Eosinophils: Friends or Foes?
The roles eosinophils are recognized to play in health and disease continue to evolve. Formerly, eosinophils were believed to fill a primary role in host defense against helminths, an intermediary one in the propagation of allergic conditions, and a pathologic one in clinical conditions characterized by systemic eosinophilia and eosinophilic infiltration of target organs. Eosinophils are increasingly understood to be positioned centrally within mammalian immune and inflammatory networks, possessing receptors for an array of inflammatory mediators and capable of producing numerous proinflammatory and homeostatic mediators. The concept has emerged that eosinophils play a major role in the modulation of allergic inflammation and in the repair of damaged tissues in diseases characterized by eosinophilic infiltration. Possible new emerging roles for eosinophils include neoplasm surveillance, tissue remodeling during puberty and pregnancy, and the restructuring of adipose tissue. The eosinophil granulocyte line appeared hundreds of millions of years ago during the evolutionary process and continues to be retained by all vertebrate species. This is strong evidence that although all the beneficial roles of eosinophils have yet to emerge, eosinophils, on balance, must be considered friends and not foes.


Endoscopic submucosal dissection in rectal tumors extending or not to the dentate line: A comparative analysis.
The feasibility of endoscopic submucosal dissection (ESD) in rectal tumors extending to the dentate line (RTDL) is unclear. To analyze the outcomes of ESD in RTDL compared to non-RTDL, with a special focus on the lower rectum location. Observational multicenter retrospective study. All patients with a rectal tumor who underwent ESD in 2013-2017 were included. A comparative analysis between RTDL and non-RTDL groups was done. Two-hundred and twenty-eight patients (median age: 69 years, range: 33-89, 51.3% male) with RTDL (n = 65, 28.5%) and non-RTDL lesions (n = 163, 71.5%) were included. There were no significant differences between the en-bloc (89.2% vs. 90.8%, p = 0.718), complete (60% vs. 71.8%, p = 0.084) and curative resection rates (58.5% vs. 68.7%, p = 0.141). The overall complication rate (4.6% vs. 8%, p = 0.370) was not different, independently of the rectal location. Local recurrence was higher in RTDL (7.3% vs. 1.5%, p = 0.065). The indication for surgery due to non-curative resections in the lower rectum was lower in RTDL (9.2% vs. 14.6%, p = 0.378). The safety, effectiveness and long-term impact of ESD in RTDL and non-RTDLs is comparable. Local recurrence in the lower rectum may be higher in RTDL.


Osteoprotegerin secreted by inflammatory and invasive breast cancer cells induces aneuploidy, cell proliferation and angiogenesis.
Osteoprotegerin (OPG) is a glycoprotein that has multifaceted role and is associated with several cancer malignancies like that of bladder carcinoma, gastric carcinoma, prostate cancer, multiple myeloma and breast cancer. Also OPG has been associated with several organ pathologies. The widespread expression of OPG suggests that OPG may have multiple biological activities that are yet to be explored. The anchorage-independent sphere cultures of the adherent cells were instrumental in our study as it provided a deeper insight into the complexity of a 3D tumor. Cytokine profiling was performed for OPG's detection in the microenvironment. ELISA and western blotting were performed to quantify the OPG secretion and measure the protein levels respectively. OPG expression was detected in human breast cancer tissue samples by IHC. To decipher OPG's role in tumor aggressiveness both recombinant human OPG as well as OPG rich and depleted breast cancer cell conditioned media were tested. Western blotting and MTT assay were performed to detect changes in signaling pathways and proliferation that were induced in presence of OPG. Onset of aneuploidy, in presence of OPG, was measured by cell cycle analysis and western blotting. Finally, human Breast Cancer qBiomarker Copy Number PCR Array was used to detect how OPG remarkably induced gene copy numbers for oncogenic pathway regulators. SUM149PT and SUM1315M02 cells secrete high levels of the cytokine OPG compared to primary human mammary epithelial cells (HMEC). High expression of OPG was also detected in human breast cancer tissue samples compared to the uninvolved tissue from the same patient. OPG induced proliferation of control HMEC spheres and triggered the onset of aneuploidy in HMEC sphere cultures. OPG induced the expression of aneuploidy related kinases Aurora-A Kinase (IAK-1), Bub1 and BubR1 probably through the receptor activator of nuclear factor kappa-B ligand (RANKL) and syndecan-1 receptors via the Erk, AKT and GSK3(3 signaling pathway. Gene copy numbers for oncogenic pathway regulators such AKT1, Aurora-A Kinase (AURKA or IAK-1), epidermal growth factor receptor (EGFR) and MYC with a reduction in the copy numbers of cyclin dependent kinase inhibitor 2A (CDKN2A), PTEN and DNA topoisomerase 2 alpha (TOP2A) were induced in presence of OPG. These results highlight the role of OPG in reprogramming normal mammary epithelial cells to a tumorigenic state and suggest promising avenues for treating inflammatory breast cancer as well as highly invasive breast cancer with new therapeutic targets.


Computed tomography demonstration of inferior lumbar (Petit's) hernia.
Inferior lumbar (Petit's) hernia is an uncommon condition resulting from a defect in the posterior abdominal wall. Such hernias may be difficult to diagnose on the basis of physical signs and symptoms. A case of unsuspected inferior lumbar hernia clearly demonstrated by computed tomography (CT) is presented. Computed tomography is useful in determining the size and contents of the hernia, permitting accurate diagnosis, and planning treatment.


Coarse particulate matter and hospitalization for respiratory infections in children younger than 15 years in Toronto: a case-crossover analysis.
The purpose of this study was to examine the association between ambient air pollution and hospitalization for respiratory infections among children who were younger than 15 years in Toronto during a 4-year period (1998-2001). Exposures averaged during periods that varied from 1 to 7 days were used to assess the effects of air pollutants, including thoracic particulate matter (PM10), fine (PM2.5) and coarse (PM10-2.5) particulate matter, carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3), on hospitalization for respiratory infections. A case-crossover design was used to calculate odds ratios for the hospitalization adjusted for daily weather conditions with an incremented exposure corresponding to the interquartile range in air pollution exposures. When particulate matter and gaseous pollutants were mutually taken into account, the effect remained pronounced for PM10-2.5 in both boys and girls. The adjusted odds ratio for 6-day average exposure to PM10-2.5 with an increment of 6.5 microg/m3 was 1.15 (95% confidence interval: 1.02-1.30) for boys and 1.18 (95% confidence interval: 1.01-1.36) for girls. The effect also remained for PM10 in boys and for NO2 in girls. PM2.5, CO, SO2, and O3 showed no significant effects on hospitalization for respiratory infection in both genders when other pollutants were taken into consideration. Our study suggested a detrimental effect of relatively low levels of ambient particulate matter and gaseous pollutants, especially coarse particulate matter and NO2, on hospitalization for respiratory infections in children.


