Children's contact with their incarcerated parents: research findings and recommendations.
Approximately 1.7 million children have parents who are incarcerated in prison in the United States, and possibly millions of additional children have a parent incarcerated in jail. Many affected children experience increased risk for developing behavior problems, academic failure, and substance abuse. For a growing number of children, incarcerated parents, caregivers, and professionals, parent-child contact during the imprisonment period is a key issue. In this article, we present a conceptual model to provide a framework within which to interpret findings about parent-child contact when parents are incarcerated. We then summarize recent research examining parent-child contact in context. On the basis of the research reviewed, we present initial recommendations for children's contact with incarcerated parents and also suggest areas for future intervention and research with this vulnerable population.


Investigating dielectric spectroscopy and soft sensing for nondestructive quality assessment of engineered tissues.
Non-destructive, inline quality monitoring techniques that can overcome the limitations of traditional, offline assays are essential to support the scale-up production of tissue engineered medical products (TEMP). In this work, we investigate a new soft-sensing approach with non-destructive dielectric spectroscopy (DS) that synergistically utilizes inline sensor data and predictive analytics to estimate unmeasured TEMP quality profiles. First, the performance of DS during the assessment of gelatin methacrylate (GelMA) constructs containing human adipose-derived stem cells was investigated in comparison to a traditional biochemical assay. The effects of two critical biofabrication parameters (photocrosslinking duration and volume of growth media) on a key scalar metric (Δϵ) were determined over 11 days of in vitro culture, where the metric was associated with the permittivity response of cells to alternating electric fields during DS and corresponding cellular metabolic activity. To enable accurate quality prediction while minimizing direct data collection to reduce the risk of cytotoxicity from prolonged exposure to the DS sensor electrodes and electric fields, we then developed a bilinear basis mixed model (BBMM) as a soft sensor. With comprehensive consideration of different variation sources, this model was designed to estimate missing permittivity profiles of constructs based on the measured DS dataset and biofabrication parameters. Results of benchmarking showed that BBMM outperformed state-of-the-art vector-prediction methods from literature in two different missing data estimation mechanisms. The high-accuracy BBMM provides a novel DS-driven soft sensing system as an inline monitoring tool suitable for scaled-up or scaled-out TEMP production systems.


Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma.
Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273-0.997; p = 0.049) when compared with ≤1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229-0.852; p = 0.015) when compared with ≤2. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111-0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140-0.790) for ZNRF3 expression >2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.


MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients.
To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. Colonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted. The miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC. The present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.


Markers of oxidative stress in erythrocytes and plasma during aging in humans.
Aging is an inevitable universal biological process, which can be characterized by a general decline in physiological function with the accumulation of diverse adverse changes and increased probability of death. Among several theories, oxidative stress/free radical theory offers the best mechanistic elucidation of the aging process and other age -related phenomenon. In the present paper , we discuss the aging process and have focused on the importance of some reliable markers of oxidative stress which may be used as biomarkers of the aging process.


The hypereosinophilic syndrome.
The hypereosinophilic syndrome is a spectrum of clinical disorders characterized by leukocytosis and marked eosinophilia without definable cause. Clinical symptoms and radiographic findings are most often due to congestive heart failure, although parenchymal lung infiltrates from the eosinophilia itself may be seen. Four documented cases with chest radiographs are presented.


Silencing circular RNAPTPN12 promoted the growth of keloid fibroblasts by activating Wnt signaling pathway via targeting microRNA-21-5p.
Keloid is a skin disease marked by fibroplasia, and fibroblasts viability plays a considerable part in keloid. Our research was devoted to assessing the involvement and mechanism of circPTPN12 in keloid. The level of circPTPN12 and miR-21-5p was estimated by qRT-PCR in keloid tissues and cells. MTT analysis was devoted to evaluating the multiplication of keloid fibroblasts. Additionally, transwell assay was dedicated to verifying cell migration and invasion. Furthermore, keloid fibroblasts apoptosis level was assessed adopting flow cytometry, and the relevancy between miR-21-5p and circPTPN12, miR-21-5p, and SMAD7 was assessed by dual luciferase assay. Similarly, RIP and RNA pull-down assay verified the relevance between genes. Moreover, levels of SMAD7 and proteins concerned in Wnt signaling pathway were appraised by Western blot. The level of circPTPN12 declined in keloid. circPTPN12 knockout could enhance the multiplication, migration, invasion, and decline apoptosis of keloid fibroblasts. Indeed, miR-21-5p could be packed with circPTPN12 sponge, SMAD7 was downstream effect factor of miR-21-5p, and miR-21-5p inhibitors partially reversed the promoting effect of silencing circPTPN12 on keloid formation. Otherwise, the level of SMAD7 was adjusted by circPTPN12 and miR-21-5p. Silencing circPTPN12 targeted miR-21-5p and activated Wnt pathway to accelerate keloid fibroblasts growth. Taken together, silencing circPTPN12 promotes the growth of keloid fibroblasts by activating Wnt pathway targeting miR-21-5p. CircPTPN12 may play a considerable part in keloid formation, which supplies a reference for molecularly targeted therapy keloid.


Dietary assessment methods for micronutrient intake in pregnant women: a systematic review.
The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence needs clear guidelines for assessing the validity of reported micronutrient intakes among vulnerable population groups. A systematic literature search identified studies validating the methodology used for measuring usual dietary intake during pregnancy. The quality of each validation study selected was assessed using a EURRECA-developed scoring system. The validation studies were categorised according to whether the study used a reference method that reflected short-term intake ( < 7 d) long-term intake ( > or = 7 d) or used biomarkers (BM). A correlation coefficient for each micronutrient was calculated from the mean of the correlation coefficients from each study weighted by the quality of the study. Seventeen papers were selected, which included the validation of fifteen FFQ, two dietary records (DR), one diet history and a Fe intake checklist. Estimates of twenty-six micronutrients by six FFQ were validated against 24-h recalls indicating good correlation for six micronutrients. Estimates of twenty-four micronutrients by two FFQ were validated against estimated DR and all had good or acceptable correlations. Estimates of fourteen micronutrients by three FFQ were validated against weighed DR indicating good correlations for five. Six FFQ were validated against BM, presenting good correlations only for folic acid. FFQ appear to be most reliable for measuring short-term intakes of vitamins E and B6 and long-term intakes of thiamin. Apart from folic acid, BM do not add any more certainty in terms of intake method reliability. When frequency methods are used, the inclusion of dietary supplements improves their reliability for most micronutrients.


Blood Pressure and the Risk of Dementia: A Dose-Response Meta-Analysis of Prospective Studies.
A number of epidemiological studies have revealed a controversial correlation between Blood Pressure (BP) and the risk of dementia, hindering translation of research into preventative practice. To meta-analyze the dose-response relationship of dementia and its subtypes to BP. Relevant studies were identified via a systematic retrieval analysis in electronic databases from inception to May 1, 2017. Linear and non-linear dose-response meta-analyses were conducted to evaluate the effects of BP on dementia risk. Twenty-three studies from 17 articles with 830631 participants and 4384 cases for all dementia, 17 studies from 12 articles with 1707445 participants and 3481 cases for Alzheimer's disease (AD) and 11 studies from 8 articles with 1693690 participants and 1067 cases for Vascular Dementia (VD) were included. We identified that the associations between BP and dementia varied with population characteristics. A nonlinear relationship was found between systolic blood pressure (SBP) and all dementia risk in population-aged ≥ 65 years (pnonlinearity <0.05). SBP between 110 and 120mmHg played a protective role in population aged 62 to 82; while SBP above 162 mmHg would significantly increase the risk in those aged 70 to 86.5. It is also noteworthy that there is a linear association between diastolic blood pressure (DBP) and AD risk in the population aged ≥ 65 years, such that the risk decreased by 3% for per 10 mmHg increase in a specific range of DBP. These findings indicate that BP management strategy for dementia prevention might be tailored according to specific population characteristics.


Changes in coagulation factors and fibrinolytic components of postmenopausal women receiving continuous hormone replacement therapy.
The effect of hormone replacement therapy (HRT) on coagulation factors and fibrinolytic components in postmenopausal women was studied for 6 months to elucidate whether continuous HRT has an influence on thrombosis. One hundred and thirty-four postmenopausal women were divided into three groups according to treatment: 39 women who had undergone hysterectomy and oophorectomy received 0.625 mg/day of conjugated equine estrogen (CEE) continuously (CEE therapy), 48 postmenopausal women received both 0.625 mg/day of CEE and 2.5 mg/day of medroxyprogesterone acetate (MPA) continuously (CEE/MPA therapy) and 47 postmenopausal women received placebo as control. The following variables were measured before treatment as well as after 1, 3 and 6 months of treatment: factor VII activity, protein C activity, fibrinogen level, antithrombin III activity, plasminogen activator inhibitor-1 (PAI-1) level and the plasma concentration of tissue-type plasminogen activator (t-PA). After 1 month of treatment, protein C activity increased by 9.6% and 11.4% of the initial value (p < 0.05), fibrinogen level decreased by 7.8% and 6.1% of the initial value (p < 0.05) and PAI-1 decreased by 19.4% and 14.3% of the initial value (p < 0.05) in the CEE therapy group and the CEE/MPA therapy group, respectively. Factor VII activity increased by 10.1% of the initial value (p < 0.05) in the CEE therapy group only. Antithrombin III and t-PA levels did not change throughout either treatment. Except for an increase in factor VII activity in the case of continuous CEE therapy, continuous HRT had no unfavorable effects on either coagulation factors or fibrinolytic components.


