alternating DNA sequence d(CA/GT)n is known to adopt the left-handed Z-form in negatively supercoiled DNA in vitro. This element represents a significant fraction of the highly repeated DNA sequences found in eukaryotic genomes. We have cloned an alternating d(CA/GT)30 sequence into SV40 minichromosomes at the unique HpaII restriction site which occurs in the transcriptional leader region of the viral late genes. By comparing the linkage differences of topoisomers obtained from viral DNA with or without the d(CA/GT)30 insert, at various stages of the lytic cycle, we conclude that this sequence does not predominate in the Z-form in vivo. Furthermore, we find that the d(CA/GT)30 sequence is packaged into nucleosomal core particles and the region of the minichromosomes which contain the d(CA/GT)30 sequence is organized as nucleosomes.


Spectroscopic and reactive characterization of mixed-metal Fe-Cr trimer nodes in metal-organic framework MIL-100.
Metal-organic framework MIL-100 is synthesized featuring heterometallic Fe and Cr M3O nodes where mixing of the metals within the nodes is evidenced using a combination of in situ IR spectroscopy, NO titrations, and CO oxidation kinetics. Reactivity data indicate distinctive properties of the bimetallic nodes.


A Novel Means-End Problem-Solving Assessment Tool for Early Intervention: Evaluation of Validity, Reliability, and Sensitivity.
To evaluate validity, reliability, and sensitivity of the novel Means-End Problem-Solving Assessment Tool (MEPSAT). Children with typical development and those with motor delay were assessed throughout the first 2 years of life using the MEPSAT. MEPSAT scores were validated against the cognitive and motor subscales of the Bayley Scales of Development. Intra- and interrater reliability, developmental trends, and differences among groups were evaluated. Changes in MEPSAT scores positively related to changes in Bayley scores across time for both groups of children. Strong intra- and interrater reliability was observed for MEPSAT scoring across all children. The MEPSAT was sensitive to identify change across time and differences in problem-solving among children with varying levels of motor delay. The MEPSAT is supported by validity and reliability evidence and is a simple tool for screening early problem-solving delays and evaluating change across time in children with a range of developmental abilities. What this adds to the evidence: The novel MEPSAT is supported by validity and reliability evidence. It is sensitive to detect problem-solving differences among young children with varying motor ability and to capture changes in problem-solving across time. It requires minimal equipment and time to administer and score and, thus, is a promising tool for clinicians to screen for early problem-solving delays or to track intervention progress in young children with or at risk for problem-solving delays.


Hereditary Syndromes in Neuroendocrine Tumors.
Oncologists should be able to discern the salient clinical features of the most common germline mutations that give rise to neuroendocrine tumors. Astute recognition of an index patient affected by a hereditary syndrome can lead to a "tip-of-the-iceberg" phenomenon whereby their entire kindred can then be proactively monitored and managed potentially with substantial reduction of morbidity and mortality. Through careful history-taking, as well as thoughtful assimilation of findings from the physical exam, biochemical laboratories, scans, and pathology reports, the clinician can spot phenotypic clues that distinguish these familial patterns from sporadic cases of tumorigenesis.


Influence of malaria endemicity and tuberculosis prevalence on COVID-19 mortality.
Regarding severe acute respiratory syndrome coronavirus 2, it is known that a substantial percentage of the adult population does not become infected when exposed to this novel coronavirus. Several studies provide an initial indication of the possible role of pre-existing immunity, whether cross-immunity or not. The possible role of latent tuberculosis (TB) and malaria has been suggested to create innate cross heterogeneous immunity. In this study, we looked for the influence of these factors on coronavirus disease 2019 (COVID-19) mortality in malaria-endemic countries. Eighty malaria-endemic countries were enrolled in this cross-sectional study. Data subjected to testing included TB prevalence, Bacillus Calmette-Guérin (BCG) vaccine coverage, malaria incidence, and COVID-19 mortality. Hierarchical multiple regression type of analysis was used for data analyses. TB prevalence per 100,000 population standardized to BCG coverage rates was taken as a direct factor in the test. Malaria incidence per 1000 population was considered an intermediate factor. The outcome was COVID-19 mortality per million population. The results showed with robust statistical support that standardized TB prevalence was significantly associated with reduced COVID-19 mortality. Malaria had an additional effect in reducing COVID-19 mortality, with a highly significant association. Malaria and standardized TB prevalence are statistically significant factors associated negatively with COVID-19 mortality.


The Mediating Role of Meaning in the Association between Stress and Health.
Stress is a common feature of life and has routinely been linked with negative health outcomes. However, meaning has been identified as a possible buffer against stress. The purpose of the current study was to examine whether the relationship between stress and health was mediated by meaning in life. Drawing from Wave 1 of the Landmark Spirituality and Health Study, a nationally representative sample of adults, participants (N = 1871) reported their level of stress in the past 12 months, current meaning in life, health (measured as minor symptoms, major conditions, and overall health), and provided a blood sample for biomarker of immune system functioning (i.e., presence of Epstein-Barr virus antibodies). Results revealed an indirect effects model in which stress was inversely associated with meaning. Higher meaning was related to better self-reported health (across minor, major, and overall health measures), which, in turn, was associated with better immune system functioning. These findings suggest that part of the negative effect of stress on health is accounted for by reduced meaning.