Functional health status in adult survivors of operative repair of tetralogy of fallot.
We aimed to determine late functional health status of the growing adult population with repaired tetralogy of Fallot (TOF). We studied all 840 patients with TOF born from 1927 through 1984 who survived to adulthood (> 18 years of age). Clinical follow-up was by chart review, telephone interview (n = 706), and echocardiographic reports (n = 339). Functional health status was assessed using Short Form-36 (SF-36) surveys (n = 396) indexed to normative data. Risk of reoperation was low (≈ 1%/year) but increased beyond age 40 years. At latest follow-up moderate or severe pulmonary regurgitation was common (54%) and right ventricular outflow tract stenosis presented in 1/3. Consequently, evidence of right ventricular dilatation and dysfunction and tricuspid regurgitation was typical. Left-sided abnormalities were also common: hypertrophy (p < 0.0001) and outflow tract dilation (p < 0.0001) with at least mild aortic regurgitation in > 50%. Cardiorespiratory symptoms were reported in 45% (palpitations 27%, dyspnea 21%, chest pain 17%). SF-36 scores were significantly below normal for 4 physical domains (p < 0.001). Decrements in physical functioning were associated particularly with older age at follow-up (p < 0.0001), associated syndromes/lesions, reoperations, ventricular dysfunction, tricuspid regurgitation, residual septal defects, and cardiorespiratory symptomatology. Echocardiographic abnormalities were more common in older patients (p < 0.0001). All 3 SF-36 domains specific to psychosocial well-being were normal. In conclusion, despite excellent survival prospects, physical compromise is common in adults with repaired TOF. Greater decrements in older patients may reflect late deterioration with advancing age or cohort effects related to historical management. Efforts to limit ventricular and outflow tract dysfunction may translate into improved late functional status.


Patients with cirrhosis and denied liver transplants rarely receive adequate palliative care or appropriate management.
Patients with cirrhosis who are receiving palliative care and are not eligible for liver transplantation (LT) are often hospitalized multiple times, with lack of expectations or understanding of death and dying. We evaluated how frequently these patients received appropriate and palliative care. We performed a retrospective study of 102 consecutive adult patients (67% men; mean age, 55 years) who were removed from the list for or declined LT from January 2005 through December 2010 at the University of Alberta, Canada. Patients' medical records were reviewed to determine their access to palliative care and relief of symptoms, the appropriateness of the goals for their care, and their requirements for acute care services. The patients' median Model for End-stage Liver Disease score was 20, and median time from denial of LT to death was 52 days (range, 10-332 days). The most common reasons that patients were removed from the transplant wait list were noncompliance or substance abuse (26%) and severe illness or organ dysfunction (25%). After patients were removed from the list, 17% received renal replacement therapy, and 48% were subsequently admitted to the intensive care unit. Patients spent a median of 14 days (range, 6-33 days) in the hospital after they were removed from the transplant wait list. On the basis of the Edmonton Symptom Assessment System, 65% of patients had evidence of pain, 58% had evidence of nausea, 10% had depression, 36% had anxiety, 48% had dyspnea, and 49% had symptoms of anorexia. Twenty-eight percent of all the patients had documentation of do not resuscitate status on their charts, and only 11% were referred for palliative care. Patients with cirrhosis who have been removed from the wait list for LT are infrequently referred for palliative care (∼ 10% of cases), although a high percentage have pain or nausea. Goals of care and do not resuscitate status are rarely discussed. Improved planning of goals of care and access to palliative services are required for these patients.


CSF markers for pathogenic processes in Alzheimer's disease: diagnostic implications and use in clinical neurochemistry.
In view of current (acetylcholine esterase (AChE) inhibitors) and future (e.g. gamma-secretase inhibitors) therapeutic compounds for treatment of Alzheimer's disease (AD), the development and evaluation of cerebrospinal fluid (CSF) biomarkers for AD has become a rapidly growing research field. Diagnostic biomarkers for AD would be especially valuable as aids to diagnosis early in the course of the disease, when correct diagnosis is difficult, and when therapeutic compounds have the greatest potential for being effective. This paper reviews CSF biomarkers for AD, with emphasis on their role in the clinical diagnosis. The two most studied biochemical markers, CSF-tau and CSF-Abeta42, have high sensitivity to identify AD, but the specificity against other dementias is lower. The addition of phosphorylated tau (P-Tau) seems to increase the specificity for the diagnosis of AD, since normal levels are found in both frontotemporal and Lewy body dementia, and in cerebrovascular disease. These CSF markers may be useful as diagnostic aids, especially to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias.


Myocardial infarction risk and hormone replacement: differences between products.
To establish the risk of myocardial infarction (MI) in users of hormone replacement therapy (HRT) compared with non-users and to compare the risk between different HRT regimens. A population-based cohort and case-control study, and a case-control study nested within a cohort of HRT users, using the UK General Practice Research Database. Differences between HRT regimen, mode of administration and duration and recency of use were examined whilst adjusting for confounding. In the cohort and case-control study, 4537 cases of MI were identified in 2.62 million observed women years, cases were age-matched to 27,220 controls. In both studies, current and past HRT use were associated with reduced risk estimates for MI compared with no prior use. MIs were less likely to be fatal amongst women who had used HRT than amongst never users (OR(adj) 0.58; 95% CI 0.45-0.75). No difference in risk was seen between current and past use, oral and transdermal HRT or between different regimens (p>0.44). In the nested study, no difference was found in the association with MI risk between different oestrogen-progestogen combinations or between different combinations and tibolone. Unopposed oestrogen use was not associated with a decrease in risk compared with combined HRT. These results are consistent with previous observational studies in supporting the hypothesis that use of postmenopausal HRT is associated with a decrease in risk of acute myocardial infarction (AMI). Case fatality differed between HRT users and non-users, suggesting a protective effect of HRT. This study does not demonstrate a difference between regimens.


