Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria-transformed leukocytes.
One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets. Theileria-transformed leukocytes display high PKA activity, but PKA is an enzyme that plays key roles in multiple cellular processes; consequently genetic ablation of kinase activity gives rise to a myriad of confounding phenotypes. By contrast, ablation of a specific kinase-substrate interaction has the potential to give more refined information and we illustrate this here by describing how surgically ablating PKA interactions with BAD gives precise information on the type of glycolysis performed by Theileria-transformed leukocytes. In addition, we provide two other examples of how ablating specific protein-protein interactions in Theileria-infected leukocytes leads to precise phenotypes and argue that constrained penetrating peptides have great therapeutic potential to combat infectious diseases in general.


Loss of function of OTUD7A in the schizophrenia- associated 15q13.3 deletion impairs synapse development and function in human neurons.
Identifying causative gene(s) within disease-associated large genomic regions of copy-number variants (CNVs) is challenging. Here, by targeted sequencing of genes within schizophrenia (SZ)-associated CNVs in 1,779 SZ cases and 1,418 controls, we identified three rare putative loss-of-function (LoF) mutations in OTU deubiquitinase 7A (OTUD7A) within the 15q13.3 deletion in cases but none in controls. To tie OTUD7A LoF with any SZ-relevant cellular phenotypes, we modeled the OTUD7A LoF mutation, rs757148409, in human induced pluripotent stem cell (hiPSC)-derived induced excitatory neurons (iNs) by CRISPR-Cas9 engineering. The mutant iNs showed a ∼50% decrease in OTUD7A expression without undergoing nonsense-mediated mRNA decay. The mutant iNs also exhibited marked reduction of dendritic complexity, density of synaptic proteins GluA1 and PSD-95, and neuronal network activity. Congruent with the neuronal phenotypes in mutant iNs, our transcriptomic analysis showed that the set of OTUD7A LoF-downregulated genes was enriched for those relating to synapse development and function and was associated with SZ and other neuropsychiatric disorders. These results suggest that OTUD7A LoF impairs synapse development and neuronal function in human neurons, providing mechanistic insight into the possible role of OTUD7A in driving neuropsychiatric phenotypes associated with the 15q13.3 deletion.


Monoamine oxidase, psychoenergizers, and tranquilizers.
1-Benzyl-2-methyl-5-methoxytryptamine (BAS) inhibits monoamine oxidase in man. This finding confirms the findings of Woolley in mice. Since BAS, a tranquilizing agent, and Marsilid, a psychoenergizer, are both monoamine oxidase inhibitors, doubt is cast upon the hypothesis, that the stimulatory effect of Marsilid is due to its ability to inhibit monoamine oxidase.


Micro magnetic stir-bar mixer integrated with parylene microfluidic channels.
Previously, we reported a micro magnetic stir-bar mixer driven by an external rotating magnetic field and its rapid mixing performance in polydimethyl-siloxane (PDMS) channels. The PDMS piece with embedded fluid channels were manually aligned to a glass substrate and assembled. In this paper, we report the fabrication and testing results of a micro magnetic stir-bar monolithically integrated in parylene surface-micromachined channels with improved design features, including small tolerance of the stir-bar to channel wall (10 microm). Using of parylene based microchannels with improved design not only provides improved mixing, but also eliminates certain problems associated with PDMS-based channels. For example, porosity of PDMS causes evaporation and absorption of chemicals and thus channels made of PDMS are prone to cross-contamination. We have also demonstrated that the magnetic stir-bar can be used to pump liquid in micro channels.


Seed-conjugated polymer bead for beta2-microglobulin removal at neutral pH.
beta2-Microglobulin (beta2m) is known to be a major factor for dialysis-related amyloidosis. We have studied beta2m removal through an aggregation process, which was initiated by a ligand that could catch the beta2m monomer and promote its aggregation into fibril. As a ligand, we have prepared beta2m fibril fragments and used them as a seed. The seed was coupled to PEGylated-PS beads to remove the monomeric beta2m from solution. The beta2m seed-conjugated resin effectively adsorbed the beta2m monomers with a capacity of 3.6 mg/ml via promoting their aggregation into fibrils on the resin at pH 7.4.


Genetic Characterization of Myoid Hamartoma of the Breast.
Myoid hamartoma of the breast is a very rare benign lesion of which only a few cases have been reported. The pathogenesis is unknown and nothing is known about its genetic constitution. We report here the genetic characterization of a myoid hamartoma of the breast. Cytogenetic, fluorescence in situ hybridization (FISH), RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing analyses were performed on a myoid hamartoma of the breast. G-Banding analysis of short-term cultured tumor cells yielded the karyotype 46,XX,t(5;12)(p13;q14)[6]/46,XX[4]. FISH showed rearrangement of the high mobility group AT-hook 2 (HMGA2) gene. RNA sequencing detected fusion of HMGA2 (12q14) with a sequence from 5p13. RT-PCR together with Sanger sequencing verified the HMGA2-fusion transcript. Myoid hamartoma of the breast may be pathogenetically related to benign connective tissue tumors with HMGA2 rearrangements, such as pulmonary hamartomas, lipomas, myolipomas, and leiomyomas.


Meyerson phenomenon.
Meyerson phenomenon is an uncommon clinical condition that is characterized by an eczematous halo surrounding a preexisting melanocytic nevus and numerous other lesions. The etiology of this condition is unknown. We suggest that the mechanism is due to the interaction between CD4 T lymphocytes and increased expression of intercellular cell adhesion molecule 1 (ICAM-1). This article provides a concise overview of Meyerson phenomenon. We present the case of a 37-year-old female with an inflamed nevus located on her thigh from no evident cause. Her condition resolved with surgical excision of the nevus. Histopathology of the specimen demonstrated spongiosis and lymphocytic infiltrate with eosinophils, which confirmed the diagnosis of Meyerson phenomenon. Meyerson phenomenon can resolve spontaneously or with treatment of either topical steroids or surgical excision. The main concern with benign lesions presenting with inflammation is malignant transformation; thus, clinicians need to be more aware of Meyerson phenomenon.


Early prediction of hospital outcomes in patients tracheostomized for complex mechanical ventilation weaning.
Tracheostomy is often performed in the intensive care unit (ICU) when mechanical ventilation (MV) weaning is prolonged to facilitate daily care. Tracheostomized patients require important healthcare resources and have poor long-term prognosis after the ICU. However, data lacks regarding prediction of outcomes at hospital discharge. We looked for patients' characteristics, ventilation parameters, sedation and analgesia use (pre-tracheostomy) that are associated with favorable and poor outcomes (post-tracheostomy) using univariate and multivariate logistic regressions. Eighty tracheostomized patients were included (28.8% women, 60 [52-71] years). Twenty-three (28.8%) patients were intubated for neurological reasons. Time from intubation to tracheostomy was 14.7 [10-20] days. Thirty patients (37.5%) had poor outcome (19 patients deceased and 11 still tracheostomized at hospital discharge). All patients discharged with tracheostomy (n = 11) were initially intubated for a neurological reason. In univariate logistic regressions, older age and higher body-mass index (BMI) were associated with poor outcome (OR 1.18 [1.07-1.32] and 1.04 [1.01-1.08], p < 0.001 and p = 0.025). No MV parameters were associated with poor outcome. In the multiple logistic regression model higher BMI and older age were also associated with poor outcome (OR 1.21 [1.09-1.36] and 1.04 [1.00-1.09], p < 0.001 and p = 0.046). Hospital mortality of patients tracheostomized because of complex MV weaning was high. Patients intubated for neurological reasons were frequently discharged from the acute care hospital with tracheostomy in place. Both in univariate and multivariate logistic regressions, only BMI and older age were associated with poor outcome after tracheostomy for patients undergoing prolonged MV weaning.


Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD.
The P2X7 receptor (P2X7R) is an ATP-gated ion channel that is a key player in oxidative stress under pathological conditions. The P2X7R is expressed in the retinal pigmented epithelium (RPE) and neural retina. Chronic oxidative stress contributes to the pathogenesis of age-related macular degeneration (AMD). Mice lacking Cu, Zn superoxide dismutase (Sod1) developed chronic oxidative stress as well as AMD-like features, but whether the P2X7R plays a causative role in oxidative stress-induced AMD is unknown. Thus, the main purpose of this study was to test if concurrent knockout (KO) of P2X7R could block AMD-like defects seen in Sod1 KO mice. Using multiple approaches, we demonstrate that Sod1 KO causes AMD-like defects, including positive staining for oxidative stress markers, 3-nitrotyrosine and carboxymethyl lysine, thinning of the RPE and retina, thickening of Bruch's membrane, presence of basal laminar and linear deposits, RPE barrier disruption and accumulation of microglia/macrophages. Moreover, we find that Sod1 KO mice accumulate more microparticles (MPs) within RPE/choroid tissues. Concurrent KO of the P2X7R protects against AMD-like defects and MP accumulation in Sod1 KO mice. Together, we show for the first time, that deficiency of P2X7R prevents in vivo oxidative stress-induced accumulation of MPs and AMD-like defects. This work could potentially lead to novel therapies for AMD and other oxidative stress-driven diseases.


Reduction of Human Norovirus GI, GII, and Surrogates by Peracetic Acid and Monochloramine in Municipal Secondary Wastewater Effluent.
The objective of this study was to characterize human norovirus (hNoV) GI and GII reductions during disinfection by peracetic acid (PAA) and monochloramine in secondary wastewater (WW) and phosphate buffer (PB) as assessed by reverse transcription-qPCR (RT-qPCR). Infectivity and RT-qPCR reductions are also presented for surrogate viruses murine norovirus (MNV) and bacteriophage MS2 under identical experimental conditions to aid in interpretation of hNoV molecular data. In WW, RT-qPCR reductions were less than 0.5 log10 for all viruses at concentration-time (CT) values up to 450 mg-min/L except for hNoV GI, where 1 log10 reduction was observed at CT values of less than 50 mg-min/L for monochloramine and 200 mg-min/L for PAA. In PB, hNoV GI and MNV exhibited comparable resistance to PAA and monochloramine with CT values for 2 log10 RT-qPCR reduction between 300 and 360 mg-min/L. Less than 1 log10 reduction was observed for MS2 and hNoV GII in PB at CT values for both disinfectants up to 450 mg-min/L. Our results indicate that hNoVs exhibit genogroup dependent resistance and that disinfection practices targeting hNoV GII will result in equivalent or greater reductions for hNoV GI. These data provide valuable comparisons between hNoV and surrogate molecular signals that can begin the process of informing regulators and engineers on WW treatment plant design and operational practices necessary to inactivate hNoVs.