End-to-side neurorrhaphy with and without perineurium.
We compared end-to-side neurorraphy with and without the perineural sheath. Twenty rats were used. The peroneal nerve was sectioned and the distal end was sutured to the lateral face of the tibial nerve. We removed the perineural sheath only on the right side, but not on the left side. The proximal end of the peroneal nerve was curved back approximately at a 100 degrees angle and implanted into the adductor muscle. Six months later, the 14 surviving animals were submitted to electrophysiological tests, sacrificed, and the nerves and muscles were taken for histological exams. On the right side, the muscles that had positive response needed an average of 258.89 mV (+/- 92.31) of electric stimulus and on the left side 298.34 mV (+/- 139.32). The average weight of the tibial cranial muscles of the right side was 0.47 g (0.18) and for the left side 0.45 g (0.15). The distal end of the peroneal nerve showed averages of 310.29 (+/- 191.34) nerve fibers on the right side and 287.71 (+/- 183.60) on the left side. The tibial nerve above the neurorraphy showed averages of 939.46 (+/- 223.51) nerve fibers on the right side and 959.46 (+/- 327.48) on the left side. The tibial nerve below the neurorraphy showed averages of 935.17 (+/- 298.65) nerve fibers on the right side and 755.31 (+/- 323.26) on the left side. The average areas of the right tibial cranial muscles were 0.0162 m2 (+/- 0.008), after 230 magnification, and 0.0152 m2 (0.0064) for the left tibial cranial muscles. The histological features of the tibial cranial muscles, taking normal as 100%, were 78.21 (+/- 20.75) on the right side and 82.14 (+/- 15.89) on the left side. The statistical analysis (Student's t test) did not reveal any difference (p > 0.05) among right and left sides for all variables. The authors concluded that the two neurorraphies (with and without perineurium) did not show any difference regarding morphological and electrophysiological features studied.


Reassessment of dapsone as a marker of acetylator phenotypes.
The ratio of metabolite to parent dapsone concentrations at 3 hours after dosing has been used as a marker of acetylator phenotypes. The absorption of dapsone is somewhat erratic with peak concentrations often found after the 3-hour determination. The present study done in 30 healthy, male volunteers compared ratios of metabolite to parent dapsone concentrations 3 hours after dosing with AUC values calculated during a 24-hour period as well as extrapolated to infinity. A single oral dose of 100 mg of dapsone was given to fasting subjects and serial blood samples were obtained over a 24-hour period and assayed by high-performance liquid chromatography for parent and acetylated metabolite. Dapsone pharmacokinetic parameters of AUC (23.4 +/- 8.6 micrograms.h/ml), half-life (24.8 +/- 11.5 hours) and apparent clearance values (81 +/- 30 ml/min) were consistent with those reported previously. Using established criteria for acetylation phenotyping, 20 percent of the subjects (6 of 30) demonstrated rapid acetylation. Bimodality in the ratios, independent of the experimental indices used to differentiate genetic metabolism, was not readily apparent. The data suggest that large variability in the pharmacokinetics of dapsone may sufficiently obscure the evidence of polymorphic metabolism. The use of dapsone as a marker of acetylator phenotyping should be limited to patient populations.


Influence of Gestational Age, Secretor, and Lewis Blood Group Status on the Oligosaccharide Content of Human Milk.
Human milk oligosaccharides (HMOs) are considered to play an important role for the infant. As the biotechnical production of some HMOs is feasible today and clinical studies are being designed, the individual variation of the total amount of HMOs and of single components is of particular importance. Our objectives were to investigate whether differences exist between term and preterm milk, milk from mothers with secretor or nonsecretor status, and a Lewis blood group (a+b-), (a-b+), or (a-b-) pattern. Within a longitudinal study 96 milk samples (colostrum, transitional, and mature milk) from 32 mothers with preterm (n = 18) and term (n = 14) infants were collected. Delipidated and deproteinized milk was subjected to porous graphitized carbon cartridges followed by high pH anion exchange chromatography with pulsed amperometric detection. Quantitation of 16 single HMOs revealed changes during the first weeks of lactation without discrepancies between term and preterm milk. Significant differences occurred between "secretor" and "nonsecretor" milk (median approximately 10 vs 5 g/L total HMOs). Lacto-N-tetraose (LNT) and lacto-N-fucopentaose (LNFP) II comprised > 55% of the total HMO content in Lewis blood group (a+b-), "nonsecretor" milk and LNT together with 2'fucosyllactose, LNFP I, and difucosyllactose approximately 60% in Lewis (a-b+), "secretor" milk. In Lewis (a-b-), "secretor" milk 80% of oligosaccharides are due to LNT, 2'fucosyllactose, and LNFP I. There are marked differences in total HMOs and single HMOs in milk depending on Lewis blood group and secretor status, which need to be taken into account in clinical studies.


[Total arthroplasty: the other surfaces; wear and tear and osteolysis].
Total replacement remains a successful solution for degenerative, inflammatory and postraumatic diseases in large joints. This treatment has considerably improved the quality of life of the patients. Despite recent innovations in biomaterials, implant design and surgical technique, there are still failures, most of them related to wear at the surface of some component. Particles are generated that produce inflammatoty and osteolytic reactions leading to implant loosening. In that case, revision surgery is mandatory to remove and substitute the worn component. The operation is far more difficult and costly, has a higher rate of complications and a worse outcome that the initial surgery. This general review of the problem is focused on the specific features of wear particles and the cellular and molecular mechanisms of the biological reactions in the osteoclastic and osteoblastic pathways. Osteolysis is described as a pathological modification of normal bone remodeling with the interaction between osteoblasts and osteoclasts as the main feature. We include some contributions of our laboratory at H U La Paz. Having reached an advanced identification of the molecular factors involved in wear osteolysis, many research groups are trying to develop potential "biologic" (non surgical) therapies for the prevention and treatment of bone loss.


The future of obstetrics and gynecology. Council on Long Range Planning and Development with the cooperation of the American College of Obstetricians and Gynecologists.
The American Medical Association Council on Long Range Planning and Development has identified trends in the environment of medicine that are likely to affect the future of obstetrics and gynecology practice. The professional liability crisis is among the most potent factors affecting the types and numbers of services that obstetricians and gynecologists will provide in the future. The setting for obstetrics and gynecology practice is likely to be affected by advances in technology and trends in delivery and reimbursement systems. Two factors with potential to affect the organization of practice are the high numbers of women entering the specialty and increasing practice expenses, largely associated with liability costs. Other factors affecting future patterns of delivery include the anticipated aging of the female population and the changing social and economic roles of women. In particular, the feminist movement has focused more attention on women's health care and is expected to have a continuing impact on the delivery of obstetric and gynecologic care. The Council concludes that the most salient issues for the specialty in the future will be the following: (1) the direction of the professional liability crisis, (2) medical practice competition, (3) the feminization of poverty, (4) ethical issues arising from technological and social imperatives, (5) the changing gender profile of the specialty, and (6) the impact of the feminist movement on women's health care.


Elevated CD44 expression predicts poor prognosis in patients with low-grade glioma.
CD44 is involved in malignant processes including cell motility, tumor growth and angiogenesis. To explore the potential role of CD44 as a prognostic biomarker in low grade gliomas (LGG), the mRNA expression levels of CD44 in tissues from 12 patients with glioma were evaluated by microarray analysis. The mRNA level of CD44 in LGG and glioblastoma multiforme (GBM) were analyzed using datasets downloaded from the publicly available Oncomine database. Reverse transcription-quantitative PCR and western blotting were used to further analyze the CD44 expression level in a set of 53 patients. Kaplan-Meier analysis was performed to identify the prognostic roles of CD44 mRNA in LGG and GBM, with data obtained from the OncoLnc and Gene Expression Profiling Interactive Analysis databases and clinical follow-ups. The present results revealed that CD44 mRNA expression levels were elevated in LGG and GBM compared with normal brain tissues. Furthermore, increased CD44 expression was associated with poor survival rates in LGG. The present study suggested that CD44 may act as an independent prognostic factor for LGG, and may be a potential therapeutic target for gliomas.


Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells.
Cytokines and chemokines are produced and secreted by a broad range of immune cells including macrophages. Remarkably, little is known about how these inflammatory mediators are released from the various immune cells. Here, the endolysosomal cation channel TRPML2 is shown to play a direct role in chemokine trafficking and secretion from murine macrophages. To demonstrate acute and direct involvement of TRPML2 in these processes, the first isoform-selective TRPML2 channel agonist was generated, ML2-SA1. ML2-SA1 was not only found to directly stimulate release of the chemokine CCL2 from macrophages but also to stimulate macrophage migration, thus mimicking CCL2 function. Endogenous TRPML2 is expressed in early/recycling endosomes as demonstrated by endolysosomal patch-clamp experimentation and ML2-SA1 promotes trafficking through early/recycling endosomes, suggesting CCL2 being transported and secreted via this pathway. These data provide a direct link between TRPML2 activation, CCL2 release and stimulation of macrophage migration in the innate immune response.


Measurement of δ13C values of soil amino acids by GC-C-IRMS using trimethylsilylation: a critical assessment.
In this study, we evaluated trimethylsilyl (TMS) derivatives as derivatization reagents for the compound-specific stable carbon isotope analysis of soil amino acids by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). We used non-proteinogenic amino acids to show that the extraction-derivatization-analysis procedure provides a reliable method to measure δ(13)C values of amino acids extracted from soil. However, we found a number of drawbacks that significantly increase the final total uncertainty. These include the following: production of multiple peaks for each amino acid, identified as di-, tri- and tetra-TMS derivatives; a number of TMS-carbon (TMS-C) atoms added lower than the stoichiometric one, possibly due to incomplete combustion; different TMS-C δ(13)C for di-, tri- and tetra-TMS derivatives. For soil samples, only four amino acids (leucine, valine, threonine and serine) provide reliable δ(13)C values with a total average uncertainty of 1.3 ‰. We conclude that trimethylsilyl derivatives are only suitable for determining the (13)C incorporation in amino acids within experiments using (13)C-labelled tracers but cannot be applied for amino acids with natural carbon isotope abundance until the drawbacks described here are overcome and the measured total uncertainty significantly decreased.


