"I think that everybody should be involved": What informs experiences of shared decision-making in supporting people living with schizophrenia spectrum disorders?
To identify facilitators and barriers associated with shared decision-making (SDM) in Australians affected by schizophrenia spectrum disorders. We surveyed 78 participants with lived experience and held 12 in-depth interviews, including seven carers. A multiple linear regression model identified two independent variables significantly associated with degree of SDM: Personal Wellbeing Index scores (ß = .32, t = 3.3, p = .001) and treatment satisfaction rating (ß =.46, t = 4.7, p < .001), indicating that higher personal wellbeing and higher treatment satisfaction were significantly related to higher degree of SDM. Two key themes were identified through interview data: a complex pathway to SDM and impacts on wellbeing. Sub-themes included: self and carer characteristics, holistic care, education and knowledge, and power balance. Generally, participants reported a desire for SDM, noting that healthcare professionals inconsistently involve them in treatment decisions. SDM is associated with treatment satisfaction and personal wellbeing among people living with schizophrenia spectrum disorders, but can be difficult to implement due to a range of challenges. There is a need to improve SDM in this population by decreasing stigma and discrimination, balancing power in consultations, increasing access to holistic treatment, and improving education and knowledge.


Reliable crystal structure predictions from first principles.
An inexpensive and reliable method for molecular crystal structure predictions (CSPs) has been developed. The new CSP protocol starts from a two-dimensional graph of crystal's monomer(s) and utilizes no experimental information. Using results of quantum mechanical calculations for molecular dimers, an accurate two-body, rigid-monomer ab initio-based force field (aiFF) for the crystal is developed. Since CSPs with aiFFs are essentially as expensive as with empirical FFs, tens of thousands of plausible polymorphs generated by the crystal packing procedures can be optimized. Here we show the robustness of this protocol which found the experimental crystal within the 20 most stable predicted polymorphs for each of the 15 investigated molecules. The ranking was further refined by performing periodic density-functional theory (DFT) plus dispersion correction (pDFT+D) calculations for these 20 top-ranked polymorphs, resulting in the experimental crystal ranked as number one for all the systems studied (and the second polymorph, if known, ranked in the top few). Alternatively, the polymorphs generated can be used to improve aiFFs, which also leads to rank one predictions. The proposed CSP protocol should result in aiFFs replacing empirical FFs in CSP research.


Slow dynamics of embedded fluid in mesoscopic confining systems as probed by NMR relaxometry.
Mesoscopic media such as porous materials or colloidal dispersions strongly influence the dynamics of the embedded fluid. In the strong-adsorption regime, it was recently proposed that the effective surface diffusion on flat surface is anomalous and exhibits long-time pathology, enlarging the time domain of the embedded-fluid dynamics towards the low-frequency regime. An interesting way to probe such a slow interfacial process is to use the field-cycling NMR relaxometry. This technique is used here to probe the fluid dynamics in two types of interfacial systems: i) a colloidal glass made of thin and flat particles; ii) a fully saturated porous media, the Vycor glass. Experimental results are critically compared to either a simple theoretical model of NMR dispersion involving elementary steps of the fluid dynamics near an interface (loops, trains, tails) or Brownian-dynamics simulations performed inside 3D reconstructions of these confined systems.


Association between age at menarche and risk of diabetes in adults: results from the EPIC-Norfolk cohort study.
Earlier age at menarche is associated with increased BMI and obesity risk from early childhood through to adulthood. We hypothesised that earlier age at menarche would also predict subsequent diabetes risk. This was a population-based prospective cohort study of 13,308 women, who were aged 40 to 75 years between 1993 and 1997 and participating in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). We used data on age at menarche and ascertained diabetes incidence to 2005. There were 734 cases of diabetes (363 incident and 371 prevalent cases). Mean age at menarche was lower in women with diabetes than in non-diabetic women (12.8 vs 13.0 years, p = 0.008). Compared with the earliest quintile (menarche at 8-11 years), women in the oldest quintile (menarche at 15-18 years) had lower BMI (25.5 vs 27.4 kg/m2, p < 0.0001) and a reduced risk of diabetes (OR 0.66 [95% CI 0.51-0.86] adjusted for age, family history, physical activity, smoking, occupational social class, parity and use of hormonal preparations). The association between age at menarche and diabetes was linear (adjusted OR 0.91 [95% CI 0.87-0.96] per 1 year later menarche) and appeared to be completely mediated by adult BMI or waist circumference (OR 0.98 [95% CI 0.93-1.03], further adjusted for BMI at age 40-75 years). Earlier age at menarche increases the risk of diabetes in women and this association appears to be mediated by increased adiposity. History of earlier menarche may help to identify women with increased subsequent risk of diabetes.


Circ_0002984 promotes proliferation, migration and inflammatory cytokine secretion and inhibits apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by inducing PCSK6 through miR-543.
Rheumatoid arthritis (RA) is inflammatory arthritic disease, and circular RNA is involved in RA development. The aim of the present work is to analyze the role of circ_0002984 in the process of RA fibroblast-like synoviocytes (RAFLSs) and the underlying mechanism. Circ_0002984, miR-543, and proprotein convertase subtilisin/kexin type 6 (PCSK6) expression levels were analyzed by quantitative real-time polymerase chain reaction or western blotting. Cell proliferation, migration, inflammatory response, and apoptosis were investigated through 5-Ethynyl-2'-deoxyuridine assay, wound-healing assay, enzyme-linked immunosorbent assay, and flow cytometry analysis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to assess the binding relationship. Circ_0002984 and PCSK6 expression were increased, while miR-543 expression was decreased in the synovial tissues of RA patients and RAFLSs. Circ_0002984 introduction facilitated RAFLS cell proliferation, migration and inflammatory response and repressed apoptosis, but circ_0002984 knockdown had an opposite role. Circ_0002984 targeted miR-543, and PCSK6 was targeted by miR-543. MiR-543 downregulation or PCSK6 overexpression restored the effects of circ_0002984 interference on RAFLS phenotypes. Circ_0002984 promoted RAFLS proliferation, migration and inflammatory cytokine secretion and inhibited apoptosis by binding to miR-543 to induce PCSK6 production, providing a potential target for RA therapy.


A nomogram to assist blastocyst selection in vitrified-warmed embryo transfer cycles.
The purpose of the study was to establish a mathematical model to help rank the order of blastocysts and assist selection of which blastocysts to warm in vitrified-thawed embryo transfer cycles. A total of 2862 women who underwent first vitrified-thawed single blastocyst transfer (SBT) between July 2015 and July 2019 were retrospectively recruited and randomized into a training set (n = 2289) and testing set (n = 573). Least absolute shrinkage and selection operator (LASSO) regression was used to screen the factors critical to live birth (LB). Subsequently, a nomogram model was established to convert the effect of each factor on LB into a measurable score. The efficacy of the model was then evaluated by the receiver operating characteristic and calibration curve. The performance of the model was also internally tested in the testing set. Maternal age, endometrial thickness, oocyte number, day-3 embryo quality, blastocyst morphology, and blastulation day were selected as the critical predictors of LB in the vitrified-thawed SBT cycle and fitted into a nomogram model. The area under the curve (AUC) of the model was 0.67, and the AUC in the testing set was 0.64, which indicates moderate discrimination. The calibration curve showed good concordance between prediction and observation. Importantly, the score of each variable in the nomogram helped to rank the order of the blastocysts resulting in LB. The nomogram model can provide guidance for embryo selection in vitrified-thawed blastocyst transfer cycles, which may help to optimize the LB rate.


The frequency in Japanese of genetic variants of 22 proteins. III. Phosphoglucomutase-1, phosphoglucomutase-2, 6-phosphogluconate dehydrogenase, adenylate kinase, and adenosine deaminase.
Five enzyme systems, PGM1, PGM2, ADA, 6-PGD and AK, were examined by electrophoresis in over 4000 samples from Hiroshima and Nagasaki for the frequencies of common and rare variants. In the PGM1 system, the PGM2(1) allele and PGM7(1) allele were found in polymorphic proportions, In addition, five kinds of slow variants and three types of fast variants of PGM1 were detected. The PGM3(1)NGS1 allele was found in five individuals from Nagasaki, but was not observed in samples from Hiroshima. There were no variants of PGM2. Three kinds of fast variants of 6-PGD were detected. No variation in AK was observed. There were no rare variants of ADA. The 6-PGDc allele had a frequency of 0.084 in Hiroshima and 0.093 in Nagasaki, and the ADA2 allele frequencies of 0.025 in Hiroshima and 0.032 in Nagasaki.


A small scale study on the effects of oral administration of the β-glucan produced by Aureobasidium pullulans on milk quality and cytokine expressions of Holstein cows, and on bacterial flora in the intestines of Japanese black calves.
The β-(1 → 3),(1 → 6)-D-glucan extracellularly produced by Aureobasidium pullulans exhibits immunomodulatory activity, and is used for health supplements. To examine the effects of oral administration of the β-(1 → 3),(1 → 6)-D-glucan to domestic animals, a small scale study was conducted using Holstein cows and newborn Japanese Black calves. Holstein cows of which somatic cell count was less than 3 x 10⁵/ml were orally administered with or without the β-(1 → 3),(1 → 6)-D-glucan-enriched A. pullulans cultured fluid (AP-CF) for 3 months, and the properties of milk and serum cytokine expression were monitored. Somatic cell counts were not significantly changed by oral administration of AP-CF, whereas the concentration of solid non fat in the milk tended to increase in the AP-CF administered cows. The results of cytokine expression analysis in the serum using ELISA indicate that the expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in all cows which were orally administered with AP-CF became slightly lower than that of control cows after the two-month treatment. On the other hand, IL-8 expression tended to indicate a moderately higher level in all treated cows after the three-month administration of AP-CF in comparison with that of the control cows. Peripartum Japanese Black beef cows and their newborn calves were orally administered with AP-CF, and bacterial flora in the intestines of the calves were analyzed by T-RFLP (terminal restriction fragment length polymorphism). The results suggest that bacterial flora are tendentiously changed by oral administration of AP-CF. Our data indicated the possibility that oral administration of the β-(1 → 3),(1 → 6)-D- glucan produced by A. pullulans affects cytokine expressions in the serum of Holstein cows, and influences bacterial flora in the intestines of Japanese Black calves. The findings may be helpful for further study on the efficacies of oral administration of β-(1 → 3),(1 → 6)-D-glucans on domestic animals.