Interlaboratory comparison of titers of antibody to Borrelia burgdorferi and evaluation of a commercial assay using canine sera.
Sixty canine serum samples were sent to 10 different diagnostic laboratories for anti-Borrelia burgdorferi antibody analysis. All laboratories knew of the study prior to receiving the samples. Agreement among all laboratories for all interpretations was 91% (546 of 600 samples). There was complete agreement among all the laboratories for only 32 (53%) of the samples. Most of the disagreements were due to differences reported by either one (15 samples) or two (7 samples) laboratories per sample. When discrepancies in interpretations existed, the interpretation reported by the majority of the laboratories was considered the standard for comparison. One laboratory had no discrepant interpretations from this standard, while the laboratory with the most discrepancies had 16. The median number of discrepancies per laboratory was five. By using pairwise comparisons between each laboratory and the majority standard, eight of the laboratories showed strong agreement and the remaining two showed fair to good agreement. The type of test used (enzyme-linked immunosorbent assay versus indirect immunofluorescence assay) did not appear to influence the number of discrepant interpretations reported. Sera considered to be positive by the majority of the laboratories usually reacted to more than five antigens in immunoblots, with at least three or more of those being intense reactions. For positive samples, reactivity was consistently present in the 60-, 41-, 31-, and 22- or 24-kDa regions. Samples considered negative usually reacted to fewer than three bands, with reactivity usually being faint. A commercially available, rapid dot blot assay showed strong agreement with the majority standard.


"GET-UP" study rationale and protocol: a cluster randomised controlled trial to evaluate the effects of reduced sitting on toddlers' cognitive development.
The educational and cognitive differences associated with low socioeconomic status begin early in life and tend to persist throughout life. Coupled with the finding that levels of sedentary time are negatively associated with cognitive development, and time spent active tends to be lower in disadvantaged circumstances, this highlights the need for interventions that reduce the amount of time children spend sitting and sedentary during childcare. The proposed study aims to assess the effects of reducing sitting time during Early Childhood Education and Care (ECEC) services on cognitive development in toddlers from low socio-economic families. We will implement a 12-months 2-arm parallel group cluster randomised controlled trial (RCT) with Australian toddlers, aged 12 to 26 months at baseline. Educators from the ECEC services allocated to the intervention group will receive professional development on how to reduce sitting time while children attend ECEC. Participants' cognitive development will be assessed as a primary outcome, at baseline and post-intervention, using the cognitive sub-test from the Bayley Scales of Infant and Toddler Development. This trial has the potential to inform programs and policies designed to optimize developmental and health outcomes in toddlers, specifically in those from disadvantaged backgrounds. Australian New Zealand Clinical Trials Registry: ACTRN12616000471482 , 11/04/2016, retrospectively registered.


Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis.
Osteoarthritis (OA) is a chronic degenerative disorder of the joint and its prevalence and severity is increasing owing to ageing of the population. Osteoarthritis is characterized by the degradation of articular cartilage and remodeling of the underlying bone. There is little understanding of the cellular and molecular processes involved in pathophysiology of OA. Currently the treatment for OA is limited to painkillers and anti-inflammatory drugs, which only treat the symptoms. Some patients may also undergo surgical procedures to replace the damaged joints. Extracellular vesicles (EV) play an important role in intercellular communications and their concentration is elevated in the joints of OA patients, although their mechanism is unclear. Extracellular vesicles are naturally released by cells and they carry their origin cell information to be delivered to target cells. On the other hand, mesenchymal stem cells (MSCs) are highly proliferative and have a great potential in cartilage regeneration. In this review, we provide an overview of the current OA treatments and their limitations. We also discuss the role of EV in OA pathophysiology. Finally, we highlight the therapeutic potential of MSC-derived EV in OA and their challenges.


Housing Satisfaction in Finland with Regard to Area, Dwelling Type and Tenure Status.
This study presents a comprehensive examination of housing satisfaction in Finland and how it associates with different types of residential area, dwelling and tenure status taking into account socio-demographic and socioeconomic variables. Associations between housing satisfaction and types of residential area, dwelling and tenure status were analysed by multivariate logistic regression using questionnaire data from a random sample of Finnish households (response rate 44%, N=1,308). Respondents from rural areas and those living in houses were statistically significantly (p<0.05) more satisfied with indoor thermal conditions in summer than respondents living in city centres (OR 2.01) and apartments (OR 1.75), respectively. Homeowners were more satisfied with the dwelling (OR 3.19), indoor air quality (OR 1.73) and thermal conditions in winter (OR 2.63), and reported moisture or mould damage (OR 0.37) and neighbour noise disturbance (OR 0.60) less frequently than tenants. Based on this study, the most important factors determining differences in housing satisfaction were tenure status and type of the dwelling. In the context of housing policy development, these results warrant a special consideration of housing quality in rental apartments. The results can also be used for making comparative assessments (e.g. detecting areas of relative strengths or needing improvement) of multifamily buildings and residential areas.


High-Throughput Separation of Long DNA in Deterministic Lateral Displacement Arrays.
Length-based separation of DNA remains as relevant today as when gel electrophoresis was introduced almost 100 years ago. While new, long-read genomics technologies have revolutionised accessibility to powerful genomic data, the preparation of samples has not proceeded at the same pace, with sample preparation often constituting a considerable bottleneck, both in time and difficulty. Microfluidics holds great potential for automated, sample-to-answer analysis via the integration of preparatory and analytical steps, but for this to be fully realised, more versatile, powerful and integrable unit operations, such as separation, are essential. We demonstrate the displacement and separation of DNA with a throughput that is one to five orders of magnitude greater than other microfluidic techniques. Using a device with a small footprint (23 mm × 0.5 mm), and with feature sizes in the micrometre range, it is considerably easier to fabricate than parallelized nano-array-based approaches. We show the separation of 48.5 kbp and 166 kbp DNA strands achieving a significantly improved throughput of 760 ng/h, compared to previous work and the separation of low concentrations of 48.5 kbp DNA molecules from a massive background of sub 10 kbp fragments. We show that the extension of DNA molecules at high flow velocities, generally believed to make the length-based separation of long DNA difficult, does not place the ultimate limitation on our method. Instead, we explore the effects of polymer rotations and intermolecular interactions at extremely high DNA concentrations and postulate that these may have both negative and positive influences on the separation depending on the detailed experimental conditions.


Low pathogenic avian influenza (H7N1) transmission between wild ducks and domestic ducks.
This article describes a virological investigation in a mixed flock of ducks and geese following detection of avian influenza virus antibodies in domestic geese. Low pathogenic H7N1 was found in both domestic and wild birds, indicating that transmission of virus was likely to have taken place between these. The importance of implementing and maintaining appropriate biosecurity measures is re-emphasized.


The entirely carbohydrate immunogen Tn-PS A1 induces a cancer cell selective immune response and cytokine IL-17.
The tumor-associated carbohydrate antigen/hapten Thomsen-nouveau (Tn; a-D-GalpNAc-ONH2) was conjugated to a zwitterionic capsular polysaccharide, PS A1, from commensal anaerobe Bacteroides fragilis ATCC 25285/NCTC 9343 for the development of an entirely carbohydrate cancer vaccine construct and probed for immunogenicity. This communication discloses that murine anti-Tn IgG3 antibodies both bind to and recognize human tumor cells that display the Tn hapten. Furthermore, the sera from immunization of mice with Tn-PS A1 contain cytokine interleukin 17 (IL-17A), which is known to possess anti-tumor function and represents a striking difference to an IL-2, and IL-6 profile obtained with anti-PS A1 sera.


Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts.
Targeted RNA-Seq combines next-generation sequencing with capture of sequences from a relevant subset of a transcriptome. When testing by capturing sequences from a tumor cDNA library by hybridization to oligonucleotide probes specific for 467 cancer-related genes, this method showed high selectivity, improved mutation detection enabling discovery of novel chimeric transcripts, and provided RNA expression data. Thus, targeted RNA-Seq produces an enhanced view of the molecular state of a set of "high interest" genes.


Comprehensive analysis of N6-methyladenosine-related lncRNAs reveals distinct hepatocellular carcinoma subtypes with immunotherapeutic implications.
Accumulating studies have demonstrated critical roles of N6-methyladenosine (m6A) modification and long noncoding RNAs (lncRNAs) in the biological processes leading to occurrence, development and chemoresistance of cancers. However, the specific identities and functional roles of lncRNAs associated with m6A modification in hepatocellular carcinoma (HCC) remain elusive. In this study, eighty-two prognostic m6A-related lncRNAs (m6A-LncRNAs) were identified in HCC datasets. Patients with HCC were classified into three subtypes (C1, C2 and C3) based on the expression of the m6A-LncRNAs. The three subtypes showed significant differences in clinical features, immune and stromal infiltration signatures, and immunotherapy sensitivity. Subclass C1 was notable for high immune and stromal cell infiltration and active immune responses, low serum α-fetoprotein (AFP) levels and high sensitivity to immune checkpoint inhibitors (ICIs). Subclass C2 showed high metabolic activities and absence of immune infiltration with favorable prognosis. Subclass C3 was associated with an exhausted immune environment, high serum AFP and poor prognosis. Notably, subclass C3 displayed high expression of immune checkpoints but failed to respond to ICIs. Finally, 12 m6A-LncRNA signatures were identified for HCC classification and validated in an external dataset. This integrated analysis indicated that the interactions between m6A methylation and lncRNAs are involved in immune and stromal cell infiltration in HCC, and may provide novel insights into precision diagnostics as well as therapeutics for HCC patients.