Pediatric usage of Omalizumab: A promising one.
Allergic and related diseases have a substantial epidemiological impact on the pediatric population. Small molecule-based medicines have been traditionally used to manage the diseases. Omalizumab is the first monoclonal antibody-based medicine used in children's allergy and shows great promises. It binds to free IgE and prevents it from binding to IgE receptors, thus interrupting the IgE-dependent allergic inflammatory cascade. Vast amounts of data demonstrate its effectiveness and well tolerance by patients, including the children. However, the drug was only approved to use in allergic asthma and chronic spontaneous urticaria (CSU), though other applications were explored in clinical trials. In this review, we summarized current pediatric applications of omalizumab in allergic diseases, focusing on its usages beyond asthma and CSU, including allergic rhinitis, allergic bronchopulmonary aspergillosis, vernal keratoconjunctivitis, food allergy and atopic dermatitis. In addition, we highlighted the unmet needs and controversial issues of anti-IgE therapy.


Giant mycotic aneurysm of the thoracic aorta.
A giant mycotic aneurysm of the thoracic aorta, which is a rare presentation of infective endocarditis, is reported.


Sex hormone binding globulin stimulates female sexual receptivity.
Sex hormone binding globulin (SHBG) is found in the brain and acts directly on plasma membrane-associated receptors in the prostate gland. Infusing SHBG into the medial preoptic area or medial basal hypothalamus of female rats increases their female sexual receptivity. SHBG, SHBG plus estradiol (SHBG-E), and SHBG-E plus oxytocin all significantly increased female sexual receptivity over vehicle or estradiol plus oxytocin infused controls, as measured by lordosis quotients and receptivity scores, at 40, and 90 min after their infusions into the medial preoptic area. When infused into the medial basal hypothalamus, SHBG-E plus oxytocin resulted in significantly increased sexual receptivity 20 and 40 min after infusion when compared to its estradiol plus oxytocin control group. SHBG produced in the brain may be released endogenously to have immediate effects on reproductive physiology and behavior.


Myalgia cruris epidemica (benign acute childhood myositis) associated with a Mycoplasma pneumonia infection.
We report the case of a 6-year-old boy who presented with difficulty ambulating and an elevated creatinine phosphokinase level following an upper respiratory tract infection. Crural myositis was diagnosed; convalescent serum was negative for viruses, but demonstrated significant titers to Mycoplasma pneumoniae. Benign acute crural myositis has not heretofore been associated with Mycoplasmal infection.


Use of Fluorescent Reporters to Analyse Dynamic and Spatial Responses to Mechanical Wounding.
Mechanical wounding of plant tissues triggers many different responses (Savatin DV, Gramegna G, Modesti V, Front Plant Sci 5:470, 2014). These are primarily mediated by the plant hormone Jasmonic Acid Isoleucine (JA-Ile). Recently, a fluorescent biosensor for JA-Ile showed that sample preparation (i.e., handling of samples) for fluorescent microscopy very often triggers wound response, even without apparent damage to the seedling, affecting downstream analyses (Larrieu A, Champion A, Legrand J, Nat Commun 6:6043, 2015). In this chapter, we describe how to overcome this technical limitation to monitor any fluorescent reporter or dye in response to wounding, using any type of fluorescent or confocal (inverted or upright, laser scanning or spinning disc) microscopes. Pharmacological or wound treatments can easily be performed and responses monitored over long periods of time. We further describe a simple method to extract and analyse quantitative data from confocal images using the open source software Fiji (Fiji Is Just ImageJ (Schindelin J, Arganda-Carreras I, Frise E, Nat Methods 9:676-682, 2012)) and OpenOffice.


Neural wiring optimization.
Combinatorial network optimization theory concerns minimization of connection costs among interconnected components in systems such as electronic circuits. As an organization principle, similar wiring minimization can be observed at various levels of nervous systems, invertebrate and vertebrate, including primate, from placement of the entire brain in the body down to the subcellular level of neuron arbor geometry. In some cases, the minimization appears either perfect, or as good as can be detected with current methods. One question such best-of-all-possible-brains results raise is, what is the map of such optimization, does it have a distinct neural domain?


Fluorescence in situ hybridization on metaphase chromosomes with biotinylated probes. In situ hybridization, biotin labeling, cosmids, gene mapping, oncogene amplification.
In situ hybridization on metaphase chromosomes have been used to localize specific nucleic acid sequences. Initially, the nucleic acid probes were labeled isotopically. Over the past few years, non isotopic techniques have considerably progressed, and are being applied to a large spectrum of biological and clinical problems.


Breaking bad news: a primer for radiologists in breast imaging.
The task of breaking bad news, whether news of need for biopsy or a new breast cancer diagnosis, is increasingly performed by breast imaging radiologists. Most radiologists have little exposure to didactic teaching or modeling for learning methods of breaking bad news. Understanding barriers for communicating bad news and general improvements in communication, such as avoiding jargon and active listening, are initial steps in learning this important task. Bad news should be communicated to a patient in a supportive environment and directly in simple, but not blunt, terms. The amount of news delivered at any one time must be judged by a patient's response. It may be preferable to deliver bad news in smaller portions to allow time for a patient to cope. The use of a "warning shot," particularly at the time of diagnostic imaging, can be helpful to alert patients to forthcoming bad news. Common patient responses to bad news include shock, disbelief, denial, fear, anger, and guilt. An empathetic response from a physician demonstrates support. In breast imaging, providing a patient with perspective about her risk for breast cancer or the characteristics of the cancer if early may instill hope without giving false reassurance. Establishing a plan, typically an appointment with a breast surgeon in the setting of breast cancer, allows a patient to have a sense of control over her disease. Offering additional support also demonstrates empathy. The task of delivering bad news is an important task that, if done well, improves patients' ability to cope with their disease.