The early stages of taxol biosynthesis: an interim report on the synthesis and identification of early pathway metabolites.
The biosynthesis of the anti-cancer drug taxol (paclitaxel) has required the collaborative efforts of several research groups to tackle the synthesis and labeling of putative biosynthetic intermediates, in concert with the identification, cloning and functional expression of the biosynthetic genes responsible for the construction of this complex natural product. Based on a combination of precursor labeling and incorporation experiments, and metabolite isolation from Taxus spp., a picture of the complex matrix of pathway oxygenation reactions following formation of the first committed intermediate, taxa-4(5),11(12)-diene, is beginning to emerge. An overview of the current state of knowledge on the early-stages of taxol biosynthesis is presented.


Translational genomics.
The term "Translational Genomics" reflects both title and mission of this new journal. "Translational" has traditionally been understood as "applied research" or "development", different from or even opposed to "basic research". Recent scientific and societal developments have triggered a re-assessment of the connotation that "translational" and "basic" are either/or activities: translational research nowadays aims at feeding the best science into applications and solutions for human society. We therefore argue here basic science to be challenged and leveraged for its relevance to human health and societal benefits. This more recent approach and attitude are catalyzed by four trends or developments: evidence-based solutions; large-scale, high dimensional data; consumer/patient empowerment; and systems-level understanding.


Behavioral and electrographic effects of opioids on kindled seizures in rats.
Our laboratory previously suggested that opioid peptides are released by an amygdaloid kindled seizure and may affect the elicitation of a subsequent seizure. The present study examined the effects of morphine, naloxone, enkephalin analogues, and conditions of morphine tolerance and withdrawal on the severity and duration of a series of amygdaloid kindled seizures. The results suggest two distinct opiate/opioid actions on seizures. The first is an anticonvulsant effect on the behavioral manifestations of seizures. This effect is seen following a high dose (50 mg/kg) of morphine or a low dose (6 mg/kg) of enkephalin analogue (LY146104), and is reversed by naloxone. The second is a naloxone-reversible prolonging effect of the high dose of morphine on the electrographic components of the seizures. Receptor affinities of these various opiate/opioid drugs suggest that these two actions are mediated by different receptors which appear not to include high affinity mu receptors.


Ribosomes of Physarum polycephalum. Subunits and protein composition.
Ribosomes from Physarum polycephalum were purified. Optimal conditions for preparation and stability of subunits were determined. KCl concentration above 200 mM induced protein dissociation from the subunits. It was observed that dissociated ribosomes were more stable in a low ionic strength buffer than in 200 mM KCl, where the 40 S was preferentially degraded by ribonucleases. Ribosomal proteins were analyzed by two-dimensional gel electrophoresis. The first dimension was carried out at pH 8.6 while the second was run at pH 4.6. The monosome contained sixty seven proteins, of which six were acidic. Two proteins were lost after subunit dissociation. Twenty six basic and two acidic proteins were observed in the 40 S subunit while the largest subunit gave thirty nine spots on the basic part of the gel and three additional spots on the acidic side. Five proteins were shared by 40 S and 60 S.


Presumed reactivation of herpes zoster ophthalmicus following laser in situ keratomileusis.
To report a case of herpes zoster ophthalmicus reactivation following laser in situ keratomileusis (LASIK) for myopia. A 54-year-old healthy male underwent uneventful bilateral LASIK for the correction of myopia and astigmatism (-5.75 -3.00 x 20 degrees right eye, -5.50 -3.00 x 170 degrees left eye). Two months following LASIK, an epithelial dendritic lesion appeared in the lower third of the corneal flap of the left eye with vesiculoulcerative lesions of the lateral side of the tip of the nose. The patient was treated with topical and oral antiviral agents and had complete recovery of the lesions in 10 days. Herpes zoster reactivation may occur following LASIK. Reactivation of herpes zoster in this case could have been coincidental, or secondary to LASIK and the subsequent use of topical corticosteroids following LASIK.


Obturator bypass with nonreversed translocated saphenous vein.
Obturator bypasses with nonreversed translocated saphenous veins were performed in two patients with femoral graft infections. There were no deaths, limb loss, or graft occlusions at two and one-half years of follow-up in the first case and one and one-half years of follow-up in the second case. The nonreversed translocated saphenous vein is a versatile graft that allows for extraanatomic autogenous reconstruction in the face of infection. In both cases, small-caliber distal saphenous veins precluded performing reversed saphenous vein grafts.


Incidence of autoimmune diseases in people living with HIV compared to a matched population: a cohort study.
The objective of this paper is to estimate incidence and relative risk of autoimmune conditions in patients living with HIV compared to an HIV-negative matched population. We conducted a retrospective study in the medico-administrative database of the province of Québec, Canada. All HIV-positive patients treated with antiretrovirals were matched to up to 4 HIV-negative controls for age, sex, and period of follow-up. The following autoimmune conditions were identified using medical billing codes: vasculitis, hematological (immune thrombocytopenic purpura and immune hemolytic anemia), ankylosing spondylitis, psoriasis and psoriatic arthritis, inflammatory bowel disease and associated arthritis, connectivitis, and systemic lupus erythematosus. Incidence rates and adjusted hazard ratios (aHR) were obtained using survival models. A total of 4245 HIV-positive patients were matched to 16493 HIV-negative patients. Autoimmune diseases were diagnosed in 407 (9.6%) HIV-positive and 508 (3%) HIV-negative patients. The aHR for autoimmune diseases associated to HIV was 2.40 95% CI [2.10-2.75]. The strongest associations were seen for hematological disorders (aHR 8.34 95% CI [6.13-11.36]), followed by ankylosing spondylitis (1.82 95% CI [1.03-3.21]), inflammatory bowel disease and associated arthritis (1.80 95% CI [1.37-2.35]), psoriasis and associated arthritis (1.69 95% CI [1.23-2.33]), and rheumatoid arthritis (1.51 95% CI [1.08-2.11]).We found no association between HIV and the incidence of vasculitis, connectivitis, and systemic lupus erythematosus, but the number of cases for these diseases were few. Autoimmune diseases are more frequent among people living with HIV than age and sex-matched population-based controls. Key Points • Strength: The major strength of this study is its large sample size of 4200 people treated as HIV infection, matched to 16000 HIV negative for sex and age. • Novelty: We found that people living with HIV were more than twice as likely to suffer from auto-immune diseases than their matched counterparts.


The effect of myostatin silencing by lentiviral-mediated RNA interference on goat fetal fibroblasts.
Myostatin is a transforming growth factor-β family member that acts as a negative regulator of skeletal muscle mass. To identify possible myostatin inhibitors that may promote muscle growth, we used RNA interference mediated by a lentiviral vector to knockdown myostatin in goat fetal fibroblast cells. We also investigated the expression changes in relevant myogenic regulatory factors (MRFs) and adipogenic regulatory factors in the absence of myostatin in goat fetal fibroblasts. Quantitative RT-PCR revealed that myostatin transcripts were significantly reduced by 75 % (P < 0.01). Western blot showed that myostatin protein expression was reduced by 95 % (P < 0.01). We also found that the mRNA expression of activin receptor IIB (ACVR2B) significantly increased by 350 % (P < 0.01), and p21 increased 172 % (P < 0.01). Furthermore, myostatin inhibition decreased Myf5 and increased MEF2C mRNA expression in goat fetal fibroblasts, suggesting that myostatin regulates MRFs differently in fibroblasts compared to muscle. In addition, the expression of adipocyte marker genes peroxisome proliferator-activated receptor (PPAR) γ and leptin, but not CCAAT/enhance-binding protein (C/EBP) α and C/EBPβ, were upregulated at the transcript level after myostatin silencing. These results suggest that we have generated a novel way to block myostatin in vitro, which could be used to improve livestock meat production and gene therapy of musculoskeletal diseases. This also suggests that myostatin plays a negative role in regulating the expression of adipogenesis related genes in goat fetal fibroblasts.


Fall Risk Assessment Scales: A Systematic Literature Review.
Falls are recognized globally as a major public health problem. Although the elderly are the most affected population, it should be noted that the pediatric population is also very susceptible to the risk of falling. The fall risk approach is the assessment tool. There are different types of tools used in both clinical and territorial settings. In the month of January 2021, a literature search was undertaken of MEDLINE, CINHAL and The Cochrane Database, adopting as limits: last 10 years, abstract available, and English and Italian language. The search terms used were "Accidental Falls" AND "Risk Assessment" and "Fall Risk Assessment Tool" or "Fall Risk Assessment Tools". From the 115 selected articles, 38 different fall risk assessment tools were identified, divided into two groups: the first with the main tools present in the literature, and the second represented by tools of some specific areas, of lesser use and with less supporting literature. Most of these articles are prospective cohort or cross-sectional studies. All articles focus on presenting, creating or validating fall risk assessment tools. Due to the multidimensional nature of falling risk, there is no "ideal" tool that can be used in any context or that performs a perfect risk assessment. For this reason, a simultaneous application of multiple tools is recommended, and a direct and in-depth analysis by the healthcare professional is essential.


Effects of alcohol consumption and restriction on home blood pressure in hypertensive patients: serial changes in the morning and evening records.
To study the time course of alcohol effects on blood pressure (BP), we examined morning and late evening home BP for 4 weeks in a regular alcohol consumption period and for 4 weeks in a alcohol restriction period in 30 Japanese men with essential hypertension (52 +/- 2 years, m +/- SE) in a randomized crossover study. Mean daily intake of alcohol were 66.5 +/- 4.7 and 10.2 +/- 1.9 ml, respectively. At the end of the regular alcohol period, morning BP had increased by 4.4 +/- 1.1/2.9 +/- 0.8 mmHg but evening BP had decreased by 7.4 +/- 1.9/5.7 +/- 1.7 mmHg. The depressor effect of alcohol on the evening BP was evident from day 1 to week 4, while the pressor effect on the morning BP was significant from week 2 regardless of the order of the two periods. These results confirm the biphasic effect of alcohol on BP, and suggest that the status of alcohol intake may markedly influence the morning-evening BP difference.


