The choice of a masking agent in the histochemical staining of metals.
The masking effects of standard masking agents (aminopolycarboxylic acids, carboxylic acids and phosphates) have been investigated in both test-tube experiments and tissue sections in order to ascertain the factors which must be considered when choosing a masking agent for the histochemical staining of a metal. The masking effects in vitro were determined by spectrophotometry through the complexing of the dye Chrome Azurol S with aluminium, beryllium, and iron at pH 5 and 7. The effects were also examined by staining metal-containing tissue sections in a Chrome Azurol S masking agent system at the same pH values. In many cases, the masking effects observed in sections did not agree with those obtained in the test-tube experiments. This means that the published values of stability constants are not a sufficient guide for choosing a suitable masking agent for the staining of metals. The discrepancy is mainly attributable to the presence of protein in a solid state when metals are stained in sections. Therefore, in the future, consideration should be given to a metal-protein or masking agent-protein interaction using a model compound such as a chelate resin. The polyphosphates are among the most useful masking agents for metal staining in acidic solutions from a practical standpoint.


Selamectin: a novel broad-spectrum endectocide for dogs and cats.
Selamectin, 25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22, 23-dihydro-5-(hydroxyimino)-avermectin B1 monosaccharide, is a novel endectocide with a unique combination of efficacy and safety in dogs and cats following both oral and topical administration. The compound is active against fleas and ticks, intestinal hookworms and ascarids, and immature heartworms. Also it is well tolerated at higher dosages than 22,23-dihydroavermectin B1a (DHAVM) or milbemycin oxime in Collies, which is a breed known to exhibit idiosyncratic sensitivity to avermectins.


Expression of yeast cytochrome c1 is controlled at the transcriptional level by glucose, oxygen and haem.
The nuclear gene for cytochrome c1 in Saccharomyces cerevisiae (CYT1) was localized on chromosome XV. Its upstream region was identified by functional complementation. Fusion to the lacZ reporter gene on a CEN plasmid allowed study of the effect of carbon sources and of specific deletion mutations on expression of the gene in yeast transformants. Detailed promoter analysis combined with expression studies in recipient strains defective in regulatory genes identified cis-acting sites and transcription factors involved in the regulated expression of the cytochrome c1 gene. These analyses showed that, in the presence of glucose, transcription of CYT1 is positively controlled by oxygen, presumably through the haem signal, and mediated by the HAP1-encoded transactivator. It is additionally regulated by the HAP2/3/4 complex which mediates gene activation mainly under glucose-free conditions. Basal transcription is, in part, effected by CPF1, a centromere and promoter-binding factor.


Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts.
Contrast-enhanced spectral mammography to compare clinical efficacy of contrast-enhanced spectral mammography (CESM) and conventional digital mammography (MMG) with histopathology as gold standard in dense breasts. A total of 143 breasts of 72 women who underwent CESM and MMG between 2011 and 2014 at Showa University Hospital were analyzed. 129 (90.2 %) of 143 breasts revealed dense breasts on MMG. 58 (40.6 %) of 143 breasts were diagnosed with breast cancer at histopathology. The remaining 85 breasts were diagnosed with benign findings after image assessments and/or core needle biopsy. CESM revealed 8 false-negative cases among 58 breast cancer cases (sensitivity 86.2 %) and 5 false-positive cases (specificity 94.1 %). Accuracy was 90.9 %. Conventional MMG was assessed true positive in 31 of 58 breast cancer cases (sensitivity 53.4 %) and false positive in 12 cases (specificity 85.9 %). Accuracy was 72.7 %. Sensitivity (p < 0.001), specificity (p = 0.016) and accuracy (p < 0.001) were significantly higher on CESM compared to MMG. MMG missed malignancy in 27 breasts. Of these, 25 were dense breasts. Of these 25, 20 (80.0 %) breasts were positive on CESM. These findings suggest that CESM offers superior clinical performance compared to MMG. Use of CESM may decrease false negatives especially for women with dense breasts.


Prevalence of gender dysphoria and suicidality and self-harm in a national database of paediatric inpatients in the USA: a population-based, serial cross-sectional study.
Transgender and non-binary young people experience discrimination that has been linked to suicidal ideation and self-harm, but few studies have examined this association systematically. We aimed to study the association between gender dysphoria-related diagnostic coding and hospital admission for suicidality or self-harm in a large representative pediatric inpatient database from the USA. Using the 2016 and 2019 Kids' Inpatient Database (KID), we identified transgender and non-binary young people (aged 6-20 years) with International Classification of Diseases (ICD)-10 codes related to gender dysphoria. We identified suicidal ideation using explicit suicidality ICD-10 codes, and self-harm using 355 self-harm ICD-10 codes. Prevalence of suicidality (primary outcome), self-harm, and the combination of suicidality and self-harm (secondary outcomes) was compared between young people with and without gender dysphoria-related codes. Univariable and multivariable regression was used to test for an association between gender dysphoria and suicidality, self-harm, or suicidality and self-harm combined. 1 090 544 individuals were included from KID 2016 and 1 026 752 from KID 2019. Gender dysphoria-related diagnoses were prevalent in 161 per 100 000 hospital admissions in KID 2016 and 475 per 100 000 hospital admissions in KID 2019. In KID 2016 and KID 2019, among individuals who were White, privately insured, or from higher median income ZIP code areas, proportionately more had gender dysphoria-related codes. Prevalence of suicidality was greater in individuals with gender dysphoria-related codes than in individuals without gender dysphoria-related codes in KID 2016 (635 [36%] of 1755 individuals with gender dysphoria-related codes vs 55 351 [5%] of 1 088 789 individuals without gender dysphoria-related codes; unadjusted prevalence ratio [PR] 7·19 [95% CI 6·75-7·66]) and KID 2019 (2680 [55%] of 4872 individuals with gender dysphoria-related codes vs 38 831 [4%] of 1 021 880 individuals without gender dysphoria-related codes; unadjusted PR 5·45 [5·30-5·60]). This association persisted in multivariable modelling adjusting for confounders in KID 2016 (adjusted PR 5·02 [95% CI 4·67-5·41]) and KID 2019 (4·14 [4·02-4·28]). Increased unadjusted and adjusted PRs for individuals with gender dysphoria-related codes, relative to those without, were also evident for self-harm and when combining suicidality and self-harm in both the 2016 and 2019 datasets. In a large representative national sample, transgender and non-binary young people with gender dysphoria-related diagnoses were frequently admitted to hospital for suicidality or self-harm. The lower rates of gender-dysphoria-related codes among young people who were non-White, publicly insured, and from low-income households suggest that underlying inequities might shape the identification and management of gender dysphoria. Structural and health-care provider-level interventions are needed to reduce discrimination and expand gender-affirming competencies to prevent adverse outcomes for hospitalised transgender and non-binary young people with gender dysphoria. National Institutes of Health.


Geothermal sweetspots identified in a volcanic lake integrating bathymetry and fluid chemistry.
We investigate fluid pathways beneath volcanic lakes using bathymetry and geochemical measurements to locate best-possible drilling sites. Highly permeable structures, such as faults, provide fluid channels that are the most suitable access points to the geothermal resource. Accurate mapping of these structures therefore guides the successful targeting of wells. Lakes, rivers or ocean, can hide surface footprints of these permeable structures, such as in our case beneath Lake Linau. High-resolution bathymetry identifies linear and conical discontinuities, which are linked to offshore tectonic structures as confirmed by surrounding outcrops and hot springs. Geochemical measurements document inflow of hot saline acidic water into the lake verifying bathymetry-located highly permeable structures. Integrating onshore well data, our bathymetry and chemical results locates an ideal drilling site into the geothermal reservoir beneath the western shore line of Lake Linau.


Companion animal models of neurological disease.
Clinical translation of novel therapeutics that improve the survival and quality of life of patients with neurological disease remains a challenge, with many investigational drug and device candidates failing in advanced stage clinical trials. Naturally occurring inherited and acquired neurological diseases, such as epilepsy, inborn errors of metabolism, brain tumors, spinal cord injury, and stroke occur frequently in companion animals, and many of these share epidemiologic, pathophysiologic and clinical features with their human counterparts. As companion animals have a relatively abbreviated lifespan and genetic background, are immunocompetent, share their environment with human caregivers, and can be clinically managed using techniques and tools similar to those used in humans, they have tremendous potential for increasing the predictive value of preclinical drug and device studies. Here, we review comparative features of spontaneous neurological diseases in companion animals with an emphasis on neuroimaging methods and features, illustrate their historical use in translational studies, and discuss inherent limitations associated with each disease model. Integration of companion animals with naturally occurring disease into preclinical studies can complement and expand the knowledge gained from studies in other animal models, accelerate or improve the manner in which research is translated to the human clinic, and ultimately generate discoveries that will benefit the health of humans and animals.


Silent Trypanosoma evansi infection in humans from India revealed by serological and molecular surveys, and characterized by variable surface glycoprotein gene sequences.
The importance of emerging atypical human trypanosomosis is gaining momentum due to increasing detection and its possible impact on human health. A cross sectional study of atypical human trypanosomosis due to Trypanosoma evansi was carried out in Kolkata and Canning area of West Bengal state of India where previously a death was reported. In this study blood and serum samples from 173 individuals were collected during August to December 2014. To check the presence of antibodies against T. evansi, card agglutination test and for the presence of T. evansi specific DNA, PCR were conducted. T. evansi infection was identified in 5.2% (9/173) human blood samples by CATT serological test (Card agglutination test for trypanosomosis). PCR targeting VSG gene sequences suggested active T. evansi infection in 2.89% (5/173). VSG gene sequences herein determined for five isolates from human cases shared high similarity (89.4-100%). Phylogenetic inference clustered the human isolates with other isolates from different host species from India and other countries, forming a clade exclusive of Indian isolates (84.0 to 100% sequence similarity). First report of symptomless human T. evansi infection detected by combined serological and PCR assays. First phylogenetic analysis of VSG gene sequences including human isolates of T. evansi in which Indian isolates of T. evansi from human and other hosts clustered in a single clade.