Hybrid Control of Digital Baker Map with Application to Pseudo-Random Number Generator.
Dynamical degradation occurs when chaotic systems are implemented on digital devices, which seriously threatens the security of chaos-based cryptosystems. The existing solutions mainly focus on the compensation of dynamical properties rather than on the elimination of the inherent biases of chaotic systems. In this paper, a unidirectional hybrid control method is proposed to improve the dynamical properties and to eliminate the biases of digital chaotic maps. A continuous chaotic system is introduced to provide external feedback control of the given digital chaotic map. Three different control modes are investigated, and the influence of control parameter on the properties of the controlled system is discussed. The experimental results show that the proposed method can not only improve the dynamical degradation of the digital chaotic map but also make the controlled digital system produce outputs with desirable performances. Finally, a pseudorandom number generator (PRNG) is proposed. Statistical analysis shows that the PRNG has good randomness and almost ideal entropy values.


Protective Effect of Mulberry (Morus alba L.) Extract against Benzo[a]pyrene Induced Skin Damage through Inhibition of Aryl Hydrocarbon Receptor Signaling.
Benzo[a]pyrene (B[a]P), a type of polycyclic aromatic hydrocarbon, is present in the atmosphere surrounding our environment. Although B[a]P is a procarcinogen, enzymatically metabolized benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) could intercalate into DNA to form bulky BPDE-DNA adducts as an ultimate carcinogenic product in human keratinocytes. The aim of this study was to evaluate the protective effect of mulberry extract, purified from the fruit of Morus Alba L., on B[a]P-induced cytotoxicity in human keratinocytes and its mechanisms of action. In this study, we confirmed that B[a]P induced nuclear translocation and the activation of aryl hydrocarbon receptor (AhR) were decreased by pretreatment of mulberry extract. Mulberry extract could decrease DNA damage through the suppression of B[a]P derived DNA adduct formation and restoration of cell cycle retardation at S phase in a dose-dependent manner. Additionally, cyanidin-3-glucoside (C3G), a major active compound of mulberry extract, showed biological activities to protect the cells from B[a]P exposure, similar to the effectivity of the mulberry extract. These results indicated that the inhibitory effect of C3G against B[a]P inducing skin cancer is attributable to repress the AhR signaling pathway.


Aging: physiological aspects and clinical implications.
Aging is not a new phenomenon, yet the physiology of aging is little understood. Several theories have been formulated to explain the aging process, ranging from immunological to free-radical theories of aging. Although the etiology of aging is important to understand, equally important is the differentiation of normal physiological changes from those associated with disease. The clinician's inability to recognize these differences may result in unnecessary testing, misdiagnoses and mismanagement of the elderly client. In addition, many of the changes associated with aging (e.g., decrease in visual acuity, impaired hearing) are potential hazards. One major role for the health care provider is to anticipate these changes, prepare the elderly client for them, and assist the elderly client in adapting to them. This article summarizes the physiological aspects of aging in the absence of disease and discusses some of the clinical implications related to these changes. Each system is addressed separately, as are the clinical implications related to that system.


The collagen network of the heart.
An extensive collagen skeleton in the myocardium is clearly demonstrable by scanning electron microscopy. This system mechanically connects myocytes to contiguous myocytes, connects myocytes to contiguous capillaries, and is responsible for orienting myocytes into anatomical units. The extent and location of the system involves it in a variety of physical parameters of the heart under both normal and abnormal conditions. The myocyte to myocyte collagen struts may provide for sarcomere alignment from cell to cell, ensure equal stretch of contiguous cells, and prevent slippage of adjacent cells. The numerous myocyte to web network connections would ensure that the entire group of cells function in a consistent fashion. The origin and course of the myocyte to capillary collagen struts could account for capillary patency during systole in the presence of high ventricular wall pressures. The complex web network surrounds groups of myocytes and is mechanically coupled to the contained myocytes. The loose collagen connections between groups easily permits slippage and rearrangement of groups of cells as expected in acute dilation. The web network itself could be the site of some of the viscoelastic properties of the heart.


Growth hormone response to a bolus injection of 1-44 growth-hormone-releasing hormone in very short children with intrauterine onset of growth failure.
The release of growth hormone (GH) during the 120 min following a bolus venous injection of 1-44 GH-releasing hormone (GHRH) 2 micrograms/kg was studied in 52 prepubertal children aged 8.4 +/- 2.1 years, having a nonfamilial growth deficiency of prenatal onset (-3.26 +/- 1.13 SDS at birth, -3.22 +/- 0.88 SDS at the time of study) and a normal response to conventional GH stimulation tests. GH release reached a peak level of 96.1 +/- 60.2 microU/ml, being significantly higher than that found in 68 non-GH-deficient very short children whose growth failure had a postnatal onset, and not significantly correlated with the response to conventional tests. 26 of the 52 intrauterine growth retardation (IUGR) patients were re-tested with GHRH in similar conditions after 6-12 months of daily subcutaneous injections of GH and 2 days without. They reached at the second test a peak plasma GH level of 91.7 +/- 56.1 microU/ml, not different from their response to the first test. These data could be taken into consideration for long-term studies of the clinical effects of GH in IUGR children with persisting severe growth deficiency.


Stabilization of Labile Lysozyme-Ligand Interactions in Native Electrospray Ionization Mass Spectrometry.
Flavonoids are polyphenolic secondary metabolites with extensive biological activities and pharmacological effects. Exploring the interactions of flavonoids with proteins may be helpful for understanding their biological processes. Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool to characterize the noncovalent protein-ligand (PL) complexes. However, some protein-flavonoid complexes are labile during electrospray ionization. Here, the labile lysozyme-flavonoid (rutin, icariin, and naringin) complexes were determined by direct ESI-MS without derivation. It has been found that low amounts of N-methylpyrrolidinone and dimethylformamide can protect labile lysozyme-flavonoid complexes away from dissociation during electrospray ionization process. The intact lysozyme-flavonoid complexes were specifically observed in mass spectra, and the measured binding affinities by ESI-MS were matched with the fluorescence data. The effects of additives on the analysis of lysozyme-flavonoid complexes were investigated by ESI-MS, combined with the molecular docking and fluorescence. This strategy was helpful to investigate the labile PL interactions by direct ESI-MS.


Severe 25(OH)vitamin-D deficiency: A risk factor for development of gestational diabetes mellitus.
To estimate the level of 25 (OH)vitamin D in gestational diabetes mellitus (GDM) and to find the correlation between level of 25(OH)vitamin D and GDM. The study was conducted on 50 diagnosed patients of GDM attending antenatal clinic in the obstetrics and gynecology department of Pt. B.D. Sharma PGIMS, Rohtak. 50 age and gestational age matched normoglycemic women were taken as control group. Procedure of study was explained to the participants and informed consent was taken. GDM women had higher age, BMI, and positive family history of type 2 DM as compared to pregnant women without GDM. The mean vitamin D in GDM women was 32.64 ± 24.33 nmol/L while in controls it was 39.90 ± 21.86 nmol/L(P = 0.033). The prevalence of severe vitamin D deficiency(<25 nmol/L) was found to be 44% among GDM women (22 out of 50 GDM women) and 20% among women with normoglycemia (10 out of 50 normoglycemic controls) with significant p value of 0.010 and odds ratio of 1.833. GDM women with BMI>25 kg/m2 had 1.799 times chances to be severely deficit in vitamin D than women with BMI<25 kg/m2 6 GDM women had mild vitamin D deficiency (>50 but <75 nmol/L) and 16 had moderate deficiency (>25 but <50 nmol/L). Only 6 GDM patients were found to be sufficient for vitamin D(>75 nmol/L). Severe vitamin D deficiency in second trimester of pregnancy is significantly associated with elevated risk for GDM.


Tailoring the CRISPR system to transactivate coagulation gene promoters in normal and mutated contexts.
Engineered transcription factors (TF) have expanded our ability to modulate gene expression and hold great promise as bio-therapeutics. The first-generation TF, based on Zinc Fingers or Transcription-Activator-like Effectors (TALE), required complex and time-consuming assembly protocols, and were indeed replaced in recent years by the CRISPR activation (CRISPRa) technology. Here, with coagulation F7/F8 gene promoters as models, we exploited a CRISPRa system based on deactivated (d)Cas9, fused with a transcriptional activator (VPR), which is driven to its target by a single guide (sg)RNA. Reporter gene assays in hepatoma cells identified a sgRNA (sgRNAF7.5) triggering a ~35-fold increase in the activity of F7 promoter, either wild-type, or defective due to the c.-61T>G mutation. The effect was higher (~15-fold) than that of an engineered TALE-TF (TF4) targeting the same promoter region. Noticeably, when challenged on the endogenous F7 gene, the dCas9-VPR/sgRNAF7.5 combination was more efficient (~6.5-fold) in promoting factor VII (FVII) protein secretion/activity than TF4 (~3.8-fold). The approach was translated to the promoter of F8, whose reduced expression causes hemophilia A. Reporter gene assays in hepatic and endothelial cells identified sgRNAs that, respectively, appreciably increased F8 promoter activity (sgRNAF8.1, ~8-fold and 3-fold; sgRNAF8.2, ~19-fold and 2-fold) with synergistic effects (~38-fold and 2.7-fold). Since modest increases in F7/F8 expression would ameliorate patients' phenotype, the CRISPRa-mediated transactivation extent might approach the low therapeutic threshold. Through this pioneer study we demonstrated that the CRISPRa system is easily tailorable to increase expression, or rescue disease-causing mutations, of different promoters, with potential intriguing implications for human disease models.