Genetic sequences that predispose to retinoblastoma and osteosarcoma.
The genetic predisposing factor for childhood retinoblastoma resides on the q14 band of human chromosome 13. However, a postulated second genetic event must take place for the disease to occur, which further research indicates involves inactivation of the remaining functional allele within 13q14. Our isolation of the gene within 13q14, called Rb, required creating a lambda-phage library that contained inserted fragments from human chromosome 13. One of the inserts, H3-8, detected a corresponding 1.8-kb HindIII fragment that was deleted in 2 of 37 retinoblastoma tumor DNAs. This suggested that the probed segment was linked to the Rb gene. A nearby probe, p7H30.7R, detected not only the human sequence but also a mouse homologue in a somatic cell hybrid carrying human chromosome 13. We used the p7H30.7R probe for RNA analysis to detect any transcripts in a retinal cell line. The analysis showed a 4.7-kb transcript in the tumor cell line but not in several retinoblastomas. We also failed to detect a transcript in four retinoblastoma and two osteosarcoma samples using a corresponding cDNA fragment termed p4.7R. We used this probe to analyze the DNA from a large group of retinoblastomas and osteosarcomas and found gross changes in genomic structure in approximately 30% of the tumor DNAs. The boundaries of homozygously deleted fragments were mapped. In the analysis of an osteosarcoma and a retinoblastoma we discovered that the endpoints of the deletions were within the confines of the genetic unit defined by the probe. This indicated that the target of inactivation was the segment under study and not a neighboring DNA sequence.


[X-ray computed tomography (CT scanner) in schizophrenia. Comparison of its results with other studies].
This paper concerns the tomodensitometric (TDM) study, with the same clinical and radiological criteria, of 78 schizophrenic patients (age: less than 60 years) from psychiatric hospitals in Madrid and from Sainte-Anne hospital (Paris). The length of evolution and the severity of disturbances seemed to be the most important causal elements of cerebral atrophy. Some TDM peculiarities appeared correlated with some clinical forms (paranoid or hebephrenic). The review of previous works illustrates the importance of some etiological conditions for the production of cerebral atrophy: age, length of evolution and, more particularly, the severity of the disease. The confrontation of the anatomo-pathological and pneumoencephalographic studies with the TDM results suggests that, if the TDM is a good indicator of ventricular dilatation, appreciation of the widening of the cerebral sulci remains difficult.


Use of Cardiac Contractility Modulation as Bridge to Transplant in an Obese Patient With Advanced Heart Failure: A Case Report.
Cardiac contractility modulation (CCM) is a novel device-based therapy in patients with heart failure with reduced ejection fraction (HFrEF). In randomized clinical trials and real-life studies, CCM has been shown to improve exercise tolerance and quality of life, reverse left ventricular remodeling and reduce hospitalization in patients with HFrEF. In this case report, we describe for the first time the use of CCM as a "bridge to transplant" in a young obese patient with advanced heart failure due to non-ischemic dilated cardiomyopathy. The patient had a poor quality of life and frequent heart failure-related hospitalizations despite the optimal medical therapy and, due to obesity, a suitable heart donor was unlikely to be identified in the short term and due to severe obesity risk of complications after implantation of a left ventricular assist device (LVAD) was very high.


Highly sensitive immunoassays based on use of liposomes without complement.
We describe a novel liposome-based immunoassay in which covalently linked hapten-cytolysin conjugates are used instead of complement and surface-immobilized immunoreagents. Stable, unilamellar liposomes containing entrapped alkaline phosphatase as a marker enzyme were prepared by dialysis of octyl glucoside from suspensions of cholesterol and egg yolk lecithin. The resulting vesicles could be immediately lysed by addition of either bee venom melittin or hapten-melittin conjugates. Using ouabain, an analog of digoxin, we synthesized conjugates that were more lytic than mellitin alone but that were inhibited in the presence of antibody. This inhibition was affected by adding competing free digoxin at various concentrations to obtain standard curves. The same liposome preparations could be lysed with a biotin-melittin conjugate, which was inhibited by avidin. The latter system was affected by free biotin and might be used to couple this approach to various heterogeneous immunoassays.


Predictive Processing in Poetic Language: Event-Related Potentials Data on Rhythmic Omissions in Metered Speech.
Predictions during language comprehension are currently discussed from many points of view. One area where predictive processing may play a particular role concerns poetic language that is regularized by meter and rhyme, thus allowing strong predictions regarding the timing and stress of individual syllables. While there is growing evidence that these prosodic regularities influence language processing, less is known about the potential influence of prosodic preferences (binary, strong-weak patterns) on neurophysiological processes. To this end, the present electroencephalogram (EEG) study examined whether the predictability of strong and weak syllables within metered speech would differ as a function of meter (trochee vs. iamb). Strong, i.e., accented positions within a foot should be more predictable than weak, i.e., unaccented positions. Our focus was on disyllabic pseudowords that solely differed between trochaic and iambic structure, with trochees providing the preferred foot in German. Methodologically, we focused on the omission Mismatch Negativity (oMMN) that is elicited when an anticipated auditory stimulus is omitted. The resulting electrophysiological brain response is particularly interesting because its elicitation does not depend on a physical stimulus. Omissions in deviant position of a passive oddball paradigm occurred at either first- or second-syllable position of the aforementioned pseudowords, resulting in a 2-by-2 design with the factors foot type and omission position. Analyses focused on the mean oMMN amplitude and latency differences across the four conditions. The result pattern was characterized by an interaction of the effects of foot type and omission position for both amplitudes and latencies. In first position, omissions resulted in larger and earlier oMMNs for trochees than for iambs. In second position, omissions resulted in larger oMMNs for iambs than for trochees, but the oMMN latency did not differ. The results suggest that omissions, particularly in initial position, are modulated by a trochaic preference in German. The preferred strong-weak pattern may have strengthened the prosodic prediction, especially for matching, trochaic stimuli, such that the violation of this prediction led to an earlier and stronger prediction error. Altogether, predictive processing seems to play a particular role in metered speech, especially if the meter is based on the preferred foot type.


The Development of a COVID-19 Control Measures Risk Matrix for Occupational Hygiene Protective Measures.
The British Occupational Hygiene Society (BOHS) COVID-19 Working Group developed a control banding matrix to provide guidance for employers and others to help assess the risks of COVID-19 infection during the pandemic. The matrix was based on occupational hygiene principles and the judgement of the occupational health practitioners involved; since objective data on workers' exposure were unavailable. Users of the matrix identify one of five exposure categories based on generic job descriptions and example occupations, and these categories are linked to generic guidance on interventions at source, on the exposure pathway and for individual workers. The risk matrix was published on the BOHS website and the guidance has been downloaded more than 2000 times. The matrix has had limited evaluation for reliability, but the data suggest that the highest exposure ranked jobs were associated with higher age-standardized mortality in Britain during the pandemic. However, there was considerable variability in exposure assignments between assessors, which underlines the need for the control guidance to be precautionary. The BOHS calls on academic researchers to undertake further work to validate the reliability of the tool.


Application of TaqMan Real-Time PCR for Detecting 'Candidatus Arsenophonus Phytopathogenicus' Infection in Sugar Beet.
The γ-proteobacterium 'Candidatus Arsenophonus phytopathogenicus' is assigned as the major pathogen of "Syndrome des basses richesses", a sugar beet disease characterised by a reduction in the sugar content of taproots and biomass yield. Despite the economic impact of this bacteriosis, diagnostics for this important pathogen currently rely on end-point PCR detection. Herein, we introduce a TaqMan qPCR for diagnostics of the agent targeting genes encoding a heat shock protein of the Hsp20 family and mannose-6-phosphate isomerase. Quantitation with synthetic oligonucleotides as standard showed that the developed TaqMan qPCR assays enable the detection of up to 100 target copies. A comparison between the TaqMan qPCR and end-point PCR for 'Ca. A. phytopathogenicus' detection was carried out on 78 sugar beet samples from different locations in southern Germany. The newly developed assays enable the fast, reliable and sensitive detection of 'Ca. A. phytopathogenicus' in sugar beet.


Symptom dimensions and their association with outcome and treatment setting in long-term schizophrenia. Results of the DSP project.
National representative samples of 1571 schizophrenia patients discharged from mental hospitals in Finland in 1990 and 1994 were interviewed 3 years after discharge. The symptom items assessed by the PANSS were factorized and orthogonal rotations were performed. Five factor dimensions, negative, positive, depressive, hostile and disorganization dimension, were obtained and correlated with data of patients' socio-demographic background, clinical history, condition and outcome. The negative dimension was more prominent in male and single patients, the depressive dimension in female and divorced patients. Patients with early onset and long duration of illness had high disorganization scores. Patients with disorganized subtype of schizophrenia had high scores in positive and disorganization dimensions. High scores in all, especially in negative and positive dimensions, were associated with poor psychosocial situation. Symptom dimensions varied also according to treatment setting at follow-up. Symptom dimensions of long-term schizophrenia patients in the community are closely associated with patients' socio-demographic background, clinical history and conditions, as well as with outcome and the treatment patients receive. A dimensional approach, instead of a categorical one, seems to be important in assessing symptomatology and its relation to outcome and interventions in schizophrenia.


Immune activation paired with intraoral sucrose conditions oral rejection.
The effects of lipopolysaccharide (LPS) and LiCl on conditioned taste aversion acquisition using intraoral infusions as the method of taste delivery was examined. Rats received two pairings of an intraorally delivered sucrose (5 ml) taste with the effects of a systemic injection of LPS, LiCl or NaCl. The magnitude of conditioning was quantified by scoring taste reactivity responses to a brief intraoral infusion of sucrose in the absence of any drug injection. Rats previously conditioned with LiCl or LPS displayed clear evidence of conditioned aversion with increased oral rejection responses relative to saline controls. Our results suggest activation of the immune system with LPS can condition consummatory aspects of ingestion when this conditioning involves intraoral fluid presentation.