Theoretical Study of ZnS Monolayer Adsorption Behavior for CO and HF Gas Molecules.
Adsorption of carbon monoxide (CO) and hydrogen fluoride (HF) gas molecules on a ZnS monolayer with weak van der Waals interactions is studied using the DFT + U method. From our calculation, the ZnS monolayer shows chemisorption with CO (E ads = -0.96 eV) and HF (E ads = -0.86 eV) gas molecules. Bader charge analysis shows that charge transfer is independent of the binding environment. A higher energy barrier for CO when migrating from one optimal site to another suggests that clustering may be avoided by the introduction of multiple CO molecules upon ZnS, while the diffusion energy barrier (DEB) for HF suggests that binding may occur more easily for HF gas upon the ZnS ML. Adsorption of the considered diatomic molecule also results in a significant variation in effective mass and therefore can be used to enhance the carrier mobility of the ZnS ML. Additionally, the calculation of recovery time shows that desirable sensing and desorption performance for CO and HF gas molecules can be achieved at room temperature (300 K).


Cellular mechanisms of circadian pacemaking: beyond transcriptional loops.
Circadian clocks drive the daily rhythms in our physiology and behaviour that adapt us to the 24-h solar and social worlds. Because they impinge upon every facet of metabolism, their acute or chronic disruption compromises performance (both physical and mental) and systemic health, respectively. Equally, the presence of such rhythms has significant implications for pharmacological dynamics and efficacy, because the fate of a drug and the state of its therapeutic target will vary as a function of time of day. Improved understanding of the cellular and molecular biology of circadian clocks therefore offers novel approaches for therapeutic development, for both clock-related and other conditions. At the cellular level, circadian clocks are pivoted around a transcriptional/post-translational delayed feedback loop (TTFL) in which the activation of Period and Cryptochrome genes is negatively regulated by their cognate protein products. Synchrony between these, literally countless, cellular clocks across the organism is maintained by the principal circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. Notwithstanding the success of the TTFL model, a diverse range of experimental studies has shown that it is insufficient to account for all properties of cellular pacemaking. Most strikingly, circadian cycles of metabolic status can continue in human red blood cells, devoid of nuclei and thus incompetent to sustain a TTFL. Recent interest has therefore focused on the role of oscillatory cytosolic mechanisms as partners to the TTFL. In particular, cAMP- and Ca²⁺-dependent signalling are important components of the clock, whilst timekeeping activity is also sensitive to a series of highly conserved kinases and phosphatases. This has led to the view that the 'proto-clock' may have been a cytosolic, metabolic oscillation onto which evolution has bolted TTFLs to provide robustness and amplify circadian outputs in the form of rhythmic gene expression. This evolutionary ascent of the clock has culminated in the SCN, a true pacemaker to the innumerable clock cells distributed across the body. On the basis of findings from our own and other laboratories, we propose a model of the SCN pacemaker that synthesises the themes of TTFLs, intracellular signalling, metabolic flux and interneuronal coupling that can account for its unique circadian properties and pre-eminence.


High-throughput scanning of breast tumor surgical specimens for low-level mutations.
Large numbers of mutations are postulated to occur as early events in carcinogenesis. For certain types of human tumors (mutator phenotypes) these mutations can be a driving force in generating clonogenic, causative genetic changes leading to multistage carcinogenesis. These low-level mutational events are highly significant due to their potential use as molecular markers for early identification of genomic instability that can lead to cancer and to their potential influence on the ability of tumors to resist drug treatment and/or metastasize. Detecting the presence and diversity of such genetic changes in human tumors is desirable due to their potential prognostic value. However, identification of these low-frequency genetic changes is difficult, since most mutations exist at mutant/wild-type ratios of <10(-3). We recently developed inverse PCR-based amplified restriction fragment-length polymorphism (iFLP), a new technology that combines inverse PCR, RFLP, and denaturing HPLC to allow scanning of the genome at several thousand positions per experiment for low-level point mutations. Using iFLP we previously demonstrated low-level mutations (mutation frequency <10(-3)) in human colon cancer cells that harbor mismatch repair deficiency and in sporadic colon cancer surgical specimens. In the present work we investigated whether low-level mutations are also present in sporadic breast cancer surgical specimens. Using iFLP we identified widespread low-level mutations in two out of ten surgical specimens examined (20%). Examination of the microsatellite instability status of these samples demonstrated that the samples are stable (MSI-S). We conclude that low-level mutations are less frequent in breast cancer than in colon cancer; however, single nucleotide instability that generates such mutations may still be present in a fraction of breast cancers.


T cell epitope definition by differential mass spectrometry: identification of a novel, immunogenic HLA-B8 ligand directly from renal cancer tissue.
In this study, we describe a differential mass spectrometric technique for the immuno-proteomic analysis of the major histocompatibility complex (MHC) peptides of a renal cell carcinoma (RCC) biopsy compared with the healthy kidney tissue of the same patient after nephrectomy. Using a stable isotope labeling approach, we could directly compare and relatively quantify 43 MHC-peptide pairs, most of which were present in similar proportions on both normal kidney and tumor. Significantly, two dominant peptides of monoisotopic masses ([M+H](+)) 973.43 u and 967.59 u, respectively, were found exclusively in the tumor sample. One of these was identified as originating from heme oxygenase-1 (HO-1), a protein involved in induction of apoptosis resistance, immuno-suppression and neoangiogenesis and reported to be up-regulated in various cancer types. Moreover, the corresponding synthetic HO-1-derived peptide was shown to be immunogenic in vitro by generation of CD8+ T cell lines with peptide-specific cytolytic activity. Thus, this peptide is an example of a differentially identified T cell epitope that could be considered as a target for immunotherapy.


Health-related quality of life 2 years after treatment with radical prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients with clinically localized prostate cancer.
To compare treatment impact on health-related quality of life (HRQL) in patients with localized prostate cancer, from before treatment to 2 years after the intervention. This was a longitudinal, prospective study of 614 patients with localized prostate cancer treated with radical prostatectomy (134), three-dimensional external conformal radiotherapy (205), and brachytherapy (275). The HRQL questionnaires administered before and after treatment (months 1, 3, 6, 12, and 24) were the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index. Differences between groups were tested by analysis of variance and within-group changes by univariate repeated-measures analysis of variance. Generalized estimating equations (GEE) models were constructed to assess between-group differences in HRQL at 2 years of follow-up after adjusting for clinical variables. In each treatment group, HRQL initially deteriorated after treatment with subsequent partial recovery. However, some dimension scores were still significantly lower after 2 years of treatment. The GEE models showed that, compared with the brachytherapy group, radical prostatectomy patients had worse EPIC sexual summary and urinary incontinence scores (-20.4 and -14.1; p < 0.001), and external radiotherapy patients had worse EPIC bowel, sexual, and hormonal summary scores (-3.55, -5.24, and -1.94; p < 0.05). Prostatectomy patients had significantly better EPIC urinary irritation scores than brachytherapy patients (+4.16; p < 0.001). Relevant differences between treatment groups persisted after 2 years of follow-up. Radical prostatectomy had a considerable negative effect on sexual functioning and urinary continence. Three-dimensional conformal radiotherapy had a moderate negative impact on bowel functioning, and brachytherapy caused moderate urinary irritation. These results provide relevant information for clinical decision making.


Synthesis of naphthazarin derivatives and identification of novel thioredoxin reductase inhibitor as potential anticancer agent.
Mammalian thioredoxin reductase (TrxR) enzymes play a crucial role in regulating multiple redox-based signaling pathways and have attracted increasing attention as promising anticancer drug targets. We report here the synthesis of a panel of naphthazarin derivatives and discovery of 2-methyl-5,8-dihydroxy-1,4-naphthoquinone (3, 2-methylnaphthazarin) as a potent cytotoxic agent with a submicromolar half maximal inhibitory concentration to the human promyelocytic leukemia HL-60 cells. Mechanism studies reveal that the compound selectively inhibits TrxR to induce oxidative stress-mediated apoptosis of HL-60 cells. Knockdown of TrxR sensitizes the cells to 3 insults, while overexpression of the functional enzyme confers resistance to the compound treatment, underpinning the physiological significance of targeting TrxR by 3. Clarification of the interaction of compound 3 with TrxR unveils a mechanism underlying the cellular action of the compound, and sheds light in considering development of the compound as a potential cancer chemotherapeutic agent.


What's New in Severe Deformity Correction: The German Perspective.
Foot deformities are found in several neurologic conditions, most typically, but not exclusively, Charcot-Marie-Tooth disease. Posttraumatic deformities and undercorrection or overcorrection of congenital talipes equinovarus are also encountered. A severely deformed foot that cannot fit into normal shoes presents a significant day-to-day challenge to the young and active patient. This article presents some basic principles for evaluating the deformity and a toolkit of procedures to deal with these complex cases.


The impact of resident involvement on tonsillectomy outcomes and surgical time.
Posttonsillectomy hemorrhage can be life-threatening, so we investigated whether patients are at increased risk with an inexperienced surgeon. There is scant information on how surgical experience affects outcomes in pediatric tonsillectomy. We hypothesized that supervised residents would have longer operative times but no difference in complication rates compared to attending surgeons. Retrospective case series of children who underwent tonsillectomy from July 2014 to April 2017 at a tertiary pediatric medical center. We assessed outcomes and operative times, based on the primary surgeon's level of training, for children (14 months to 22 years) who underwent tonsillectomy. A total of 7,606 children were included (mean age 7.0 ± 4.1 years, 51% female) with a mean body mass index (BMI) of 18.6 ± 5.48 kg/m2 ; 76% were white; and 13% were black. Residents assisted with tonsillectomy in 43% of cases. The readmission rate (5%-6%) was not different (P = 0.48) by level of experience. Similarly, return to the operating room for control of hemorrhage (3.3%-3.5%) did not differ by level of experience (P = 0.95). The median procedure time for adenotonsillectomy was shortest for attendings (9 minutes), followed by fellows (13 minutes), and residents (14 minutes, P < 0.0001). Among residents, time for adenotonsillectomy decreased significantly with each increasing year of training (P < 0.0001) from postgraduate year (PGY) 1 (17 minutes), to PGY2 (15 minutes), to PGY3 (14 minutes), and to PGY4 (12.5 minutes). Attending surgeons completed tonsillectomy more quickly, and operative times decreased with increasing experience level. However, there was no difference in readmission or postoperative hemorrhage rates between residents and attending surgeons. 4 Laryngoscope, 130:2481-2486, 2020.