Temporal lobe epilepsy with ictal ecstatic state and interictal behavior of hypergraphia.
The authors describe an epileptic patient with ictal ecstatic experiences and an interictal behavioral change of hypergraphia. The patient had a temporal lobe EEG spike focus in the dominant hemisphere. The ecstatic states can be considered true epileptic auras, i.e., simple partial seizures originating in the temporal lobe or the nearby structures. Hypergraphia in this patient seemed to be related to temporal lobe ictal focus in the dominant hemisphere.


Corrigendum: Seasonal decline in leaf photosynthesis in perennial switchgrass explained by sink limitations and water deficit.
[This corrects the article DOI: 10.3389/fpls.2022.1023571.].


Characterization of tumor-associated fucogangliosides from PC 12 pheochromocytoma cells.
PC 12h pheochromocytoma cells were subcutaneously transplanted into rat. We found the transplanted tumors accumulated some fucogangliosides associated with PC 12 cells. These gangliosides were isolated and purified by DEAE-Sephadex A-25 and Iatrobeads column chromatographies. Their structures were determined by fast atom bombardment mass spectrometry, proton nuclear magnetic resonance spectrometry, permethylation study, and sequential degradation using various exoglycosidases and mild acid hydrolysis. Two tumor-associated fucogangliosides were found to possess the blood group B determinant as follows: G6: IV2Fuc alpha, IV3Gal alpha, II3NeuAc, GgOse4Cer; G11: IV2Fuc alpha, IV3Gal alpha, II3 (NeuAc)2, GgOse4Cer. A ganglioside with the similar structure as ganglioside G6 was isolated from rat hepatoma cells (Holmes, E.H., and Hakomori, S-I. (1982) J. Biol. Chem. 257, 7698-7703). However, ganglioside G11 has not previously been reported in the literature. These fucogangliosides reacted with the monoclonal antibody prepared by immunizing mice with PC 12h cells. Other fucogangliosides were also found to accumulate in the transplanted tumor tissues. They were identified as fucosyl-GM1 and fucosyl-GDlb. These fucogangliosides did not react with the monoclonal antibody against PC 12h cells.


Constructing channel structures based on the assembly of p-sulfonatocalix[4]arene nanocapsules and [M(bpdo)3]2+ (M=Cu, Zn).
Novel channel structures based on [M(bpdo)(3)](2+) and p-sulfonatocalix[4]arene nanocapsules have been established; these are sustained exclusively by charge-assisted pi...pi interactions and sorption experiments show the porous materials have selective guest sorption properties.


Transplants for the elderly in myeloma.
In this issue of Blood, Gay et al provide important new information that can be used to design future phase 3 trials.


Use of filgrastim as adjuvant therapy in patients with AIDS-related cytomegalovirus retinitis.
Neutropenia in AIDS predisposes to bacterial infection. Granulocyte colony-stimulating factor (filgrastim) can reverse neutropenia. To determine the effects of filgrastim on bacterial infections, hospitalization, and mortality in patients with cytomegalovirus retinitis and AIDS. Using a person-time analysis, a retrospective cohort study of filgrastim adjuvant therapy in three multicenter clinical trials of anti-cytomegalovirus therapy during the period 1990-1997 measured filgrastim use, bacterial infections, and mortality. Of 719 patients, 379 patients used filgrastim for 31% of the follow-up time. There was an inverse relationship between the 389 confirmed bacterial infections, including 186 bacteremias, and absolute neutrophil counts. Before adjustment for CD4 T-cells counts and antibiotic/antiretroviral therapy, filgrastim was associated with reduced risk of catheter-related bacteremia [relative risk (RR), 0.52; P = 0.02] and repeat bacterial infection (RR, 0.41; P = < 0.01). After adjustment, the RR of catheter-related bacteremia with filgrastim use was decreased (RRadj, 0.69; P = 0.16) and the RR of repeat bacterial infection with filgrastim use was of marginal significance (RRadj, 0.57; P = 0.07), possibly due to the confounding effect of trimethoprim-sulfamethoxazole on all bacteremia (RRadj, 0.55; P = < 0.01). Unrelated to bacteremia, filgrastim use was associated with a 56% reduction in mortality (P < 0.01). There was a large survival benefit associated with filgrastim use in this study but the reasons for this benefit are unclear. Although a reduction in crude risk of some bacterial infections with filgrastim use was detected, after adjustment for potentially confounding factors these risks were smaller and no longer statistically significant.


[Antigenic determinant study of the hemagglutinin in the composition of influenza viruses A subtype H1N1 by an indirect solid-phase radioimmunological analytical method].
A comparative study of antigenic determinants of influenza A virus, subtype H1N1, hemagglutinins isolated in 1947-1953 and in 1977-1979 was carried out. The competitive capacity of 8 virus strains for antibody of 4 hyperimmune antisera to A/Fm/1/47, A/Moscow/Pan/52, A/USSR/090/77, and A/Brazil/11/78 viruses was studied by solid-phase radioimmunoassay (SPRIA) in two modifications: in the homologous and heterologous systems. The analysis of competition in the heterologous system permits one to study isolated subpopulations of antibody homologous to viruses fixed on the solid phase. The combination of both modifications allows investigations of a wider spectrum of antibodies than those possible in the homologous system alone. The results of the study showed the antigenic determinants of hemagglutinin exposed on the surface of particles of different influenza A virus strains to differ in their capacity to stimulate antibody synthesis. The analysis of the time course of changes in the antigenic properties of hemagglutinin regions of similar structure in various viral strains may facilitate prognosing of evolution of virus strains of the same subtype.


Psychological reactions to air pollution.
Interviews with a large representative sample of Los Angeles residents reveal that these citizens are somewhat aware and concerned about air pollution, but not knowledgeable about its causes. Direct behaviors to reduce causes of pollution or one's exposure to it are rare. A moderate percentage of people seek out information about air pollution or complain about it. Fewer follow state health advisories by reducing automobile driving or restricting activity during air pollution episodes. Preliminary modeling of citizen compliance with air pollution health advisories suggest that personal beliefs about negative health effects are a important predictor of compliance. Finally, modest but significant relationships are noted between ambient photochemical oxidants and anxiety symptoms. The latter finding controls for age, socioeconomic status, and temperature.