Nuclease-mediated gene editing by homologous recombination of the human globin locus.
Tal-effector nucleases (TALENs) are engineered proteins that can stimulate precise genome editing through specific DNA double-strand breaks. Sickle cell disease and β-thalassemia are common genetic disorders caused by mutations in β-globin, and we engineered a pair of highly active TALENs that induce modification of 54% of human β-globin alleles near the site of the sickle mutation. These TALENS stimulate targeted integration of therapeutic, full-length beta-globin cDNA to the endogenous β-globin locus in 19% of cells prior to selection as quantified by single molecule real-time sequencing. We also developed highly active TALENs to human γ-globin, a pharmacologic target in sickle cell disease therapy. Using the β-globin and γ-globin TALENs, we generated cell lines that express GFP under the control of the endogenous β-globin promoter and tdTomato under the control of the endogenous γ-globin promoter. With these fluorescent reporter cell lines, we screened a library of small molecule compounds for their differential effect on the transcriptional activity of the endogenous β- and γ-globin genes and identified several that preferentially upregulate γ-globin expression.


Two Nkx-3-related genes are expressed in the adult and regenerating central nervous system of the urodele Pleurodeles waltl.
We report the isolation and characterization of two NK-3-related genes (PwNkx-3.2 and PwNkx-3.3) and their expression patterns during embryonic development, in the adult CNS, and during tail regeneration in the urodele Pleurodeles waltl. PwNkx-3.2 is the ortholog of the mouse and Xenopus genes, Bapx 1 and Xbap, but PwNkx-3.3 has no known homologue in any other vertebrate. We demonstrate that PwNkx-3.2 and PwNkx-3.3 exhibit graded axial expression patterns in adult spinal cord. During tail regeneration, the two genes are expressed in the wound epidermis, the regenerating muscle masses, the regenerating neural tube, the spinal ganglia, and the cartilage rod. The spatial distribution of transcripts in the CNS suggests that these genes could participate in maintaining the position information along the anteroposterior axis and may explain the ability of the adult CNS to regenerate. During tail regeneration, both genes could be implicated in the reformation of the axial skeleton.


Management of intracorneal epithelial cysts with ethanol irrigation and cyst wall excision: A clinicopathologic report.
The clinical and pathologic characteristics and the surgical treatment of 2 patients with intrastromal corneal epithelial cysts are described. This interventional case report presents 2 young patients with decreased vision and cosmetic impairment caused by intracorneal epithelial cysts. The first patient had history of strabismus surgery, and the second patient had undergone corneal laceration repair. The cysts had enlarged gradually and dissected into the cornea, threatening the visual axis. Both patients were treated with drainage of cyst contents, chemical cytodestruction with 96% ethanol for 1 minute in a closed system, followed by cyst wall excision. Corneal clarity and appearance improved significantly after surgery. In the first patient, best-corrected visual acuity was 20/20 before the operation and remained stable. In the second patient, best-corrected visual acuity improved from 20/400 to 20/60 after the procedure. Histopathologic findings revealed that the cyst walls were composed of nonkeratinized stratified squamous epithelium. No recurrence was noted up to 8 and 3 months in the first and second patients, respectively. No complication occurred during the follow-up period. Intracorneal epithelial cysts may be treated safely and effectively with a combination of drainage of cyst contents, irrigation with 96% ethanol, and cyst wall excision with good visual and cosmetic results.


Machine Learning Study of the Magnetic Ordering in 2D Materials.
Magnetic materials have been applied in a large variety of technologies, from data storage to quantum devices. The development of two-dimensional (2D) materials has opened new arenas for magnetic compounds, even when classical theories discourage their examination. Here we propose a machine-learning-based strategy to predict and understand magnetic ordering in 2D materials. This strategy couples the prediction of the existence of magnetism in 2D materials using a random forest and the Shapley additive explanations method with material maps defined by atomic features predicting the magnetic ordering (ferromagnetic or antiferromagnetic). While the random forest model predicts magnetism with an accuracy of 86%, the material maps obtained by the sure independence screening and sparsifying method have an accuracy of ∼90% in predicting the magnetic ordering. Our model indicates that 3d transition metals, halides, and structural clusters with regular transition-metal sublattices have a positive contribution in the total weight deciding the existence of magnetism in 2D compounds. This behavior is associated with the competition between crystal field and exchange splitting. The machine learning model also indicates that the atomic spin orbit coupling (SOC) is a determinant feature for the identification of the patterns separating ferro- from antiferromagnetic order. The proposed strategy is used to identify novel 2D magnetic compounds that, together with the fundamental trends in the chemical and structural space, pave novel routes for experimental exploration.


Morbidity and mortality of 109 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC) performed at a community hospital.
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is playing an increasing role in the management of isolated peritoneal dissemination of gastrointestinal malignancies. Historically this surgery is associated with a high morbidity and mortality. Recognizing this, our study was developed to prospectively evaluate morbidity and mortality after cytoreductive surgery with HIPEC performed at a community hospital. From January 19, 2005 to January 9, 2008, 109 consecutive patients successfully underwent cytoreductive surgery with HIPEC for peritoneal surface malignancies. All cases were performed by a single surgeon at a 323-bed community hospital. Using an institutional review board approved study we prospectively evaluated postoperative complications using the standard National Institutes of Health morbidity and mortality grading system. There was no 30-day or inpatient mortality. Overall grade III and IV morbidity was 30.2% (33 of 109 patients); 29.3% of the patients had at least one grade III complication, with the most common being postoperative anemia requiring a blood transfusion in 20 of the 109 patients (18.3%). Eight patients (7.3%) had wound infections, and three patients (2.7%) developed pneumonia. One patient required computerized tomography guided drainage of a pelvic abscess. There were 3 (2.7%) grade IV complications, with only one patient requiring reoperation. Recent studies at tertiary medical centers have shown acceptable morbidity and mortality with this procedure. Our study demonstrates that this procedure can be safely performed in the community setting as well if surgeons, other medical professionals, and ancillary caregivers have great experience in this procedure.


Representation of social work agencies: new definition, special issues, and practice model.
Social Work administrators currently must respond to very diverse audiences in representing their agencies and programs. While skills in public relations, reporting, and community relations are viewed as essential, professional social work literature provides only limited conceptualizations and practice models. The authors propose a new definition of representation in social work agencies and suggest functional areas within which organized activities can be developed. The paper also includes: 1) a discussion of how several special issues such as the perception of welfare as stigma and agency interdependency affect the implementation of representational strategies; 2) a planning model that will assist administrators in strengthening the representation of their agencies' programs.


Access to small size distributions of nanoparticles by microwave-assisted synthesis. Formation of Ag nanoparticles in aqueous carboxymethylcellulose solutions in batch and continuous-flow reactors.
This article examines the effect(s) of the 2.45-GHz microwave (MW) radiation in the synthesis of silver nanoparticles in aqueous media by reduction of the diaminesilver(i) complex, [Ag(NH(3))(2)](+), with carboxymethylcellulose (CMC) in both batch-type and continuous-flow reactor systems with a particular emphasis on the characteristics of the microwaves in this process and the size distributions. This microwave thermally-assisted synthesis is compared to a conventional heating (CH) method, both requiring a reaction temperature of 100 degrees C to produce the nanoparticles, in both cases leading to the formation of silver colloids with different size distributions. Reduction of the diaminesilver(i) precursor complex, [Ag(NH(3))(2)](+), by CMC depended on the solution temperature. Cooling the reactor during the heating process driven with 390-Watt microwaves (MW-390W/Cool protocol) yielded silver nanoparticles with sizes spanning the range 1-2 nm. By contrast, the size distribution of Ag nanoparticles with 170-Watt microwaves (no cooling; MW-170W protocol) was in the range 1.4-3.6 nm (average size approximately 3 nm). The overall results suggest the potential for a scale-up process in the microwave-assisted synthesis of nanoparticles. Based on the present data, a flow-through microwave reactor system is herein proposed for the continuous production of silver nanoparticles. The novel flow reactor system (flow rate, 600 mL min(-1)) coupled to 1200-Watt microwave radiation generated silver nanoparticles with a size distribution 0.7-2.8 nm (average size ca. 1.5 nm).


Metformin Can Alleviate the Symptom of Patient with Diabetic Nephropathy Through Reducing the Serum Level of Hcy and IL-33.
Interleukin-33 (IL-33) and homocysteine (Hcy) were found to be up-regulated in patients with diabetic nephropathy (DN), and the present study aimed to investigate whether metformin (MT) can influence the serum levels of IL-33 and Hcy in patients with DN. Sixty patients with type 2 diabetes mellitus (DM) were divided into DM group (albumin: Alb <20 mg/L), DN group (Alb >20mg/L), and DN+ MT treatment group, with 20 cases in each group. Patients in each group were treated with insulin for 3 months, and patients in DN+MT group was treated with insulin+MT for 3 months. The serum levels of IL-33, urinary microalbumin excretion rate (UAE), body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), creatinine (Cr), cystatin C (CysC) and Hcy were measured before and after medication. Twenty normal subjects were involved as control. BMI, Hcy and TC were reduced and HDL-C was increased of patients had been treated with metformin and insulin. UAE, Cr, Ccr and CysC had no differences before and after treatment. The serum level of IL-33 significantly up-regulated in patients with DN, and MT treatment significantly decreased the serum level of IL-33 in patients with DN. Metformin could alleviate the symptom of patient with DN through decreasing the serum level of IL-33 and Hcy.


Brønsted acid catalyzed cyclization of propargylic alcohols with thioamides. Facile synthesis of di- and trisubstituted thiazoles.
A general and efficient method to prepare 2,4-di- and trisubstituted thiazoles via p-TsOH·H(2)O-catalyzed cyclization of trisubstituted propargylic alcohols with thioamides is described. The reaction was accomplished in moderate to excellent product yields under mild conditions that did not require the exclusion of air and moisture and offers an operationally simplistic and convenient route to this synthetically useful aromatic heterocycle.