Cardiomyocyte-like cells differentiation from non β-catenin expression mesenchymal stem cells.
Recent studies have shown that block wnt/β-catenin signaling pathway is integrant for cardiomyocytes differentiation from bone marrow mesenchymal stem cells (MSCs). By transducing the MSCs with lentivirus which contain β-catenin interference RNA, we screened out the non β-catenin expression clone. In the establishment of knockdown β-catenin in MSCs, we investigated the role of 5-azacytidine (5-aza), salvianolic acid B (salB), and cardiomyocytes lysis medium (CLM) in inducing MSCs to differentiate into cardiomyocyte-like cells. A method for culturing MSCs and cardiomyocytes was established. Purified MSCs were investigated by flow cytometry. The MSCs were positive for CD90 and CD29, but negative for CD34 and CD45. Meanwhile, the cardiomyocytes contracted spontaneously after 24 h of seeding into the plates. The fourth-passage non-β-catenin expression MSCs were divided into eight groups: control group, 5-aza, salB, CLM, 5-aza + salB, 5-aza + CLM, salB + CLM, and 5-aza + salB + CLM. The gene and protein expression of cTnT, α-actin, β-myosin, β-catenin, and GSK-3β were detected by quantitative real-time PCR and Western blotting. Our results showed that cTnT expression in 5-aza + salB + CLM group was ninefold higher than in the control group in the non-β-catenin MSCs model, implying that cardiomyocytes differentiation from MSCs is an extremely complicated process and it is necessary to consider the internal and external environmental conditions, such as suitable pharmaceutical inducers, cardiomyocytes microenvironments, inhibition of the negative signaling pathway and so on.


Bacterial lymphadenitis with the picture of a lymphoepithelioid cell lymphoma--Lennert's lymphoma.
Three cases with the typical light microscopic picture of lymphoepithelioid cell lymphoma (so-called Lennert's lymphoma) were investigated by electron microscopy. Surprisingly, Lennert's lymphoma could be excluded in two cases. These two cases exhibited, in addition to pleomorphic lymphocytes and epithelioid cells, macrophages with accumulations of bacteria, indicating that a bacterial infection was the cause of the disease. By comparing the typical case of Lennert's lymphoma with the other cases, we found several criteria for distinguishing between Lennert's lymphoma and bacterial lymphadenitis. In bacterial lymphadenitis: (1) small and medium-sized lymphocytes exhibited a wide cytological spectrum whereas the lymphocytes in Lennert's lymphoma were relatively uniform; the lymphocytes with prominent lysosome-like granules found in Lennert's lymphoma were not seen; (2) cytology and distribution of epithelioid cells were similar to those in Lennert's lymphoma; (3) epithelioid venules contained recirculating lymphocytes, which were rarely found in Lennert's lymphoma; (4) numerous interdigitating reticulum cells, fibroblasts and myofibroblasts were seen, but not in Lennert's lymphoma; (5) focal increase in reticulin fibres was the main difference in light microscopy; (6) rod-shaped bacteria were accumulated in the cytoplasm of a few macrophages. The presence of bacteria could not be demonstrated unequivocally by light microscopy. In both cases the large number of intracytoplasmic bacteria suggests that this unusual and until now unknown lymphadenitis is the result of an infection caused by facultative intracellular parasitic bacteria. The outcome of bacterial lymphadenitis that gives the false impression of Lennert's lymphoma is uncertain. Cure was achieved in one of our cases. The other patient died before therapy was commenced.


Novel sustainable metallic powder production process with water used as milling medium.
Today, Fe-Al intermetallic compounds are receiving a great interest from the mechanical, aerospace, and biomedical industries. A novel production process for Fe-Al intermetallic powders based on the generation of metallic tapes by rapid solidification and disintegration by water vapor was proposed. In this research work, a comparison is made between the energy required to manufacture of Fe-Al powder using the aforementioned process and one of the most commonly used manufacturing processes within the industry such as mechanical alloying. In addition, some other benefits of the proposed manufacturing process are analyzed. To carry out this comparison, the theoretical equations that take into account the most important variables involved during the process such as the type of material and hardness, the initial and final particle size, the grinding stages and the heating of the treatment powder were considered. In the case of calculating the energy required for the new proposed process, the two main stages were considered such as (1) the production of FeAl metal tape and (2) the subsequent transformation of the tape into powder by means of injection water vapor. For the first stage, the CASTRIP process is considered, and for the second stage, the energy required for the generation steam. Although the calculations may have certain limitations, it is obvious that the energy required to Fe-Al powder production using the new process is much lower than that required by mechanical alloying, resulting in at least three orders of magnitude lower (2.75 × 106 versus 2.206 × 109 kJ/ton). This lower energy implies considerable economic savings in the production process. On the other hand, when using water as a grinding medium during the process, it results in less environmental and acoustic pollution, less manipulation risks for humans and finally, no harmful agents or additives are used, making the proposed process sustainable.


[Acute lymphoblastic leukemia in developing countries: Management from the transplant indication (allo/auto) until post-transplant follow-up. Guidelines from the SFGM-TC].
Management of acute lymphoblastic leukemia (ALL) patients in countries with limited resources depends on the means of prognostic stratification, available treatment and logistics. During the 12th annual harmonization workshops of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated working group reviewed the literature in order to elaborate unified guidelines for allogeneic hematopoietic cell transplantation (Allo-HCT) in this disease. Conventional poor prognostic factors can be used to determine the indication of allo-HCT in first remission. Patients lacking a HLA-matched related donor can be allografted with a haploidentical donor allo-HCT if available. Chemotherapy based conditioning regimen can be used if TBI is not available, because the probability to find a radiotherapy department with the capacity for total body irradiation is low. For patients with Philadelphia chromosome positive (Phi+) ALL, post-transplantation tyrosine kinase inhibitors as a systematic maintenance strategy is recommended. Autologous HCT is optional for Phi+ ALL patients with negative minimal residual disease, who not eligible for allo-HCT. Patients with refractory/relapsed disease have a poor prognosis which highlights the importance of acquiring in the future new therapies such as: blinatumumab, inotuzumab, and CAR-T cells.


In vitro interaction of eukaryotic elongation factor 2 with synthetic oligoribonucleotide that mimics GTPase domain of rat 28S ribosomal RNA.
Eukaryotic elongation factor 2 (eEF2) catalyzed the translocation of peptidyl-tRNA from the ribosomal A site to the P site. In this paper, the interaction between eEF2 and GTD RNA, a synthetic oligoribonucleotide that mimicked the GTPase domain of rat 28S ribosomal RNA, was studied in vitro. The purified eEF2 could bind to GTD RNA, forming a stable complex. Transfer RNA competed with GTD RNA in binding to eEF2, whereas poly(A), poly(U) and poly(I, C) did not interfere with the interaction between eEF2 and GTD RNA, demonstrating that the tertiary structure of RNA might be necessary for the recognition of and binding to eEF2. The complex formation of eEF2 with GTD RNA was inhibited by SRD RNA, a synthetic oligoribonucleotide mimic of Sarcin/Ricin domain RNA of rat 28S RNA. Similarly, GTD RNA inhibited the interaction between eEF2 and SRD RNA. This fact implies that these small oligoribonucleotides probably share similar recognition or binding identity elements in their tertiary structures. In addition, the binding of eEF2 to GTD RNA could be obviously weakened by the ADP-ribosylation of eEF2 with diphtheria toxin. These results indicate that eEF2 behaves differently from prokaryotic EF-G in binding to ribosomal RNA.


Vapor-Assisted Powder Synthesis and Oriented MOF-CVD Thin Films of the Metal-Organic Framework HKUST-1.
A vapor-assisted synthesis method was developed for the metal-organic framework (MOF) HKUST-1 in both powder and film format. The use of a solvent template supplied from the vapor phase is essential to form the framework under these conditions. Chemical vapor deposition of HKUST-1 films (MOF-CVD) results in smooth films that show the expected adsorption behavior. Interestingly, the HKUST-1 films obtained this way show a (111) preferred crystallographic orientation.


A biochemical basis for 1,2-dibromo-3-chloropropane-induced male infertility: inhibition of sperm mitochondrial electron transport activity.
A rapid decrease in male fertility in laboratory animals exposed to 1,2-dibromo-3-chloropropane (DBCP) has been suggested to be due, in part, to a postglycolytic inhibition of sperm carbohydrate metabolism. The present studies were performed to identify the specific site of DBCP-induced inhibition of intermediary metabolism. 14CO2 generation by epididymal sperm, isolated from Fischer 344 rats, was measured using radiolabeled tricarboxylic acid (TCA) cycle intermediates: acetyl CoA, citrate, alpha-ketoglutarate, and succinate. There was 0-28% inhibition of CO2 generation after addition of 0.5 mM DBCP and 81-98% inhibition with 3 mM DBCP, with all four substrates. The activities of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, malate dehydrogenase, and lactate dehydrogenase were not inhibited by DBCP. Since the DBCP-induced inhibition of metabolism of different substrates to CO2 was similar, and since DBCP did not inhibit enzyme activities of glycolysis or the TCA cycle, a common site of inhibition was suspected. In evaluations of mitochondrial electron transport chain activity, DBCP (3 mM) inhibited oxygen consumption resulting from metabolism of endogenous substrates plus alpha-ketoglutarate or malate by about 80%. When succinate, an FAD-dependent oxidation, was used as a substrate, oxygen consumption was not inhibited by DBCP. It is concluded that DBCP inhibits sperm carbohydrate metabolism at the NADH dehydrogenase step in the mitochondrial electron transport chain.


The influence of temperature on the functional response of the dragonfly Celithemis fasciata (Odonata: Libellulidae).
1) Functional response curves were constructed for Celithemis fasciata larvae feeding on 6 different densities of midge larvae at 10, 15, 20, and 25°C. Values for attack rate and handling time were estimated with Rogers's random predator equation. 2) Polynomial regression revealed that the functional response curves were linear although a tendency toward decreasing consumption rates at higher densities was shown. 3) The mean number of prey eaten increased with temperature; however, temperature did not alter the fundamental shape of the functional response curve. 4) The attack rate and handling time were linearly related to temperature in general, but changed relatively little between 15 and 20° C.