Anatomically correct three-dimensional coronary artery reconstruction using frequency domain optical coherence tomographic and angiographic data: head-to-head comparison with intravascular ultrasound for endothelial shear stress assessment in humans.
To develop a methodology that permits accurate 3-dimensional (3D) reconstruction from FD-OCT and angiographic data enabling reliable evaluation of the ESS distribution, and to compare the FD-OCT-derived models against the established models based on angiography/IVUS. Fifteen patients (17 coronary arteries) who underwent angiography, FD-OCT and IVUS examination during the same procedure were studied. The FD-OCT and IVUS lumen borders were placed onto the 3D luminal centreline derived from angiographic data. Three-dimensional geometry algorithms and anatomical landmarks were used to estimate the orientation of the borders appropriately. ESS was calculated using computational fluid dynamics. In 188 corresponding consecutive 3-mm segments, FD-OCT- and IVUS-derived models were highly correlated for lumen area (r=0.96) and local ESS (r=0.89) measurements. FD-OCT-based 3D reconstructions had a high diagnostic accuracy for detecting regions exposed to proatherogenic low ESS identified on the IVUS-based 3D models, considered as the gold standard (receiver operator characteristic area under the curve: 94.9%). FD-OCT-based 3D coronary reconstruction provides anatomically correct models and permits reliable ESS computation. ESS assessment in combination with the superior definition of plaque characteristics by FD-OCT is expected to provide valuable insights into the effect of the haemodynamic environment on the development and destabilisation of high-risk plaques.


Using a diagnostic model based on routine laboratory tests to distinguish patients infected with SARS-CoV-2 from those infected with influenza virus.
The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice. Between January 2018 and March 2020, 1,027 NCPP and 1,140 IP were recruited from Tongji hospital. Routine blood examination, biochemical indicators and coagulation function analysis were simultaneously performed in all participants. There was no sex predominance in NCPP. The NCPP were frequently encountered in the sixth and seventh decades of life. The mean age of NCPP (56±16 years) was higher than IP (47±17 years), but without statistical difference. Although most results of routine laboratory tests between NCPP and IP had no significant differences, some laboratory tests showed an obvious change in NCPP. It was observed that NCPP had significantly decreased white blood cells, alkaline phosphatase and d-dimer compared with IP. However, the results of lactate dehydrogenase, erythrocyte sedimentation rate and fibrinogen were significantly increased in NCPP compared with IP. The diagnostic model based on a combination of 18 routine laboratory indicators showed an area under the curve of 0.796 (95% CI, 0.777-0.814), with a sensitivity of 46.93% and specificity of 90.09% when using a cut-off value of 0.598. Some routine laboratory results had statistical difference between NCPP and IP. A diagnostic model based on a combination of routine laboratory results provided an adjunct approach in the differential diagnosis between NCPP and IP.


A simplified estimate of the effective reproduction number R t using its relation with the doubling time and application to Italian COVID-19 data.
A simplified method to compute R t , the effective reproduction number, is presented. The method relates the value of R t to the estimation of the doubling time performed with a local exponential fit. The condition R t = 1 corresponds to a growth rate equal to zero or equivalently an infinite doubling time. Different assumptions on the probability distribution of the generation time are considered. A simple analytical solution is presented in case the generation time follows a gamma distribution.


National Trends in Transplantation-Associated Intensive Care Unit Admission in South Korea From 2010 to 2019.
We aimed to investigate the mortality and associated factors among patients admitted to the intensive care unit (ICU) after transplantation in South Korea. The South Korean National Health Insurance Service database was used as the data source. All adult patients (age ≥18 years) who were admitted to the ICU for organ transplantation-related causes from January 1, 2010 to December 31, 2019 (10 years) were included. Transplantation-associated ICU admissions were defined as admissions to the ward and ICU after transplantation or to the ICU before transplantation. A total of 23,994 ICU admissions after transplantation were included in the analysis (mean [SD] age: 52.7 [10.7] years; men: 67.0%; kidney transplantation: n = 9638; liver transplantation: n = 12,196; heart and/or lung transplantation: n = 1829; pancreas or small bowel transplantation: n = 331). Transplantation-associated ICU admissions gradually increased from 1666 in 2010 to 3014 in 2019. The 1-year mortality rates were 21.2%, 12.3%, 4.2%, and 3.0% after heart and/or lung, liver, pancreas or small bowel, and kidney transplantation, respectively. Invasive life support procedures during ICU stay, comorbidities, and older age were potential risk factors for 1-year mortality after transplantation. Transplantation-associated ICU admissions gradually increased from 2010 to 2019 in South Korea. The 1-year mortality rate after transplantation was the highest in the heart and/or lung transplantation group, followed by those of the liver, pancreas or small bowel, and kidney transplantation groups.


Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma: Early clinical experience.
Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u-HCC), changes in hepatic function during therapy have yet to be reported. This retrospective clinical study aimed to elucidate early responses to Atez/Bev. From September 2020 to April 2021, 171 u-HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin-bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively. In initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR-6W/DCR-6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR-6W/DCR-6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post-progression treatment following lenvatinib (ORR-6W/DCR-6W = 7.7%/79.5%), for which no known effective post-progression treatment has been established. In 111 patients who underwent a 6-week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (-2.525 ± 0.419 vs -2.323 ± 0.445, p < .001), but then recovered at 6-weeks (-2.403 ± 0.452) as compared to 3-weeks (p = .001). During the observation period, the most common adverse events were appetite loss (all grades) (12.3%), general fatigue/hypertension (all grades) (11.1%, respectively), and urine protein (all grades) (10.5%). Atez/Bev might have therapeutic potential not only as first but also later-line treatment of existing molecular target agents. In addition, this drug combination may have less influence on hepatic function during the early period, as the present patients showed a good initial therapeutic response.


Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases.
The catalytic activity of Syk-family tyrosine kinases is regulated by a tandem Src homology 2 module (tSH2 module). In the autoinhibited state, this module adopts a conformation that stabilizes an inactive conformation of the kinase domain. The binding of the tSH2 module to phosphorylated immunoreceptor tyrosine-based activation motifs necessitates a conformational change, thereby relieving kinase inhibition and promoting activation. We determined the crystal structure of the isolated tSH2 module of Syk and find, in contrast to ZAP-70, that its conformation more closely resembles that of the peptide-bound state, rather than the autoinhibited state. Hydrogen-deuterium exchange by mass spectrometry, as well as molecular dynamics simulations, reveal that the dynamics of the tSH2 modules of Syk and ZAP-70 differ, with most of these differences occurring in the C-terminal SH2 domain. Our data suggest that the conformational landscapes of the tSH2 modules in Syk and ZAP-70 have been tuned differently, such that the autoinhibited conformation of the Syk tSH2 module is less stable. This feature of Syk likely contributes to its ability to more readily escape autoinhibition when compared to ZAP-70, consistent with tighter control of downstream signaling pathways in T cells.


Quasi-elastic laser light scattering from solutions and gels of hemoglobin S.
Quasi-elastic light scattering has been used to examine solutions and gels of deoxyhemoglobin S. The autocorrelation function is found to decay with a characteristic exponential relaxation which can be ascribed to the diffusion of monomer (64,000 molecular weight) hemoglobin S molecules. In the absence of polymers, the relaxation time is in good agreement with previous measurements of the diffusion coefficient for solutions of normal human hemoglobin. In the presence of the polymer phase, a large (greater than 200-fold) increase in the scattered intensity is observed but no contribution to the decay of the autocorrelation function from the motion of the aligned polymer phase can be detected. Heterodyning between the time-independent scattering amplitude from the polymers and the time-dependent scattering of the diffusing monomers results in a twofold increase in the relaxation time arising from monomer diffusion.


Patient Selection for Oesophagectomy: Impact of Age and Comorbidities on Outcome.
Surgical resection of oesophageal cancer is a major procedure with potential for significant morbidity and mortality. Patient selection can be challenging, as operative benefit must be balanced against risk and impact on quality of life. This study defines modern trends in patient selection, and evaluates the impact of age, stage, and comorbidities on complications and survival following oesophagectomy, in a tertiary Australian experience. Data were compiled across two 15-year operative eras ('Era 1': 1981-1995; and 'Era 2': 1996-2010), with patients followed minimum 3 years. A total of 180 unselected records were analysed (powered for a relative hazard ratio of 0.5). Analyses defined patient selection trends, and for Era 2, the impact of age, comorbidities (Charlson score), and disease (T/N stage) on complications (Clavien-Dindo grade) and survival (Kaplan-Meier). A further sub-analysis was conducted with data divided into three 10-year periods. The age of operated patients increased from Era 1 to 2 (mean+5 years; P<0.001), but survival and complication rates were unchanged, including in patients≥75 years (P>0.5). In Era 2, reflecting recent practice, survival duration matched T/N stage (P<0.001) but was independent of age at surgery (P=0.56) and comorbidity score (P=0.78). However, grade of worst post-operative complication, including death (rate: 3.8%), was correlated with both age (P<0.01) and comorbidity score (P<0.01). Older patients are now undergoing oesophagectomy. However, if they are selected appropriately, then older patients and those with comorbidities can expect similar stage-matched survival outcomes to younger fitter patients, despite their higher operative risk. Poor outcomes persist in patients with locally advanced disease, and selection in this group should prioritise quality of life.


Association between prescription drug benefit and hospital readmission rates.
To determine whether primary care medicine clinic (PCMC) patients with a prescription drug benefit were associated with a lower rate of hospital readmissions. This study was a retrospective, single-center, cohort study of PCMC patients who had at least 1 hospital readmission in 2011. Eligible patients were divided into 2 groups: patients without prescription drug benefits and patients with prescription drug benefits. Three hundred fifty-two patients met our inclusion criteria. The number of hospital readmissions for patients with a prescription drug benefit was higher than those with no prescription drug benefit (2.453 ± 2.49 vs 1.88 ± 1.91; P = .052). The length of index admission and the length of hospital readmission in days were higher in patients with no prescription drug benefits (index admission, 5.29 ± 6.38 vs 4.59 ± 4.50; P = .428) (readmission, 5.31 ± 5.90 vs 4.48 ± 4.33, P = .166). The number of days to readmission was higher in those with drug benefits (58.12 ± 63.54 vs 53.39 ± 53.47; P = .316). When patient data were separated by CCI scores, it was noted that patients with pharmacy benefits had significantly more hospital readmissions in each CCI score category except for patients with a CCI of 6. Although not statistically significant, patients with prescription drug benefits had more hospital readmissions but shorter hospital lengths of stay. Significant data linking hospital readmissions and prescription insurance benefits, if found in future studies, would provide helpful guidance to health care systems.


Preparation of reference strains for validation and comparison of mycoplasma testing methods.
To optimize growth conditions for preparation of stocks of mycoplasma reference strains to obtain highly viable and disperse samples with low ratios of genomic copy (GC) number to that of colony forming units (CFU). These stocks are required for assessment of relative limits of detection (LOD) of alternative nucleic acid testing (NAT)-based methods in comparison to the conventional microbiological methods. A kinetics study was used to assess the changes in ratios between the numbers of GC and CFU at different growth phases of six different mycoplasma cultures Acholeplasma laidlawii, Mycoplasma gallisepticum, Mycoplasma arginini, Mycoplasma fermentans, Mycoplasma orale and Mycoplasma pneumoniae. All tested mycoplasmas demonstrated low GC/CFU ratios (≤ 10) within the log and early stationary growth phases. A significant increase in GC/CFU ratios was observed at the very late stationary and death phases, when the titre of cultures has declined. Similar patterns of GC/CFU profiles were observed for A. laidlawii and Myc. gallisepticum co-cultured with suspension of Chinese hamster ovary (CHO) cells. Tested mycoplasma strains harvested at the exponential-early stationary phases of growth demonstrated the lowest GC/CFU ratios and low propensity to form filamentous structures or aggregates under proposed conditions and can be used for the preparation of a mycoplasma reference panel for methods comparability study. This study shows that the preparation and use of viable mycoplasma reference strains with low CG/CFU ratios is the most reliable way to adequately evaluate the LOD of alternative NAT-based mycoplasma testing methods.