Rationally Designed Synthetic Haptens to Generate Anti-Ciguatoxin Monoclonal Antibodies, and Development of a Practical Sandwich ELISA to Detect Ciguatoxins.
"Ciguatera" fish poisoning (CFP) is one of the well-known food poisoning caused by the ingestion of fish that have accumulated trace amounts of ciguatoxins (CTXs). CFP affects more than 50,000 individuals annually. The difficulty in preventing CFP comes from the lack of reliable methods for analysis of CTXs in contaminated fish, together with the normal appearance, taste, and smell of CTX-contaminated fish. Thus, a sensitive, accurate, routine, and portable analytical method to detect CTXs is urgently required. Monoclonal antibodies (mAbs) specific against either wing of major CTX congeners (CTX1B, 54-deoxyCTX1B, CTX3C, and 51-hydroxyCTX3C) were generated by immunizing mice with rationally designed synthetic haptens-KLH conjugates instead of the CTXs. Haptenic groups with a surface area greater than 400 Å2 are required to produce mAbs that can strongly bind to CTXs. Furthermore, a highly sensitive fluorescence-based sandwich enzyme-linked immunosorbent assay (ELISA) was developed. This protocol can detect and quantify four major CTX congeners (CTX1B, 54-deoxyCTX1B, CTX3C, and 51-hydroxyCTX3C) with a limit of detection (LOD) of less than 1 pg/mL. The LOD determined for this sandwich ELISA is sufficient to detect CTX1B-contaminated fish at the FDA guidance level of 0.01 ppb.


Giant right atrium: a long-term complication of rheumatic heart disease.
Giant right atrium (RA) is a rare entity often seen during childhood due to congenital anomalies. Limited literature has reported such finding in patients with rheumatic valvular heart disease. Here we present a case of a 68-year-old female with a history of rheumatic valve disease treated with a Starr Edwards mechanical ball-in-cage mitral valve replacement and tricuspid valve annuloplasty ring procedures. The patient developed heart failure and had multiple hospital admissions over three decades for heart failure exacerbations mostly triggered by medication and dietary non-compliance. She eventually developed a giant RA that filled most of her thorax. This case demonstrates an extreme form of cardiac remodeling caused by long-term rheumatic valvular heart disease.


A stem-loop of Tetrahymena telomerase RNA distant from the template potentiates RNA folding and telomerase activity.
The ribonucleoprotein enzyme telomerase adds telomeric repeats to the ends of linear chromosomes. The Tetrahymena telomerase reverse transcriptase (TERT) protein and the telomerase RNA can be reconstituted into an active complex in vitro in rabbit reticulocyte lysates. We have probed the structure of the telomerase RNA in the reconstituted complex with RNases T1 and V1. Upon TERT binding to the RNA, sites of both protection and enhancement of cleavage were observed, suggesting potential protein-binding sites and conformational changes in the RNA. Especially prominent was a large region of RNase V1 protection in stem-loop IV. A number of loop IV mutants still bound TERT but showed drastic decreases in the level of telomerase activity and the loss of protein-dependent folding of the pseudoknot region of the telomerase RNA. The telomerase activity defect and the misfolding of the pseudoknot were partially separable, leading to the proposal of two functions for stem-loop IV: to aid in the folding of the pseudoknot and to function more directly in the active site of telomerase. Thus an RNA element far from the template makes a major contribution to Tetrahymena telomerase enzyme activity.


Improving efficiency through workflow optimization in a pharmacist-run diabetes clinic.
To evaluate the impact of hiring nonclinical support staff on pharmacist productivity and diabetes control outcomes in internal medicine clinics of an integrated healthcare system. A retrospective, longitudinal cohort study was conducted. Patients were included if they were contacted by telephone for a diabetes consultation with a clinical pharmacist from July 1, 2015, through June 30, 2017. Nonclinical support staff were hired in July 2016 to schedule patient appointments with the clinical pharmacists. The primary outcome was the average rate of completed telephone encounters per month before and after hiring of nonclinical support staff. The secondary outcome was the mean change in glycated hemoglobin (HbA1c) level in patients who had a laboratory assay completed within 90 days of clinical pharmacist outreach. The tertiary outcome was the call completion rate for scheduled appointments vs unscheduled calls. In total, 6,709 patients were included; their average age was 55 years. After the intervention, the mean (SD) rate of completed telephone encounters increased from 61% (3.8%) to 77% (3.5%) (P < 0.001). Small improvements were noted in glycemic control, as measured by the mean (SD) percentage of patients with an HbA1c concentration of <8%, which increased from 31% (5.2%) to 42% (3.0%) (P < 0.001), and the mean (SD) change in average HbA1c concentration, which increased from 8.9% (0.2%) to 8.5% (0.1%) (P < 0.001). Throughout the study, scheduled calls were more likely to be completed than unscheduled calls (mean [SD] completion rate, 66% [9.0%] vs 74% [6.0%]; P < 0.001). Hiring nonclinical support staff led to greater efficiency among the clinical pharmacist team, yielding a higher volume of telephone interactions, a modest overall decrease in HbA1c values, and an increased likelihood of reaching patients by phone.


Rhodium(III)-catalysed decarboxylative C-H functionalization of isoxazoles with alkenes and sulfoxonium ylides.
Decarboxylative C-H functionalization of isoxazoles with electron-deficient alkenes and sulfoxonium ylides at the C5 position was achieved in the presence of rhodium(iii) catalysts to give the corresponding alkenylation and acylmethylation products, respectively.


Biochemical analysis of a mutant Tetrahymena lacking outer dynein arms.
Tetrahymena thermophila mutants homozygous for the oad mutation become nonmotile when grown at the restrictive temperature, and axonemes isolated from nonmotile mutants lack approximately 90% of their outer dynein arms. Electrophoretic analyses of axonemes isolated from nonmotile mutants (oad axonemes) indicate they contain significantly fewer of the 22 S dynein heavy chains that axonemes isolated from wild-type cells (wild-type axonemes) contain. The 22 S dynein heavy chains that remain in axonemes isolated from nonmotile, oad mutants are assembled into 22 S dynein particles that exhibit wild-type levels of ATPase activity. Two-dimensional gel electrophoresis of oad axonemes show that they are deficient in no proteins other than those proteins thought to be components of 22 S dynein. This report is the first formal proof that outer dynein arms in Tetrahymena cilia are composed of 22 S dynein.


Corticosteroids for acute adult bacterial meningitis.
Bacterial meningitis in adults is a severe disease, with high fatality and morbidity rates. Experimental studies showed that the inflammatory response in the subarachnoid space is associated with unfavorable outcome. In these experiments, corticosteroids, and in particular dexamethasone, were able to reduce the inflammatory cascades in the subarachnoid space. The use of corticosteroids as adjunctive therapy in adults with bacterial meningitis was evaluated in eight studies, performed over 45 years. Most studies on adjunctive dexamethasone therapy in adults with bacterial meningitis suffered from methodological flaws. In 2002, a trial with sufficient study-power to show significant differences was published. This study showed that adjunctive dexamethasone therapy reduced the rate of unfavorable outcomes from 25 to 15% in adults with bacterial meningitis. In this study, adjunctive treatment with dexamethasone was given before or with the first dose of antibiotics, without serious adverse effects. A quantitative review showed a consistent beneficial effect of dexamethasone on mortality and a borderline statistical beneficial effect on neurologic sequels. On the basis of available evidence, adjunctive dexamethasone therapy should be initiated before or with the first dose of antibiotics and continued for four days in all adults with suspected or proven community bacterial meningitis in high-income countries, regardless of bacterial etiology. Since prompt use of dexamethasone and appropriate antibiotics improves the prognosis of adults with bacterial meningitis, hospitals will need protocols to include dexamethasone with the initial antibiotic therapy.


Short communication: Genetic correlation and heritability of milk coagulation traits within and across lactations in Holstein cows using multiple-lactation random regression animal models.
Genetic parameters of milk rennet coagulation time (RCT) and curd firmness (a30) among the first 3 lactations in Holstein cows were estimated. The data set included 39,960 test-day records from 5,216 Estonian Holstein cows (the progeny of 306 sires), which were recorded from April 2005 to May 2010 in 98 herds across the country. A multiple-lactation random regression animal model was used. Individual milk samples from each cow were collected during routine milk recording. These samples were analyzed for milk composition and coagulation traits with intervals of 2 to 3 mo in each lactation (7 to 305 DIM) and from first to third lactation. Mean heritabilities were 0.36, 0.32, and 0.28 for log-transformed RCT [ln(RCT)] and 0.47, 0.40, and 0.62 for a30 for parities 1, 2, and 3, respectively. Mean repeatabilities for ln(RCT) were 0.53, 0.55, and 0.56, but 0.59, 0.61, and 0.68 for a30 for parities 1, 2 and 3, respectively. Mean genetic correlations between ln(RCT) and a30 were -0.19, -0.14, and 0.02 for parities 1, 2, and 3, respectively. Mean genetic correlations were 0.91, 0.79, and 0.99 for ln(RCT), and 0.95, 0.94, and 0.94 for a30 between parities 1 and 2, 1 and 3, and 2 and 3, respectively. Due to these high genetic correlations, we concluded that for a proper genetic evaluation of milk coagulation properties it is sufficient to record RCT and a30 only in the first lactation.