Immunotherapy in Genitourinary Cancers: Role of Surgical Pathologist for Detection of Immunooncologic Predictive Factors.
Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis, and testicles. Each tumor entity presents with unique biological characteristics, especially in terms of immunobiology. The immune landscape of genitourinary malignancies differs between immunoreactive tumors like urothelial carcinoma or carcinomas of the kidney, for which several immunotherapeutic treatment options have been approved in the past years. In contrast, prostate cancer presents with low immunogenicity and previous trials exploring immune checkpoint inhibitors and other immunotherapeutic agents did not proof substantial survival benefits. In this review, we are presenting a streamlined overview on the role of surgical pathologists within the contemporary practice of immune oncology. It includes current indications for pathologic programmed death-ligand 1 (PD-L1) assessment and important pathologic considerations on PD-L1 testing harmonization including interassay and algorithm variabilities. In addition, we will discuss emerging biomarkers beyond PD-L1 and their potential to predict immunotherapy responses including tumor mutational burden, microsatellite instability, gene expression signatures, and histologic factors.


Lyophilization of cationic lipid-protamine-DNA (LPD) complexes.
Cationic lipid-based gene delivery systems have shown promise in transfecting cells both in vitro and in vivo. However, these systems tend to form aggregates in liquid formulation during storage, which has limited their clinical applications. As a result, lyophilization of these systems has recently become a subject of increasing interest. In this paper, lyophilization of LPD, a novel cationic lipid-based gene delivery system, was studied. Both particle size and transfection efficiency could be preserved in the presence of sufficient amount of appropriate lyoprotectant. A series of monosaccharides and disaccharides, including dextrose, galactose, mannose, lactose, maltose, sucrose and trehalose, were evaluated for their lyoprotective effect and disaccharides showed more superior protection to monosaccharides. The effect of different freezing protocols for lyophilization was also evaluated and no significant difference was found. However, for freeze-thawing, fast freezing caused less aggregation. Finally, nonlyophilized LPD and LPD lyophilized with 10% sucrose were stored at different temperatures and their stability was followed for eight weeks. Lyophilized LPD could be stored at room temperature without significant change in particle size or loss of transfection efficiency.


Quantile regression for survival data in modern cancer research: expanding statistical tools for precision medicine.
Quantile regression links the whole distribution of an outcome to the covariates of interest and has become an important alternative to commonly used regression models. However, the presence of censored data such as survival time, often the main endpoint in cancer studies, has hampered the use of quantile regression techniques because of the incompleteness of data. With the advent of the precision medicine era and availability of high throughput data, quantile regression with high-dimensional predictors has attracted much attention and provided added insight compared to traditional regression approaches. This paper provides a practical guide for using quantile regression for right censored outcome data with covariates of low- or high-dimensionality. We frame our discussion using a dataset from the Boston Lung Cancer Survivor Cohort, a hospital-based prospective cohort study, with the goals of broadening the scope of cancer research, maximizing the utility of collected data, and offering useful statistical alternatives. We use quantile regression to identify clinical and molecular predictors, for example CpG methylation sites, associated with high-risk lung cancer patients, for example those with short survival.


Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis.
Prevention of inflammatory bowel disease (IBD) relies on tight control of inflammatory, cell death and autophagic mechanisms, but how these pathways are integrated at the molecular level is still unclear. Here we show that the anti-inflammatory protein A20 and the critical autophagic mediator Atg16l1 physically interact and synergize to regulate the stability of the intestinal epithelial barrier. A proteomic screen using the WD40 domain of ATG16L1 (WDD) identified A20 as a WDD-interacting protein. Loss of A20 and Atg16l1 in mouse intestinal epithelium induces spontaneous IBD-like pathology, as characterized by severe inflammation and increased intestinal epithelial cell death in both small and large intestine. Mechanistically, absence of A20 promotes Atg16l1 accumulation, while elimination of Atg16l1 or expression of WDD-deficient Atg16l1 stabilizes A20. Collectively our data show that A20 and Atg16l1 cooperatively control intestinal homeostasis by acting at the intersection of inflammatory, autophagy and cell death pathways.


Transcutaneous acupoint electrical stimulation in preventing and treating nausea and vomiting in patients receiving electroconvulsive therapy.
A significant number of patients complain of nausea after general anesthesia and electroconvulsive therapy (ECT). Nausea is second only to headache as the most frequent and troublesome systemic side effect of ECT. The most common treatment of this is antiemetic drugs. Transcutaneous acupoint electrical stimulation (TAES) is a nonpharmacologic method for preventing and treating nausea and vomiting. TAES can alleviate motion sickness, reduce the incidence of vomiting caused by chemotherapy, and treat pregnancy-induced nausea and vomiting. TAES has been shown to reduce the incidence of postoperative nausea after general anesthesia. This is the first report to review the effectiveness of TAES in preventing and treating nausea and vomiting in 11 patients receiving ECT. Nine of these patients had a good response to TAES. One patient had a mixed response, and 1 did not respond to TAES.


ARD1-mediated aurora kinase A acetylation promotes cell proliferation and migration.
Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125. The double mutations at K75/K125 abolished the kinase activity of AuA. Moreover, the double mutant AuA exhibited diminished ability to promote cell proliferation and cell migration. Mechanistic studies revealed that AuA acetylation at K75/K125 promoted cell proliferation via activation of cyclin E/CDK2 and cyclin B1. In addition, AuA acetylation stimulated cell migration by activating the p38/AKT/MMP-2 pathway. Our findings indicate that ARD1-mediated acetylation of AuA enhances cell proliferation and migration, and probably contributes to cancer development.


Effects of heat treatment on Raman spectra of two-layer 12C/13C graphene.
The Raman spectra of two-layered graphene on a silicon substrate were studied in the temperature range from 298 to 1073 K in an inert atmosphere. Isotopic engineering was used to fabricate two-layer graphene specimens containing (13)C atoms in the top layer and (12)C atoms in the bottom layer, which allowed the behavior of each particular layer to be distinguished as a function of temperature. It is demonstrated that the top layer exhibits much lower Raman temperature coefficients than the bottom one for both the G and the G' modes. We suggest that the changes in the Raman spectra of graphene observed during thermal cycling are predominantly caused by a superposition of two effects, namely, the mechanical stress in graphene exerted by the substrate and the intrinsic changes in the graphene lattice caused by the temperature itself. The top graphene layer is proposed to be more relaxed than the bottom graphene layer and thus reflects almost exclusively the temperature variations as a freestanding graphene layer would.


Removal of aldrin, dieldrin, heptachlor, and heptachlor epoxide using activated carbon and/or Pseudomonas fluorescens free cell cultures.
Degradation of aldrin (1,2,3,4,10,10-Hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5-8-dimethanonaphthalene), heptachlor (1H-1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methano indene), dieldrin (1aalpha,2beta,2aalpha,3beta,6beta,6aalpha,7beta,7aalpha)-3,4,5,6,9,9-Hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-2,7:3,6-d-methanonaphtha[2,3-b]oxirene, and heptachlor epoxide (1aalpha, 1bbeta,2alpha,5alpha,5alphabeta,6beta,6aalpha-2,3,4,5,6,7,7-Heptachloro-1a,1b,5,5a,6,6a-hexahydro-2,5-methano-2H-inden[1,2-b]-oxirene) was tested using free cultures of Pseudomonas fluorescens under controlled conditions. Pesticide concentrations were monitored by gas chromatography during 120 h. Percentages of degradation and biodegradation rates (BDR) were calculated. Data showed a trend suggesting a relation between chemical structure and degradability. Degradation kinetics for each pesticide tested showed that the highest degradation rates were found in the first 24 h. Kinetics data were adjusted to an empirical equation in order to predict their behavior, and the correlation coefficients obtained were satisfactory. Gas chromatography/mass spectrometry (GC/MS) analysis of the final extracts allowed the identification of chlordene and monodechlorodieldrin, which have been reported as final metabolite produced in the biodegradation of this kind of compounds. Regarding adsorption of pesticides on activated vegetal carbon, we concluded that removal efficiencies between 95.45 and 97.18% can be reached, depending on the pesticide and the carbon dose applied. The values for K from the Freundlich equation were quite similar for the four pesticides (between 1.0001 and 1.04), whereas the n values were quite different for each pesticide in the following order of affinity: dieldrin > aldrin > heptachlor epoxide > heptachlor. Equilibrium times, very important for scaling up the process, were between 43 min and 1 h, for the heptachlor epoxide and the heptachlor, respectively.


Prospects of high-resolution resonant X-ray inelastic scattering studies on solid materials, liquids and gases at diffraction-limited storage rings.
The spectroscopic technique of resonant inelastic X-ray scattering (RIXS) will particularly profit from immensely improved brilliance of diffraction-limited storage rings (DLSRs). In RIXS one measures the intensities of excitations as a function of energy and momentum transfer. DLSRs will allow for pushing the achievable energy resolution, signal intensity and the sampled spot size to new limits. With RIXS one nowadays probes a broad range of electronic systems reaching from simple molecules to complex materials displaying phenomena like peculiar magnetism, two-dimensional electron gases, superconductivity, photovoltaic energy conversion and heterogeneous catalysis. In this article the types of improved RIXS studies that will become possible with X-ray beams from DLSRs are envisioned.


Paclitaxel alleviates liver fibrosis induced by bile duct ligation in rats: Role of TGF-β1, IL-10 and c-Myc.
Liver fibrosis is a global health issue that causes morbidity and mortality with no currently available treatment. It has been shown that low dose paclitaxel (PTX) can stabilize microtubules and inhibit the profibrotic transforming growth factor-beta 1 (TGF-β1) signaling pathway. In this study the effect of treatment with low dose PTX was examined using a model of cholestatic liver fibrosis. Bile-duct ligation (BDL) was induced in rats for 2 weeks then PTX (0.3 mg/kg/ip) was administered three times a week for 2 weeks. Administration of PTX ameliorated BDL-induced elevation in biomarkers of hepatocellular damage (alanine transaminase; ALT and aspartate transaminase; AST) and obstructive cholestatic injury (total bilirubin and gamma glutamyl transferase; γ-GT). PTX was able to correct the increase in liver weight to body weight ratio and the bile duct proliferation induced by BDL. Additionally, PTX treatment corrected the BDL-induced fibrosis of portal tracts, elevation of hydroxyproline content and increased alpha smooth muscle actin (α-SMA) mRNA and protein expression. This antifibrotic effect of PTX was further examined through its inhibitory effect on TGF-β1 mRNA and protein expression in addition to c-Myc mRNA expression. Furthermore, PTX rectified the BDL-induced decrease in interleukin-10 (IL-10) mRNA and protein expression. In conclusion, this study suggests that PTX at low dose has the potential to treat BDL-induced liver fibrosis in rats possibly through suppression of TGF-β1 and c-Myc and activation of IL-10 pathways.