One-pot three-component Biginelli-type reaction to synthesize 3,4-dihydropyrimidine-2-(1H)-ones catalyzed by Co phthalocyanines: Synthesis, characterization, aggregation behavior and antibacterial activity.
The synthesis of a novel phthalonitrile derivative with pyridine-2-thiol and 2,4,6-trimethylphenylamine substituents functionalized groups and its peripherally tetrasubstituted cobalt phthalocyanine and cationic phthalocyanines complexes were reported. The aggregation investigations carried out in different concentrations indicate that Co Phthalocyanines compounds 3,4 do not have any aggregation behavior for the concentration range of 6×10(-4)-14×10(-6)M in DMSO. The ion binding properties of Co Phthalocyanines compounds 3,4 show the formation of stable complex with Co(2+). In addition 3,4-Dihydropyrimidin-2(1H)-one derivatives were synthesized by modified Biginelli cyclocondensation reaction catalyzed by MPc as Lewis base. The structures of the synthesized compounds have been successfully characterized by the spectroscopic methods (IR, (1)H NMR, (13C)NMR, UV-Vis, mass spectrometry, elemental analysis and NMR 2D). The influence of substrate/catalyst ratio, solvent was also investigated to find optimal reaction on this synthesis for getting the highest conversion. Different parameters were examined for finding optimal conditions of catalysis. In addition; the compounds 3-11 were investigated for antimicrobial activity. Most of them exhibited important antimicrobial activity.


Free fatty acid metabolic profile and biomarkers of isolated post-challenge diabetes and type 2 diabetes mellitus based on GC-MS and multivariate statistical analysis.
Isolated post-challenge diabetes (IPD, 2h-PG ≥11.1mmol/L and FPG <7.0mmol/L) is often ignored in screening for diabetes by fasting plasma glucose (FPG) levels. The aim of this study was to investigate the metabolic profiles of serum free fatty acids (FFAs) and to identify biomarkers that can be used to distinguish patients with IPD from those with type 2 diabetes mellitus (T2DM) or healthy control individuals. FFA profiles of the subjects were investigated using gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used for classification and prediction among the three groups. The predictive correct rates were 92.86% for IPD and healthy control individuals and 90.70% for T2DM and healthy control individuals, indicating that PLS-DA could satisfactorily distinguish IPD individuals from healthy controls and those with T2DM. Finally, palmitic acid, stearic acid, oleic acid, linoleic acid and α-linolenic acid were identified as potential biomarkers for distinguishing IPD from healthy control and T2DM individuals. These potential biomarkers might be helpful for diagnosis and characterization of diabetes.


Leukemia inhibitory factor receptor α-chain: a potential method for acute promyeloid leukemia therapy.
Leukemia inhibitory factor (LIF) affects multiple types of leukemia cells in vitro through its functional receptor LIFR, which comprises a complex of the LIFR α-chain (LIFRα) and gp130. Researchers have recently observed that the C-terminus of the LIFRα cytoplasmic domain contains as many conserved YXXQ motifs as gp130 (C-terminal triple YXXQ motifs, LIFRα-CT3), whose free structure has been shown to be capable of activating STAT3 phosphorylation in the cytoplasm and consequently activating STAT3-related downstream molecules in the nucleus. This process can induce pathological acute myeloid leukemia (AML) or acute promyeloid leukemia (APL) cells to differentiate into mature granulocytes, simulating the LIF-related differential cascade. This process reduces or inhibits the side effects caused by toxic all-trans retinoid acid (ATRA), which has long been used as a fundamental medication for treating AML/APL in clinical practice despite its related high relapse rate. Therefore, we believe that it is possible to maximize the beneficial effects of LIF by enriching LIFRα-CT3 in AML/APL cell cytoplasm. The aims of this work were to enrich LIFRα-specific motifs in leukemia cells using molecular biological methods and evaluate the use of membrane-permeable polypeptides as a novel possible AML/APL therapy in combination with or independent of ATRA-based chemotherapy.


Virologic response using directly observed therapy in adolescents with HIV: an adherence tool.
Virologic response to highly active antiretroviral therapy (HAART) treatment of HIV infection depends on viral sensitivity to antiretrovirals and excellent medication adherence. Adolescents with vertically acquired HIV may require complicated regimens because of significant treatment experience and often have poor medication adherence. A retrospective chart review identified five adolescents with vertically acquired HIV and plasma HIV viral load rebound or nonresponse on a stable HAART regimen followed by a period of directly observed therapy (DOT) in a clinic or hospital setting with serial viral load measurements. Four subjects had a virologic response (mean decline, 1.15 log10) after DOT. A response to HAART can be seen despite antiretrovirals resistance using DOT and treatment-experienced patients seemingly unresponsive to HAART may be nonadherent even with reassuring adherence measures. A period of clinic-monitored DOT may allow diagnosis of nonadherence, discussion of medication barriers, and avoidance of unnecessary medication changes.


Blood supply to the uterus in preeclampsia.
Uterine fundal and low segment arcuate artery velocimetry was studied in normal pregnant women and in severe preeclamptic patients. The waveform velocity of the preeclamptic group revealed large differences between systole and diastole, as well as an increased resistance index. Furthermore, the abnormality was more severe in the fundal than in the low segment arcuate measurement.


Computational tradeoffs in multiplex PCR assay design for SNP genotyping.
Multiplex PCR is a key technology for detecting infectious microorganisms, whole-genome sequencing, forensic analysis, and for enabling flexible yet low-cost genotyping. However, the design of a multiplex PCR assays requires the consideration of multiple competing objectives and physical constraints, and extensive computational analysis must be performed in order to identify the possible formation of primer-dimers that can negatively impact product yield. This paper examines the computational design limits of multiplex PCR in the context of SNP genotyping and examines tradeoffs associated with several key design factors including multiplexing level (the number of primer pairs per tube), coverage (the % of SNP whose associated primers are actually assigned to one of several available tube), and tube-size uniformity. We also examine how design performance depends on the total number of available SNPs from which to choose, and primer stringency criterial. We show that finding high-multiplexing/high-coverage designs is subject to a computational phase transition, becoming dramatically more difficult when the probability of primer pair interaction exceeds a critical threshold. The precise location of this critical transition point depends on the number of available SNPs and the level of multiplexing required. We also demonstrate how coverage performance is impacted by the number of available snps, primer selection criteria, and target multiplexing levels. The presence of a phase transition suggests limits to scaling Multiplex PCR performance for high-throughput genomics applications. Achieving broad SNP coverage rapidly transitions from being very easy to very hard as the target multiplexing level (# of primer pairs per tube) increases. The onset of a phase transition can be "delayed" by having a larger pool of SNPs, or loosening primer selection constraints so as to increase the number of candidate primer pairs per SNP, though the latter may produce other adverse effects. The resulting design performance tradeoffs define a benchmark that can serve as the basis for comparing competing multiplex PCR design optimization algorithms and can also provide general rules-of-thumb to experimentalists seeking to understand the performance limits of standard multiplex PCR.