Stopped-flow, classical, and dynamic light scattering analysis of matrix protein binding to nucleocapsids of vesicular stomatitis virus.
During the process of assembly of enveloped viruses, binding of the nucleoprotein core of the virus (nucleocapsid) to the host membrane is mediated by the viral matrix (M) protein. Light scattering properties of vesicular stomatitis virus (VSV) nucleocapsids and nucleocapsid-M protein (NCM) complexes assembled in vivo were determined following solubilizaton of the virion envelope with detergents at varying ionic strength to vary the extent of M protein binding. Three factors were found to contribute to the light scattering properties of VSV nucleocapsids: their conformation, extent of self-association, and amount of bound M protein. All three were affected by changes in ionic strength but could be distinguished by several parameters. Conformational changes in nucleocapsids and NCM complexes occurred rapidly (millisecond time scale) upon changing salt concentration and were reflected in changes in the angular dependence of light scattering intensity (i.e., changes in radius of gyration, RG). Changes in extent of self-association occurred relatively slowly (seconds to minutes time scale) and could be distinguished by the concentration dependence of the apparent molecular mass and diffusion coefficient of the NCM complex. Changes in M protein binding occurred on an intermediate time scale (t1/2 approximately one s) and reflected changes in both molecular mass and RG. The data presented here provide criteria for assessing binding of M protein to nucleocapsids under conditions of minimal perturbation of the NCM complex assembled in vivo and at low protein concentrations so that self-association of the NCM complex was minimal and reversible.


Bactericidal capability of blood platelets in eutrophic newborns.
Bactericidal activity of the blood platelets from cord blood of 69 eutrophic newborns differed in relation to sex. In female newborns we noted 8.13% killed Staphylococcus aureus ATCC 6538 P, whereas in male newborns only 2.92%. These data point to the role of platelets in unspecific defense against infections.


Renal function and blood pressure response to dietary salt restriction in normotensive men.
The interindividual variability of the blood pressure response to changes in dietary sodium intake might be traced in part to heterogeneity in renal adaptation. To further explore this possibility, we evaluated glomerular filtration rate and tubular sodium handling in 47 healthy male volunteers from the Olivetti factory in Naples who were studied on their habitual sodium-rich diet (urinary sodium, 184 +/- 9 mmol/24 h) and after 3 days of a salt-restricted diet (urinary sodium, 69 +/- 5 mmol/24 h). Individual salt sensitivity, defined as the mean blood pressure change recorded after the shift from habitual to low sodium diet, significantly and directly correlated with glomerular filtration rate and absolute proximal sodium reabsorption during the habitual diet. When the entire population was divided into tertiles of salt sensitivity, the group with the highest salt sensitivity showed higher blood pressure, glomerular filtration rate, and absolute proximal sodium reabsorption during the habitual diet compared with the least salt-sensitive group; however, during the low NaCl diet, no differences were detectable between the groups. Twenty-four-hour urinary sodium was similar across the groups. We conclude that relative hyperfiltration and altered tubular sodium handling may occur in salt-sensitive normotensive individuals on a high sodium diet and that NaCl restriction may offset these abnormalities.


Borrelia burgdorferi bba66 gene inactivation results in attenuated mouse infection by tick transmission.
The impact of the Borrelia burgdorferi surface-localized immunogenic lipoprotein BBA66 on vector and host infection was evaluated by inactivating the encoding gene, bba66, and characterizing the mutant phenotype throughout the natural mouse-tick-mouse cycle. The BBA66-deficient mutant isolate, Bb(ΔA66), remained infectious in mice by needle inoculation of cultured organisms, but differences in spirochete burden and pathology in the tibiotarsal joint were observed relative to the parental wild-type (WT) strain. Ixodes scapularis larvae successfully acquired Bb(ΔA66) following feeding on infected mice, and the organisms persisted in these ticks through the molt to nymphs. A series of tick transmission experiments (n = 7) demonstrated that the ability of Bb(ΔA66)-infected nymphs to infect laboratory mice was significantly impaired compared to that of mice fed upon by WT-infected ticks. trans-complementation of Bb(ΔA66) with an intact copy of bba66 restored the WT infectious phenotype in mice via tick transmission. These results suggest a role for BBA66 in facilitating B. burgdorferi dissemination and transmission from the tick vector to the mammalian host as part of the disease process for Lyme borreliosis.


Diadenosine polyphosphates increase cytosolic calcium and attenuate angiotensin-II-induced changes of calcium in vascular smooth muscle cells.
The effects of diadenosine tetraphosphate (AP4A), diadenosine pentaphosphate (AP5A), and diadenosine hexaphosphate (AP6A) on the cytosolic free calcium concentration ([Ca2+]i) were evaluated in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent dye technique. A concentration-dependent increase of [Ca2+]i by AP4A, AP5A, and AP6A was observed in VSMC. Additions of 10 micromol/l AP4A, AP5A, and AP6A significantly increased [Ca2+]i in VSMC by 224 +/- 98 nmol/l (n = 6; p < 0.01, 205 +/- 27 nmol/l (n = 14; p < 0.01), and 269 +/- 98 nmol/l (n = 5; p < 0.05), respectively. Additions of AP4A, AP5A, and AP6A only 120 s prior to angiotensin II (Ang II) administration significantly attenuated the Ang-II-induced changes of [Ca2+]i in VSMC from 1,053 +/- 174 nmol/l to 283 +/- 42 nmol/l, 591 +/- 112 nmol/l, and 477 +/- 79 nmol/l, respectively (each p<0.01) as compared to the control). The AP6A-induced changes of [Ca2+]i were inhibited by the blockers of P2 purinoceptors, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid, but not by the inhibitor of P2y purinoceptors, reactive blue. Adenosine triphosphate (ATP) also increased [Ca2+]i in VSMC, whereas the purinoceptor P2x agonist, alpha,beta-methylene-ATP, had no effect on [Ca2+]i in VSMC. Therefore diadenosine polyphosphates may induce changes of [Ca2+]i by interacting with purinoceptors and may be involved in local regulation of vascular resistance evoked by the Ca(2+)-dependent contractile response of VSMC.


[Latex allergy--an increasing problem in clinical practice].
In the last few years the allergenic potential of rubber has been receiving more and more attention. Its widespread application in medical devices and everyday objects has increased exposure to this allergen. The central role of rubber in the prevention of HIV infection has certainly played a part in this development. Latex allergy manifests itself as immediate type allergy (type I), delayed type allergy (type IV) or as a combination of both types of hypersensitivity. In this review the different types of latex allergy are illustrated by means of selected case reports. Immediate type allergy to latex leads to contact urticaria, but it may also cause generalized urticaria, bronchial asthma or even anaphylactic reactions (contact urticaria syndrome). Hence, not only dermatologists and allergologists are confronted with latex allergy. Immediate type hypersensitivity can be proven by skin prick test and RAST (radio allergosorbent test). Contact dermatitis in patients using rubber gloves is generally due to delayed type hypersensitivity to rubber additives. However, a recently observed case suggests the possibility of isolated delayed type hypersensitivity to natural latex.


[Castleman's disease: first case in Gabon].
Castleman's disease is an atypical lymphoproliferative disorder characterized by hyperplasia of lymphoid structures with vascular proliferation. It has rarely been diagnosed in black African populations. The purpose of this report is to describe the first case in Gabon. The patient was a 47-year-old black African man. Outcome was fatal.


Maxwell's macroscopic equations, the energy-momentum postulates, and the Lorentz law of force.
We argue that the classical theory of electromagnetism is based on Maxwell's macroscopic equations, an energy postulate, a momentum postulate, and a generalized form of the Lorentz law of force. These seven postulates constitute the foundation of a complete and consistent theory, thus eliminating the need for actual (i.e., physical) models of polarization P and magnetization M , these being the distinguishing features of Maxwell's macroscopic equations. In the proposed formulation, P(r,t) and M(r,t) are arbitrary functions of space and time, their physical properties being embedded in the seven postulates of the theory. The postulates are self-consistent, comply with the requirements of the special theory of relativity, and satisfy the laws of conservation of energy, linear momentum, and angular momentum. One advantage of the proposed formulation is that it sidesteps the long-standing Abraham-Minkowski controversy surrounding the electromagnetic momentum inside a material medium by simply "assigning" the Abraham momentum density E(r,t)xH(r,t)/c2 to the electromagnetic field. This well-defined momentum is thus taken to be universal as it does not depend on whether the field is propagating or evanescent, and whether or not the host medium is homogeneous, transparent, isotropic, dispersive, magnetic, linear, etc. In other words, the local and instantaneous momentum density is uniquely and unambiguously specified at each and every point of the material system in terms of the E and H fields residing at that point. Any variation with time of the total electromagnetic momentum of a closed system results in a force exerted on the material media within the system in accordance with the generalized Lorentz law.


Executive cognitive dysfunction and ADHD in cocaine dependence: searching for a common cognitive endophenotype for addictive disorders.
Cocaine-dependent individuals (CDI) present executive cognitive function (ECF) deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD) on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI + ADHD) would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI). We evaluated 101 adults, including 69 cocaine-dependent subjects (divided in CDI and CDI + ADHD) and 32 controls. ECF domains were assessed with Digits Forward (DF), Digits Backward (DB), Stroop Color Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery (FAB). DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood) were retrospectively assessed by the Wender-Utah Rating Scale (WURS). There were no significant differences between CDI + ADHD, CDI, and controls in estimated intellectual quotient (IQ), socioeconomic background, education (in years), and pre-morbid IQ (p > 0.05). SCWT and WCST scores did not differ across groups (p > 0.05). Nevertheless, CDI and CDI + ADHD performed more poorly than controls in total score of the FAB (p < 0.05). Also, CDI + ADHD did worse than CDI on DF (F = 4.756, p = 0.011), DB (F = 8.037, p = 0.001), Conceptualization/FAB (F = 4.635, p = 0.012), and Mental flexibility/FAB (F = 3.678, p = 0.029). We did not find correlations between cocaine-use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p = 0.016) and with the total score of the FAB (p = 0.017). CDI + ADHD presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on executive dysfunction in CDI. It remains to be investigated by future studies if symptoms such as impulsivity or a pre-existing ECF dysfunction could represent underlying cognitive endophenotypes that would substantially increase the risk for acquiring addictive disorders.


Two-component chiral phase transfer catalysts: enantioselective esterification of an N-acylated amino acid.
[see reaction]. The first example of a two-component chiral phase transfer catalyst is described which, operating in a biphasic solvent system, preferentially esterifies one enantiomer of a racemic N-acylated amino acid. The two-component catalyst is comprised of an achiral quaternary ammonium ion and a proline-derived chiral selector initially developed for the liquid chromatographic separation of enantiomers.