Coexistence of ETV6/RUNX1 and MLL aberrations in B-cell precursor acute lymphoblastic leukemia discloses a small subclass of BCP-ALL.
Out of 76 pediatric cases of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) positive for ETV6/RUNX1 (previously TEL/AML1) resulting from t(12;21), 7 cases revealed coexistence of ETV6/RUNX1 and MLL aberrations. One case of der(21) duplication with ETV6/RUNX1 exhibited a novel MLL translocation variant t(6;11)(p21.1p23;q13q25), with translocation of 3' telomeric MLL and deletion of 5' centromeric MLL. Another case of der(21) duplication with ETV6/RUNX1 showed MLL rearrangement upon Southern blotting. The remaining five ETV6/RUNX1-positive cases had MLL allelic deletion. ETV6/RUNX1 and MLL aberration clone size in these cases was suggestive of ETV6/RUNX1 as an early primary event, originating in the embryonic or infant stage and developing into leukemia by later acquisition of MLL aberration, ETV6 loss, and ETV6/RUNX1 duplication as secondary events. To date, the prognosis has been favorable, which seems to be compatible with ETV6/RUNX1-positive ALL. We conclude that the cases with coexisting ETV6/RUNX1 and MLL aberrations probably exist as a small, hidden group of ETV6/RUNX1-positive BCP-ALL, which invites further investigation, in large series from different populations, to confirm the findings and establish the biological mechanisms and prognostic significance.


A novel collagen/platelet-rich plasma (COL/PRP) scaffold: preparation and growth factor release analysis.
Platelet-rich plasma (PRP) has been widely used in clinical practice for more than 20 years because it causes the release of many growth factors. However, the burst release pattern and short release period of PRP have become obstacles to its application. An optimal controllable release system is an urgent need for researchers. This study investigated whether collagen/PRP (COL/PRP) scaffolds can serve as a vehicle for the controllable release of growth factors. We fabricated a novel scaffold that integrates PRP activated by thrombin or collagen into type I collagen. The mechanical properties, cytotoxicity, and transforming growth factor β1 (TGF-β1), platelet derived growth factor (PDGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) content were evaluated. Our results demonstrate that the COL/PRP scaffolds were not cytotoxic to L-929 fibroblasts. The PDGF and FGF content in the thrombin group was at a higher level and lasted for a long period of time. Collagen and thrombin played the same role in the release of TGF-β1 and VEGF. These data suggest that the novel COL/PRP scaffolds provide a carrier for the controllable release of growth factors and may be used in tissue- regenerative therapies.


Antipyretic, anti-inflammatory and analgesic activity of Acacia hydaspica R. Parker and its phytochemical analysis.
Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles. Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, (1)H NMR, (13)C NMR and (2)D NMR spectroscopic analyses, and also by comparison with reported literature. Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p < 0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E2 (PGE2) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica. These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.


The prognostic value of the head-shaft angle on hip displacement in children with cerebral palsy.
Hip displacement is the second most common deformity in cerebral palsy (CP). The risk for hip displacement is related to the Gross Motor Function Classification System (GMFCS). Recently, the head-shaft angle (HSA) has been identified as a predictor for hip displacement and the aim of this study is to assess the predictive value of the HSA for hip displacement in CP. In this retrospective cohort, we performed radiological measurements in 50 children on both hips. In children with GMFCS level II (30 hips), III (30 hips), IV (20 hips) and V (20 hips), we measured the HSA and migration percentage (MP) in three age intervals: age two years (T1), age four years (T2) and age seven years (T3). At T1, the HSA was larger (more valgus) in hips that will displace than in hips that will not displace (174° vs. 166°; p = 0.001) and was also larger in higher GMFCS levels (IV-V vs. II-III) (172° vs. 165°; p < 0.001). At T1, GMFCS [odds ratio (OR) 14.7; p = 0.001] and HSA (OR 1.102; p = 0.043) were predictors for hip displacement at T3, but at T2, MP (OR 1.071; p = 0.010) was the only predictor for hip displacement at T3. The HSA at two years is larger in hips that will displace and larger in children with higher GMFCS levels (IV-V). At age two years, GMFCS and HSA are valuable predictors for hip displacement, but at the age of four years, only MP should be used in the prediction of hip displacement. Prognostic study, level II.


Are doping tests in sports trustworthy?: Athletes suffer from insufficiently defined criteria for doping tests: Athletes suffer from insufficiently defined criteria for doping tests.
The lack of clearly defined criteria for doping tests carries a great risk of punishing innocent athletes and undermines the fight against doping in international sports.


Investigations on anti-Aspergillus properties of bacterial products.
To investigate the anti-Aspergillus properties of bacterial products. In the present study, 12 bacterial strains were screened for antifungal activity against Aspergilli. The culture supernatant and lysates of Pseudomonas aeruginosa, Bacillus cereus, Escherichia coli (BL21, DH5alpha, HB101, XL Blue), Klebsiella pneumoniae, Streptomyces thermonitrificans, Streptococcus pneumoniae, Enterobacter aerogenes, Staphylococcus aureus and Salmonella typhi were examined for antifungal activity in protein concentration ranging from 1000.0 to 7.8 microg ml-1 using microbroth dilution assay. The lysate of Salm. typhi and E. coli BL21 exhibited the maximum activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Their in vitro minimum inhibitory concentrations (MICs) were found to be 15.6-31.2 microg ml-1 by microbroth dilution and spore germination inhibition assays. In disc diffusion assay, a concentration of 3.1 microg disc-1 of Salm. typhi lysate showed significant activity against Aspergilli. Escherichia coli BL21 exhibited similar activity at 6.2 microg disc-1. The work on identification of molecule endowed with antimycotic properties is in progress. The products of Salm. typhi and E. coli demonstrated significant activity against Aspergillus species. This is the first time that E. coli has been reported for anti-Aspergillus activity. It could be an important source of biologically active compounds useful for developing better new antifungal drugs/or probiotics.


Accumulated hippocampal formaldehyde induces age-dependent memory decline.
Aging is an important factor in memory decline in aged animals and humans and in Alzheimer's disease and is associated with the impairment of hippocampal long-term potentiation (LTP) and down-regulation of NR1/NR2B expression. Gaseous formaldehyde exposure is known to induce animal memory loss and human cognitive decline; however, it is unclear whether the concentrations of endogenous formaldehyde are elevated in the hippocampus and how excess formaldehyde affects LTP and memory formation during the aging process. In the present study, we report that hippocampal formaldehyde accumulated in memory-deteriorating diseases such as age-related dementia. Spatial memory performance was gradually impaired in normal Sprague-Dawley rats by persistent intraperitoneal injection with formaldehyde. Furthermore, excess formaldehyde treatment suppressed the hippocampal LTP formation by blocking N-methyl-D-aspartate (NMDA) receptor. Chronic excess formaldehyde treatment over a period of 30 days markedly decreased the viability of the hippocampus and down-regulated the expression of the NR1 and NR2B subunits of the NMDA receptor. Our results indicate that excess endogenous formaldehyde is a critical factor in memory loss in age-related memory-deteriorating diseases.


Electronic and energy level structural engineering of graphitic carbon nitride nanotubes with B and S co-doping for photocatalytic hydrogen evolution.
The ideal photocatalyst used for photocatalytic water splitting requires strong light absorption, fast charge separation/transfer ability and abundant active sites. Heteroatom doping offers a promising and rational approach to optimize the photocatalytic activity. However, achieving high photocatalytic performance remains challenging if just relying on single-element doping. Herein, Boron (B) and sulfur (S) dopants are simultaneously introduced into graphitic carbon nitride (g-C3N4) nanotubes by supramolecular self-assembly strategy. The developed B and S co-doped g-C3N4 nanotubes (B,S-TCN) exhibited an outstanding photocatalytic performance in the conversion of H2O into H2 (9.321 mmol g-1h-1), and the corresponding external quantum efficiency (EQE) reached 5.3% under the irradiation of λ = 420 nm. It is well evidenced by the closely combined experimental and (density functional theory) DFT calculations: (1) the introduction of B dopants can facilitate H2O adsorption and drive interatomic electron transfer, leading to efficient water splitting reaction. (2) S dopants can stretch the VB position to promote the oxidation ability of g-C3N4, which can accelerate the consumption of holes and thus inhibit the recombination with electrons. (3) the simultaneous introduction of B and S can engineer the electronic and energy level structural of g-C3N4 for optimizing interior charge transfer. Finally, the purpose of maximizing photocatalytic performance is achieved.


Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells.
The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASMC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASMC proliferation.


Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by β-catenin in mice.
We previously showed that mouse alpha-fetoprotein (AFP) enhancer 3 activity is highly restricted to pericentral hepatocytes in the adult liver. Here, using transgenic mice, we show that the upstream enhancer of the rat glutamine synthetase gene is also active, specifically in pericentral regions. Activity of both enhancers is lost in the absence of β-catenin, a key regulator of zonal gene expression in the adult liver. Both enhancers contain a single, highly conserved T-cell factor/lymphoid enhancer factor binding site that is required for responsiveness to β-catenin. We also show that endogenous AFP messenger RNA levels in the perinatal liver are lower when β-catenin is reduced. These data identify the first distinct zonally active regulatory regions required for β-catenin responsiveness in the adult liver, and suggest that postnatal AFP repression and the establishment of zonal regulation are controlled, at least in part, by the same factors.