Clozapine does activate nigrostriatal dopamine neurons in unanesthetized rats.
Antipsychotic drugs are traditionally classified as typical or atypical on the basis of their property to cause or not to cause extrapyramidal side-effects. A widely accepted selectivity for the mesolimbic, vs. the nigrostriatal, dopaminergic system is postulated to underlie the existence of fewer or no extrapyramidal side-effects during treatment with atypical neuroleptics. In order to verify this hypothesis we examined the effect of acute clozapine on nigrostriatal dopaminergic neurons recorded from non-anaesthetised and from chloral hydrate-anaesthetised rats. Extracellular single-unit recording coupled with antidromic activation from the neostriatum was used. Intravenous administration of cumulative doses of clozapine (1.25-10 mg/kg) increased the firing rate of nigrostriatal dopaminergic neurons in non-anaesthetised rats, but failed to significantly modify the activity of the same units under chloral hydrate anesthesia. These results indicate that acute clozapine activates nigrostriatal dopamine cells in non-anaesthetised rats and cast doubts about a direct link between the lack of significant extrapyramidal side-effects and the selectivity of atypical neuroleptics, such as clozapine, for the mesolimbic dopamine system.


PirB negatively regulates the inflammatory activation of astrocytes in a mouse model of sleep deprivation.
Reactive astrocytes play a potential regulatory role in sleep deprivation (SD). Paired immunoglobulin-like receptor B (PirB) is expressed in reactive astrocytes, suggesting that PirB may participate in regulating the inflammatory response of astrocytes. We used lentiviral and adeno-associated viral approaches to interfere with the expression of PirB in vivo and in vitro. C57BL/6 mice were sleep deprived for 7 days and neurological function was measured via behavioral tests. We found that overexpressed PirB in SD mice could decrease the number of neurotoxic reactive astrocytes, alleviate cognitive deficits, and promote reactive astrocytes tended to be neuroprotective state. IL-1α, TNFα, and C1q were used to induce neurotoxic reactive astrocytes in vitro. Overexpression of PirB relieved the toxicity of neurotoxic astrocytes. Silencing PirB expression had the opposite effect and exacerbated the transition of reactive astrocytes to a neurotoxic state in vitro. Moreover, PirB-impaired astrocytes demonstrated STAT3 hyperphosphorylation which could be reversed by stattic (p-STAT3 inhibitor). Furthermore, Golgi-Cox staining confirmed that dendrite morphology defects and synapse-related protein were significantly increased in PirB-overexpressed SD mice. Our data demonstrated that SD induced neurotoxic reactive astrocytes and contributed to neuroinflammation and cognitive deficits. PirB performs a negative regulatory role in neurotoxic reactive astrocytes via the STAT3 signaling pathway in SD.


Observations on choline acetyltransferase containing structures in the CD-1 mouse brain.
Central cholinergic structures within the CD-1 mouse were evaluated by immunohistochemical visualization of choline acetyltransferase (ChAT) using the monoclonal antibody AB8. Rostrally, cholinergic neurons were seen within the neostriatum, medial septal nucleus (Ch1), ventral (Ch2) and horizontal (Ch3) limb nuclei and nucleus basalis-substantia innominata complex (Ch4). Caudally, cholinergic neurons were seen in the cuneiformis-pedunculopontine nuclei (Ch5), lateral dorsal tegmental (Ch6) and parabigeminal (Ch8) nuclei as well as the medial habenular nucleus and cranial motor nuclei. Additional cholinergic perikarya were found in the hippocampus and cerebral cortex. ChAT stained fibers were observed in the cerebral cortex and in many fiber fascicles.


Antimicrobial susceptibility of inpatient urinary tract isolates of gram-negative bacilli in the United States: results from the study for monitoring antimicrobial resistance trends (SMART) program: 2009-2011.
The Study for Monitoring Antimicrobial Resistance Trends is an ongoing global surveillance program that has monitored the susceptibilities of Gram-negative bacilli from inpatient urinary tract infections (UTIs) since late 2009. This analysis reports on the in vitro susceptibility of 2,135 isolates collected by 24 US sites from hospitalized patients with UTIs between 2009 and 2011. Minimum inhibitory concentrations and susceptibility were determined according to the guidelines of the Clinical and Laboratory Standards Institute. Of the isolates collected, 88.6% (1,892) were Enterobacteriaceae, which included 48.9% (n = 1,045) Escherichia coli, 14.5% (n = 310) Klebsiella pneumoniae, 6.4% (n = 136) Proteus mirabilis, 2.5% (n = 54) Klebsiella oxytoca, and 16.3% (n = 347) other Enterobacteriaceae species. Overall, 6.8% of E coli, 10.3% of K pneumoniae, 3.7% of P mirabilis, and 11.1% of K oxytoca isolates were extended-spectrum β-lactamase-producing strains. Of the Enterobacteriaceae isolates, 67.5% were community associated and 26.9% were hospital associated (5.7% had no demographics). Highest overall rates of activity for the study period were seen with amikacin, ertapenem, and imipenem. The least active antimicrobials tested were ampicillin-sulbactam, ciprofloxacin, and levofloxacin. Ertapenem, imipenem, and amikacin were the most active study drugs against extended-spectrum β-lactamase-producing strains, although the activity against extended-spectrum β-lactamase-producing K pneumoniae did not exceed 69% throughout the study period. The results of the Study for Monitoring Antimicrobial Resistance Trends surveillance study document the rates of antimicrobial resistance in UTI pathogens in the United States, which can assist health care practitioners in selecting the appropriate treatment for UTIs.