Towards Chinese clinical named entity recognition by dynamic embedding using domain-specific knowledge.
The task of electronic medical record named entity recognition (NER) refers to automatically identify all kinds of named entities in the medical record text. Chinese clinical NER remains a major challenge. One of the main reasons is that Chinese word segmentation will lead to the wrong downstream works. Besides, existing methods only use the information of the general field, not consider the knowledge from field of medicine. To address these issues, we propose a dynamic embedding method based on dynamic attention which combines features of both character and word in embedding layer. Domain knowledge is provided by word vector trained by domain dataset. In addition, spatial attention is added to enable the model to obtain more and more effective context encoding information. Finally, we conduct extensive experiments to demonstrate the effectiveness of our proposed algorithm. Experiments on CCKS2017 and Common dataset shows that the proposed method outperforms the baseline.


Minimization of free radical damage by metal catalysis of multivitamin/multimineral supplements.
Multivitamin/multimineral complexes are the most common dietary supplements. Unlike minerals in foods that are incorporated in bioorganic structures, minerals in dietary supplements are typically in an inorganic form. These minerals can catalyze the generation of free radicals, thereby oxidizing antioxidants during digestion. Here we examine the ability of a matrix consisting of an amino acid and non-digestible oligosaccharide (AAOS) to blunt metal-catalyzed oxidations. Monitoring of ascorbate radical generated by copper shows that ascorbate is oxidized more slowly with the AAOS matrix than with copper sulfate. Measurement of the rate of oxidation of ascorbic acid and Trolox® by catalytic metals confirmed the ability of AAOS to slow these oxidations. Similar results were observed with iron-catalyzed formation of hydroxyl radicals. When compared to traditional forms of minerals used in supplements, we conclude that the oxidative loss of antioxidants in solution at physiological pH is much slower when AAOS is present.


Non-invasive papillary carcinoma of the bladder associated with carcinoma in situ.
We evaluated 129 patients with low grade, low stage transitional cell carcinoma of the bladder with a minimum followup of 5 years. In addition to the phenomena recognized as indicators of a serious clinical problem (grade greater than I, rapid recurrence, multiple tumors and lamina propria invasion) the identification of carcinoma in situ and/or atypia in normal, incidentally resected mucosa adjacent to the tumor was found to be a positive predictor for subsequent muscle invasion. Ten of 12 patients with carcinoma in situ and 9 of 25 patients with atypia were among 39 who experienced invasion.


Feasibility of predicting allele specific expression from DNA sequencing using machine learning.
Allele specific expression (ASE) concerns divergent expression quantity of alternative alleles and is measured by RNA sequencing. Multiple studies show that ASE plays a role in hereditary diseases by modulating penetrance or phenotype severity. However, genome diagnostics is based on DNA sequencing and therefore neglects gene expression regulation such as ASE. To take advantage of ASE in absence of RNA sequencing, it must be predicted using only DNA variation. We have constructed ASE models from BIOS (n = 3432) and GTEx (n = 369) that predict ASE using DNA features. These models are highly reproducible and comprise many different feature types, highlighting the complex regulation that underlies ASE. We applied the BIOS-trained model to population variants in three genes in which ASE plays a clinically relevant role: BRCA2, RET and NF1. This resulted in predicted ASE effects for 27 variants, of which 10 were known pathogenic variants. We demonstrated that ASE can be predicted from DNA features using machine learning. Future efforts may improve sensitivity and translate these models into a new type of genome diagnostic tool that prioritizes candidate pathogenic variants or regulators thereof for follow-up validation by RNA sequencing. All used code and machine learning models are available at GitHub and Zenodo.


Racial differences in the prevalence of intraocular lens implants in the United States.
We generated population-based estimates of the prevalence of intraocular lens implants by using the 1988 Medical Device Implant Supplement to the National Health Interview Survey. This national survey of a probability sample of the civilian noninstitutionalized United States population comprised 47,485 households and 122,310 persons. To produce national projections, we used survey respondent-reported data based on 1,941 reported intraocular lenses in 1,337 persons. Projected to the United States population, an estimated 2.6 million people had a total of 3.8 million lens implants. The predominant reason for the implant was cataract. The intraocular lens replacement rate was 0.9%. The use of intraocular lens implants was statistically significantly different from the general population in persons with the following socioeconomic characteristics: age (65 years or older), race (white), gender (female), annual family income (less than $20,000, although more commonly at or above the poverty threshold), and education (less than high school). The prevalence rates per 1,000 persons according to age were as follows: 0.3 for persons 44 years old or younger, 9.9 for persons 45 to 64 years old, 33.3 for persons aged 65 to 69 years, 63.5 for persons aged 70 to 74 years, and 113.5 for persons 75 years old or older.(ABSTRACT TRUNCATED AT 250 WORDS)