Quality of life and its measurement: important principles and guidelines.
The importance of the valid assessment of quality of life (QOL) is heightened with the increased use of the QOL construct as a basis for policies and practices in the field of intellectual disability (ID). This article discusses the principles that should guide the measurement process, the major interrogatories (i.e. who, what, when, where, why, and how) of QOL measurement, issues and procedures in the cross-cultural measurement of QOL, and the current uses of QOL data. Based on the above methods, the article presents a number of important guidelines regarding QOL measurement. From a measurement perspective the use of the QOL construct is changing. Initially it was used as a sensitizing notion, social construct, and unifying theme. Increasingly, it is being used as conceptual framework for assessing quality outcomes, a social construct that guides quality enhancement strategies, and a criterion for assessing the effectiveness of those strategies. This new role places additional emphasis on the valid assessment of one's QOL.


Computational model of response maps in the dorsal cochlear nucleus.
The neurons in the mammalian (gerbil, cat) dorsal cochlear nucleus (DCN) have responses to tones and noise that have been used to classify them into unit types. These types (I-V) are based on excitatory and inhibitory responses to tones organized into plots called response maps (RMs). Type I units show purely excitatory responses, while type V units are primarily inhibited. A computational model of the neural circuitry of the mammalian DCN, based on the MacGregor neuromime, was used to investigate RMs of the principal cells (P-cells) that represent the fusiform and giant cells. In gerbils, fusiform cells have been shown to have primarily type III unit response properties; however, fusiform cells in the cat DCN are thought to have type IV unit response properties. The DCN model is based on a previous computational model of the cat (Hancock and Voigt Ann Biomed Eng 27: 73-87, 1999) and gerbil (Zheng and Voigt Ann Biomed Eng 34: 697-708, 2006) DCN. The basic model for both species is architecturally the same, and to get either type III unit RMs or type IV unit RMs, connection parameters were adjusted. Interestingly, regardless of the RM type, these units in gerbils and cats show spectral notch sensitivity and are thought to play a role in sound localization in the median plane. In this study, further parameter adjustments were made to systematically explore their effect on P-cell RMs. Significantly, type I, type III, type III-i, type IV, type IV-T and type V unit RMs can be created for the modeled P-cells. Thus major RMs observed in the cat and gerbil DCN are recreated by the model. These results suggest that RMs of individual DCN projection neurons are the result of specific assortment of excitatory and inhibitory inputs to that neuron and that subtle differences in the complement of inputs can result in different RM types. Modulation of the efficacy of certain synapses suggests that RM type may change dynamically.


JAK inhibitors: current position in treatment strategies for use in inflammatory bowel disease.
Our expanding knowledge of the pathophysiology of inflammatory bowel disease (IBD) has led to the development of a multitude of new therapies, including parenterally administrated biologic agents and new oral small molecules. Tofacitinib is the first compound of a promising class of new small molecules approved for the treatment of IBD. This pan-Janus kinase (JAK) inhibitor (JAKi) targets the four isoforms of cytokine associated JAKs (JAK1, JAK2, JAK3 and TYK2). Next generations JAKi with marked selectivity for specific JAK isoforms or gut-restricted effect are in development, with promising results in phase I and II clinical trials. Whether increased JAK selectivity will translate into more favorable clinical efficacy and safety profiles remains to be demonstrated in larger clinical trials. Here we provide an overview of the clinical and pharmacological aspects of these drugs and discuss how they may be incorporated in the current treatment paradigm for Crohn's disease and ulcerative colitis.


Mastication and oral health-related quality of life in removable denture wearers with Alzheimer disease.
Alzheimer disease (AD) can affect masticatory function, affecting oral health-related quality of life (OHRQoL). Whether oral rehabilitation with conventional removable prostheses can restore masticatory function and improve OHRQoL in these individuals is unknown. The purpose of this clinical study was to evaluate the influence of oral rehabilitation with removable prostheses on masticatory efficiency and OHRQoL in elders with and without AD. Thirty-two elders with mild AD (n=16, mean age=76.7 ±6.3 years) or without AD (n=16, mean age=75.2 ±4.4 years) were recruited. All participants first underwent masticatory efficiency and OHRQoL evaluations, and 2 months after insertion of new removable prostheses, the variables were reassessed. Masticatory efficiency was determined using the sieving method, and OHRQoL was measured by applying the Geriatric Oral Health Assessment Index (GOHAI). The data from the baseline and after insertion of the new removable prostheses were compared by paired t test. Group differences at each time point were assessed by t test (α=.05). After insertion of the new removable prostheses, masticatory efficiency and OHRQoL improved in both the elders with AD and the control. At baseline, elders with AD had lower masticatory efficiency and higher OHRQoL than controls (P<.05). After removable prosthesis insertion, elders with AD continued to show lower masticatory efficiency values than controls, but their OHRQoL was similar. Oral rehabilitation with new removable prostheses improved the masticatory efficiency and OHRQoL of elders with and without AD, although masticatory efficiency did not reach control levels in elders with AD.


Direct transfer of newly-fixed nitrogen from free-living epiphyllous microorganisms to their host plant.
Nitrogen fixed by epiphyllous microorganisms on the surfaces of Welfia georgii pinnae was transferred to the host leaf. Rates of transfer could account for 10-25% of the N content of the leaf. These data represent the first time that direct transfer of N from free-living N fixers can occur through the leaf surface.


An Exploratory Study: Transition to Adulthood for College Students with Type 1 Diabetes and Their Parents.
The transition to college and adulthood can be challenging for young adults with chronic health conditions and their parents. Few studies have simultaneously explored the experiences of college students and their parents during the transition to college. The purpose of this study was to explore the transition to adulthood for college students with type 1 diabetes (T1D) and their parents. A descriptive exploratory study was conducted with college students with T1D and their parents. Data were collected online using quantitative surveys and open-ended questions. Descriptive statistics were generated for quantitative measures. Analysis of responses to open-ended questions used qualitative description. College students (18-24 years) and parents described challenges with life-stage stress, diabetes management worries, and concern about T1D-related long-term complications. Respondents also described the critical role of the college peer network for support and help in case of crisis situations. Students reported stress related to uncertainty in diabetes management, while parents described constant worry about their child's diabetes. Findings support the importance of assessing anticipated and current stressors of college students with T1D and other chronic health conditions and their parents during and after transition to college. Nurses can support students and parents by providing anticipatory guidance about the transition to college. Assistance identifying established sources of support on college campuses, as well as planning for potential crisis situations, may help reduce stress experienced by students and parents.


Socio-economic outcome of paraplegia compared to lower limb amputation.
The socio-economic outcome was retrospectively compared between patients with traumatic lower limb amputation and those with paraplegia due to a spinal cord injury (SCI). To evaluate the effect of specific rehabilitative procedures on the socio-economic outcome. Paraplegic Centre at the University Hospital in Zurich, Switzerland. Accidents occurring in a collective of 1.9 million persons in Switzerland over 3 years were included in the study. Fifty-six persons with unilateral amputation of lower limbs were compared with 54 persons with paraplegia. The follow-up was assessed over 5 years. The following data was obtained in patients with amputations compared to those with SCI (median values): (1) hospital stay: 150 versus 164 days; (2) the work was taken up after 689 versus 616 days; (3) the global average case costs amounted to SFr. 491.000 versus SFr. 606.000 during the first 5 years after injury; (4) the permanent degree of disability was determined to 40% versus 42%. Except for the global costs, all differences were not significant. There are only a few differences between the socio-economic outcomes between patients with lower limb amputations and those with paraplegia. It remains unclear if the highly specialised rehabilitation services provided for patients with SCI accounts for the similarity since individuals with SCI have additional neurogenic dysfunction of the bladder and bowel. Alternatively, the data may suggest a need for greater rehabilitation services for amputees or may reflect a threshold effect in rehabilitation outcomes.


Expression of clusterin in normal and preeclamptic placentas.
Clusterin is a multifunctional protein that is up-regulated during many different pathophysiological states. Clusterin may be related to a compensation mechanism involving aggregation of soluble proteins, inhibition of complement-mediated cell damage, adaptive regeneration or apoptosis. Clusterin may increase in response to cell damage that results from hypoxic stress in the preeclamptic placenta. The goal of this study was to measure clusterin expression and localization in normal and preeclamptic placental tissues. Immnunohistochemical and double immunofluorescent staining for clusterin was performed on eight normal and eight preeclamptic placental tissues, and clusterin expression was quantified by Western blotting. Immunohistochemical analysis of clusterin in placental tissues obtained from normal pregnancies and those with preeclampsia showed localization of clusterin mainly in the syncytiotrophoblasts and villous endothelial cells. In the double immunofluorescent staining, clusterin was detected in the cytoplasm. The Western blot analysis showed that clusterin expression in the placental tissues of the preeclampsia group was significantly higher than in the normal pregnancy group. Increased expression of clusterin in placental tissues might play an important role in the pathogenesis of preeclampsia.


Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage.
Acute blood pressure (BP) reduction is the first-line treatment for acute spontaneous intracerebral hemorrhage (ICH); however, recent research suggests that intensive BP reduction along with cerebral small vessel disease (cSVD) is a risk factor for remote DWI lesions (RDWILs). We aimed to delineate the interplay between cSVD and BP reduction therapy on the risk of RDWILs. We enrolled 303 patients who underwent brain magnetic resonance imaging within 7 days after acute spontaneous ICH. RDWILs were categorized as occurring in borderzone (BZ) or non-BZ areas. We examined the effect of cSVD, acute BP reduction, and their interaction on RDWILs. RDWILs were observed in 34 (11%) patients (59.8 ± 10.3-years-old, 24% male). RDWILs were associated with a larger acute weighted average mean arterial pressure (MAP) reduction in the initial 24 h after ICH onset and a higher total cerebral microbleed (CMB) count. Intensive MAP changes (odds ratio (OR) per 10 mmHg 1.76, 95% confidence interval (CI) 1.03-3.20), total CMBs burden (OR per 10 CMBs 1.21, 95% CI 1.08-1.39), and presence of lobar CMBs (OR 7.33, 95% CI 1.59-55.6) were risk factors for RDWILs at BZ, but not at non-BZ. Furthermore, a significant interaction was observed between lobar CMBs and MAP reduction on increased risk of RDWILs at BZ (p = 0.030). cSVD modulates the effect of acute BP reduction on the risk of RDWILs. Patients with extensive microangiopathy have a higher risk of developing cerebral ischemic changes in BZ during unstable hemodynamic status.