Psychometric Validation of the Korean Version of the Family-Centered Care Questionnaire-Revised.
Background and Purpose: Family-centered care (FCC) is a philosophy of care that applies to all areas of pediatric nursing and is a key component of the care model for patient safety and management activities in the medical environment of hospitalized children. The aim of this study was to translate and evaluate the psychometric properties of the Korean version of the Family-Centered Care Questionnaire-Revised (FCCQ-R). Methods: A total of 239 questionnaires were completed by pediatric nurses at four consenting general hospitals. Results: Fourteen items were removed from the original questionnaire through exploratory factor analysis and nine subscales were reduced to five. The factor loadings of the 30 items on the five subscales ranged from 0.50-0.80. The model of the Korean version of the questionnaire was validated by an exploratory and confirmatory factor analysis. Reliability analysis for internal consistency showed an acceptable to high Cronbach's α of 0.96 in total and the subscales ranged from 0.59-0.92. Conclusions: This study verified the validity and reliability of the tool to measure the perception of FCC. Future research will need to correlate FCC with more relevant measures, such as the nurse-parent partnership measure tool, to confirm predictive and concurrent validity. The Korean version of the FCCQ-R of 30 questions on five subscales is a valid and reliable measurement of Korean nurses' perceptions of FCC.


Development of leprosy in a patient with rheumatoid arthritis during treatment with etanercept: a case report.
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder. There is a clear association between some disease-modifying drugs used to treat RA and infection. The introduction of the anti-tumor necrosis factor (TNF) therapies has improved the outcome of severe RA. The TNF-antagonism may increase susceptibility to granulomatous pathogens such as Mycobacterium tuberculosis, Listeria monocytogenes, and Histoplasma capsulatum. We report the case of a 37-year-old woman with RA receiving an anti-TNF agent, who developed a rash on her back and both legs, which was finally diagnosed as tuberculoid leprosy. This is the first case of leprosy due to anti-TNF therapy reported in Europe. Clinicians should be aware of this and other types of atypical and serious infections that patients may suffer from when treated with anti-TNF agents.


Effects of 17 beta-estradiol and progesterone on agonist-stimulated inositol phospholipid breakdown in uterine smooth muscle.
Inositol phospholipid breakdown, from a [3H]inositol-labelled pool, induced by a variety of contractile agents was monitored in uterine smooth muscle slices pretreated with estradiol-17 beta or estradiol-17 beta and progesterone by measuring the accumulation of [3H]inositol phosphates. Agonist potencies for stimulating [3H]IP accumulation were not affected by hormone treatment but the maximum responses were dependent upon hormonal state. Maximum responses to carbachol, norepinephrine, prostaglandin F2 alpha were increased in progesterone-dominated tissues but maximum responses to oxytocin were unaffected. Inhibition of agonist-induced responses by competitive receptor antagonists confirmed the receptor specificity of carbachol-, norepinephrine- and oxytocin-mediated responses. Partial membrane depolarization (25 mM K+) did not affect agonist-induced maximal responses in either estrogen- or progesterone-dominated tissue. These data suggest that gonadal steroid hormones affect agonist-dependent intracellular calcium mobilization processes.


Postmenopausal hyperthecosis: functional dysregulation of androgenesis in climacteric ovary.
Hyperandrogenism of ovarian origin is rare in postmenopausal women. However, there is evidence that the ovaries of postmenopausal women are active endocrine glands, secreting mainly androgens. A postmenopausal woman sought treatment for progressive hirsutism. Endocrine evaluation revealed androgen excess. Transvaginal ultrasound revealed enlarged ovaries. Hysterectomy and bilateral oophorectomy were recommended. However, surgery had to be withheld for 6 months while the patient recovered from an acute myocardial infarction. In the interim, the patient's hyperandrogenemia was successfully treated with monthly injections of the gonadotropin-releasing hormone agonist (GnRH), leuprolide acetate. This report illustrates the potential for postmenopausal ovaries to become active androgen-secreting endocrine organs. It also demonstrates the efficacy of pharmacologic intervention for postmenopausal ovarian hyperthecosis when the patient is a poor surgical candidate.


Erratum: A review of auditory processing and cognitive change during normal ageing, and the implications for setting hearing aids for older adults.
[This corrects the article DOI: 10.3389/fneur.2023.1122420.].


Calmodulin levels in psoriasis and other skin disorders.
Calmodulin was measured in a range of skin disorders characterized by some degree of epidermal hyperproliferation and/or dyskeratinization. In psoriasis the marginal zone of spreading plaques was also investigated. Within the spectrum of diseases we studied, calmodulin increase proved to be rather specific for lesional skin of psoriasis and seborrheic dermatitis; high levels were also found in psoriatic scales. Calmodulin increase in the marginal zone of the psoriatic lesion parallelled the sharp morphological demarcation. Although calmodulin may play a role in the maintenance of epidermal hyperproliferation in psoriasis, it seems unlikely to be of significance in its initiation.


AMP deaminase from the gill of the mullet Chelon labrosus R.: purification and effects of pH, phosphate and monovalent cations.
The AMP deaminase from the gill of Chelon labrosus was purified about 250-fold by chromatography on cellulose-phosphate. At low and high substrate concentration, a sharp pH optimum was found between pH 6.7 and 6.9. The enzyme was found to be relatively insensitive to physiological concentrations of inorganic phosphate. Na+ and K+ were activators of gill AMP deaminase, Na+ being the most efficient. Effects of possible changes in the intracellular concentrations of these cations on enzyme activity are discussed.


Predefined three tier business intelligence architecture in healthcare enterprise.
Business Intelligence (BI) has caused extensive concerns and widespread use in gathering, processing and analyzing data and providing enterprise users the methodology to make decisions. Different from traditional BI architecture, this paper proposes a new BI architecture, Top-Down Scalable BI architecture with defining mechanism for enterprise decision making solutions and aims at establishing a rapid, consistent, and scalable multiple applications on multiple platforms of BI mechanism. The two opposite information flows in our BI architecture offer the merits of having the high level of organizational prospects and making full use of the existing resources. We also introduced the avg-bed-waiting-time factor to evaluate hospital care capacity.