Predicting EDC concentrations in a river mixing zone.
The fate and transport of endocrine disrupting chemicals (EDCs) in ambient river waters is a major concern associated with effluents from municipal wastewater treatment plants (WWTPs). This paper presents a methodology for quantifying the spatial distribution of EDCs in a river mixing zone. The core of the technical analysis is based on a two-dimensional steady-state analytical model characterized by ambient turbulence in the receiving water. This model was first calibrated with mass transport data from field measurements for a conservative substance (electrical conductivity) and then used to predict aqueous-phase EDC concentrations throughout a WWTP mixing zone. To demonstrate the usefulness of this methodology for water quality management purposes, the modeling framework presented in this paper was used to determine a lumped in-stream attenuation rate constant (k(d)=3 d(-1)) for 17β-estradiol under natural conditions. This rate constant likely accounts for the combined contributions of physical sorption, photolysis, microbial and chemical degradation, and the measured value is highly consistent with previously published results from bench-scale removal experiments.


Effects of long-term Wuqinxi exercise on working memory in older adults with mild cognitive impairment.
Although physical exercise may improve memory in older adults, whether the Chinese traditional fitness exercise Wuqinxi improves working memory and delays cognitive deterioration in older adults with mild cognitive impairment (MCI) has not been assessed in randomized controlled experiments. Fifty older adults with MCI based on their Montreal Cognitive Assessment scores were randomized to either a Wuqinxi exercise group or a non-exercise control group. The exercise group engaged in Wuqinxi once a week for 60 min each session for 40 weeks. Participants in the control group received no intervention and maintained their regular living habits. The n-back paradigm was used to measure changes in working memory before and after Wuqinxi exercise. In the 0-back task, the response speed of older adults with MCI who participated in Wuqinxi was faster than that of older adults with MCI in the non-exercise control group (P = 0.031); there was no significant difference in accuracy between the two groups (P > 0.05). In the 1-back and 2-back tasks, there was no significant difference in response times or in accuracy between the two groups (P > 0.05). In this randomized controlled study, participation in long-term Wuqinxi delayed the deterioration of working memory in older adults with MCI, suggesting that this exercise may be an effective intervention to delay or prevent the progression of MCI to Alzheimer's disease.


Is Malassezia nana the main species in horses' ear canal microbiome?
The objective of this study was to characterize genotypically Malassezia spp. isolated from the external ear canal of healthy horses. Fifty-five horses, 39 (70.9%) males and 16 (29.1%) females, from different breeds and adults were studied. External ear canals were cleaned and a sterile cotton swab was introduced to collect cerumen. A total of 110 samples were cultured into Dixon medium and were incubated at 32°C for up to 15 days. Macro- and micromorphology and phenotypic identification were performed. DNA was extracted, strains were submitted to polymerase chain reaction technique, and the products obtained were submitted to Restriction Fragment Length Polymorphism using the restriction enzymes BstCI and HhaI. Strains were sent off to genetic sequencing of the regions 26S rDNA D1/D2 and ITS1-5.8S-ITS2 rDNA. Malassezia spp. were isolated from 33/55 (60%) animals and 52/110 (47%) ear canals. No growth on Sabouraud dextrose agar was observed, confirming the lipid dependence of all strains. Polymerase chain reaction-Restriction fragment length polymorphism permitted the molecular identification of Malassezia nana - 42/52 (81%) and Malassezia slooffiae - 10/52 (19%). Sequencing confirmed RFLP identification. It was surprising that M. nana represented over 80% of the strains and no Malassezia equina was isolated in this study, differing from what was expected.


Pinch strength analyses in lacertus syndrome.
Lacertus syndrome is defined as proximal median nerve entrapment at the lacertus fibrosus. We aimed to analyze change in pinch strengths in patients who underwent median nerve release at the lacertus fibrosus under WALANT (wide-awake local anesthesia, no tourniquet). Pinch strength was measured with a pinch gauge. Subjective DASH score and pain, numbness in the operated extremity and satisfaction on visual analog scales were analyzed before and 6 weeks after surgery. There were 32 patients. Median nerve release under the lacertus fibrosus elicited statistically significant increases in tip-to-tip, lateral and tripod pinch strength at postoperative week 6. Improvements in DASH score, pain and paresthesia were also statistically significant. For lacertus syndrome treatment, mini-incision release of the lacertus fibrosus under WALANT was satisfactory and increased pinch strength significatively. Therapeutic, Level IV - Case series.


Different precompression does not reduce the diagnostic value of virtual touch tissue imaging and quantification (VTIQ) in breast lesions, especially for the ratio of the shear wave velocity between lesions and surrounding tissues.
To investigate the accuracy of virtual touch tissue imaging and quantification (VTIQ) in the diagnosis of benign and malignant breast lesions under four different precompression levels. The shear wave velocity (SWV) ratios of lesion to surrounding tissue were also added for diagnosis. 167 female patients with breast lesions were included in this single center prospective study. VTIQ was performed under four different precompression levels. The SWV of the lesion, surrounding fat, and gland tissue were measured at the same depth as much as feasible 7 times. The breast lesions studied were all histopathologically confirmed. The VTIQ parameters were compared between precompression levels. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic performance of each parameter of the VTIQ. The VTIQ parameters of the malignant lesions were significantly higher than those of benign lesions in all precompression levels (P < 0.001). SWV of the lesion, fat, and gland tissue increased significantly with increasing precompression. The VTIQ parameters had great diagnostic performance for breast lesions in all precompression levels (AUC = 0.765-0.911). There was no significant difference between the precompression levels of the lesion-to-fat SWV ratio and the lesion-to-gland SWV ratio in benign and malignant lesions, and the cut-off coefficients of variation were 7.42% and 8.55%, respectively. Precompression can increase the stiffness of breast lesions, fat and gland tissues, but does not reduce diagnostic value of VTIQ parameters in the breast. Under different precompression levels, the diagnosis of breast lesions by the ratio of the SWV of the lesion to the surrounding tissues is more stable.


Isoelectric focusing of proteins using a pH gradient created by a concentration gradient of nonelectrolytes in solution.
A new method of producing a stable pH gradient in buffer solutions is suggested, obtained by the concentration gradient of a nonelectrolyte in buffer solutions as a result of the gradual change in the dielectric properties of the solution. The maximal concentrations of nonelectrolyte which do not influence the protein configuration allow a pH gradient with a range of two pH units to be produced. It is suggested that the properties of some polyols (i.e. glycerol or mannitol) be used to change the pH of the borate buffer for the production of greater pH gradient with a range of up to 4-5 pH units. Creating the gradient of concentration of polyols, one can obtain a pH gradient in borate buffer solutions. Though the polylydroxyl compound-borate complexes posses mobility in an electric field, a stable pH gradient can be achieved during 12 days of electrophoresis. The isoelectric focusing of haemoglobin, human serum albumin and immunoglobulins was carried out in both systems suggested. These findings were compared with isoelectric focusing in Ampholines. There was a good agreement between the methods compared. The possible differences are discussed.


The temperature dependance of photoinhibition in the tropical basidiomycete lichen Cora pavonia E. Fries.
The response of net photosynthesis (NP) and dark respiration to periods of high insolation exposure was examined in the tropical basidiomycete lichen Cora pavonia. Photoinhibition of NP proved quite dependant on temperature. Rates of light saturated NP were severely impaired immediately after pretreatment high light exposure at temperatures of 10, 20 and 40°C, while similar exposure at 30°C resulted in only minimal photoinhibition. Apparent quantum yield proved an even more sensitive indicator of photoinhibition, reduced in all temperature treatments, although inhibition was again greatest at low and high temperatures. Concurrent exposure to reduced O2 tensions during high light exposure mitigated some of the deleterious effects of high light exposure at 10 and 20°C, suggesting an interaction of O2 with the inactivation of photosynthetic function. This represents the first reported instance of light dependant chilling stress in lichens, and may be an important limitation on the distribution of this and other tropical lichen species. This narrow range of temperatures within which thalli of C. pavonia can withstand periods of high insolation exposure coincides with that faced by hydrated thalli during rare periods of high insolation exposure within the cloud/shroud zone on La Soufrière, and points to the necessity of considering periods of atypical or unusual climatic events when interpreting patterns of net photosynthetic response, both in tropical and in north temperate lichen species.


Usefulness of intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis treatment.
Cryptococcal meningitis is a severe infection among immunosuppressed individuals, with a high mortality rate. Although amphotericin B is the first-choice drug for treatment, its use is restricted when adverse effects are clinically problematic. The usefulness of intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis treatment has been unconfirmed. We evaluated the efficacy of intraventricular infusion of amphotericin B through Ommaya reservoirs. We retrospectively analyzed 10 consecutive patients with cryptococcal meningitis who were refractory to systemic administration of antifungal drugs. Fever or nausea occurred in most patients. However, no patient complained of serious complications such as renal toxicity. Seven patients recovered completely or partially, whereas three patients died. To establish the efficacy of the intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis, a prospective investigation should be designed to compare those treated according to the updated guidelines and those treated with antifungal drugs through the Ommaya reservoirs.


[Cerebral vasoreactivity: Concordance of breath holding test and acetazolamide injection in current practice: 20 cases of asymptomatic carotid artery stenosis].
Cerebral vasoreactivity (CVR) is the ability of the brain's vascular system to keep cerebral blood inflow stable. Impaired CVR is a risk marker of stroke in patients with asymptomatic carotid stenosis. The gold standard to assess CVR with transcranial ultrasound is acetazolamide (ACTZ) injection. The breath holding test (BHT) might be easier to perform. CVR proved to be efficient in laboratory conditions but not in routine practice. To study the validity of BHT versus ACTZ in routine practice in a vascular exploration unit in patients with asymptomatic carotid stenosis. Study of concordance of BHT and ACTZ, to assess CVR in patients consecutively explored on the same day. Eighteen patients with 20 carotid stenosis were included. The temporal window was missing in 20% of cases. Only 11 out of the 20 procedures were analyzed. Concordance was low between BHT and ACTZ to assess CVR (k=0.3714). BHT cannot replace ACTZ injection. It might be a first-step test so that ACTZ injection might be avoided if CVR is normal. Our present results must be confirmed by further study enrolling many more patients.