Acute ethanol administration produces larger spatial and nonspatial memory impairments in 29-33 month old rats compared to adult and 18-24 month old rats.
The average age of the population in many countries is continuing to increase. Older people continue to consume alcohol, often in a binge like fashion. Previous research has demonstrated that older human subjects and aged animal subjects have an increased sensitivity to the effects of ethanol on a variety of behaviors. However, it has yet to be determined if acute ethanol exposure impairs spatial and/or nonspatial memory to a greater extent in aged rats compared to adult rats. In the current studies we trained male rats ranging in age from young adult (2 months of age) to aged rats (29-33 months of age) in the standard nonspatial task followed by the standard spatial task in the Morris water maze. Only animals deemed "cognitively-spared", that is aged animals that learn as well as young animals, were administered one of two doses of moderate ethanol and had their memory tested 30 min later. Acute ethanol administration produced similar performance impairments in spatial and nonspatial memory in all cognitively-spared animals except for the 29-33 month old animals which showed a significantly greater cognitive impairment in both tasks. In addition, blood ethanol levels were similar across all ages. The present work adds to the growing literature on the selective effects of acute ethanol exposure in aged animals.


Sludge management modeling to enhance P-recovery as struvite in wastewater treatment plants.
Interest in phosphorus (P) recovery and reuse has increased in recent years as supplies of P are declining. After use, most of the P remains in wastewater, making Wastewater Treatment Plants (WWTPs) a vital part of P recycling. In this work, a new sludge management operation was studied by modeling in order to recover P in the form of struvite and minimize operating problems due to uncontrolled P precipitation in WWTPs. During the study, intensive analytical campaigns were carried out on the water and sludge lines. The results identified the anaerobic digester as a "hot spot" of uncontrolled P precipitation (9.5 gP/kg sludge) and highlighted possible operating problems due to the accumulation of precipitates. A new sludge line management strategy was simulated therefore using DESASS© software, consisting of the elutriation of the mixed sludge in the mixing chamber, to reduce uncontrolled P precipitation and to obtain a P-rich stream (primary thickener supernatant) to be used in a crystallization process. The key operating parameters were found to be: the elutriation flow from the mixing chamber to the primary thickener, the digestion flow and the sludge blanket height of the primary thickener, with optimized values between 70 and 80 m3/d, 90-100 m3/d and 1.4-1.5 m, respectively. Under these operating conditions, the preliminary results showed that P concentration in the primary thickener overflow significantly increased (from 38 to 100 mg PO4-P/L), which shows that this stream is suitable for use in a subsequent crystallization reactor to recover P in the form of struvite.


Thyroid autoimmunity and IVF/ICSI outcomes in euthyroid women: a systematic review and meta-analysis.
Thyroid autoimmunity (TAI) - the presence of anti-thyroid peroxidase and/or anti-thyroglobulin antibodies - affects 8-14% of reproductively-aged women. It is hotly debated whether TAI adversely affects IVF/ICSI outcomes. This systematic review and meta-analysis evaluated the relationship between thyroid autoimmunity (TAI) and IVF/ICSI outcomes, both overall and amongst euthyroid women of known age using strict criteria for grouping pregnancy outcomes. The review was registered with PROSPERO: CRD42019120947. Searches were undertaken in MEDLINE, EMBASE, Web of Science and Cochrane Database from Inception-March 2020. Primary outcomes were clinical pregnancy rate, clinical miscarriage rate, biochemical pregnancy loss, livebirth rate per-cycle and live birth rate per clinical pregnancy (CP). 14 studies were included in the meta-analysis. Compared with women who tested negative for thyroid autoantibodies (TAI-), there was no significant difference in clinical pregnancy rate overall (OR 0.86; 95%CI [0.70, 1.05]; P = 0.14; 11 studies; I2 = 29.0%), or in euthyroid women (OR 0.88; 95%CI [0.69, 1.12]; P = 0.29; 10 studies; I2 = 32.0%). There was also no significant difference in clinical miscarriage rate overall (OR 1.04; 95%CI [0.52, 2.07]; P = 0.908; 8 studies; I2 = 53%), or in euthyroid women (OR 1.18; 95%CI [0.52, 2.64]; P = 0.69; 7 studies; I2 = 54%). There was no significant difference in biochemical pregnancy loss (OR 1.14; 95%CI [0.48, 2.72]; P = 0.769; 4 studies; I2 = 0.0%), live birth rate per cycle (OR 0.84; 95%CI [0.67, 1.06]; P = 0.145; I2 = 1.7%), live birth rate per clinical pregnancy (OR 0.67; 95%CI [0.28, 1.60]; P = 0.369; I2 = 69.2%), both overall and in euthyroid women as all studies included consisted of euthyroid women only. There was also no significant difference in number of embryos transferred, number of oocytes retrieved, mean maternal age or TSH levels overall or in euthyroid women. The findings of the present study suggest that thyroid autoimmunity has no effect on pregnancy outcomes in euthyroid women alone, or in euthyroid women and women with subclinical hypothyroidism.


Metoclopramide and extrapyramidal symptoms: a case report.
Metoclopramide is a useful medication in the anesthesia provider's armamentarium. Its primary indication in the preoperative phase is to reduce gastric contents and increase lower esophageal sphincter tone for pharmacologic pulmonary aspiration prophylaxis. Metoclopramide can precipitate extrapyramidal symptoms (EPS)/drug-induced movement disorders (DIMD). Tardive dyskinesia and Parkinsonism is generally seen after long-term use, whereas dystonia and akathisia can occur after a single dose of metoclopramide. Recognition of dystonia and/or akathisia by the perianesthesia nurse after the administration of metoclopramide is important for prompt treatment of this distressing condition. It is imperative that the perianesthesia nurse is knowledgeable in metoclopramide's basic pharmacology, uses as an anesthetic adjunct, guidelines for administration, and EPS/DIMD associated reactions, as well as measures that may reduce the incidence and/or facilitate treatment of this medication-induced condition. This case report presents a male patient in his 40s experiencing akathisia after a single 10-mg dose of metoclopramide.


The use of innovative and efficient nanocomposite (magnetic graphene oxide) for the reduction on of Fusarium mycotoxins in palm kernel cake.
Adsorption plays an important role in the removal of mycotoxins from feedstuffs. The main objective of this study was to investigate the efficacy of using magnetic graphene oxide nanocomposites (MGO) as an adsorbent for the reduction of Fusarium mycotoxins in naturally contaminated palm kernel cake (PKC). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to assess the mycotoxins in animal feed. Target mycotoxins included the zearalenone (ZEA), the fumonisins (FB1 and FB2) and trichothecenes (deoxynivalenol (DON), HT-2 and T-2 toxin). Response surface methodology (RSM) was applied to investigate the effects of time (3-7 h), temperature (30-50 °C) and pH (3-7) on the reduction. The response surface models with (R2 = 0.94-0.99) were significantly fitted to predict mycotoxins in contaminated PKC. Furthermore, the method ensured a satisfactory adjustment of the polynomial regression models with the experimental data except for fumonisin B1 and B2, which decrease the adsorption of magnetic graphene oxide (MGO). The optimum reduction was performed at pH 6.2 for 5.2 h at of 40.6 °C. Under these optimum conditions, reduced levels of 69.57, 67.28, 57.40 and 37.17%, were achieved for DON, ZEA, HT-2, and T-2, respectively.


Environmentally sustainable: How are the practices in the organic food tourist route?
This study analyzes Environmentally Sustainable Practices (ESPs) in the Organic Food Tourist Route (OFTR) in South Brazil. Data collection included interviews with open and closed questions about ESPs and the Barometer of Tourism Sustainability (BTS) tool. Eight owners or managers of OFTR's enterprises answered questions online or personally. Content analysis and descriptive statistics were used. Results indicated that tourism enterprises adopt ESPs according to each reality since some are dedicated to producing and commercializing organic products, while others are dedicated to lodging and guided tours. Managers realize the importance of adopting ESPs, enabling a decrease in expenses and the supply of organic products. Since tourists are concerned and careful with the environment nowadays, sustainability must be considered, becoming a differential. The enterprises develop ESPs, which makes the route potentially sustainable, following the standards established by the BTS. In order to achieve the "sustainable" level, the enterprises on the route need to improve their performance in many items whose results were less sustainable. From a theoretical perspective, this study contributed to understanding how ESPs were developed in enterprises and how they contribute to tourism development. The understanding of tourist routes expanded with an emphasis on sustainability, the environmental dimension, the ESPs, and organic agriculture. The BTS enabled the assessment of the sustainability of OFTR's enterprises.


VDAC1 negatively regulates melanogenesis through the Ca2+-calcineurin-CRTC1-MITF pathway.
Melanocytes produce melanin for protecting DNA from ultraviolet exposure to maintain genomic stability. However, the precise regulation of melanogenesis is not fully understood. VDAC1, which is mainly localized in the outer mitochondrial membrane, functions as a gatekeeper for the entry or exit of Ca2+ between mitochondria and the cytosol and participates in multiple physiological processes. Here, we showed a novel role of VDAC1 in melanogenesis. Depletion of VDAC1 increased pigment content and up-regulated melanogenic genes, TYR, TYRP1, and TYRP2 Knockdown of VDAC1 increased free cytosolic Ca2+ in cultured melanocytes at the resting state, which activated calcineurin through the Ca2+-calmodulin-CaN pathway. The activated CaN dephosphorylated CRTC1 to facilitate its nuclear translocation and ultimately up-regulated the transcription of the master regulator of melanogenesis MITF. Consistently, depletion of Vdac1 in mice led to up-regulation of the transcription of MITF and thereafter its targeted melanogenic genes. These findings suggest that VDAC1 is an important negative regulator of melanogenesis, which expands our knowledge about pigment production and implies its potential role in melanoma.