Nonmedically indicated induction in morbidly obese women is not associated with an increased risk of cesarean delivery.
The prevalence of morbid obesity (body mass index ≥40 kg/m2) in women aged 20-39 years was 7.5% in 2009 through 2010. Morbid obesity is associated with an increased risk of stillbirth compared with normal body mass index, especially >39 weeks' gestation. The data regarding increased risk of cesarean delivery associated with nonmedically indicated induction of labor compared to expectant management in morbidly obese women are limited. We sought to compare the cesarean delivery rate of nonmedically indicated induction of labor with expectant management in morbidly obese women without other comorbidity. This was a retrospective cohort study from the Consortium on Safe Labor of morbidly obese women with singleton, cephalic gestations without previous cesarean, chronic hypertension, or gestational or pregestational diabetes between 37 0/7 and 41 6/7 weeks' gestation. We examined maternal outcomes including cesarean delivery, operative delivery, third- or fourth-degree laceration, postpartum hemorrhage, and composite maternal outcome (any of: transfusion, intensive care unit admission, venous thromboembolism). We also examined neonatal outcomes including shoulder dystocia, macrosomia (>4000 g), neonatal intensive care unit admission, and composite neonatal outcome (5-min Apgar score <5, stillbirth, neonatal death, or asphyxia or hypoxic-ischemic encephalopathy). Adjusted odds ratios with 95% confidence intervals were calculated, controlling for maternal characteristics, hospital type, and simplified Bishop score. Analyses were conducted at early and full term (37 0/7 to 38 6/7 and 39 0/7 to 40 6/7 weeks' gestation, respectively). Women who delivered between 41 0/7 and 41 6/7 weeks' gestation were included as expectant management group. Of 1894 nulliparous and 2455 multiparous morbidly obese women, 429 (22.7%) and 791 (32.2%) had nonmedically indicated induction, respectively. In nulliparas, nonmedically indicated induction was not associated with increased risks of cesarean delivery and was associated with decreased risks of macrosomia (2.2% vs 11.0%; adjusted odds ratio, 0.24; 95% confidence interval, 0.05-0.70) at early term and decreased neonatal intensive care unit admission (5.1% vs 8.9%; adjusted odds ratio, 0.59; 95% confidence interval, 0.33-0.98) at full term compared with expectant management. In multiparas, nonmedically indicated induction compared with expectant management was associated with a decreased risk of macrosomia at early term (4.2% vs 14.3%; adjusted odds ratio, 0.30; 95% confidence interval, 0.13-0.60), cesarean delivery at full term (5.4% vs 7.9%; adjusted odds ratio, 0.64; 95% confidence interval, 0.41-0.98), and composite neonatal outcome (0% vs 0.6%; adjusted odds ratio, 0.10; 95% confidence interval, <.01-0.89) at full term. In morbidly obese women without other comorbidity, nonmedically indicated induction was not associated with an increased risk of cesarean delivery.


The potential toxicity of polystyrene nanoplastics to human trophoblasts in vitro.
Nanoplastics (NPs), the emerging contaminants in recent years, widely distributed in the environment and are bioaccumulated and biomagnified in organisms through food chain. A growing number of studies have detected plastic particulates in human placenta and blood. However, few studies have focused on their effects during human pregnancy. Herein, human trophoblast HTR-8/Svneo cells were used to evaluate the effects and the possible mechanism of 100-nm polystyrene NPs on placental trophoblasts at the maternal-fetal interface. The results showed that NPs entered the trophoblastic cytoplasm, decreased cell viability, caused cell cycle arrest, reduced the cell migration and invasion abilities, increased level of intracellular reactive oxygen species and the production of proinflammatory cytokines (TNF-α and IFN-γ) in a dose-dependent manner. Furthermore, global transcriptome sequencing (RNA-Seq) was performed on HTR-8/Svneo cells with or without 100 μg/mL PS-NP exposure for 24 h. A total of 344 differentially expressed genes were detected. The gene functions for regulation of leukocyte differentiation, response to stimulus, cell cycle, apoptotic process, and cell adhesion were enriched. Thyroid hormone, Hippo, TGF-β and FoxO signaling pathways were activated. Collectively, our data provided evidences for the adverse consequences of NPs on the biological functions of trophoblasts, which provided new insights into the potential trophoblast toxicity of NPs in mammals.


Co-occurrence of cfr-mediated linezolid-resistance in ST398 LA-MRSA and non-aureus staphylococci isolated from a pig farm.
Linezolid resistance, mediated by the cfr gene, which confers resistant phenotypes to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antimicrobials, has emerged in S. aureus and non-aureus staphylococci (NAS). Moreover, due to the transferable potential via plasmids, the spread of cfr among staphylococci is of great concern. In the present study, we investigated the prevalence of cfr-mediated linezolid resistance in ST398 methicillin-resistant S. aureus (MRSA) and NAS strains isolated from a pig farm. Among the 26 staphylococci isolates collected from a pig farm, 14 cfr-harboring ST398 MRSA and NAS (S. epidermidis, S. pasteuri, S. cohnii, and S. rostri) strains were resistant to linezolid and also carried the fexA gene. Comparative genome analysis of cfr-carrying linezolid-resistant ST398 MRSA and NAS (S. pasteuri, S. cohnii, and S. epidermidis) strains revealed that the segments harboring cfr in different staphylococcal strains showed ≥ 99 % sequence identity and the corresponding region containing the cfr, fexA, and Tn558 elements were located in a 38-kb plasmid, designated pSA12 of ST398 MRSA. These observations indicate that the cfr-carrying plasmids and/or fragments may be disseminated among staphylococci in a pig farm and possibly transmitted to staphylococci of human origin, subsequently posing a threat to public health. This is the first report of the co-existence of cfr in linezolid-resistant ST398 MRSA and NAS isolated from a pig farm in South Korea.