Drug therapy of diabetes in the elderly.
The prevalence of type 2 diabetes mellitus is increasing in the elderly. Although type 1 diabetic patients are living longer, over 95% of elderly people affected with diabetes have type 2 diabetes. This segment of the population, comprising men and women older than 65 years of age, is more likely to develop coexisting illnesses predisposing to the development of diabetes and complicating its management. In addition to changes in lifestyle, inherent age-related changes in carbohydrate metabolism contribute to the development of type 2 diabetes in old age. The long-term outcome of tight blood sugar control in the elderly is not known. Nevertheless the principles of management of type 2 diabetes in the elderly are essentially the same as in young- or middle-aged diabetic patients. Lifestyle modifications remain the cornerstone of medical therapy. When diet and exercise fail to achieve proper glycemic control, oral pharmacologic therapy and/or insulin therapy is indicated. The recently available oral glucose lowering agents in the market along with the newer types of insulin can be used in elderly diabetic patients. The effect of aging on metabolism and drug elimination kinetics must, however, be taken into consideration. In particular, it should be borne in mind that the risk of hypoglycemia is more deleterious in the elderly and should be avoided. In this review, the various pharmacologic agents available for the management of diabetes will be reviewed and some pertinent clinical guidelines will be suggested.


Geoenvironmental properties of a Cr(VI)-contaminated soil treated by alkali-activated GGBS under freeze-thaw cycles: Insights into Cr species transformation and microscopic mechanism.
Stabilization/solidification is the most frequently used method for treating soils contaminated by heavy metals; however, degradation of the treatment will occur under freeze-thaw (F-T) cycles. In this paper, a low-carbon emission by-product, ground granulated blast furnace slag (GGBS), was adopted as a binder to treat Cr(VI)-contaminated soil after alkali excitation. Built on the usage scenarios of subgrade materials, the impact of F-T cycles and initial water content on the geoenvironmental properties of the treated soils, including leaching toxicity, unconfined compressive strength (UCS), pH, Eh, and permeability, were discussed. To investigate the mechanisms of the changing properties, this study analyzed the chemical morphology of Cr, the micromorphology of the reaction products, and the pore characteristics. The results demonstrated that negative impact of F-T cycles on treatment effectiveness was low at the optimal water content. After 28 F-T cycles, the Cr(VI) component increased by 6.4 %, and the leached Cr concentration showed a significant increase, especially for specimens with low water content. A new solid phase with mixed valence Mn(III/IV), mainly composed of birnessite and manganite, was observed via microscopic analysis. During the first 3 F-T cycles, the content of hydration gel increased by 0.18 %, and the cumulative pore volume decreased such that the UCS increased by an average of 1.2 MPa. This study demonstrated that a few F-T cycles would result in a secondary alkali-activated GGBS reaction, enhancing the treatment effect. However, additional F-T cycles would create an oxidizing environment under which the initially precipitated Cr(III) would react with manganese oxide, resulting in more Cr(VI) released. The degree of reoxidation was closely related to the initial water content of the solidified soil.


mCelsr1 is an evolutionarily conserved seven-pass transmembrane receptor and is expressed during mouse embryonic development.
Mcelsr1 encodes a protein of 3034 amino acids predicted to contain seven membrane spanning domains having homology to a group of peptide hormone binding G-protein coupled receptors. Its extracellular domain comprises epidermal growth factor-like repeats, laminin A G-domains and cadherin repeats. Homologous genes have been identified in C. elegans and D. melanogaster suggesting that the Celsr gene family is ancient. mCelsr1 mRNA expression precedes gastrulation, is subsequently restricted primarily to ectodermal derivatives and is tightly regulated in the developing central nervous system (CNS). We observe segmentally-restricted gene expression in the developing hindbrain and in the spinal cord dynamic dorso-ventrally restricted 'stripes' of expression.


Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer.
Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m(-2) PPX or 75 mg m(-2) docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease. Median survival (6.9 months in both arms, hazard ratio=1.09, P=0.257), 1-year survival (PPX=25%, docetaxel=29%, P=0.134), and time to progression (PPX=2 months, docetaxel=2.6 months, P=0.075) were similar between treatment arms. Paclitaxel poliglumex was associated with significantly less grade 3 or 4 neutropenia (P<0.001) and febrile neutropenia (P=0.006). Grade 3 or 4 neuropathy (P<0.001) was more common in the PPX arm. Patients receiving PPX had less alopecia and did not receive routine premedications. More patients discontinued due to adverse events in the PPX arm compared to the docetaxel arm (34 vs 16%, P<0.001). Paclitaxel poliglumex and docetaxel produced similar survival results but had different toxicity profiles. Compared with docetaxel, PPX had less febrile neutropenia and less alopecia, shorter infusion times, and elimination of routine use of medications to prevent hypersensitivity reactions. Paclitaxel poliglumex at a dose of 210 mg m(-2) resulted in increased neurotoxicity compared with docetaxel.


Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother-child cohort study in Crete, Greece.
Maternal thyroid hormones' supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid dysfunction with child neuropsychological development from infancy to early childhood. We included 757 mother-child pairs from the prospective 'Rhea' cohort on Crete, Greece. Maternal thyroid functioning was assessed by quantitative analysis of serum thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies and thyroglobulin antibodies at early gestation (mean=14 weeks). Neuropsychological assessment was based on Bayley Scales of Infant Development (18 months of age), McCarthy Scales of Children's Abilities (4 years of age), Raven's Coloured Progressive Matrices, Trail Making Test and Finger Tapping Test (6 years of age). In multivariate adjusted linear regression analyses, maternal hypothyroxinemia was associated with decreased verbal scores at 4 years and reduced motor speed at 6 years of age. Maternal thyroid autoimmunity was associated with decreased child perceptual and motor ability at 4 years of age. Four trajectories of longitudinal non-verbal cognitive development were identified and children exposed to maternal thyroid autoimmunity had increased risk for belonging to an adverse trajectory ('low': adjusted relative risk ratio (RRR) = 2.7 95% CI: (1.4, 5.2), 'high-decreasing': adjusted RRR = 2.2 95% CI: (1.2, 4.0), 'low-increasing': adjusted RRR = 1.8 95% CI: (1.0, 3.2)). Maternal hypothyroxinemia is associated with reduced offspring verbal and motor ability. Maternal thyroid autoimmunity is associated with decreased offspring perceptual performance and motor ability and increased risk for adverse non-verbal cognitive development from infancy to childhood.


Uniform trend in layer-by-layer deposition of heteropolytungstates.
The layer-by-layer deposition of films including polyoxometalates (POMs) results in a very interesting range of applications in various fields such as electrochemical devices and as photochromic coatings. However, the fundamental knowledge of the parameters responsible for tuning the properties of the film (i.e. relation between the structure and composition of the POM and the properties of the final film) is still lacking. The current work establishes the relationship between the film thickness, the quantity of POM incorporated in each layer and the electrochemical response of the (PAH-POM)x coatings, where PAH is poly(allylamine hydrochloride). The results presented in this work show that the film thickness, composition and electrochemical activity scale proportionally with the number of W atoms in a series of heteropolytungstates ranging from 5 to 48 (P2W5, PW12, P2V3W15, P2W18, P5W30, P8W48). The obtained results allow us to establish a method to predict the behavior as well as the properties of the film based on the nature of the POM used.


The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats.
One popular way of measuring visual attentional processes in the rat is using 5-choice serial reaction time task (5-CSRTT). This paradigm requires subjects to detect brief flashes of light presented in a pseudorandom order in one of five spatial locations over a large number of trials. For this task, the animals are trained for approximately 30-40 daily sessions during which they gradually learn to respond in the appropriate aperture within a certain amount of time. If they fail to respond, respond in the wrong hole or at an inappropriate time, a short period of darkness (time-out) is presented as punishment and no reward is delivered. The 5-CSRTT provides the possibility to test the effects of various neural, pharmacological and behavioral manipulations on discrete and somewhat independent measures of behavioral control, including accuracy of discrimination, impulsivity, perseverative responses and response latencies.


Borderline personality disorder in Irish Travellers: a cross-sectional study of an ultra-high-risk group.
Irish Travellers are a marginalised ethnic minority with poor health outcomes, especially in mental health: the suicide rate in this population is 6-7 times that in the general population. There is a paucity of research into associated clinical risk factors including self-harm and mental illnesses. To examine the prevalence and treatments of mental disorders among Travellers attending a community mental health team (CMHT) in Galway. This is a cross-sectional study of the CMHT database, and included all Travellers who were active cases on the study day were included in this study. Travellers formed 12.4% (51 out of 410) of the active caseload of the mental health service. The mean age was 35.7 years (SD 13.1). The most common mental disorder was depressive disorder (16/51, 31.4%). Of 51 patients, 25.5% (13/51) were diagnosed with BPD: 7 had other comorbid mental disorders. Patients diagnosed with BPD are significantly more likely to be prescribed psychopharmacotherapy (t = 2.834, p = 0.007). A diagnosis of BPD was significantly associated with history of self-harm after controlling for age and gender (OR 2.3, p = 0.005). This study shows that there is a significant overrepresentation of Travellers in mental health services, suggesting significant need for accessible and acceptable interventions. Those with a BPD diagnosis have a significantly higher risk of self-harm, representing an ultra-high-risk population. These findings can be used to plan future service development projects to better meet the needs of this population: they may require specially adapted version of the mentalisation-based treatment programme.


Bohunician technology and thermoluminescence dating of the type locality of Brno-Bohunice (Czech Republic).
Results of thermoluminescence (TL) dating of 11 heated flint artifacts from the 2002 excavation at Brno-Bohunice, Czech Republic, are presented. The samples are from the eponym locality for the Bohunician, an industrial type considered technologically transitional between Middle and Upper Paleolithic core reduction strategies. The Bohunician is the first early Upper Paleolithic technocomplex in the Middle Danube of Central Europe and, therefore, is implicated in several issues related to the origins of modern humans in Europe. The Bohunician provides an example of how one technological strategy combines crested blade initiation of a core with the surficial (almost Levalloisian) reduction of blanks as blades and points. As the Middle Danube lacks antecedents of the behavioral steps within this technology, several hypotheses of inter-regional cultural transmission, with and without hominin gene flow, could explain the appearance of the Bohunician. The elucidation of the temporal context of Bohunician assemblages is, therefore, a critical step in understanding the behavioral, and potentially biological, succession in this region. Radiocarbon age estimates from charcoal associated with Bohunician sites suggest a wide age range between 33 and 41 ka 14C BP, which is also observed for individual sites. TL dating of heated flint artifacts provides ages on the calendric time scale of an archeological event, the firing. The weighted mean of 48.2+/-1.9 ka BPTL for 11 heated flint samples from Brno-Bohunice provides the first non-radiocarbon data on archeological material from the Bohunician. The TL dating, in conjunction with the archeological and sedimentological analysis, allows the evaluation of the integrity of this new type-collection. The hypothetical possibility of the incorporation of Szeletian artifacts (i.e., leaf points) into the site formation processes can therefore be refuted.