Repeated measurement of nasal lavage fluid chemokines in school-age children with asthma.
Inflammatory processes at the mucosal surface may play a role in maintenance of asthma pathophysiology. Cross-sectional studies in asthmatic patients suggest that chemokines such as interleukin 8 (IL-8) are overproduced by respiratory epithelium. To test the hypothesis that chemokine levels are persistently elevated in the respiratory secretions of asthmatic children at a stable baseline. We measured nasal lavage fluid (NLF) levels of chemokines and other mediators at 3- to 4-month intervals in a longitudinal study of asthmatic children, with nonasthmatic siblings as controls. In a linear mixed-model analysis, both family and day of visit had significant effects on nasal mediators. Thus, data for 12 asthmatic-nonasthmatic sibling pairs who had 3 or more same-day visits were analyzed separately. For sibling pairs, median eosinophil cationic protein levels derived from serial measurements in NLF were elevated in asthmatic patients compared with nonasthmatic patients, with a near-significant tendency for elevation of total protein and eotaxin levels as well. However, no significant differences were found for IL-8 or several other chemokines. Ratios of IL-13 or IL-5 to interferon-gamma released by house dust mite antigen-stimulated peripheral blood mononuclear cells, tested on a single occasion, were significantly increased for asthmatic patients. Substantial temporal and family-related variability exists in nasal inflammation in asthmatic children. Although higher levels of eosinophil cationic protein are usually present in NLF of patients with stable asthma compared with patients without asthma, chemokines other than eotaxin are not consistently increased. Eosinophil activation at the mucosal surface is a more consistent predictor of asthmatic symptoms than nonspecific elevation of epithelium-derived inflammatory chemokine levels.


Evidence that HIV-1 restriction factor SAMHD1 facilitates differentiation of myeloid THP-1 cells.
SAMHD1 counteracts HIV-1 or HIV-2/SIVsmm that lacks Vpx by depleting the intracellular pool of nucleotides in myeloid cells and CD4+ quiescent T cells, thereby inhibiting the synthesis of retroviral DNA by reverse transcriptase. Depletion of nucleotides has been shown to underline the establishment of quiescence in certain cellular systems. These observations led us to investigate whether SAMHD1 could control the transition between proliferation and quiescence using the THP-1 cell model. The entry of dividing THP-1 myeloid cells into a non-dividing differentiated state was monitored after addition of phorbol-12-myristate-13-acetate (PMA), an inducer of differentiation. Under PMA treatment, cells overexpressing SAMHD1 display stronger and faster adhesion to their support, compared to cells expressing a catalytically inactive form of SAMHD1, or cells depleted of SAMHD1, which appear less differentiated. After PMA removal, cells overexpressing SAMHD1 maintain low levels of cyclin A, in contrast to other cell lines. Interestingly, SAMHD1 overexpression slightly increases cell adhesion even in the absence of the differentiation inducer PMA. Finally, we found that levels of SAMHD1 are reduced in proliferating primary CD4+ T cells after T cell receptor activation, suggesting that SAMHD1 may also be involved in the transition from a quiescent state to a dividing state in primary T cells. Altogether, we provide evidence that SAMHD1 may facilitate some aspects of THP-1 cell differentiation. Restriction of HIV-1 by SAMHD1 may rely upon its ability to modify cell cycle parameters, in addition to the direct inhibition of reverse transcription.


Total body fat and the risk of Barrett's oesophagus - a bioelectrical impedance study.
Body mass index is associated with the risk of Barrett's oesophagus (BO). It is uncertain whether this is related to total body fat or other factors that correlate with body mass index. We aimed to quantify the association between total body fat (measured by bioelectrical impedance) and risk of BO and examine if this association was modified by gastro-oesophageal reflux (GOR) and abdominal obesity. In 2007-2009, we surveyed 235 cases (69% Males, Mean age 62.1 years) and 244 age and sex matched population controls from a population based case-control study of BO. We conducted structured interviews, standard anthropometry and bioimpedance analysis of total body fat. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression analysis. There was a significantly increased risk of BO among those in the highest tertile of total body fat weight (OR 2.01; 95%CI 1.26-3.21) and total body fat percentage (OR 1.86; 95%CI 1.10-3.15). These risks were largely attenuated after adjustment for GOR and waist circumference. There was a significantly increased risk of BO among those in the highest tertile of waist circumference (OR 2.21; 95%CI 1.39-3.51) and this was minimally attenuated after adjustment for total body fat and moderately attenuated after adjustment for GOR. Total body fat is associated with an increased risk of BO but this appears to be mediated via both abdominal obesity and GOR. These findings provide evidence that abdominal obesity is more important than total body fat in the development of BO.


Development of behavioral tolerance to delta 9-THC without alteration of cannabinoid receptor binding or mRNA levels in whole brain.
The effect of repetitive administration of delta-9-tetrahydrocannabinol (delta 9-THC) in mice on behavioral and biochemical tolerance was determined in this study. Mice were injected twice daily with 10 mg/kg delta 9-THC for 6.5 days. On day 8, spontaneous activity was assessed or whole-brain homogenates were prepared for the cannabinoid receptor binding and mRNA studies. Although a twenty-sevenfold tolerance to delta 9-THC was observed in the behavioral assay, there was no significant alteration in receptor binding or mRNA levels.


Characterization of atmospheric PM10 and related chemical species in southern Taiwan during the episode days.
The concentrations of atmospheric PM10 on days with episodes of pollution were examined at four different sampling sites (CC, DL, LY, and HK) in southern Taiwan. The related to particulates water-soluble ionic species (Na+, K+, Mg2+, Ca2+, NH4+, Cl-, NO3-, SO4(2-)), carbonaceous species (EC and OC) and metallic species (Zn, Ni, Pb, Fe, Mn, Al, Si, V) were also analyzed. On the episode days of this study, the PM10 mass concentration ranged from 155 to 210 microgm(-3), from 150 to 208 microgm(-3), from 182 to 249 microgm(-3), and from 166 to 228 microgm(-3) at CC, DL, LY, and HK, respectively. The results indicate that the dominant water-soluble species were SO4(2-), NO3-, NH4+, and Cl- at the four sampling sites on these days. Moreover, the high sulfate and nitrate conversion values (SOR and NOR) presented herein suggest that secondary formations from SO2 to SO4(2-) and from NO2 to NO3- are present in significant quantities in the atmosphere of southern Taiwan on episode days. In particular, high SOR and NOR verified that both SO4(2-) and NO3- dominated the increase of atmospheric PM10 concentration in southern Taiwan on episode days.


Beyond transanal total mesorectal excision: short-term outcomes of transanal total mesorectal excision in locally advanced rectal cancer requiring resection beyond total mesorectal excision.
The aim of this work was to define the role of transanal total mesorectal excision (taTME) in locally advanced rectal cancer (LARC) requiring resection beyond the mesorectal plane. We performed a retrospective review of the outcomes of a case series of patients undergoing taTME for rectal cancer with mesorectal fascia or adjacent organ involvement. Eleven patients (six men) underwent taTME for LARC requiring resection beyond total mesorectal excision (TME). All had a restorative procedure. The transabdominal approach was open in five and minimally invasive in six cases. All patients required the resection of at least one adjacent structure, including presacral fascia, internal iliac vessels, nerve roots, uterus, vagina or seminal vesicles. Four patients required a pelvic side-wall lymph node dissection and four had intraoperative radiotherapy. In all cases, the transanal approach was useful to disconnect the rectum distally, resect adjacent organs or control the R1 risk-point. Three patients had a complication of Clavien-Dindo grade III or above (one mechanical bowel obstruction, one pelvic collection and one urine sepsis). There were no anastomotic complications. Ten patients had an R0 resection. During a median follow-up of 11 (8.6-16) months there were no local recurrences, but two patients had distant metastases. During the study period, eight patients underwent closure of their stoma whilst the remaining three have had normal anastomotic assessments and will be closed in the future. This early series shows that implementation of taTME for resections beyond TME may be feasible and safe in a highly selected setting.


Thought-based interaction with the physical world.
Operating a brain-computer interface (BCI) is a skill that individuals must learn. A recent study demonstrated that successful skill acquisition enables human individuals to control telepresence robotic devices in three-dimensional physical space using the non-invasive electroencephalogram (EEG). Although the results are very promising, there is room for improvement in the future.


Effect of acute coronary syndrome patients' education on adherence to dual antiplatelet therapy.
To assess the effect of acute coronary syndrome (ACS) patients' education on their adherence to dual antiplatelet therapy (DAPT) and on lifestyle modifications. Patients who were prescribed acetyl salicylic acid and clopidogrel DAPT within 15 days of having an ACS event were enrolled in this study. Patients were randomized into two arms: the first arm received the study intervention, which consisted of education on coronary artery disease and the importance of sustained platelet inhibition, whereas the second arm was the control group. Both arms received education on lifestyle modifications. Patients completed six visits over 1 year. At each visit, pill count was used to assess adherence to DAPT, data on lifestyle modifications were collected, and changes in weight and waist circumference were recorded. Cardiovascular risk factors were recorded at baseline and the occurrence of new events was monitored throughout the study. There were 153 patients in Arm 1 and 168 in Arm 2. At Month 6, 99.3% of patients in Arm 1 were adherent compared with 94.4% in Arm 2 (p = 0.016). At Month 12, 303 (94.4%) patients from the overall population were adherent to DAPT and there was no significant difference between the two arms (p = 0.443). In addition, no statistically significant difference was found in mean change in weight (3 kg vs. 2 kg, p = 0.064) or mean change in waist circumference (3.5 cm vs. 2.6 cm, p = 0.071) between the two arms. There was a significant decrease in the percentage of smokers (p < 0.001) and a significant increase in the percentage of physically active patients (p < 0.001) within each arm between baseline and Month 12, but the percent change in smokers (z = 1.72, p = 0.085) and percent change in physically active patients (z = 0.76, p = 0.447) between the two arms were not significantly different. Fourteen myocardial infarctions and two strokes occurred throughout the study period. Patient education on DAPT showed short-term effect on adherence to treatment. More effective education methods should be developed to improve long-term DAPT adherence.