Historical perspectives in critical care medicine: blood transfusion, intravenous fluids, inotropes/vasopressors, and antibiotics.
Significant progress in critical care medicine has been the result of tireless observation, dedicated research, and well-timed serendipity. This article provides a historical perspective for four meaningful therapies in critical care medicine: blood transfusion, fluid resuscitation, vasopressor/inotropic support, and antibiotics. For each therapy, key discoveries and events that have shaped medical history and helped define current practice are discussed. Prominent medical and social pressures that have catalyzed research and innovation in each domain are also addressed, as well as current and future challenges.


The role of positron emission tomography in oncology and other whole-body applications.
Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth.


[Indications for surgical treatment of carpal acroparesthesia. Results at the orthopedic hospital of Florence University].
The indication for surgical intervention is established if a conservative treatment gives unsatisfactory or no success, if the symptoms are acute and severe, the course progressive and if there are neurological attacks. The author reports favorable results of operation in the primary forms: 94.4% pure acroparesthesias, 92.4% in acroparesthesias with neurological symptoms. About 84.6% success was obtained in the posttraumatic forms.


On the use and misuse of genomic and neuroimaging science in forensic psychiatry: current roles and future directions.
Dramatic advances in the understanding of the neurobiological bases of human behavior have prompted excitement and controversy surrounding the ethical, legal, and social applications of this knowledge. The authors critically examine the promise and challenges of integrating genomic and neuroimaging techniques into legal settings. They suggest criteria for enhancing the viability of incorporating these data within a legal context and highlight several recent developments that may eventually allow genetic and neuroimaging evidence to meet these criteria and play a more prominent role in forensic science and law.


White matter involvement in anoxic encephalopathy in adults.
The computed tomographic findings in two adult patients with acute and delayed anoxic encephalopathy affecting predominantly the cerebral white matter are presented.


Screening for health-related quality of life in children and adolescents: Optimal cut points for the KIDSCREEN-10 for epidemiological studies.
Generic measures of health-related quality of life are important in pediatrics. Here, we try to establish optimal cut points for the self-report and parental-report versions of the KIDSCREEN-10. We re-analyzed data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study. In total, data from 2566 children, 2136 younger adolescents, and 2740 older adolescents were used. The KIDSCREEN-10 was contrasted to three different anchors: the strength and difficulties questionnaire, self-rated general health, and chronic diseases. A kernel-based method and bootstrapping were used to determine the optimal cut points and their variability. We found large differences in HRQoL between children with vs. without mental health problems but there is only medium-to-small differences in HRQoL between children with vs. without chronic diseases and children with self-rated good vs. poor physical health. Acceptable levels of classification accuracy were found in relation to mental health problems for all versions (AUCs between 0.77 and 0.79), but only for the parental-report version in relation to general health and for no version in relation to chronic diseases. Cut points identified as optimal differed systematically between parental-report versions (cut point = 41.13) and self-report for younger (cut point = 42.52) and older adolescents (cut point = 40.29). The results aid the interpretation of KIDSCREEN-10 in epidemiological studies. Specifically, we suggest a cut point of 41 should be used to interpret the parental-report version of the KIDSCREEN and 40 and 42, respectively, for young and older adolescents.


Circumcision: its nature and practice among some ethnic groups in southern Nigeria.
A questionnaire survey carried out in five rural communities in mid-southern Nigeria documents the degree and range of male and female circumcision practices among Bini, Esan, Etsako, Ijaw and Ukwuani ethnic groups. Two hundred and eighty adults (154 males and 126 females) reported on themselves and their 1417 children (757 sons and 660 daughters). Circumcision of both sexes remains widely practised, though the timing of the event and extent of surgery show wide variations among, and sometimes, within ethnic groups. The commonest reason for the practice is a strong desire to continue ethnic traditions. Altered sexual urge for women, increased sexual performance for men, protection of baby's health, as well as general reproductive and aesthetic consideration are also important reasons. Traditional surgeons usually perform the operation and few complications were reported to be associated with the procedure in either sex. Female circumcision in this area is not as destructive or mutilating as in some Arabic and East African cultures. Because of the relatively low rate of complications a major campaign against circumcision in these areas does not at present seem warranted.


Astrocytic development in fetal parietal cortex grafted to cerebral and cerebellar cortex of immature rats.
Pieces of cortex cerebri anlage were dissected out from 16- to 17-day-old fetuses and transplanted to the cortical and cerebellar regions of 5- to 6-day-old rat pups. Twelve animals with grafts in the cortical region and 5 animals with grafts in the cerebellar region were studied 1.5-4 months later. Cresyl violet stained sections revealed no gross difference in either cell morphology, cell density or cell distribution between grafts in the two locations. A molecular layer-like zone was present on all free surfaces of the grafts, whether facing a ventricle or the meninges. The astrocytic development was studied using immunohistochemistry with antibodies against glial fibrillary acidic protein, (GFA), and the S-100 protein. Both antibodies visualized starshaped astrocytes and perivascular membranes surrounding blood vessels. Semi-quantitative measurements as well as computerized image analysis showed that the total amount of GFA-like immunoreactivity was much higher in both types of grafts than in corresponding host cortex cerebri. No differences in amount of S-100-like immunoreactivity could be demonstrated. As S-100 is thought to be a more general astrocytic marker than GFA, this suggests that the difference in GFA-like immunoreactivity is due mainly to an increased amount of GFA within the individual astrocytes. It is concluded that grafts of fetal cortex cerebri pieces to the CNS of young hosts develop a profound astrocytic reaction characterized by an increased amount of GFA-like immunoreactivity.