The phylogenetic placement of chondrichthyes: inferences from analysis of multiple genes and implications for comparative studies.
Elasmobranch fishes (sharks and rays) have proven valuable for inferring general and specific properties of molecular evolution through comparative studies with crown group vertebrates because they are the most ancient group of gnathostomes. Recent studies have questioned the conventional phylogenetic placement of sharks in the vertebrate tree, however. In this paper I review the importance of the basal position of Chondrichthyes for comparative biology and compile evidence from multiple, independent genes to evaluate the phylogenetic placement of sharks. The results suggests that alternative phylogenetic hypotheses of the relationships among the Chondrichthyes, Actinopterygii and Sarcopterygii can not be refuted with available data, implying that the assumption of the basal placement of sharks in the vertebrate tree is suspect. Resolving the phylogeny of basal vertebrates is important for testing hypotheses about the evolution of vertebrates, and the current lack of a robust phylogeny limits evolutionary inferences that can be gained from comparative studies that include sharks and rays.


[Reference guidelines for the 12-Item Short-Form Health Survey version 2 based on the Catalan general population].
The SF-12 health survey is the short version of the SF-36. The main interpretation strategy for these health related quality of life (HRQL) questionnaires is the use of population based reference values. This study aims to obtain the population based norms for the Spanish version of SF-12 version 2 (SF-12v2), to evaluate its construct validity and to compare the scores obtained by the standard and the specific method of calculation. We analyzed a subsample of the Catalan Health Interview Survey (n=4,261), representative of the general non-institutionalized population. Median and percentiles were calculated for each of the 8 dimensions and for the component summaries, stratified by sex and age groups. The construct validity was evaluated by comparing known groups, applying ANOVA. The results for the known groups analysis supported the hypothesis established a priori (P<.001): worse physical health for persons with mobility problems (EQ-5D) (37.8 vs 52), with restriction in activities (41.8 vs 51.2), and with greater number of chronic disorders (from 43.2 to 53.9); and worse mental health with problems of anxiety/depression (EQ-5D) (42.2 vs 51.9). The scores obtained by the 2 different methods of calculation were similar, except for General Health and Vitality. The SF-12v2 is a valid instrument to measure HQRL in our environment. The obtained norms facilitate the interpretation of SF-12v2 scores in the clinical practice, research and health policy. We recommend the use of the specific method of calculation for national HRQL comparison and the standard one for international comparison.


Prognostic implications of the 8th edition American Joint Committee on Cancer (AJCC) staging system in oral cavity squamous cell carcinoma.
The American Joint Committee on Cancer (AJCC) has changed the staging system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging manual to include depth of invasion (DOI) of the primary tumor as a modifier to the T category and extranodal extension (ENE) to upstage node positive OSCC. This study aims to evaluate the performance of the AJCC 8 pathologic staging system in OSCC and compare it to its predecessor (AJCC 7). Analysis of 663 patients with OSCC from a prospective database was performed using the Cox proportional hazards competing risk model. The prognostic performance of the pathologic staging system was assessed using the Akaike Information Criterion (AIC) and Harrell's concordance index (C-index). AJCC 8 led to upstaging of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited monotonicity and poor stratification between stage groups I to III. The estimates for model performance reveal that AJCC 8 has modest predictive capacity for overall survival (OS) and disease specific survival (DSS) (Harrell's C of 0.70 and 0.74, respectively) but is superior to AJCC 7 (Harrell's C of 0.65 and 0.69, respectively). The AJCC 8 staging system is more complex than its former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it performs better in stratifying survival of OSCC patients by stage.


I-conotoxin superfamily revisited.
The I-conotoxin superfamily (I-Ctx) is known to have four disulfide bonds with the cysteine arrangement C-C-CC-CC-C-C, and the members inhibit or modify ion channels of nerve cells. Recently, Olivera and co-workers (FEBS J. 2005; 272: 4178-4188) have suggested that the previously described I-Ctx should now be divided into two different gene superfamilies, namely, I1 and I2, in view of their having two different types of signal peptides and exhibiting distinct functions. We have revisited the 28 entries presently grouped as I-Ctx in UniProt Swiss-Prot knowledgebase, and on the basis of in silico analysis have divided them into I1 and I2 superfamilies. The sequence analysis has provided a framework for in silico annotation enabling us to carry out computer-based functional characterization of the UniProtKB/TrEMBL entry Q59AA4 from Conus miles and to predict it as a member of the I2 superfamily. Furthermore, we have predicted the mature toxin of this entry and have proposed that it may be an inhibitor of voltage-gated potassium channels.


Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level.
To evaluate the role of small amounts of prostatic tissue dihydrotestosterone (DHT) as a stimulus to epithelial cell protein synthesis, we studied tissue from 27 patients given various androgen-blocking drugs for 1 week before transurethral resection of the prostate (TURP) and measured epithelial protein synthesis and DHT levels in the tissue specimens. Test drugs before TURP included megestrol acetate 160 mg per day, with and without Tamoxifen 40 mg per day, or ketoconazole 1200 mg per day. The tissue was processed immediately and epithelial cells separated by digestion of tissue with 0.5% collagenase. After separation, epithelial cells were labelled with either 3H-leucine or L-35S-methionine. The DHT level was measured in whole prostatic tissue. Megestrol acetate alone and with tamoxifen significantly decreased both the incorporation of 3H-leucine into protein and the tissue concentration of DHT; megestrol acetate plus ketoconazole significantly decreased L-35S-methionine incorporation into protein and the DHT level. When the data correlating DHT with protein synthesis using both labelling techniques were combined, the curves were parallel and a strong correlation was noted between DHT and protein synthesis over a wide range of values (P less than 0.001). These results suggest that in hormone-dependent prostatic cancer even small amounts of prostatic DHT such as may occur from adrenal androgens following castration may significantly stimulate protein synthesis of the tumour epithelial cells.


Nanoelectrochemical quantification of single-cell metabolism.
At the most fundamental level, the behavior of tissue is governed by the activity of its single cells. A detailed examination of single-cell biology is necessary in order to gain a deeper understanding of disease progression. While single-cell genomics and transcriptomics are mature due to robust amplification strategies, the metabolome is difficult to quantify. Nanoelectrochemical techniques stand poised to quantify single-cell metabolism as a result of the fabrication of nanoelectrodes, which allow one to make intracellular electrochemical measurements. This article is concerned with intracellular nanoelectrochemistry, focusing on the sensitive and selective quantification of various metabolites within a single, living cell. We will review the strong literature behind this field, discuss the potential deleterious effects of passing charge inside cells, and provide future outlooks for this promising avenue of inquiry. We also present a mathematical relationship based on Faraday's Law and bulk electrolysis theory to examine the consumption of analyte within a cell due to passing charge at the nanotip.Graphical abstract.


Arterial Evaluation.
The vascular lab (VL) is a powerful tool in diagnosing arterial disease, including peripheral and aortic disease, which is cornerstone of many VLs. This article discusses the indications, protocol, and diagnostic criteria of noninvasive testing for peripheral arterial disease and contrast enhanced ultrasound after endovascular repair of aortic aneurysm.


Targeting Health Behaviors to Reduce Health Care Costs in Pediatric Psychology: Descriptive Review and Recommendations.
Recent efforts to enhance the quality of health care in the United States while reducing costs have resulted in an increased emphasis on cost containment and the introduction of new payment plans. The purpose of this review is to summarize the impact of pediatric health behavior change interventions on health care costs. A review of PubMed, PsycINFO, and PEDE databases identified 15 articles describing the economic outcomes of pediatric health behavior change interventions. Data describing the intervention, health outcome, and economic outcome were extracted. All interventions targeting cigarette smoking (n = 3) or the prevention of a chronic medical condition (n = 5) were predicted to avert hundreds of dollars in health care costs per patient. Five of the seven interventions targeting self-management were associated with reductions in health care costs. Pediatric health behavior change interventions may be a valuable component of efforts to improve population health while reducing health care costs.


Determination of the isotope effect of the enzymatic oxidation of (R)Carnitine by displacement of the equilibrium via mass action.
An isotope effect of the dehydrogenation of (R) Carnitine [(R) 3-hydroxy-4-trimethylaminobutyric acid hydrochloride] catalyzed by (R) carnitine dehydrogenase [(R) carnitine: NAD oxidoreductase E.C. 22.214.171.124] from Pseudomonas aeruginosa was measured at different temperatures. It was found that k1H/k3H does not vary greatly with changes of temperature. The value of 3 for k1H/k3H measured at small initial conversions strongly indicated that the rate limiting step of the oxidation of (R) carnitine is the cleavage of the C-H bond at C3.


Sustained nerve-mediated contractions of guinea-pig ileum during morphine withdrawal by washout.
The effects of morphine withdrawal by washout were examined in ilea from guinea-pigs pretreated by subcutaneous implantation of two pellets, each containing 155 mg morphine. One week later preparations of the longitudinal muscle-myenteric plexus were set up in vitro in a modified Krebs solution containing morphine (1 microM). Within 5-15 min after washing in morphine-free Krebs, the preparations exhibited marked spontaneous contractions which became maximal after 20-60 min. The contractions resulting from morphine washout were greatly reduced by TTX and by hyoscine but not by hexamethonium, suggesting that excitation involved predominantly the cholinergic myenteric motor neurons, and was thus similar to that underlying the contraction induced by naloxone. In contrast to the naloxone-induced contractions, however, those resulting from morphine washout were well sustained during periods of recording up to 5 h. Morphine washout therefore provides conditions suitable for investigating the mechanisms underlying the variety of withdrawal signs observed in the ileum in vitro.