Stratified analysis of the correlation between gestational weight gain and birth weight for gestational age: a retrospective single-center cohort study in Japan.
Japan has an exceptionally high proportion of low-weight births and underweight women. It has been suggested that an appropriate increase in gestational weight gain (GWG) for underweight women will help to prevent low birth weight. The current strategy aims to raise the desired value of GWG equally for all pregnant women within the underweight category. However, it remains elusive whether or not the relationship between GWG and birth weight for gestational age (BW/GA) are uniformly equivalent for all the women. We performed a retrospective cohort analysis of women who delivered their newborns at Tokyo Medical and Dental University Hospital from 2013 to 2017. First, in order to examine the direct effect of an increase or decrease in GWG on BW/GA, we analyzed the correlation between inter-pregnancy differences in GWG and BW/GA using a sub-cohort of women who experienced two deliveries during the study period (n = 75). Second, we dichotomized the main cohort (n = 1114) according to BW/GA to verify our hypothesis that the correlation between GWG and BW/GA differs depending on the size of the newborn. The inter-pregnancy difference in BW/GA was not correlated with that of GWG. However, the correlation between BW/GA of siblings was high (r = 0.63, p = 1.9 × 10- 9). The correlation between GWG and BW/GA in women who delivered larger-sized newborns was higher (r = 0.17, p = 4.1 × 10- 5) than that in women who delivered smaller-sized newborns (r = 0.099, p = 1.9 × 10- 2). This disparity did not change after adjustment for pre-pregnancy BMI. The mean birth weight in the dichotomized groups corresponded to percentile 52.0 and 13.4 of the international newborn size assessed by INTERGROWTH-21st standards. In our study, GWG was positively correlated with BW/GA for heavier neonates whose birth weights were similar to the average neonatal weight according to world standards. However, caution might be required for low-birth-weight neonates because increased GWG does not always result in increased birth weight.


Naturally acquired ovine-adapted nematode infections in young cattle and their treatment with eprinomectin 5% w/v extended-release injection.
The objective of this controlled study was to determine the anthelmintic efficacy of eprinomectin 5% w/v extended-release injection (Eprinomectin ERI; LONGRANGE®, Boehringer Ingelheim Animal Health) against primarily ovine-adapted gastrointestinal strongylid nematode (GIN) parasites in naturally infected young cattle. Eighteen calves which grazed on a sheep-dominated mixed sheep-cattle farm were randomly allocated into two equal groups (saline [control] or Eprinomectin ERI, administered each at 1 mL/50 kg body weight once subcutaneously), treated and euthanized 14 days thereafter for a differential GIN count. Ten species of strongylid nematodes were recovered from the control calves (ovine-adapted Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis, Cooperia curticei, Nematodirus battus, Chabertia ovina; bovine-adapted Ostertagia ostertagi, Cooperia oncophora, Nematodirus helvetianus; 'generalist' Trichostrongylus axei). Adult GIN counts ranged from 1,540 to 5,244 for the control calves and from zero to 110 for the Eprinomectin ERI-treated calves. Accepting the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products anthelmintic guidelines criteria on adequacy of infections to be demonstrated in the control animals, this study showed that Ch. ovina, C. curticei, H. contortus, N. battus, T. axei, and T. colubriformis were reduced significantly (p < 0.0001) by ≥ 98.7% in the animals treated with Eprinomectin ERI. In conclusion, Eprinomectin ERI treatment was efficacious against a range of ovine-adapted nematode parasites in naturally infected young cattle.


Interaction between parasite and tick vector.
Interaction of tick vectors with Borrelia species including B. burgdorferi, rickettsias and piroplasms has been demonstrated by describing selected phenomena. In particular, the various environments inside the tick vector have been considered, including the midgut lumen, gut epithelial cells, body cavities and tissues. Intracellular parasitism occurs in different compartments of the host cell: parasitophorous vacuoles (Anaplasma marginale), phagolysosomes (Coxiella spp.), cytoplasm (Rickettsia, spp. piroplasms) or nucleus (some rickettsiae).


Contact Aspiration with the New ARC Catheter for Thrombectomy of Acute Ischemic Stroke: Single-Center Results.
Contact aspiration has gained growing acceptance in endovascular stroke therapy. The safety and efficacy data of the novel ARC catheter (Medtronic, Irvine, California, USA) used for intracranial thrombectomy have been poorly evaluated thus far. We report our preliminary results with the ARC with regard to angiographic reperfusion, duration of thrombectomy, safety, and clinical outcome at 90 days. In a single-center series including 20 large-vessel occlusion stroke patients who were collected prospectively, we retrospectively evaluated the safety and efficacy profiles of the ARC intracranial catheter for first-line contact aspiration. Successful reperfusion was defined as modified Thrombolysis in Cerebrovascular Infarction (mTICI) scores 2b-3 at final angiogram and functional independence as modified Rankin Scale score 0-2 at 90 days. Median admission National Institutes of Health Stroke Scale score was 15, and previous intravenous thrombolysis was administered in 12 patients (60%). Proximal occlusion was located in the anterior circulation in 16 patients (80%). Primary aspiration alone was successful in 10 of 15 patients (67%) within a median time of 26 minutes. Overall successful reperfusion was achieved in 16 patients (80%) within a median time of 31 minutes. There were no device-related events. Median National Institutes of Health Stroke Scale score was 2.5 at discharge. Six of 17 patients (35%) were independent, and 6 (35%) died at 90 days. Symptomatic intracerebral hemorrhage occurred in 5%. In our initial experience, the ARC appears safe and efficient for contact aspiration thrombectomy in large-vessel stroke therapy. However, improvement of its distal navigability needs further development to improve the success of aspiration alone, and large prospective studies are warranted.


Nilotinib induces apoptosis and autophagic cell death of activated hepatic stellate cells via inhibition of histone deacetylases.
Increasing hepatic stellate cell (HSC) death is a very attractive approach for limiting liver fibrosis. Tyrosine kinase inhibitors have been shown to have anti-fibrotic properties, but the mechanisms are poorly understood. Here, we identified the mechanism of action of the second-generation tyrosine kinase inhibitor nilotinib in inducing HSC death. Human HSC line (LX-2) and rat HSCs were treated with nilotinib and its predecessor, imatinib, in the absence or presence of various blockers, known to interfere with death signaling pathways. Nilotinib, but not imatinib, induced progressive cell death of activated, but not quiescent, HSCs in a dose-dependent manner. Activated HSCs died through apoptosis, as denoted by increased DNA fragmentation and caspase activation, and through autophagy, as indicated by the accumulation of autophagic markers, light chain (LC)3A-II and LC3B-II. Although inhibition of caspases with Z-VAD-FMK suppressed nilotinib-induced HSCs' apoptosis, there was no increase in HSCs' survival, because autophagy was exacerbated. However, blocking the mitochondrial permeability transition pore (mPTP) opening with cyclosporin A completely abolished both apoptosis and autophagy due to nilotinib. Moreover, nilotinib treatment decreased the protein expression of histone deacetylases 1, 2 and 4. Interestingly, pretreament with C646, a selective p300/CBP histone acetyl transferase inhibitor, resulted in diverting nilotinib-induced apoptosis and autophagy towards necrosis. In conclusion, the identification of mPTP as a target of nilotinib in activated HSCs suggests coordination with histone deacetylases inhibition to induce apoptosis and autophagy. Thus, our study provides novel insights into the anti-fibrotic effects of nilotinib.


Nutrition care of AIDS patients.
Often the complications of the acquired immunodeficiency syndrome (AIDS) have a negative impact on nutritional status. Weight loss and protein depletion are commonly seen among the AIDS population. Though the relationship between disease progression and nutritional status has not been established, maintaining good nutritional status may support response to treatment of opportunistic infections and improve patient strength and comfort. Increased nutrient needs, decreased nutrient intake, and impaired nutrient absorption contribute to malnutrition in AIDS patients. Causes of decreased nutrient intake and absorption may be poor appetite, oral and esophageal pain, mechanical problems with eating, and gastrointestinal complications (diarrhea and malabsorption). Causes of these impediments to maintaining nutritional status are discussed, and suggestions to overcome them are given. Dietitians working with AIDS patients need to understand how the complications of the disease might affect nutritional status so that strategies for nutrition treatment can be developed. Nutrition care of AIDS patients requires that dietitians and their support personnel provide supportive, nonjudgmental care. The patients should be included in decision making regarding their nutrition care. Caring for AIDS patients in the community and through home care agencies represents an area in need of the expertise of a dietetics professional.


Chemotherapy of metastatic renal cancer.
The appearance of metastatic disease heralds disaster for the vast majority of patients with renal carcinoma. A few spontaneous regressions of established metastases have been reported but no systemic chemotherapeutic treatment withstood the test of time or critical analysis. This analysis requires objective remissions in measurable metastatic disease evaluated against well-defined prognostic factors in relation to survival with quality of life for the patient. No single agent chemotherapy achieved a desired 20% response rate and only a few combination studies, especially with immunotherapy, reported significant clinical results. We recommend that the variable biological potential of renal metastatic disease be harnessed in prospective multicentric phase I/II trials with strict response and prognostic criteria to search for new antineoplastic agents for this disease.


Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest.
Different subsets of the tRNA pool in human cells are expressed in different cellular conditions. The 'proliferation-tRNAs' are induced upon normal and cancerous cell division, while the 'differentiation-tRNAs' are active in non-dividing, differentiated cells. Here we examine the essentiality of the various tRNAs upon cellular growth and arrest. We established a CRISPR-based editing procedure with sgRNAs that each target a tRNA family. We measured tRNA essentiality for cellular growth and found that most proliferation-tRNAs are essential compared to differentiation- tRNAs in rapidly growing cell lines. Yet in more slowly dividing lines, the differentiation-tRNAs were more essential. In addition, we measured the essentiality of each tRNA family upon response to cell cycle arresting signals. Here we detected a more complex behavior with both proliferation-tRNAs and differentiation tRNAs showing various levels of essentiality. These results provide the so-far most comprehensive functional characterization of human tRNAs with intricate roles in various cellular states.