A revision of the planthopper genus Chionomus Fennah (Hemiptera: Fulgoroidea: Delphacidae).
The planthopper genus Chionomus Fennah, 1971 (Hemiptera: Fulgoroidea: Delphacidae) currently includes three Neotropical species, removed from the polyphyletic genus Delphacodes Fieber, 1866. Morphological and molecular evidence further redefine Chionomus to include ten additional species (eight species removed from Delphacodes, two described as new, viz. Chionomus dolonus n. sp. and C. herkos n. sp.), with another four species synonymized. Phylogenetic analyses of morphological and molecular sequence data of the mitochondrial gene Cytochrome Oxidase I provide support for the monophyly of Chionomus. We use a mixed model Bayesian optimality criterion to define phylogenetic relationships among Chionomus and support paraphyly of the original definition of Chionomus (with respect to Delphacodes) and monophyly of the revised genus.


Endovascular repair of diffuse atherosclerotic occlusive disease using stented grafts.
Minimally invasive techniques have greatly influenced the practice of surgery in the past two decades, especially the vascular surgical specialty. Current technological advances and refinements have allowed for the application of less invasive or percutaneous endovascular techniques to the treatment of arterial aneurysms and peripheral vascular occlusive disease. While balloon angioplasty and stenting for occlusive disease have proven successful in certain vascular beds (such as common iliac arteries), infrainguinal results are generally less impressive. This paper reviews the results of the application of covered stent-grafts to peripheral arterial occlusive disease, both at the aortoiliac and infrainguinal anatomical levels. The review includes the results of iliac artery stented graft placement utilizing a combined open surgical and endovascular technique at Mount Sinai Medical Center.


The Influence of Basic Psychological Needs and Passion in Promoting Elite Young Football Players' Development.
Motivational variables and cognitive skills have been identified as important in an athlete's development. The aim of this study is to explore the influence of each basic psychological needs satisfaction on player's development regarding reflection and concentration disruption with the mediation of types of passion in Spanish young elite football players. A total of 487 elite U18 male football players (Mage = 17.43, SD = 0.71) completed measures of basic psychological needs satisfaction, passion for football, reflective thinking, and concentration disruption. Measurement models were defined using exploratory structural equation models. The results provide support for the model, where each psychological needs satisfaction prompted reflection and had a negative influence on concentration disruption with the mediation of harmonious passion. In addition, obsessive passion mediated the positive relationship between competence satisfaction and concentration disruption. Finally, competence and relatedness satisfaction influenced the development of reflection directly and positively and, exclusively, relatedness satisfaction had a negative influence in a direct way on concentration disruption. In sum, our results highlight that (a) the environment of young footballers through psychological needs satisfaction has a positive (i.e., reflection) or negative (i.e., concentration disruption) influence on the field, but only with the mediation of harmonious passion, (b) in a competitive environment, the perception of competence can have a positive influence on concentration disruption, but only with the development of obsessive passion as a mediator, and (c) relatedness satisfaction plays a key role in distinguishing between reflection and concentration disruption.


Enhanced Signal-to-Noise and Fast Calibration of Optical Tweezers Using Single Trapping Events.
The trap stiffness us the key property in using optical tweezers as a force transducer. Force reconstruction via maximum-likelihood-estimator analysis (FORMA) determines the optical trap stiffness based on estimation of the particle velocity from statistical trajectories. Using a modification of this technique, we determine the trap stiffness for a two micron particle within 2 ms to a precision of ∼10% using camera measurements at 10 kfps with the contribution of pixel noise to the signal being larger the level Brownian motion. This is done by observing a particle fall into an optical trap once at a high stiffness. This type of calibration is attractive, as it avoids the use of a nanopositioning stage, which makes it ideal for systems of large numbers of particles, e.g., micro-fluidics or active matter systems.


Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis.
Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015-2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03-4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50-10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16-2.06]; Pinteraction=0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00-8.05] versus absent: aOR, 1.98 [95% CI, 0.65-6.03]; Pinteraction=0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25-11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01-3.83]; Pinteraction=0.16). Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.


Epidemiology of Kawasaki disease.
In this paper we review the main epidemiologic characteristics of Kawasaki disease (KD) and summarize the results of a prospective incidence survey conducted in Finland from 1981 to 1992, supplemented with some previously unpublished data. The epidemiologic features of KD have been well established in studies conducted during the past 20 years. However, continuous surveillance of KD is important to maintain a high level of awareness of the disease and to detect possible new risk factors. Epidemiologic studies should also be focused on individuals who have had KD to ascertain the final outcome of the disease, including the possible risk of premature coronary atherosclerosis.


Diabetes quality of care at a university community in Beirut.
To assess the quality of diabetes mellitus (DM) care provided by a group of family doctors in Beirut. An observational study, conducted at the American University of Beirut Medical Center-Family Medicine Clinics (AUBMC-FMC), examined the electronic health records (EHRs) of the beneficiaries of the Health Insurance Plan at the American University of Beirut (AUB-HIP) who were older than 20 years (n = 9469) in 2009. The eligible population included patients with DM (n = 701). Several provider/patient-directed interventions were introduced in the late 2000s, including a comprehensive EHRs system with point-of-care computer reminders, a provider financial incentive based on an annual performance appraisal ranked against that of the US Healthcare Effectiveness Data and Information Set (HEDIS) Comprehensive Diabetes Care indicators, as well as periodic up-to-date training. Optimal control for HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and blood pressure were found in 58.6%, 51.0%, 22.4%, 53.3% and 60.2% of the population, respectively. 64.1% and 70.0% received screening for diabetic nephropathy and a dilated eye examination, respectively. When benchmarked against the HEDIS Comprehensive Diabetes Care indicators, the AUB-HIP's quality of care was 13% higher than the average of all plans in the United States. Screening for nephropathy, however, did not reach the above benchmark. Benchmarking served as an important tool in evaluating the current DM care offered and in detecting gaps, yet interventions are recommended for further improvement.


Calibration and reliability of a school food checklist: a new tool for assessing school food and beverage consumption.
There is a pressing need in Australia and other countries to develop systems for monitoring secular trends in childhood obesity and related behavioural and environmental determinants. Energy from foods and beverages consumed at school is an accessible indicator of children's eating patterns and we have developed a school food checklist (SFC) to measure this. The SFC records the number of serves and source (home, canteen, vending machine) of 20 food and beverage categories. This study aims to assess the accuracy and to calibrate the SFC by comparing it to a weighed record (WR) and to evaluate inter-recorder reliability. Participants were 910 primary school children aged 5 to 12 years from a rural township in Victoria, Australia. WR were collected from a non-random sub-sample of 106 and a second sub-sample (n=46) had intake measured twice using the SFC to assess inter-recorder reliability. Mean energy values were 2992 kJ +/- 924 and 3008 kJ +/- 952 for the SFC and WR respectively and the correlation coefficient was strong (Pearson r = 0.77). The mean difference between the WR and SFC methods was 15 kJ (95% CI, -107 kJ to 138 kJ) and the limits of agreement (+2 standard deviations) were +/- 1270 kJ. The SFC overestimated the energy/serve of breads and fruit drinks and under-estimated energy/serve from fat spreads, biscuits/crackers, muesli/fruit bars and fruit. Inter-recorder reliability was good (kappa 0.51). The SFC was designed to measure energy from food and beverages in schools. It has good accuracy and reliability and the revised version should further improve accuracy of the instrument.


Relation of blood glucose levels to the changes in plasma levels of various hydrolytic enzymes in diabetic patients.
Plasma levels of various hydrolytic enzymes in diabetic patients, as diagnosed by their blood glucose levels, were compared with those of control subjects. Most of the levels of the aminopeptidase activities examined were significantly increased, while those of angiotensin-converting enzyme (ACE) and esterase decreased, in diabetic patients. The results of multivariate analysis suggest that the increased aminopeptidase activities are related rather to secondary organ lesions than to the primary pancreatic lesion. It seems that the blood glucose level is not necessarily a good indicator of metabolic abnormalities underlying this pathological condition.


A comparative study on healthcare employee satisfaction between Japan and China.
To explore essential characteristics of healthcare employee satisfaction by comparing Japan and China in terms of job satisfaction model, satisfaction level, and the crucial factors predicting overall job satisfaction. A questionnaire was developed with 35 facet-specific job-related satisfaction and 10 general satisfaction items. The Japanese survey collected 474 responses (74% response rate). Two additional items were added in the Chinese survey and 429 responses were collected (69%). The same five-factor satisfaction model was acquired from both countries with an additional factor labelled "relationship with patients" for China. Applying these factors, a moderate satisfaction level was observed for all professional groups in China, whereas it varied in Japan. A moderate-to-high satisfaction was seen for physicians, a moderate level for pharmacists and technologists, and a low level for nurses. Japanese physicians were significantly more satisfied than Chinese physicians, whereas Japanese nurses were less satisfied than Chinese nurses. Both countries shared crucial predictors of overall job satisfaction that were reputation, growth and development, and work demands and workload. Additionally, financial rewards and relationship with patients were critically important for the Chinese. Japanese and Chinese healthcare employees shared the job satisfaction model with an extra factor for Chinese. Satisfaction levels were similar for pharmacists and technologists in the two countries, but largely different for physicians and nurses. Because crucial satisfaction factors differed, it is suggested that strategies to improve job satisfaction should be specific to culture and profession, eg, in Chinese hospitals, management should support more to employees especially physicians for dealing with conflicts and medical disputes with patients.