Laryngeal effects and respiration in the suckling opossum.
Electromyogram (EMG) activity of the posterior cricoarytenoid (PCA muscles were active, but was otherwise closed. Larynx closure may contribute to the end-inspiratory pauses often observed in the intact animal. During inhalation of an asphyxiant test gas in place of room air, PCA and diaphragm activity generally increased; and increases in anesthesia decreased the EMG activity of both muscles. Water on the larynx transiently abolished both PCA and diaphragm discharge; but EMG activity returned to the PCA muscles before the diaphragm. Further, reactivation of the diaphragm was not always accompanied by a synchronized burst of PCA activity. Therefore, it is possible under some conditions to dissociate the motor outputs from the PCA muscles and diaphragm in this immature mammal.


A new "flagship" ciliate, Pseudostylonychia obliquocaudata n. gen., n. sp. (Ciliophora, Hypotricha), from South Korea.
The morphology, ontogenesis, and molecular phylogeny of a new ciliate, Pseudostylonychia obliquocaudata n. gen., n. sp., discovered in a semiterrestrial habitat in South Korea, were investigated. The new species is characterized by an obovate or triangular body with pointed posterior end. The caudal area is distinctly obliquely truncated rightwards. Pseudostylonychia n. gen. is established and characterized by the obovate or triangular body, Stylonychia-like infraciliature and macronuclear pattern, and undulating membranes in Laurentiella pattern. It is also characterized by the involvement of cirri III/2 and IV/3 in primordia formation. SEM investigations show that the resting cyst has high, spirally arranged ridges. Phylogenetic analyses based on SSU rRNA gene sequences show that the new species is placed as a sister to the clade containing sequences of Stylonychia mytilus complex, Stylonychia (Metastylonychia), and Coniculostomum. Furthermore, Stylonychia koreana Kumar et al., 2016 nov. stat. is raised to species level based on the differences in the cyst morphology between the two subspecies of S. ammermanni. Also, Metastylonychia Kumar and Foissner, 2017 nov. stat. is raised to genus rank based on the new molecular data and the morphological and ontogenetic differences to Coniculostomum and Stylonychia.


[Oral sex and HIV among men who have sex with men].
Sexual transmission of the human immunodeficiency virus (HIV) continues to pose a public health problem worldwide. Men who have sex with men are still at differential risk of infection. Although there is evidence to claim that HIV can be transmitted by oral sex, the perception of this risk is ambiguous and relates paradoxically to behavior change. New models of risk perception must be developed in various areas of knowledge to obtain a fuller understanding of this phenomenon.


5-Aminolevulinic acid formation from glutamate via the C5 pathway in Clostridium thermoaceticum.
A cell-free extract of the anaerobic eubacterium, Clostridium thermoaceticum, catalyzes the synthesis of 5-aminolevulinic acid (ALA) from glutamate via the C5 pathway. The enzyme reaction resembles that of higher plants and algae in cofactor requirements and sensitivity to ribonuclease. From the phylogenetic distribution it is proposed that the C5 pathway evolved earlier than the ALA synthase pathway.


Atypical HUS with multiple complement system mutations triggered by synthetic psychoactive drug abuse: a case report.
Atypical hemolytic uremic syndrome is a rare disorder with an estimated annual incidence of about two cases per million in the adult population. It is caused by the overactivation of the alternative pathway of the complement system. The disease can be triggered by many factors, including pregnancy, viral diseases, and sepsis; approximately 30% of atypical hemolytic uremic syndrome cases are caused by unknown processes. We present a case of a patient with C3-complement system mutations and aHUS triggered by the use of a new synthetic psychoactive drug.


A timeline of surgical lighting - Is automated lighting the future?
High quality surgical lighting is central to successful performance in the operating room and therefore to both patient care and treatment. This article discusses the origins of surgical lighting from the 1800s to today, with a focus on the four main forms. Their uses, advantages, and disadvantages are evaluated in an effort to identify the improvements required to improve today's current state of surgical lighting. Whilst these four mainstream types have served well for the past thirty years, the literature exposes opportunities for improvement and can be used to guide the pathway to transition from manual conventional methods to a more automated lighting (AL) approach. The concept of AL has been proposed using established and known technical approaches such as artificial intelligence (AI), 3D sensor tracking algorithms and thermal imaging. Whilst AL seems incredibly promising, further focused research must be undertaken to maximise its' effectiveness and allow for successful integration of this new technology into operating rooms today.


Implementation and Feasibility of Clinical Genome Sequencing Embedded Into the Outpatient Nephrology Care for Patients With Proteinuric Kidney Disease.
The diagnosis and management of proteinuric kidney diseases such as focal segmental glomerulosclerosis (FSGS) are challenging. Genetics holds the promise to improve clinical decision making for these diseases; however, it is often performed too late to enable timely clinical action and it is not implemented within routine outpatient nephrology visits. We sought to test the implementation and feasibility of clinical rapid genome sequencing (GS) in guiding decision making in patients with proteinuric kidney disease in real-time and embedded in the outpatient nephrology setting. We enrolled 10 children or young adults with biopsy-proven FSGS (9 cases) or minimal change disease (1 case). The mean age at enrollment was 16.2 years (range 2-30). The workflow did not require referral to external genetics clinics but was conducted entirely during the nephrology standard-of-care appointments. The total turn-around-time from enrollment to return-of-results and clinical decision averaged 21.8 days (12.4 for GS), which is well within a time frame that allows clinically relevant treatment decisions. A monogenic or APOL1-related form of kidney disease was diagnosed in 5 of 10 patients. The genetic findings resulted in a rectified diagnosis in 6 patients. Both positive and negative GS findings determined a change in pharmacological treatment. In 3 patients, the results were instrumental for transplant evaluation, donor selection, and the immunosuppressive treatment. All patients and families received genetic counseling. Clinical GS is feasible and can be implemented in real-time in the outpatient care to help guiding clinical management. Additional studies are needed to confirm the cost-effectiveness and broader utility of clinical GS across the phenotypic and demographic spectrum of kidney diseases.


An efficient protein production system via gene amplification on a human artificial chromosome and the chromosome transfer to CHO cells.
Gene amplification methods play a crucial role in establishment of cells that produce high levels of recombinant protein. However, the stability of such cell lines and the level of recombinant protein produced continue to be suboptimal. Here, we used a combination of a human artificial chromosome (HAC) vector and initiation region (IR)/matrix attachment region (MAR) gene amplification method to establish stable cells that produce high levels of recombinant protein. Amplification of Enhanced green fluorescent protein (EGFP) was induced on a HAC carrying EGFP gene and IR/MAR sequences (EGFP MAR-HAC) in CHO DG44 cells. The expression level of EGFP increased approximately 6-fold compared to the original HAC without IR/MAR sequences. Additionally, anti-vascular endothelial growth factor (VEGF) antibody on a HAC (VEGF MAR-HAC) was also amplified by utilization of this IR/MAR-HAC system, and anti-VEGF antibody levels were approximately 2-fold higher compared with levels in control cells without IR/MAR. Furthermore, the expression of anti-VEGF antibody with VEGF MAR-HAC in CHO-K1 cells increased 2.3-fold compared with that of CHO DG44 cells. Taken together, the IR/MAR-HAC system facilitated amplification of a gene of interest on the HAC vector, and could be used to establish a novel cell line that stably produced protein from mammalian cells.


Orthogonality constrained inverse regression to improve model selectivity and analyte predictions from vibrational spectroscopic measurements.
In analytical chemistry spectroscopy is attractive for high-throughput quantification, which often relies on inverse regression, like partial least squares regression. Due to a multivariate nature of spectroscopic measurements an analyte can be quantified in presence of interferences. However, if the model is not fully selective against interferences, analyte predictions may be biased. The degree of model selectivity against an interferent is defined by the inner relation between the regression vector and the pure interfering signal. If the regression vector is orthogonal to the signal, this inner relation equals zero and the model is fully selective. The degree of model selectivity largely depends on calibration data quality. Strong correlations may deteriorate calibration data resulting in poorly selective models. We show this using a fructose-maltose model system. Furthermore, we modify the NIPALS algorithm to improve model selectivity when calibration data are deteriorated. This modification is done by incorporating a projection matrix into the algorithm, which constrains regression vector estimation to the null-space of known interfering signals. This way known interfering signals are handled, while unknown signals are accounted for by latent variables. We test the modified algorithm and compare it to the conventional NIPALS algorithm using both simulated and industrial process data. The industrial process data consist of mid-infrared measurements obtained on mixtures of beta-lactoglobulin (analyte of interest), and alpha-lactalbumin and caseinoglycomacropeptide (interfering species). The root mean squared error of beta-lactoglobulin (% w/w) predictions of a test set was 0.92 and 0.33 when applying the conventional and the modified NIPALS algorithm, respectively. Our modification of the algorithm returns simpler models with improved selectivity and analyte predictions. This paper shows how known interfering signals may be utilized in a direct fashion, while benefitting from a latent variable approach. The modified algorithm can be viewed as a fusion between ordinary least squares regression and partial least squares regression and may be very useful when knowledge of some (but not all) interfering species is available.


Antigenic and nucleotide characterization of a herpesvirus isolated from Pacific harbor seals (Phoca vitulina richardsii).
This report describes the antigenic and nucleotide characterization of a herpes-like virus that has been isolated from the adrenal tissues of neonatal Pacific harbor seals. Infection with this virus has been previously implicated as a major cause of death of animals undergoing rehabilitation. Comparison and phylogenetic analysis of sequenced fragments of the DNA polymerase, glycoprotein B and glycoprotein D genes, and immunofluorescence assay using herpesvirus-specific monoclonal antibodies, demonstrated close similarity of the Pacific harbor seal herpesvirus to European isolates of phocid herpesvirus-1 (PHV-1) and other alpha-herpesviruses affecting terrestrial carnivores.


[Surgery and postoperative radiation therapy in primary retroperitoneal sarcomas: experience of the cancer centre Alexis-Vautrin].
Surgical resection remains the standard treatment for patients with resectable retroperitoneal sarcomas. The aim of this study was to retrospectively analyse the outcomes of patients with primary retroperitoneal sarcoma. We analysed data of 50 patients with primary retroperitoneal sarcoma who underwent curative-intent resection from 1975 to 2008. External beam radiotherapy and chemotherapy were delivered postoperatively. Demographics, surgical, pathological variables and chemo/radiation therapy were analysed as prognosis factors. There were 22 males and 28 females (mean age 54 ± 13 years). Surgery required visceral resections in 30 patients. There were 16 leiomyosarcomas, 25 liposarcomas and eight other sub-types. Twenty-one patients had clear surgical margins. Twenty-eight patients received postoperative external beam radiotherapy (median 45 Gy) and 15 received chemotherapy. At the end of the follow-up (median 55 months), local recurrence occurred in 39% (n=14) among R0/R1 resection group (n=36). Postoperative external beam radiotherapy tends to increase the time of local recurrence from surgery (27 vs. 13 months, P=0.05). The overall survival rates were 81%, 55% and 46% at 1, 3 and 5 years, respectively. Although R0 resection (P=0.01), well tumour differentiation (P=0.004) and postoperative external beam radiotherapy (P=0.02) significantly influenced overall survival in univariate analysis, only R0 resection was an independent prognostic factor in a multivariate analysis. We confirm the pre-eminence of radical surgery with negative margins as major prognostic factor and the benefit of postoperative radiotherapy.