Implementation of pharmacist recommendations in patients with type 2 diabetes enrolled in an employer-sponsored health plan.
The new, employee health plan (EHP) focused, population health initiative was established at Atrium Health Wake Forest Baptist in October 2020. The initiative's goals are to reduce health care costs and optimize patient care by providing patient-specific recommendations to help manage chronic disease states in the ambulatory care setting. This project's purpose is to quantify and categorize pharmacist recommendations implemented and not implemented. Describe the implementation of pharmacist recommendations in a new, population health program. Eligible patients: >18 years of age, diagnosed with type 2 diabetes, baseline HbA1c > 8%, and enrolled in the EHP. Patients were identified retrospectively through an electronic health record report. The primary endpoint assessed the proportion of pharmacist recommendations implemented. Interventions implemented and not implemented were categorized and reviewed for timely optimization of patient care and quality improvement. Overall, 55.7% of pharmacist recommendations were implemented. The most common reason recommendations were not implemented was that they were not addressed by the provider. The most common pharmacist recommendation was a drug therapy addition. Recommendations were implemented in a median time of 44 days. Over half of pharmacist recommendations were implemented. Provider communication and awareness was identified as a barrier for this new initiative. Increasing provider education and advertisement of pharmacist services should be considered to increase future implementation rates. The project identified a need for optimization of timely patient care by prioritizing patient charts prior to their next applicable provider visit.


A case series sharing novel experience of treating viral pandemic cases of morbid, mid aged, mild, moderate & severe grade with only Ayurvedic Medicines.
In ongoing viral pandemic named as COVID-19 also Severe Acute Respiratory illness (SARI) or Flue Like illness (FLI) reported surging in many cities of India and many of the patients opted for traditional medicine, in spite of they have been given a option of contemporary line of treatment instructed by health authorities, they opted to take traditional indian medicine that is Ayurvedic medicine. Present case series is a same novel experience of early diagnosing and treating mid aged, morbid individuals who took only Ayurvedic treatment and could get out of the disease without any complications. This case series had 10 mid aged, morbid patients with maximum symptoms of COVID-19 disease and their hemogram and CRP was suggestive of moderate to severe type COVID-19/FLI/SARI. They were diagnosed by contemporary methods of pathology and treated with Ayurvedic classical medicines Tamra Sinduradi Yoga and Bhunimbadi Kwath for 20 days along with continuing the medicines for their ongoing morbidities. All 10 patients showed recoveries without any complications, they reduced their all symptoms, drastic reduction in their CRP and corrections in their hemograms were observed and also they showed any complications neither physically nor in their pathological tests. Hence it can be concluded that early diagnosis and treating it with Ayurvedic medicine can manage viral pandemic issue in a very successful way.


Predictors of sarcopenia in young hospitalized patients living with HIV.
The prevalence of sarcopenia in hospitalized people living with HIV is underdiagnosed, as assessment instruments are not always available. This study aimed to identify factors related to sarcopenia, correlating their anthropometric and clinical markers in hospitalized people living with HIV. This was an observational cross-sectional clinical study, carried out from September 2018 through October 2019. Handgrip strength, muscle mass index, calf circumference and gait speed test were evaluated in recruited patients within three days of hospital admission. The sample consisted in 44 patients, mostly men (66%), black (68%), young adults (41.65±12.18 years) and immunodeficient (CD4 cell count 165 cells/mm3 [34.25-295.5]). Sarcopenia was present in 25% of the sample. Calf circumference showed a significant correlation with CD4 cell count and viral load (p<0.05) while handgrip strength and gait speed test did not. Calf circumference>31cm and gait speed test>0.8m/s reduced the chance of sarcopenia by 60% (OR=0.396 [-1.67 to -0.18]; p<0.05) and 98% (OR=0.02 [-8.16 to 0.13]; p<0.05) respectively. Calf circumference>31cm and gait speed test>0.8m/s are associated with a reduced chance of sarcopenia in hospitalized HIV patients.


The ribosomal proteins of drosophila melanogaster. IV. Characterization by two-dimensional gel electrophoresis of the ribosomal proteins from nine postembryonic developmental stages.
The ribosomal proteins from nine postembryonic developmental stages of Drosophila melanogaster were analyzed by two-dimensional gel electrophoresis. The ribosomal protein patterns thus obtained constitute reliable control patterns against which any potential mutant can be compared. Furthermore, the results provide increased evidence for a qualitative and quantitative change in the protein composition of the total population of ribosomes which occurs mainly during the third larval instar. Two acidic proteins were found, which may be homologous with rat liver ribosomal proteins L40/L41 and E. coli proteins L7/L12.


Seed mass of angiosperm woody plants better explained by life history traits than climate across China.
Seed mass is a basic trait in studies of functional ecology. Examining how seed mass is affected by biotic and abiotic factors could improve our understanding of ecological strategies in plants. Here we examined the relationships of seed mass with 13 climate variables and seven life history traits, and partitioned the relative effects of life history traits vs. climate, based on seed mass data for 1265 woody angiosperm species in China. Our results showed that seed mass decreased with latitude, and most climate variables were positively correlated with seed mass. Geographic seed mass pattern was affected by both energy and water availability in the growing season, but the effect of energy availability was more important. Seed mass was also significantly related to other traits such as growth form, fruit type, dispersal mode, breeding system, leaf habit, fruit development time, and minimum juvenile period, with growth form and dispersal mode being the most closely related traits. Our results showed that climate explained much less variation in seed mass than life history traits, and that phylogeny played an important role in shaping the large-scale patterns of seed mass.