[Laparoscopic appendectomy in advanced stages of appendicitis].
The laparoscopic stapling appendectomy (LA) is a safe and efficient procedure for all forms of appendicitis. Overall, LA was performed in 51.8% of 280 patients with advanced appendicitis, in 1998 in more than 85%, due to increasing experience. In these cases, the appendix was dissected in double-staple technique and extracted in an endo-bag. The postoperative outcome was uncomplicated even in advanced appendicitis, a reoperation had to be done in 2 patients (1.4%). Wound infections occurred only in 3.5% of patients with LA compared to 8.2% with open appendectomy, the mortality was 0%.


Considering complementary and alternative medicine alternatives in cases of life-threatening illness: applying the best-interests test.
In this article we explore decision-making about treatment when a child faces a life-threatening illness but conventional treatment presents substantial risk and uncertain benefit. When is it acceptable for parents to decide to use complementary and alternative medicine as an alternative, rather than a complement, to conventional care? We use the example of a young child suffering from progressive glycogen storage disease, for whom liver transplant offers the only prospect of a cure. Without a liver transplant, the disease usually results in death within a few years. However, experience using transplant to treat this illness has been limited, success is far from ensured, and the risks (including death and continued progression of the disease) are substantial. The child's parents, who are first-generation immigrants, consider the risks of the transplant unjustified because it still does not offer good prospects for a healthy future. They believe that traditional Chinese medicine could help remediate their daughter's disease. In the article we (1) review parents' obligation to make treatment decisions in the best interests of their child, (2) explain limits on parents' decision-making authority, (3) explore how "best interests" are determined, focusing on cases of serious illness for which conventional treatment is risky and benefit is possible but uncertain, (4) explain the standard of care that physicians must meet in advising about treatment, and (5) outline factors that clinicians and parents should take into account when making decisions.


[Current concepts in the acute treatment of cerebrovascular insults].
Up to the present, treatment strategies for acute cerebral ischemia have not shown scientifically proven efficacy. Based upon new knowledge on stroke pathogenesis and experimental data, new concepts of cerebral ischemia treatment are being clinically tested. The main therapeutic instrument is clot lysis by systemic or local application of thrombolytic drugs or the use of cytoprotective agents. For both treatment strategies clinical trials to show efficacy are ongoing or planned. Early reperfusion can be obtained by fibrinolysis, but its clinical usefulness has yet to be proven.


Heightened circulating levels of antimicrobial peptides in tuberculosis-Diabetes co-morbidity and reversal upon treatment.
The association of antimicrobial peptides (AMPs) with tuberculosis-diabetes comorbidity (PTB-DM) is not well understood. To study the association of AMPs with PTB-DM, we examined the systemic levels of cathelicidin (LL37), human beta defensin- 2 (HBD2), human neutrophil peptides 1-3, (HNP1-3) and granulysin in individuals with either PTB-DM, PTB, latent TB (LTB) or no TB infection (NTB). Circulating levels of cathelicidin and HBD2 were significantly higher and granulysin levels were significantly lower in PTB-DM compared to PTB, LTB or NTB, while the levels of HNP1-3 were significantly higher in PTB-DM compared to LTB or NTB individuals. Moreover, the levels of cathelicidin and/or HBD2 were significantly higher in PTB-DM or PTB individuals with bilateral and cavitary disease and also exhibited a significant positive relationship with bacterial burden. Cathelidin, HBD2 and HNP1-3 levels exhibited a positive relationship with HbA1c and/or fasting blood glucose levels. Finally, anti-tuberculosis therapy resulted in significantly diminished levels of cathelicidin, HBD2, granulysin and significantly enhanced levels of HNP1-3 and granulysin in PTB-DM and/or PTB individuals. Therefore, our data demonstrate that PTB-DM is associated with markedly enhanced levels of AMPs and diminished levels of granulysin.


Influence of dietary conjugated linoleic acids (CLA) and age at slaughtering on meat quality and intramuscular collagen in rabbits.
To assess the effects of dietary conjugated linoleic acids (CLA) on meat composition and intramuscular collagen (IMC), 144 New Zealand White rabbits, half males half females, 55 days old (1.8 kg LW), were assigned to three weight- and sex- balanced groups and given the following dietary supplements: 0.5% sunflower oil, (C); 0.25% sunflower oil plus 0.25% CLA (T1); and 0.5% CLA (T2). The CLA was prepared from sunflower oil and contained 65% CLA isomers, half cis-9, trans-11 and half trans-10, cis-12. Six males and six females from each group (total 36) were slaughtered at 76, 90 and 104 days of age (corresponding to 2.5, 2.8, and 3.1 kg BW, respectively). The lean fraction was higher and the water content significantly higher in the meat of T2 compared to C and T1 for all ages combined. At the third slaughtering (104 days) the meat fat content was significantly lower in group T2. For all ages combined, IMC content, IMC hydroxylysylpyridinoline (HLP) concentration (index of collagen cross-linking) and IMC maturity (HLP/IMC) were significantly lower in the intermediate supplementation group (T1) compared to C and T2, and were also lower in animals slaughtered at 90 days. CLA supplementation has limited effects on the chemical composition of rabbit meat, with positive effects on meat texture and tenderness after supplementation up to 35 days at 0.25%, and a significant decrease in fat content only at high slaughter weight and high supplementation level (0.5%).


Maternal and neonatal sepsis caused by Haemophilus influenzae type d.
A 29-year-old pregnant woman was admitted to hospital with signs of sepsis and threatened pre-term labour. The premature neonate also showed signs of sepsis. Haemophilus influenzae biotype III was cultured from a midstream urine sample taken from the mother, maternal placental swabs and neonatal blood cultures. The placental and neonatal isolates were both found to be serotype d by PCR, and were indistinguishable by PFGE.


Circulating concentrations, cerebral output of the CINC-1 and blood–brain barrier disruption in Wistar rats after pneumococcal meningitis induction.
Pneumococcal meningitis is a severe infectious illness of the central nervous system (CNS), with high rates of lethality and morbidity, being that the microorganism and the host's inflammatory response are responsible for cerebral complications. Moreover, the blood–brain barrier (BBB) itself secretes cytokines and, because of the bipolar nature of the BBB, these substances can be secreted into either the CNS compartment or in the blood, so patients with acute bacterial meningitis frequently develop sepsis. Therefore, the aim of this study was to evaluate the cytokine/chemokine levels in different vessels and the BBB integrity after pneumococcal meningitis induction. Wistar rats were infected with Streptococcus pneumoniae, and the BBB integrity was investigated using Evan's blue dye. Also, blood from the carotid artery and jugular vein was collected in order to perform tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-60 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) analyses by enzyme-linked immunosorbent assay (ELISA). CINC-1 levels were increased at 6 h in the arterial plasma and at 3 and 6 h in the jugular plasma. We observed BBB breakdown between 12 and 24 h in the hippocampus and at 12 and 18 h in the cortex after pneumococcal meningitis induction. The increase of CINC-1 occurred prior to the BBB breakdown. CINC-1 is a neutrophil chemoattractant and it may be related to early events in the pneumococcal meningitis pathophysiology.


Partial breast radiation for early-stage breast cancer.
This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. Newly published retrospective studies, with follow-up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment.


Brodie Abscess in Children: A 10-Year Single Institution Retrospective Review.
Brodie abscess is a subacute hematogenous osteomyelitis characterized by intraosseous abscess formation. Treatment recommendations and clinical outcomes for this unusual infection are not well established. We report 15 cases of Brodie abscess in a 10-year retrospective review of pediatric patients at Texas Children's Hospital and describe their clinical presentation and outcomes.


Hydration, Orientation, and Conformation of Methylglyoxal at the Air-Water Interface.
Aqueous-phase processing of methylglyoxal (MG) has been suggested to constitute an important source of secondary organic aerosol (SOA). The uptake of MG to aqueous particles is higher than expected because its carbonyl moieties can hydrate to form geminal diols, as well as because MG and its hydration products can undergo aldol condensation reactions to form larger oligomers in solution. MG is known to be surface active, but an improved description of its surface behavior is crucial to understanding MG-SOA formation. These studies investigate MG adsorption, focusing on its hydration state at the air-water interface, using a combined experimental and theoretical approach that involves vibrational sum frequency spectroscopy, molecular dynamics simulations, and density functional theory calculations. Together, the experimental and theoretical data show that MG exists predominantly in a singly hydrated state (diol) at the interface, with a diol-tetrol ratio at the surface higher than that for the bulk. In addition to exhibiting a strong surface activity, we find that MG significantly perturbs the water structure at the interface. The results have implications for understanding the atmospheric fate of methylglyoxal.


Examining the state-trait anxiety relationship: a behavioural genetic approach.
State and trait anxiety define different aspects of anxiety, and may represent environmentally and genetically mediated components of this phenotype. Furthermore their relationship, where trait anxiety is expressed through levels of state anxiety under threatening circumstances, may represent a process of interplay between a genetic vulnerability factor and an environmental stressor. To test these hypotheses, we explored genetic and environmental influences on measures of state and trait anxiety in a sample of 1058 twins (521 males and 537 females) aged 8-16. The results were consistent with these hypotheses. State anxiety is largely influenced by environmental factors in males and females whereas trait anxiety shows moderate genetic effects and substantial non-shared environment effects. Their association was accounted for by non-shared environmental effects, with modest genetic and shared environmental inputs. The implications of these results for vulnerability mechanisms involving stress reactivity on anxiety are discussed.


New Technologies for Outcome Measures in Retinal Disease: Review from the European Vision Institute Special Interest Focus Group.
Novel diagnostic tools to measure retinal function and structure are rapidly being developed and introduced into clinical use. Opportunities exist to use these informative and robust measures as endpoints for clinical trials to determine efficacy and to monitor safety of therapeutic interventions. In order to inform researchers and clinician-scientists about these new diagnostic tools, a workshop was organized by the European Vision Institute. Invited speakers highlighted the recent advances in state-of-the-art technologies for outcome measures in the field of retina. This review highlights the workshop's presentations in the context of published literature.