A comprehensive review on the decabromodiphenyl ether (BDE-209)-induced male reproductive toxicity: Evidences from rodent studies.
Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), are employed in various manufactured products to prevent fires, slow down their spread and reduce the resulting damages. Decabromodiphenyl ether (BDE-209), an example of PBDEs, accounts for approximately 82 % of the total production of PBDEs. BDE-209 is a thyroid hormone (TH)-disrupting chemical owing to its structural similarity with TH. Currently, increase in the level of BDE-209 in biological samples has become a major issue because of its widespread use. BDE-209 causes male reproductive toxicity mainly via impairment of steroidogenesis, generation of oxidative stress (OS) and interference with germ cell dynamics. Further, exposure to this chemical can affect metabolic status, sperm concentration, epigenetic regulation of various developmental genes and integrity of blood-testis barrier in murine testis. However, the possible adverse effects of BDE-209 and its mechanism of action on the male reproductive health have not yet been critically evaluated. Hence, the present review article, with the help of available literature, aims to elucidate the reproductive toxicity of BDE-209 in relation to thyroid dysfunction in rodents. Further, several crucial pathways have been also highlighted in order to strengthen our knowledge on BDE-209-induced male reproductive toxicity. Data were extracted from scientific articles available in PubMed, Web of Science, and other databases. A thorough understanding of the risk assessment of BDE-209 exposure and mechanisms of its action is crucial for greater awareness of the potential threat of this BFR to preserve male fertility.


Will personalized drugs for cardiovascular disease become an option? - Defining 'Evidence-based personalized medicine' for its implementation and future use.
It is generally accepted that the implementation of pharmacogenomics and, more broadly, personalized medicine will have to be 'evidence-based'. However, there is a lack of consensus on the level of evidence required to justify the use of pharmacogenomic testing in clinical practice. In the cardiovascular field, this lack of agreement has led to somewhat contradicting recommendations by different organizations regarding the clinical utility and use of pharmacogenomic tests or information. Here, we argue that randomized, controlled trials are paramount in order to enable and accelerate the widespread implementation of pharmacogenomics, not only to demonstrate the clinical efficacy and cost-effectiveness of such tests, but because such level of evidence is required to support the considerable changes associated with the implantation of pharmacogenomics in clinical practice.


[Differences between the so-called Szczecin-localization method of treating the squint and the traditional methods].
The author shows the differences which have arisen between the methods for the last 35 years. The differences concern both the conservative and surgical treatments. Differences in the treatment of the squints in adults and infants in the first year of life are discussed. The author also presents discrepancies in the criteria of cure.


Two hydroxyflavanones isolated from Scutellaria baicalensis roots prevent colitis-associated colon cancer in C57BL/6 J mice by inhibiting programmed cell death-1, interleukin 10, and thymocyte selection-associated high mobility group box proteins TOX/TOX2.
Colorectal cancer was the second leading cause of mortality in 2019 and the number of new colorectal cancer cases was the highest in 2018 and 2019 in Japan. The present study investigated the inhibitory effects of 2(S)-2',5,6',7-tetrahydroxyflavanone and 2 (R), 3(R)-2',3,5,6'-7-pentahydroxyflavanone on the incidence and growth of tumors in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated mice. The intraperitoneal administration of AOM (10 mg/kg) on day 0 induced colorectal carcinogenesis. Mice were given free and unlimited access to drinking water containing 1.5% (w/v) DSS on days 5 - 8, 30 - 33, and 56 - 57. They were orally administered tetra- and penta-hydroxyflavanones (10 and 30 mg/kg) for 10, 11, and 14 days followed by discontinuation intervals of 20 and 15 days. Cytokine, chemokine, programmed cell death-1 (PD-1), cyclooxygenase (COX)-2, and thymocyte selection-associated high mobility group box protein (TOX)/TOX2 expression levels were measured using their respective ELISA kits and an immunohistochemical analysis. The number and area of tumors decreased by 60.6 and 72.9% in mice administered 10 mg/kg tetra- and pentahydroxyflavanones, respectively, with reductions of 95.0 and 87.0% in Ki-67-positive cells, 91.7 and 92.7% in COX-2-postive cells, and 83.1 and 93.8% in TOX/TOX2-positive cells, respectively, in the colon. On the other hand, two tera- and pentahydroxyflavanone had no effect on p53 (a tumor suppressor by cell cycle arrest and apoptosis)-positive cells. The administration of 10 mg/kg tetra- and pentahydroxyflavanones to AOM/DSS-treated mice also resulted in decreases of 59.5 and 42.5% in IL-10 levels and 58.1 and 93.9% in PD-1 levels, respectively, in the colon. The inhibitory effects of tetra- and pentahydroxyflavanones on the growth of colon tumors in AOM/DSS-treated mice appear to be associated with decreases in the colon levels of IL-10 and PD-1 through the down-regulated expression of COX-2 and CD8+ T-cell exhaustion by TOX/TOX2 in the tumor microenvironment.


Bridging the gap from prenatal karyotyping to whole-genome array comparative genomic hybridization in Hong Kong: survey on knowledge and acceptance of health-care providers and pregnant women.
The use of array comparative genomic hybridization (aCGH) has been increasingly widespread. The challenge of integration of this technology into prenatal diagnosis was the interpretation of results and communicating findings of unclear clinical significance. This study assesses the knowledge and acceptance of prenatal aCGH in Hong Kong obstetricians and pregnant women. The aim is to identify the needs and gaps before implementing the replacement of karyotyping with aCGH. Questionnaires with aCGH information in the form of pamphlets were sent by post to obstetrics and gynecology doctors. For the pregnant women group, a video presentation, pamphlets on aCGH and a self-administered questionnaire were provided at the antenatal clinic. The perception of aCGH between doctors and pregnant women was similar. Doctors not choosing aCGH were more concerned about the difficulty in counseling of variants of unknown significance and adult-onset disease in pregnant women, whereas pregnant women not choosing aCGH were more concerned about the increased waiting time leading to increased anxiety. Prenatal aCGH is perceived as a better test by both doctors and patients. Counseling support, training, and better understanding and communication of findings of unclear clinical significance are necessary to improve doctor-patient experience.


A multifactorial survey of neonatal juandice.
Concern about a neonatal jaundice rate of 8-6 per cent prompted a retrospective survey of 981 full term infants. There was a highly significant association between increased oxytocin dosage and neonatal jaundice in induced labours. A significant association was also demonstrated between neonatal jaundice and both breast-feeding and minor infections. No association was demonstrated between neonatal jaundice and the method of delivery of birth weight. The results of the survey suggest that while oxytocin in high doses should be used with caution, the benefits obtained from the drug outweigh the risk of hyperbilirubinaemia which it may cause.


The three-dimensional structure of human bactericidal/permeability-increasing protein: implications for understanding protein-lipopolysaccharide interactions.
Gram-negative bacterial infections are often complicated by the inflammatory properties of lipopolysaccharides (LPS) on or released from the bacterial outer membrane. When present in the mammalian bloodstream, LPS can trigger a series of pathological changes, sometimes resulting in septic shock. Two related mammalian proteins, bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP), are known to affect the LPS-induced inflammatory response and are, therefore, of clinical interest. The recently determined three-dimensional structure of human BPI provides information on the overall protein fold, domain organization, and conserved regions of these two proteins. In addition, the discovery of two apolar lipid binding pockets in BPI indicates a possible site of interaction with LPS. The BPI structure is a powerful tool for the design of site-directed mutants, peptide mimetics/inhibitors, and BPI/LBP chimeras. These studies should help further define the functions of BPI and LBP, and their mechanism of interaction with LPS.


The associations between prenatal phthalate exposure and childhood glycolipid metabolism and blood pressure: An updated systematic review and a pilot meta-analysis of prospective cohort studies.
This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was performed in MEDLINE, Web of Science and CNKI (Chinese National Knowledge Infrastructure) until June 5, 2023. A total of seven studies with 5746 children (2646 girls and 3100 boys) were finally included. Four, three and two studies investigated the effects of maternal phthalate exposure on childhood blood pressure (BP), blood lipids and blood glucose profiles, respectively. The pilot meta-analysis suggested that di-2-ethylhexyl phthalate (DEHP) metabolite exposure was associated with a decrease in childhood z-systolic BP (SBP, β = -0.169, 95% CI = -0.338-0.001). Furthermore, the pooled results showed negative relationships of prenatal ∑DEHP exposure with z-SBP (β = -0.109, 95% CI = -0.163 to -0.055) and z-diastolic BP (DBP, β = -0.126, 95% CI = -0.182 to -0.069) in girls. In addition, MEP exposure was associated with z-SBP in girls (β = -0.227, 95% CI = -0.387 to -0.066). The pooled result showed a positive relationship between prenatal ∑DEHP exposure and triglycerides (β = 0.103, 95% CI = 0.028-0.178). The overall results revealed that exposure to ∑DEHP throughout gestation was associated with a decrease in insulin (β = -0.074, 95% CI = -0.144 to -0.004) and glucose (β = -0.129, 95% CI = -0.199 to -0.058) in boys. Interestingly, there was an inverse relationship of prenatal mono- 3 -carboxypropyl phthalate (MCPP) exposure with glucose in pubertal boys (β = -3.749, 95% CIs = -6.758 to -0.741) but not found in postpubertal children. In conclusion, prenatal phthalate exposure interfered with cardiovascular risk in children with gender-specific differences and was influenced by puberty. Overall, prenatal ∑DEHP was negatively associated with systolic blood pressure in girls and with insulin and glucose in boys but increased the level of triglycerides.