Combining network pharmacology, RNA-seq, and metabolomics strategies to reveal the mechanism of Cimicifugae Rhizoma - Smilax glabra Roxb herb pair for the treatment of psoriasis.
Psoriasis is a prevalent chronic inflammatory skin condition marked by immune cell infiltration and keratinocyte abnormal proliferation. Cimicifugae Rhizoma - Smilax glabra Roxb (CS) herb pair, the main component of Shengma Detoxification Decoction, has been proven effective for the treatment of psoriasis. However, the mechanism is yet to be deciphered. To explore the mechanism of CS for the treatment of psoriasis. The imiquimod-induced psoriasis-like lesion mouse model was used to identify the targets and the molecular mechanisms of CS. Network pharmacology combined with RNA-seq strategy was employed to predict the targets and mechanisms of CS for psoriasis. Metabolomics approaches were used to demonstrate the complexity of CS for the treatment of psoriasis. Finally, a compound-response-enzyme-gene network was constructed based on the multi-omics results to elucidate potential connections. The CS herb pair could significantly improve psoriatic lesions and reduce the inflammatory cell infiltration and proliferation of keratinocytes in skin lesions. Network pharmacology predicted that TNF, JNK, IL-6, and IL-1β could be potential targets. RNA-seq data revealed that CS could significantly regulate genes and signaling pathways associated with Th17 responses, such as IL-36, IL-1β, CCl2, CXCL16, keratin 14, keratin 5, and antimicrobial peptides S100A8 and S100A9 well as MAPK, mTOR, and other signaling pathways. Further experimental data validated that CS treatment remarkably reduced the expression of inflammatory cytokines and factors, such as CCL2, CCL7, IL1F6, IL-17, IL-23, IL-1β, TNF-α, and IL-6, and inhibited the phosphorylation of p38 and ERK1/2. This indicated that CS exerts its therapeutic effect by inhibiting the MAPK signaling pathways. In addition, metabolomic analyses demonstrated that CS treatment improved seven metabolic pathways, these included phenylalanine, tyrosine, pyruvate metabolism, carnitine metabolism, etc. Four key metabolites (L-Arginine, L-Phenylalanine, L-Carnitine, O-Acetylcarnitine) and nine differential genes (CMA1, PCBD2, TPSAB1, TPSB2, etc.) were identified that affected amino acid metabolism, carnitine metabolism, and other pathways contributing to the infiltration of Th17 cells in psoriatic lesions. CS could alleviate IMQ-induced psoriasis-like dermatitis by reducing the expression of cytokines and chemokines mediated by the MAPK pathway, and improved amino acid and carnitine metabolism in vivo. Our study is the first to demonstrate the complex mechanism of CS for the treatment of psoriasis and provides a new paradigm to elucidate the pharmacological effects of Traditional Chinese Medicine (TCM) drugs for psoriasis from multiple perspectives.


Accessory pathway analysis using a multimodal deep learning model.
Cardiac accessory pathways (APs) in Wolff-Parkinson-White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.


The emergency nurse responses to triage interruptions and how these responses are perceived by patients: An observational, prospective study.
Healthcare providers' responses to triage interruptions in the emergency department affect quality of care. The purposes for this study were to (1) Examine the relationship between nurses' response to triage interruption and each of, patients' perceived confidence in nurses' technical skills, perceived competence of triage nurse, and satisfaction with the triage experience, (2) Examine the relationship between nurses' response to triage interruption and nurse demographics. Using an observational, prospective design, this study was conducted in an adult academic level 1 trauma center. Data collection tools were: The Triage Interruptions Assessment Tool, Triage and Provider Satisfaction and Confidence Survey, and Demographic Questionnaire. The number of observed triage interviews is 93. Of them, 66 interviews were interrupted. No significant relationships were found between nurses' response to the interruption and patients' perceived confidence in nurses' technical skills, competence of triage nurse, or satisfaction with triage experience. There were no significant relationships between nurses' response to triage interruptions and nurses' demographics. Triage interruptions in the emergency environment are common and most often result in delays in care. In the current study, this has not been shown to affect patients' satisfaction. Nurses' individual characteristics did not affect their responses to triage interruptions.


Population diversity of Staphylococcus intermedius isolates from various host species: typing by 16S-23S intergenic ribosomal DNA spacer polymorphism analysis.
Twelve 16S-23S ribosomal DNA intergenic spacer (ITS-PCR) types were identified among 57 Staphylococcus intermedius isolates from humans and other animals. Six ITS-PCR types were host specific, and most human and canine strains belonged to the same types (A and J). Pigeon, horse, and mink strains appeared more heterogeneous.


CCAAT/enhancer binding proteins play a role in oriLyt-dependent genome replication during MHV-68 de novo infection.
Murine gammaherpesvirus 68 (MHV-68), a member of the gammaherpesvirus family, replicates robustly in permissive cell lines and is able to infect laboratory mice. MHV-68 has emerged as a model for studying the basic aspects of viral replication and host-virus interactions of its human counterparts. Herpesvirus genome replication is mediated through a cis-element in the viral genome called the origin of lytic replication (oriLyt). A family of transcription factors, CCAAT/enhancer binding proteins (C/EBPs), assists in oriLyt-mediated DNA replication during gammaherpesvirus reactivation. In this study, we examined the role of C/EBPs in gammaherpesvirus DNA replication during de novo infection, using MHV-68 as a model. We found that C/EBP α and β bind to the CCAAT boxes in the MHV-68 oriLyt core region both in vitro and in vivo, as demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. A dominant negative form of C/EBPs significantly impaired the lytic replication efficiency of MHV-68 on both the plasmid and genome levels in a replication assay, indicating that functional C/EBPs are required for maximal MHV-68 genome DNA replication. Collectively, our data demonstrate that C/EBPs interact with the oriLyt core region and play an important role in MHV-68 lytic DNA replication during de novo infection.