Addressing Complex Matrix Interference Improves Multiplex Food Allergen Detection by Targeted LC-MS/MS.
The frequent use of precautionary food allergen labeling (PAL) such as "may contain" frustrates allergic individuals who rely on such labeling to determine whether a food is safe to consume. One technique to study whether foods contain allergens is targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) employing scheduled multiple reaction monitoring (MRM). However, the applicability of a single MRM method to many commercial foods is unknown as complex and heterogeneous interferences derived from the unique composition of each food matrix can hinder quantification of trace amounts of allergen contamination. We developed a freely available, open source software package MAtrix-Dependent Interference Correction (MADIC) to identify interference and applied it with a method targeting 14 allergens. Among 84 unique food products, we found patterns of allergen contamination such as wheat in grains, milk in chocolate-containing products, and soy in breads and corn flours. We also found additional instances of contamination in products with and without PAL as well as highly variable soy content in foods containing only soybean oil and/or soy lecithin. These results demonstrate the feasibility of applying LC-MS/MS to a variety of food products with sensitive detection of multiple allergens in spite of variable matrix interference.


Whole Body Vibration Exercise for Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
This study systematically reviews previous work on the effects of whole body vibration exercise (WBVE) on pain associated with chronic musculoskeletal disorders. Seven electronic databases (PubMed, Embase, CINAHL, Web of Science, Cochrane, Physiotherapy Evidence Database [PEDro], and the China National Knowledge Infrastructure) were searched for articles published between January 1980 and September 2018. Randomized controlled trials involving adults with chronic low back pain (CLBP), osteoarthritis (OA), or fibromyalgia were included. Participants in the WBVE intervention group were compared with those in the nontreatment and non-WBVE control groups. Data were independently extracted using a standardized form. Methodological quality was assessed using PEDro. Suitable data from 16 studies were pooled for meta-analysis. A random effects model was used to calculate between-groups mean differences at 95% confidence interval (CI). The data were analyzed depending on the duration of the follow-up, common disorders, and different control interventions. Alleviation of pain was observed at medium term (standardized mean difference [SMD], -0.67; 95% CI, -1.14 to -0.21; I2, 80%) and long term (SMD, -0.31; 95% CI, -0.59 to -0.02; I2, 0%). Pain was alleviated in osteoarthritis (OA) (SMD, -0.37; 95% CI, -0.64 to -0.10; P<.05; I2, 22%) and CLBP (SMD, -0.44; 95% CI, -0.75 to -0.13; P<.05; I2, 12%). Long-term WBVE could relieve chronic musculoskeletal pain conditions of OA (SMD, -0.46; 95% CI, -0.80 to -0.13; P<.05; I2, 0%). WBVE improved chronic musculoskeletal pain compared with the treatment "X" control (SMD, -0.37; 95% CI, -0.61 to -0.12; P<.05; I2, 26%), traditional treatment control (SMD, -1.02; 95% CI, -2.44 to 0.4; P>.05; I2, 94%) and no treatment control (SMD, -1; 95% CI, -1.76 to -0.24; P<.05; I2, 75%). Evidence suggests positive effects of WBVE on chronic musculoskeletal pain, and long durations of WBVE could be especially beneficial. However, WBVE does not significantly relieve chronic musculoskeletal pain compared with the traditional treatment. Further work is required to identify which parameters of WBVE are ideal for patients with chronic musculoskeletal pain.


Unveiling the molecular structure and two-photon absorption properties relationship of branched oligofluorenes.
Organic molecules have been intensively studied during the last few decades because of their photonics and biological applications. In this material class, the fluorene molecules present outstanding optical features, for example, high values of two-photon absorption (2PA) cross-sections, visible transparency, and high fluorescence quantum yield. Also, it is possible to improve the nonlinear optical response by modifying the fluorene molecular structure. In this context, herein, we have synthesized V and Y-shaped branching oligofluorenes containing two and three fluorene moieties in each branch. Such a molecular strategy may exponentially enhance the nonlinear optical response due to the coherent coupling among the molecular arms. Thus, we combined the use of femtosecond Z-scan spectroscopy and white light transient absorption spectroscopy (TAS) to understand the molecular structure and 2PA property relationship of branching oligofluorenes. The results show that there is a universal relationship between the 2PA cross-section and the effective π-electron number (Neff) given by σ2PA(GM) = (079 ± 0.03)Neff2, which is independent of the molecular shape (linear, V or Y-shaped). Therefore, the intramolecular charge transfer responsible for the cooperative effect among the branches does not occur. This statement is corroborated by the results of the femtosecond TAS technique.


Are children living near high-voltage power lines at increased risk of acute lymphoblastic leukemia?
In the National Cancer Institute/Children's Cancer Group case-control study of childhood acute lymphoblastic leukemia (1989-1993), living in a home with a high-voltage wire code was not associated with disease risk. To further investigate risk near power lines, the authors analyzed distance to transmission and three-phase primary distribution lines within 40 m of homes and created an exposure index of distance and strength of multiple power lines (408 case-control pairs). Neither distance nor exposure index was related to risk of childhood acute lymphoblastic leukemia, although both were associated with in-home magnetic field measurements. Residence near high-voltage lines did not increase risk.


Association of CHKA polymorphism (rs3794186) with α-fetoprotein levels in hepatocellular carcinoma.
Choline kinase α (CHKA) has been identified to be associated with cancer development and progression. In this study, we investigated whether exonic single nucleotide polymorphisms (SNPs) of the CHKA gene are associated with hepatocellular carcinoma (HCC). Among all SNPs in the 3'-untranslated region (UTR), 5'-UTR and the coding region of CHA, only two SNPs (rs3794186 and rs11481) in the 3'-UTR had a heterozygosity above 0.1 and a minor allele frequency above 0.1. Therefore, we selected and assessed these two SNPs (rs3794186 and rs11481) in 189 HCC patients and 194 controls. Genetic data were analyzed using the SNPAnalyzer Pro, SNPStats and Haploview programs. No SNPs of the CHKA gene were found to be associated with the risk of HCC development. Upon analysis of the clinical characteristics of HCC, the genotypic frequency of rs3794186 was significantly associated with serum α-fetoprotein (AFP) levels (P=0.022 in the co-dominant 1 model, P=0.0045 in the dominant model and P=0.0052 in the log-additive model). A significant difference in the allelic frequency of rs3794186 was also observed between the high AFP (>200 ng/ml) group and the low AFP (≤200 ng/ml) group [P=0.009, odds ratio (OR) = 0.33, 95% confidence interval (95% CI) = 0.14-0.75]. The T allele frequency of rs3794186 was lower in the high AFP group (6.6%) compared to that in the low AFP group (17.8%). Our results suggest that CHKA SNPs (rs3794186 and rs11481) are not associated with HCC development; however, rs3794186 may correlate with serum AFP levels in HCC.


[Hypertension and salt intake in an urban population].
To evaluate the salt intake and urinary Na+/K+ ratio in a randomized sample from an ethnically mixed urban population. A randomized residential sample of 2,268 individuals aged 25-64 in Vit ria, ES, was selected, of whom 1,663 (73.3%) reported to the hospital for standardized tests. Salt, Na+ and K+ intake was estimated from 12-hour urine excretion (7 p.m. to 7 a.m.) and from the monthly salt consumption at home reported in the interview. Clinic arterial pressure was measured twice under standard conditions by two trained investigators, using mercury sphygmomanometry. The Student t and Tukey tests were utilized for statistical analysis. Urinary Na+ excretion was higher in men and individuals of lower socioeconomic level (P<0.000). No difference between ethnic groups was observed. K+ excretion was unrelated to socioeconomic level and ethnicity, but was significantly higher among men (25 18 vs. 22 18 mEq/12h; P=0.002). Positive linear correlation was observed between urinary Na+ excretion and systolic (r=0.15) and diastolic (r=0.19) arterial pressure. Hypertensive individuals showed higher urinary Na+ excretion and Na+/K+ ratio than normotensive individuals. Reported salt intake was around 50% of the intake estimated from 12-hour urine collection (around 45% of 24-hour urinary excretion). Salt intake is strongly influenced by socioeconomic level and may partially explain the higher prevalence of hypertension in lower socioeconomic classes.


Unilateral scrotal pyocele in ram caused by Staphylococcus capitis.
A massive unilateral scrotal pyocele caused by Staphylococcus capitis in a 6-year-old ram is reported. Ultrasound examination of the right hemiscrotum showed an irregular hyperechoic mass in an anechoic fluid. A dense exudate was collected from the scrotum for microbiological analysis. Grossly, there was an extensive greenish purulent exudate and a completely atrophied right testis. Coagulase-negative S. capitis was isolated in pure culture. To the authors' knowledge, this is the first report of genital infection by S. capitis in rams. This microorganism should be included in the differential diagnosis of ovine genital infections.


Laryngohyoid and cervical vertebra lesions after a fall from a low height.
The aim of this study was to determine the frequency and nature of cervical trauma in the case of low-height falls (up to 2.50 m). A retrospective study was carried out on 114 autopsy cases that died after low-height falls. For each case, age, sex, manner and cause of death, estimated height of fall, ground type, type of primary impact, type of laryngeal and hyoid bone trauma, presence of associated local trauma in the neck and cephalic region, and toxicological data were reported. Fractures of the hyoid bone and/or of the laryngeal cartilages were present in 2.5% of the cases (n = 3). Cervical soft tissue bruising was found in 13% of the cases (n = 15). About 6% of the cases (n = 7) showed blunt cervical vertebral column trauma, including 3 cases with ruptured intervertebral disk. Interpretation and mechanisms of these lesions are discussed.


Psychological distress and positive gain in mothers of children with autism, with or without other children with neurodevelopmental disorders.
Although a wealth of literature has focused on the parenting experiences of mothers of children with autism spectrum disorder (ASD), there is a lack of research about mothers who are parenting a child with ASD, and who have other children with neurodevelopmental disorders. In this matched-comparison study, 10 mothers of a child with ASD and other typically developing children (ASD-TD) were compared to 10 mothers of a child with ASD who also had other children with neurodevelopmental disorders (ASD-NDD). Mothers completed self-report measures of mental health and positive gain. Results indicated no significant between-group differences for mental health, although mothers in the ASD-NDD group reported increased positive gain compared to mothers in the ASD-TD group. Further research is needed to understand practical support needs and theory development.