Photoanisotropic incoherent-to-coherent optical conversion.
A new approach to incoherent-to-coherent optical conversion based on a real-time five-wave-mixing technique in photoanisotropic organic film is presented. A uniform grating is written holographically in the sample and then erased locally by an incident white-light image. Subsequent coherent diffraction of the spatially modulated grating imposes the incoherent image upon the reading laser beam, permitting subsequent coherent optical processing. A theoretical analysis of the holographic recording and erasing mechanism in these photoanisotropic materials is presented, and the saturation is shown to be responsible for the grating intermodulation that produces the incoherent-to-coherent conversion. Experimental results of white-light images converted to inverted coherent images in real time are presented, and the resolution is shown to exceed 28 line pairs/mm.


Submerged (under-liquid) floating of light objects.
A counterintuitive submerged floating of objects lighter than the supporting liquid was observed. Polymer plates with dimensions on the order of magnitude of the capillary length were hydrophilized with cold air plasma were floated in an "under-liquid" regime (totally covered by liquid) when immersed in water or glycerol. Profiles of liquid surfaces curved by polymer plates are measured. We propose a model explaining the phenomenon. The floating of Janus plates is reported.


6-Pentadecylsalicylic acid: an antithrombin component isolated from the stem of Rhus semialata var. roxburghii.
Bioassay-directed fractionation of the n-hexane extract of the stem of Rhus semialata Murr. var. roxburghii DC (Anacardiaceae) has led to the isolation of 6-pentadecylsalicylic acid. It showed antithrombin activity at 50 micrograms/ml in the amidolytic method. It also prolonged the clotting time in a dose-dependent manner in the clotting assay of thrombin-fibrinogen interaction.


Sub-classification of Hidradenitis suppurativa: a cross-sectional study.
The typical Hidradenitis Suppurativa (HS) patient is a young woman with axillary and groin involvement, but the spectrum of the disease presentation is broad and no internationally acknowledged sub-classification of the disease exists to date. It is however speculated that different, yet unidentified, subtypes may respond differently to different treatments or carry a different prognosis. Classification according to self-reported clinically meaningful outcomes for patients offer practical advantages. Our objective was to build an empirical framework for sub-classification of HS patients based on the frequency of HS flares in various anatomic locations, using a cross-sectional questionnaire-based design. All patients with a clinically confirmed diagnosis of HS registered at our department until March 1, 2017 were invited to participate. The frequency of HS flares in various anatomic locations was used for identification of possible HS subtypes using Principal Component Analysis (PCA) and cluster analysis. A total of 524 (62%) of 845 invited patients answered the questionnaire; 402 (76.7%) were female. From the cluster analysis, we identified two possible subtypes of HS, labeled the "upper type" and the "lower type". The "upper type" was characterized by repeated outbreaks in axillary and mammary regions. Meanwhile, the "lower type" was characterized by outbreaks in the inguinal, genital, perianal, and gluteal regions. Our findings support the notion that HS can be sub-classified and imply that the pattern of where lesions are located may be an important element in future HS sub-classification systems.


A first exploration of genome size diversity in sponges.
The phyla known as early-branching lineages of animals have become the subject of increasing interest from the perspectives of genomics and evolutionary biology. Unfortunately, data on even the most fundamental properties of their genomes, such as genome size, remain very scarce. In this study, genome size estimates are reported for 75 species of sponges (phylum Porifera) representing 33 families and 12 orders, marking the first large survey of genome size diversity for an early-branching phylum. Sponge genome sizes averaged around 0.2 pg but exhibited a 17-fold range overall (0.04-0.63 pg). In addition, the results of comparisons of two methods of genome size quantification (flow cytometry and Feulgen image analysis densitometry) are presented, thereby facilitating future work on these animals. Some particularly promising avenues for future investigation are highlighted.


Self-assembly and near perfect macroscopic alignment of fluorescent triangulenium salt in spin-cast thin films on PTFE.
Highly fluorescent, discotic trioxatriangulenium dyes were aligned by simple spin-casting on substrates with friction transferred PTFE layers. The fluorescent crystalline thin films show near perfect macroscopic alignment on centimeter large areas directly from spin-casting. Gracing Incidence X-ray Diffraction (GIXD) unambiguously allowed the determination of a long-range order unit cell as well as its orientation with respect to the PTFE fibers. Further analysis of the X-ray data, in conjunction with polarized absorption spectroscopy, suggest a lamellar packing model with alternating layers of alkyl chains and ionic dyes oriented parallel to the substrate. This structure results in a highly anisotropic electrostatic potential around the cationic chromophore, causing significant shifts in energy and orientation of the optical transitions. Thus, the optical properties of the material are, to a large extent, controlled by the position of the otherwise inert PF6(-) counterions. The bright fluorescence from the films is also polarized parallel to the PTFE alignment layer. Doping of the thin films with fluorescent energy acceptor traps shows that efficient exciton migration takes place in the thin films. The excellent exciton transfer capabilities, in conjunction with the perfect alignment, might be of interest in future applications in solar energy harvesting or as thin film sensors.


Let's talk about the evidence.
In some cases, the new studies support current practice and standards of care, but for many topics, the new evidence suggests we ought to change our practice, either by stopping something we are currently doing or by starting to do something new.


Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation.
Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n = 16) and low-risk (n = 91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108 ± 26 vs 127 ± 40 podocytes/106 um3 , P = .03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min2 in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors.


[Effects of methamphetamine on responsiveness to conditioned fear stress].
The present study examined the effect of repeated methamphetamine (MA) pretreatment on conditioned fear stress in male Wistar-King rats. Rats received MA or the vehicle according to the repeated escalating dose schedule (1.25, 2.5, 3.75, 5 mg/kg s.c x2/every other day for a week). After a 5 day drug abstinent period, the rats were exposed to conditioned fear stress (CFS; exposure to an environment paired previously with footshock). Repeated but not single MA pretreatment significantly increased conditioned freezing behavior, suggesting that rats previously exposed to chronic MA are hypersensitive to subsequent stress than control rats. Repeated MA treatment did not decrease basal dopamine concentrations in the brain. Furthermore, repeated co-administration of MK-801 (non-competitive NMDA antagonist), amfonelic acid (dopamine reuptake inhibitor) or fluoxetine (serotonin reuptake inhibitor) with MA did not alter the enhanced freezing behavior. Taken together, it seems that MA-induced hypersensitivity to stress is not due to the neurotoxic effect of MA. While co-administration of SCH23390 (D1/5 antagonist) or raclopride (D2/3 antagonist) had no effect on the MA-induced increase in freezing, co-administration of nemonapride (D2/3/4 antagonist) prevented this increase. These results suggest that MA-induced enhancement of anxiety might be mediated by D4 receptors. The homovanilic acid (HVA) levels in the striatum were elevated by footshock in MA-treated rats but not in saline-treated rats. Furthermore, MA-treated rats showed increased metabolism of dopamine (DA) in the medial prefrontal cortex (mPFC), even when placed in the shock chamber without shocks. The HVA levels in the striatum in MA-treated rats were more elevated by CFS than these in saline-treated rats. These results suggest that the striatum DA system, as well as the mPFC DA system suggested previously, may be associated with emotional hypersensitivity to stress following repeated MA treatment.


Design of a Versatile pH-Responsive Hydrogel for Potential Oral Delivery of Gastric-Sensitive Bioactives.
A pH-responsive hydrogel system was prepared by free radical polymerization of acrylamide and methyl acrylic acid in the presence of N-N'-methylene bisacrylamide. Sodium bicarbonate was further applied as a blowing agent, which afforded a porous hydrogel structure. The hydrogel system achieved a constant super swelling rate within simulated intestinal buffer (~4%/min) and remained relatively static within simulated gastric buffer (~0.8%/min). The hydrogel system was able to achieve matrix resilience greater than 30% under a relatively high strain of 40%. In addition, the hydrogel system demonstrated significant swelling properties in response to simulated intestinal environmental over 24 h, with contrasting characteristics in simulated gastric buffer. The hydrogel demonstrated type IV isotherm porosity characteristics, with remarkable MRI and SEM variations in gastric and intestinal simulated fluids. Drug loading was observed to be greater than 98% using theophylline as a prototype drug, evaluating its controlled release kinetics over 24 h. The hydrogel exhibited substantial pH-responsive activity, which could be used as a versatile platform for targeted release of gastric-sensitive therapeutics to the small intestine.


Human antibody responses to HIV type 1 glycoprotein 41 cloned in phage display libraries suggest three major epitopes are recognized and give evidence for conserved antibody motifs in antigen binding.
A large panel of human Fab fragments against the gp41 subunit of the HIV-1 envelope glycoprotein was isolated by panning six phage-displayed antibody libraries against recombinant gp41. The libraries were prepared from HIV-1-seropositive donors. Twenty-three Fabs recognizing conformation-dependent determinants on gp41 were isolated. Further selection of libraries against (1) gp41 ligated with Fabs from the initial selection and against (2) a recombinant gp41-containing gp140 protein yielded five additional Fabs. Competition of members of the Fab panel with one another and with previously described antibodies revealed a series of overlapping specificities that were conveniently grouped into three major epitope clusters. The majority of Fabs recognized epitopes involving residues 649-668 (previously known as the cluster II region), numbered using the Los Alamos LAI sequence. A second set of Fabs reacted with an epitope involving residues 584-609 (known as the cluster I region). Another set of Fabs appeared to recognize a third conformational epitope that has been termed the cluster III region. This third Fab epitope group demonstrated some overlap with both clusters I and II in binding assays. None of the Fabs neutralized HIV-1 laboratory strains at biologically significant concentrations. This tends to support the opinion that a vaccine based on the gp41 molecule has the drawback that neutralizing epitopes of gp41 are rare and/or unfavorably presented to the immune system. Analysis of heavy chain sequences revealed common CDR3 motif sequences in several antibodies, which appears to be an interesting consequence of a persistent immune response to conserved antigen structures.