Limb defects in a fetus with homozygous alpha-thalassemia.
A fetus with homozygous alpha-thalassemia (alpha-thal) who displayed limb reduction defects is described. These kinds of congenital anomalies should be surveyed by sonography in at-risk pregnancies and included in genetic counseling prior to in utero fetal therapy.


Predictive dynamical modeling and stability of the equilibria in a discrete fractional difference COVID-19 epidemic model.
The SARSCoV-2 virus, also known as the coronavirus-2, is the consequence of COVID-19, a severe acute respiratory syndrome. Droplets from an infectious individual are how the pathogen is transmitted from one individual to another and occasionally, these particles can contain toxic textures that could also serve as an entry point for the pathogen. We formed a discrete fractional-order COVID-19 framework for this investigation using information and inferences from Thailand. To combat the illnesses, the region has implemented mandatory vaccination, interpersonal stratification and mask distribution programs. As a result, we divided the vulnerable people into two groups: those who support the initiatives and those who do not take the influence regulations seriously. We analyze endemic problems and common data while demonstrating the threshold evolution defined by the fundamental reproductive quantity R 0 . Employing the mean general interval, we have evaluated the configuration value systems in our framework. Such a framework has been shown to be adaptable to changing pathogen populations over time. The Picard Lindelöf technique is applied to determine the existence-uniqueness of the solution for the proposed scheme. In light of the relationship between the R 0 and the consistency of the fixed points in this framework, several theoretical conclusions are made. Numerous numerical simulations are conducted to validate the outcome.


The Transitive-Unaccusative Alternation: A Cross-Modal Priming Study.
The relationship between different linguistic manifestations of an eventuality-denoting concept, referred to in the literature as diatheses or voices, is well-studied in theoretical linguistics. Among researchers studying this phenomenon, it is widely agreed that there is a systematic relationship between the various diatheses of a concept. However, when a specific alternation is addressed, the nature of this relationship, namely, its directionality, is at debate. This research employs the much-debated transitive-unaccusative alternation as a case-study and reports the results of two cross-modal priming experiments designed to explore how Hebrew speakers perceive it. The results reveal an asymmetry between the facilitating effects of transitives and unaccusatives, thus suggesting that the relationship between these diatheses is directional. As a whole, this study demonstrates that theoretical debates regarding derivational relationships can be addressed by means of psycholinguistic research.


Is thrombophilia a risk factor for placenta-mediated pregnancy complications?
To determine if thrombophilia is a risk factor for placenta-mediated pregnancy complications (PMPC) (i.e., preeclampsia, intrauterine growth restriction (IUGR), placental abruption, intrauterine fetal death and recurrent pregnancy loss). A 5-year retrospective cohort study. Ongoing pregnancies in women with an antecedent PMPC with thrombophilia were compared with the pregnancies in similar women without thrombophilia. The main outcome measures were mean birth weight deviations, corrected for gestational age, and recurrence of PMPC. Low-molecular-weight heparin (LMWH) was employed for thromboprophylaxis only. Mann-Whitney's, Fisher's and Chi-square tests were employed for comparison. PMPC recurred in 10/43 (23 %) in the thrombophilia group and in 7/41 (17 %) in the non-thrombophilia group, P < 0.059. The mean birth weight deviations were not significantly different either: -7.2 versus -3.0 %, respectively. LMWH, as could be expected, was used more often in thrombophilia patients (39/43 vs. 10/41, P < 0.001). Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH.


Antioxidant activity of synthetic diarylamines: a mitochondrial and cellular approach.
We investigated the antioxidant properties of two synthetic diarylamines, MJQ1 and MJQ2. For one of them (MJQ1) the synthesis procedure is herein described. The compounds showed maximal protection of ADP/Fe(2+) induced mitochondrial lipid peroxidation for 50nM (MJQ1) and 60muM (MJQ2) concentrations. Both compounds were also effective in the prevention of mitochondrial DeltaPsi collapse. The effective antioxidant dose of MJQ1 in mitochondria (50nM) also proved to protect lipid peroxidation in PC12 cells and the effect seems not to be related with the compound's iron chelating ability. The modified structure of MJQ1 clearly resulted in an improvement of its antioxidant and toxic profile, evaluated in mitochondria and whole cells. This study demonstrates a high potential of these diarylamines, as radical scavengers, whose chemical structures can be manipulated if a specific target is well characterized.


Predictive value of blood measurement of Complement System proteins and metabolic components for early detection of obstetric complications linked to poor placental function.
Preeclampsia-eclampsia syndrome (PES) is associated with severe obstetric complications and there are no efficient methods available for an early detection. We studied blood concentration of some immunological and metabolic markers in association with obstetric outcome in healthy pregnant women and patients with obstetric risk factors, by ELISA and biochemical tests. Patients with complications showed higher levels of CRP and C4 positively correlated with Triglycerides and Cholesterol concentrations. Our results provide evidence that Immunological and metabolic alterations contribute to obstetric complications and that biomarkers linked to these alterations could be useful for an early detection of these problems.


Menstruation-Associated Acute Pancreatitis in Patients with Hereditary Pancreatitis.
Two adolescent girls presented with recurrent episodes of menstrual cycle-associated acute pancreatitis and are diagnosed with hereditary pancreatitis, a cause of chronic pancreatitis. Hereditary pancreatitis should remain in the differential diagnosis for teenage girls with catamenial acute pancreatitis and family history of pancreatic disease.


Synthesis of substituted hydantoins in low melting mixtures.
A novel domino synthesis of 1,3,5-trisubstituted hydantoin derivatives has been developed in low melting L-(+)-tartaric acid-DMU melt mixtures. The functionalized hydantoins are obtained in good yields from β,γ-unsaturated ketoacids and urea under environmentally benign and simple reaction conditions.


Racial disparities in linkage to care among patients with substance use disorders.
Peer support specialists (PSSs) can effectively link patients with substance use disorders (SUD) to treatment. These specialists can engage patients in treatment after emergency department (ED) visits or inpatient hospitalization, crucial points in time when these patients have contact with the health care system. We describe success of PSSs in recruiting SUD patients into treatment, with attention to racial disparities in linkage to care. This is a retrospective, observational cohort study performed at an urban, academic medical center. Patients with SUD who indicated interest in pursuing addiction treatment were linked with PSSs by staff at discharge from the ED or inpatient hospitalization. PSSs then transported willing patients to a partnering addiction treatment facility. The treatment facility provided data on successful linkage to care, defined as enrolling in an inpatient or outpatient treatment program. Our primary outcome was successful enrollment in treatment after engagement. The secondary outcome was patients' agreement to transport to the treatment facility after engagement by a PSS. We performed subgroup analysis of patients by self-described race. A total of 785 patients met inclusion criteria for the study: 168 Black patients and 617 White patients. White patients were more likely than Black patients to be enrolled in treatment by PSSs (adjusted odds ratio [aOR; 95% confidence interval {CI}] = 1.61 [1.11 to 2.34]), after adjusting for the effects of age, sex, insurance, and marital status, p = 0.012. We found no statistically significant differences between races in agreeing to be transported for the total sample or inpatient subjects. For ED patients, White individuals were more likely to be transported to treatment compared to Black or African American patients (adjusted odds ratio [aOR; 95% confidence interval {CI}] = 1.50 [1.00 to 2.23]). Our results provide evidence of racial disparities in successful linkage to care by PSSs among patients with SUD. Fewer Black patients were successfully linked to care when approached in the ED, where the majority of these patients were engaged, and after controlling age, sex, insurance, and marital status. Future research should study factors that drive these disparities, and how to successfully link all patients to care.


A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody.
Bedinvetmab, a fully canine anti-nerve growth factor monoclonal antibody, was evaluated in dogs for control of osteoarthritis-related pain in a study conducted to support registration in the USA. Randomized, double-blind, placebo-controlled, multicenter, parallel-group study. General practice client-owned dogs with osteoarthritis (n = 272). Dogs were block randomized 1:1 to placebo (saline, n = 137) or bedinvetmab (n = 135; 0.5-1.0 mg kg-1) administered subcutaneously, once monthly. The primary end point, day 28 Canine Brief Pain Inventory (CBPI) treatment success (TS), required pain severity score (PSS; 0-10) decrease ≥1 and pain interference score (PIS; 0-10) decrease ≥ 2. CBPI TS rates [and number needed to treat (NNT)], change in scores [and standardized effect size (ES)], change in quality of life (QoL) and bedinvetmab half-life were calculated. Significant (p < 0.05) improvement with bedinvetmab over placebo occurred (days 28, 42, 56, 84) for CBPI TS. Of cases evaluable for day 28 CBPI TS (placebo, n = 131; bedinvetmab, n = 128), success rates were 36.6% and 47.4%, respectively (p = 0.0410) (NNT, 9.3; PSS and PIS ES, 0.3). CBPI TS increased after the second dose in both groups, plateaued for bedinvetmab at day 42 and decreased for placebo beginning day 84. Day 84 NNT (4.3), PSS (0.4) and PIS (0.5) showed continued improvement with monthly dosing. After the first dose, mean (± standard deviation) bedinvetmab half-life was 19.1 (8.3) days. Adverse events were similar between groups and not considered treatment-related. There was a significant effect of bedinvetmab versus placebo on all CBPI components (PIS, PSS, QoL). These results corroborated those previously reported and provide further support of safety and effectiveness of bedinvetmab (0.5-1.0 mg kg-1) administered subcutaneously at monthly intervals to dogs for control of osteoarthritis-related pain.


[Sebaceous gland reaction as a test method in the rapid determination of the blastomogenic activity of chemical substances].
The comprehensive experimental materials have shown that the sebaceous glands response to the action of carcinogenic substances is the most specific one since it develops within a short period of time and is revealed under the action of relatively small doses. Some practical recommendations are given as to the use of the sebaceous glands reaction as a tentative test for rapid detection of carcinogenic substances.