Infancy- and childhood-onset dyschromatoses.
The dyschromatoses are a group of pigmentary disorders characterized clinically by mixed and often guttate hypopigmented and hyperpigmented lesions. There are many conditions that present with dyschromatosis, including genodermatoses, inflammatory skin diseases, infections, drug and chemical use, and nutritional disorders. Some conditions have extracutaneous features. Poikiloderma (a combination of hypo- and hyperpigmentation with telangiectasia and atrophy) must be excluded. In this article, we describe the dyschromatoses typically presenting in infancy and childhood, most of which are genodermatoses. The approach we have taken in classifying them is based on organ involvement. We hope this article will serve as a guide for dermatologists to the recognition of these uncommon conditions.


Determination of bromide ion residues in broccoli after fumigation with methyl bromide by nonsuppressed ion-chromatography.
A nonsuppressed ion chromatography method using conductivity detection was performed to determine the concentration of bromide ions in broccoli following fumigation with methyl bromide (MB). After fumigation by MB with concentration up to 40 g/m3, bromide residue (BR) was considerably increased from the trace amount on unfumigated broccoli to about 12 ppm on fumigated broccoli. For probing the location of BR, broccoli was divided into stems and florets. The BRs were measured separately, and the results indicated that BRs only appear in the florets of broccoli.


[Treatment of patients with lower urinary tract symptoms in Moscow].
In recent years, there has been a persistent tendency to a decrease in surgical treatment of patients with lower urinary symptoms (LUTS). This fact can be explained by variety drugs which have acceptable safety and high efficiency for treatment of urinary disorders. As part of our survey of men in Moscow region, the trends in prescribing the different drugs for the LUTS was studied. In addition, the duration of therapy and patient adherence were analyzed. A prospective multicenter epidemiological study "Characteristics of lower urinary tract symptoms in men in the Moscow region" was carried out using data obtained from April 1 to May 31, 2017 with anonymous survey of 525 men with mean age of 64.2+/-9.93 years, living in Moscow and went to the urologist with urinary disorders. All respondents answered questions from specially designed questionnaire consisted from 140 items. All medical data were analyzed, including received drugs, the duration of the therapy and subjective assessment of efficiency. A total of 419 patients from 525 (79.8%) received any kind of therapy. The most commonly used drugs were -blockers, which consisted 65% of all prescriptions. Other drugs were administered significantly rarely. It is surprisingly, that 85.6% of respondents in Moscow region received the original -blockers, not generic drugs. Satisfaction rate was 74.3%. Most of patients (58.3%) had received -blockers for 1-3 years and 33.3% administered these drugs for more than 3 years. Combined drug therapy was the second most popular (25.5%). The most commonly used combination included -blockers and inhibitors of 5-reductase. In 90.6% cases the appointment was made by urologist. Drug therapy is the most popular treatment in patients with LUTS. Our data suggest that -blockers as monotherapy or in combination with inhibitors of 5-reductase is the most often prescribed therapy. These results are in concordance with the main conclusions of international studies dedicated to this issue.


Analysis of the Influence of Waste Seashell as Modified Materials on Asphalt Pavement Performance.
An increasing amount of waste seashells in China has caused serious environmental pollution and resource waste. This paper aims to solve these problems by using waste seashells as modified materials to prepare high-performance modified asphalt. In this study, seashell powder (SP) and stratum corneum-exfoliated seashell powder (SCESP) were adopted to prepare 10%, 20% and 30% of seashell powder-modified asphalt (SPMA) and stratum corneum-exfoliated seashell powder-modified asphalt (SCESPMA) by the high-speed shear apparatus, respectively. The appearance and composition of two kinds of SPs were observed and determined by the scanning electron microscope (SEM). The types of functional groups, temperature frequency characteristics, low temperature performance and adhesion of SPMA were tested by the Fourier-transform infrared (FTIR) spectrometer, dynamic shear rheometer (DSR), bending beam rheometer (BBR) and contact angle meter. The results show that the SP and SCESP are rough and porous, and their main component is CaCO3, which is physically miscible to asphalt. When the loading frequency ranges from 0.1 Hz to 10 Hz, the complex shear modulus (G*) and phase angle (δ) of SPMA and SCESPMA increase and decrease, respectively. At the same load frequency, SCESPMA has a larger G* and a smaller δ than SPMA. At the same temperature, SCESPMA has a larger rutting factor (G*/sin δ) and better high-temperature deformation resistance than SPMA. SP and SCESP reduce the low-temperature cracking resistance of asphalt, of which SCESP has a more adverse effect on the low-temperature performance of asphalt than SP. When SP and SCESP are mixed with asphalt, the cohesion work (Waa), adhesion work (Was) and comprehensive evaluation parameters of water stability (ER1, ER2 and ER3) of asphalt are improved. It is shown that both SP and SCESP have good water damage resistance, of which SCESP has better water damage resistance than SP. These research results have important reference value for the application of waste biological materials in asphalt pavement.


Quantitative structure-activity relationships study of a series of imidazole derivatives as potential new antifungal drugs.
The Quantitative Structure-Activity Relationships (QSAR) has been developed to relate antifungal activity against Candida albicans and Rhodotorula glutinis of new imidazole derivatives with their physico-chemical and structural properties. For 265 imidazole derivatives the most significant statistically equations has been obtained with correlation coefficients R=0.800 and R=0.820 in case of activity against Ca. and Rh.g., respectively. The overall antifungal activity has been described by means of size and bulkiness related parameters as well as polar and lipophilic interactions. The significance of lipophilicity in terms of n-octanol/water partition coefficient, ClogP, on antifungal potency against both fungi has been investigated. QSAR equations for different classes of antifungal activity have been obtained. With a very high probability level (92% and 96%) the weak or very weak antifungal potency against C.a. can be determined and thus the number of required experiments can be reduced.


Investigation into the transplacental transmission of Encephalitozoon cuniculi in rabbits.
An investigation into the transmission of Encephalitozoon cuniculi was undertaken in both naturally- and experimentally-infected rabbits. Only 2 nurslings were found with rising antibody titres at 8-10 weeks of age, when infection could have been caused by environmental contamination.


A one-pot synthesis of a 243-allyl dendrimer under ambient conditions.
[reaction: see text] Hydrosilylation of a nonaallyl dendritic core using HSi(Me)(2)Cl followed by reaction with a phenolate dendronic brick bearing three allyl groups, followed by repetition of this sequence of reactions twice, allows a one-pot synthesis of a 243-allyl dendrimer under ambient conditions.


Pan-cerebral sodium elevations in vascular dementia: Evidence for disturbed brain-sodium homeostasis.
Vascular dementia (VaD) is the second most common cause of cognitive impairment amongst the elderly. However, there are no known disease-modifying therapies for VaD, probably due to incomplete understanding of the molecular basis of the disease. Despite the complex etiology of neurodegenerative conditions, a growing body of research now suggests the potential involvement of metal dyshomeostasis in the pathogenesis of several of the age-related dementias. However, by comparison, there remains little research investigating brain metal levels in VaD. In order to shed light on the possible involvement of metal dyshomeostasis in VaD, we employed inductively coupled plasma-mass spectrometry to quantify the levels of essential metals in post-mortem VaD brain tissue (n = 10) and age-/sex-matched controls (n = 10) from seven brain regions. We found novel evidence for elevated wet-weight cerebral sodium levels in VaD brain tissue in six out of the seven regions analyzed. Decreased cerebral-potassium levels as well as increased Na/K ratios (consistent with high tissue sodium and low potassium levels) were also observed in several brain regions. These data suggest that reduced Na+/K+-exchanging ATPase (EC 22.214.171.124) activity could contribute to the contrasting changes in sodium and potassium measured here.


The efficacy of toddler-parent psychotherapy to increase attachment security in offspring of depressed mothers.
The efficacy of toddler-parent psychotherapy (TPP) as a preventive intervention for promoting secure attachment in the offspring of depressed mothers was evaluated, 63 mothers with major depressive disorder being randomly assigned to TPP (n = 27) or to a no treatment group (n = 36) and compared with a control group (n = 45) of women with no current or past mental disorder. At baseline, comparable and higher rates of attachment insecurity were found in the two depressed offspring groups as compared with the non-depressed control group. At the post-treatment follow-up, offspring in the intervention group attained rates of secure attachment that were comparable with those of youngsters in the non-depressed control group. In contrast, the children in the depressed control group continued to demonstrate a greater rate of attachment insecurity than children in the non-depressed control group. The findings support the efficacy of an attachment-theory based model of intervention for fostering developmental competence in the offspring of depressed mothers.


Decreased CD3 zeta molecules of T lymphocytes from patients with hepatocellular carcinoma associated with hepatitis C virus.
Most hepatocellular carcinomas (HCC) occur in chronic liver disease. Under such conditions, an impaired cellular immune response is often observed, but the mechanisms of this deficiency are unclear. The down-modulation of CD3 zeta (a key molecule in signal-transducing factor of T cell receptor) leads to a reduction in the function of T cells. In this study, we demonstrated the decreased expression of CD3 zeta on T cells from hepatitis C virus (HCV) infected hosts and HCC patients and clarified the correlation between the expression of CD3 zeta and tumor progression. Flowcytometrical analysis of CD3 zeta on peripheral T lymphocytes from 12 HCV infected hosts and 36 HCC bearing patients showed a significantly lower CD3 zeta expression than normal controls. Compared with tumor infiltrating T lymphocytes (TIL), intrahepatic T lymphocytes (IHL) and peripheral T lymphocytes (PBL) from 11 HCC bearing patients, the expression of CD3 zeta on TIL was significantly lower than PBL, and the expression level of CD3 zeta on IHL was almost equal to that on TIL. These results suggest that the down-modulation of CD3 zeta of T lymphocytes in HCV infected hosts may be one of the reasons why multicentric occurrence and intrahepatic metastasis occur more frequently in HCC patients than another malignancies.