Examination of parental effect on the progeny diapause by reciprocal cross test in the cabbage beetle, Colaphellus bowringi.
The cabbage beetle, Colaphellus bowringi Baly (Coleoptera: Chrysomelidae), a serious pest of crucifers in China, undergoes summer or winter diapause in the soil as an adult. In the present study, the incidence of diapause were measured in reciprocal crosses between a high-diapause strain (HD strain) and a laboratory-selected nondiapausing strain (ND strain) under different photoperiods and temperatures, to explore parental influences on the progeny diapause. Sensitivity to photoperiod in the selected nondiapausing strain was nearly eliminated at 25 °C, whereas sensitivity to temperature of the selected nondiapausing strain was retained under continuous darkness at 20 and 22 °C. Reciprocal crosses between the HD strain and the ND strain showed that the incidence of diapause in the progeny was always intermediate to that of the parents under different photoperiods and temperatures, suggesting that diapause induction was determined by both female and male parents. There was a significant effect of temperature; temperature interacted with reciprocal cross on diapause induction, whereas no significant effect of reciprocal cross was demonstrated. The incidence of diapause in ♀(ND) × ♂(HD) was the same as in ♀(HD) × ♂(ND) under continuous darkness at 18 °C (100%) and 26 °C (0%), but the former was higher than that in ♀(HD) × ♂(ND) under continuous darkness at 22 °C, suggesting that female parent does not exhibit strong influence on the diapause response to temperature. There was a significant effect of photoperiod and reciprocal cross on diapause induction, whereas no significant interactive effect on diapause induction was demonstrated. Incidence of diapause in ♀(HD) × ♂(ND) was always higher than in ♀(ND) × ♂(HD) at 25 °C and 12:12 L:D, 14:10 L:D, and 16:8 L:D, suggesting a strong maternal influence on the diapause response to photoperiod, though a significant difference was observed only at 14:10 L:D. Our results support the idea that diapause induction is determined by both female and male parents. However, results also indicated that a strong maternal influence on diapause was exhibited only in response to photoperiod.


Impact of healthcare-associated sepsis on mortality in critically ill infants.
Healthcare-associated sepsis (HAS) is a life-threatening complication in neonatal intensive care. Research into the impact of HAS on mortality adjusted for comorbidities is however limited. We conducted a historical cohort study to evaluate impact of HAS on mortality stratified by birth weight and risk factors for mortality in the HAS cohort. HAS was defined according to the National Institute of Child Health and Human Development criteria. Logistic regression was used to calculate adjusted odds of mortality. Of 5134 admissions, 342 infants developed HAS (6.7 %). Mortality in the total and HAS cohort was 5.6 and 10.5 %, respectively. The majority of HAS was caused by commensals (HAS-COM, 59.4 %) and 40.6 % by recognized pathogens (HAS-REC). Adjusted for comorbidities, "HAS-REC" is only a risk factor for mortality in newborns >1500 g (adjusted odds ratio [aOR] 2.3, confidence interval [CI] 1.1-4.9). Post-hoc analysis identified HAS-REC as an independent risk factor for mortality in infants with gastrointestinal disease (aOR 4.8, CI 2.1-10.8). "Renal insufficiency," "focal intestinal perforation," and "necrotizing enterocolitis" are independent risk factors for mortality in the HAS cohort (aOR 13.5, CI 4.9-36.6; aOR 7.7, CI 1.5-39.2; aOR 2.1, CI 1.0-4.7, respectively). For very low birth weight infants (≤1500 g), several comorbidities overrule the impact of HAS on mortality. After adjustment for comorbidities, HAS-REC independently predicts in-hospital mortality in heavier infants and in those with gastrointestinal disease. • The relationship between healthcare-associated sepsis and mortality is influenced by the causative pathogen and is confounded by comorbidities. • Research on impact of healthcare-associated sepsis on mortality adjusted for comorbidities is limited as well as research on independent risk factors for mortality in neonates with sepsis. What is New: • We included a large list of comorbidities and stratified risk by birth weight in order to assess the true effect of healthcare-associated sepsis on mortality. • Risk for mortality was calculated for commensal flora and for recognized pathogens as causative micro-organisms.


Hyperbolic resonances of metasurface cavities.
We propose a new class of optical resonator structures featuring one or two metasurface reflectors or metacavities and predict that such resonators support novel hyperbolic resonances. As an example of such resonances we introduce hyperbolic Tamm plasmons (HTPs) and hyperbolic Fabry-Perot resonances (HFPs). The hyperbolic optical modes feature low-loss incident power re-distribution over TM and TE polarization output channels, clover-leaf anisotropic dispersion, and other unique properties which are tunable and are useful for multiple applications.


Gamma and neutrino radiation dose from gamma ray bursts and nearby supernovae.
Supernovae and gamma ray bursts are exceptionally powerful cosmic events that occur randomly in space and time in our galaxy. Their potential to produce very high radiation levels has been discussed, along with speculation that they may have caused mass extinctions noted from the fossil record. It is far more likely that they have produced radiation levels that, while not lethal, are genetically significant, and these events may have influenced the course of evolution and the manner in which organisms respond to radiation insult. Finally, intense gamma radiation exposure from these events may influence the ability of living organisms to travel through space. Calculations presented in this paper suggest that supernovae and gamma ray bursts are likely to produce sea-level radiation exposures of about I Gy with a mean interval of about five million years and sea-level radiation exposures of about 0.2 Gy every million years. Comets and meteors traveling through space would receive doses in excess of 10 Gy at a depth of 0.02 m at mean intervals of 4 and 156 million years, respectively. This may place some constraints on the ability of life to travel through space either between planets or between planetary systems. Calculations of radiation dose from neutrino radiation are presented and indicate that this is not a significant source of radiation exposure for even extremely close events for the expected neutrino spectrum from these events.


Natural particles can armor emulsions against lipid oxidation and coalescence.
Traditional functional ingredients, such as conventional emulsifiers (surfactants, animal-derived proteins), and synthetic antioxidants may become obsolete in the development of clean-label, plant-based, sustainable food emulsions. Previously, we showed that tailor-made antioxidant-loaded particles can yield both physically and oxidatively stable emulsions, and we expected that natural particles with related properties could also show these beneficial effects. Here, we investigated Pickering emulsions prepared with natural plant particulate materials. Particles that showed weak aggregation in acidic aqueous media, indicating a relatively hydrophobic surface, were able to physically stabilize oil-in-water emulsions, through either Pickering stabilization (powders of matcha tea, spinach leaves, and spirulina cake), or an increase in viscosity (pineapple fibers). Matcha tea and spinach leaf particle-stabilized emulsions were highly stable to lipid oxidation, as compared to emulsions stabilized by conventional emulsifiers. Taking this dual particle functionality as a starting point for emulsion design is, in our view, essential to achieve clean-label food emulsions.


[Cancer of unknown primary site].
Patients with cancer of unknown primary site represent 0.5 to 9 percent of all cancer patients with a major incidence in people aged 50 to 70 years. The most common histological diagnosis is adenocarcinoma. The vast majority of patients have at least two different metastatic sites involved at the moment of the diagnosis. Among the identified occult primaries lung and pancreas constitute the majority. Histological diagnosis, age, sex, performance status, tumor burden and organs involved are the most important prognostic factors. Complete medical history and physical examination are able to reveal symptoms and signs in more than 90 percent of patients. Routine laboratory tests, serum tumor markers, imaging studies and endoscopies will complete the diagnostic approach. The pathologic assessment of biopsied material is usually initiated by light microscopic examination: additional pathologic studies, including histochemistry, electron microscopy and genetic analysis are frequently and productively employed. Locoregional treatment can be curative in a few and selected cases and is more often offered with a palliative intent. The elective treatment for metastatic disease is represented, in the vast majority of cases, by systemic chemotherapy with different schedules according to pathological diagnosis. Best supportive care is sometimes the best choice. It is recommended to treat such patients in the context of clinical trials.


Sustainable Use of Apple Pomace (AP) in Different Industrial Sectors.
In many countries, apple pomace (AP) is one of the most produced types of agri-food waste (globally, it is produced at a rate of ~4 million tons/year). If not managed properly, such bio-organic waste can cause serious pollution of the natural environment and public health hazards, mainly due to the risk of microbial contamination. This review shows that AP can be successfully reused in different industrial sectors-for example, as a source of energy and bio-materials-according to the idea of sustainable development. The recovered active compounds from AP can be applied as preservatives, antioxidants, anti-corrosion agents, wood protectors or biopolymers. Raw or processed forms of AP can also be considered as feedstocks for various bioenergy applications such as the production of intermediate bioenergy carriers (e.g., biogas and pyrolysis oil), and materials (e.g., biochar and activated carbon). In the future, AP and its active ingredients can be of great use due to their non-toxicity, biodegradability and biocompatibility. Given the increasing mass of produced AP, the commercial applications of AP could have a huge economic impact in the future.


C60 -mediated molecular shape sorting: separation and purification of geometrical isomers.
A supramolecular crystallization-based approach has been developed for the shape-dependent separation of geometrical isomers under near-ambient conditions. Difficulties to separate such isomers arise because of their very similar physical properties. The present approach relies on the ability of C60 to preferentially form solvate crystals with molecules of a specific geometry. Subsequently, these molecules are released upon mild heating to regenerate pure C60 . By taking isomers of xylene and trimethylbenzene (TMB) as examples, we show that one of the isomers can be extracted from the rest with very high purity. To separate TMB isomers, a new C60 -1,3,5-TMB solvate was developed, which led to the isolation of isomer purities greater than 99.6 %. Versatility, a low operating temperature of approximately 100 °C, a separation efficiency of more than 10 weight % of C60 per cycle, and reagent recyclability makes this a promising molecular shape-sorting approach.