Cancer incidence and adverse pregnancy outcome in registered nurses potentially exposed to antineoplastic drugs.
To determine the relationships of potential occupational exposure to antineoplastic drugs with cancer incidence and adverse pregnancy outcomes in a historical prospective cohort study of female registered nurses (RNs) from British Columbia, Canada (BC). Female RNs registered with a professional regulatory body for at least one year between 1974 and 2000 formed the cohort (n = 56,213). The identifier file was linked to Canadian cancer registries. An RN offspring cohort from 1986 was created by linkages with the BC Birth and Health Status Registries. Exposure was assessed by work history in oncology or cancer agencies (method 1) and by estimating weighted duration of exposure developed from a survey of pharmacists and nursing unit administrators of all provincial hospitals and treatment centers and the work history of the nurses (method 2). Relative risks (RR) were calculated using Poisson regression for cancer incidence and odds ratios (OR) were calculated for congenital anomaly, stillbirth, low birth weight, and prematurity incidence, with 95% confidence intervals. In comparison with other female RNs, method 1 revealed that RNs who ever worked in a cancer center or in an oncology nursing unit had an increased risk of breast cancer (RR = 1.83; 95% CI = 1.03 - 3.23, 12 cases) and their offspring were at risk for congenital anomalies of the eye (OR = 3.46, 95% CI = 1.08 - 11.14, 3 cases). Method 2 revealed that RNs classified as having the highest weighted durations of exposure to antineoplastic drugs had an excess risk of cancer of the rectum (RR = 1.87, 95% CI = 1.07 - 3.29, 14 cases). No statistically significant increased risks of leukemia, other cancers, stillbirth, low birth weight, prematurity, or other congenital anomalies in the RNs' offspring were noted. Female RNs having had potential exposure to antineoplastic drugs were not found to have an excess risk of leukemia, stillbirth, or congenital anomalies in their offspring, with the exception of congenital anomalies of the eye, based on only three cases; however, elevated risks of breast and rectal cancer were observed.


Correlation of visual function impairment and OCT findings in patients with Stargardt disease and fundus flavimaculatus.
To investigate the relationship between morphologic lesions of the retina and functional abnormalities in patients with Stargardt disease (STGD) and fundus flavimaculatus (FFM). DESIGN. Case-controlled, prospective, comparative observational study. A complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT), was performed in 61 eyes of 32 consecutive patients with STGD/FFM and in 60 eyes of 30 matched healthy control subjects. Furthermore, fundus-related perimetry was performed in 12 of the affected eyes. The age ranged from 21 to 71 years in STGD/FFM patients and from 21 to 72 years in controls. BCVA ranged from 20/20 to 20/400 and from 20/20 to 20/32, respectively, in STGD/FFM patients and in controls. A foveal thinning was found by OCT Stratus in almost all cases (average 160 microm) compared with controls (average 210 microm) (p<0.001). BCVA impairment significantly correlated to the degree of foveal thinning (r2=0.16; p=0.0014). Moreover, in STGD/FFM patients the authors observed two types of hyperreflective deposits which were not correlated with BCVA impairment or foveal thinning. In addition, fundus-related perimetry revealed a stable fixation in 8/12 eyes, that was predominantly central in only 4 of these eyes. A smaller degree of foveal thinning correlated to a more stable fixation (p=0.0108), even if not predominantly central (p=0.0218). In this series, lower visual acuity and unstable fixation correlated with a greater transverse foveal thinning. OCT and fundus-related perimetry may be useful tools in STGD/FFM patients.


mHealth for the Self-management of Knee Osteoarthritis: Scoping Review.
Educating patients on the self-management of knee osteoarthritis (OA) reportedly reduces pain, improves activities of daily living, and even reduces health care costs. This scoping review will summarize the current evidence on mobile health (mHealth) and smartphone app-based disease self-management for patients with knee OA. PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and CINAHL were systematically searched in May 2021 using the keywords "knee osteoarthritis," "mobile health," and "self-management." Studies that investigated patients with knee OA based on radiography or clinical diagnosis were included. The following criteria were applied to the mobile phone apps included in the search-derived studies: the ability to (1) record and manage symptoms, (2) provide patient education, and (3) guide and record activities of daily living. Studies eligible for inclusion in this scoping review were interventional trials or observational studies published in English. This scoping review included 8 reports, of which 3 were randomized controlled trials and 1 was a conference abstract. Most studies provided data on the outcomes of pain, physical function, and quality of life. An increasing number of reports are addressing the effectiveness of mHealth in patients with knee OA, and the data suggest that mHealth efficacy is similar to conventional management of health. RR2-10.17504/protocols.io.buuxnwxn.


(5S)-5-Methyl-3-phenyl-2-sulfanyl-idene-1,3-thia-zolidin-4-one.
In the title mol-ecule, C(10)H(9)NOS(2), the 2-sulfanyl-idene-thia-zolidin-4-one mean plane and phenyl ring form a dihedral angle of 81.7 (1)°. In the crystal, C-H⋯π inter-actions link mol-ecules into helical chains in [010].


Comparison of 24-h volume and creatinine-corrected total urinary polyphenol as a biomarker of total dietary polyphenols in the Invecchiare InCHIANTI study.
Polyphenols have beneficial effects on several chronic diseases but assessing polyphenols intake from self-reported dietary questionnaires tends to be inaccurate and not very reliable. A promising alternative is to use urinary excretion of polyphenols as a proxy measure of intake. The best method to assess urinary excretion is to collect 24-h urine. However, since collecting 24-h urine method is expensive, time consuming and may be difficult to implement in large population-based studies, measures obtained from spot urine normalized by creatinine are commonly used. The purpose of the study was to evaluate the correlation between polyphenols dietary intake and total urinary polyphenol excretion (TPE), expressed by both 24-h volume and urinary creatinine normalization in 928 participants from the InCHIANTI study. Dietary intake data were collected using a validated food frequency questionnaire. Urinary TPE was analyzed by Folin-Ciocalteau assay. Both urinary TPE expression models were statistically correlated (r=0.580), and the partial correlation coefficient improved (pr=0.722) after adjusting for the variables that modify the urinary creatinine excretion (i.e. gender, age, BMI, physical activity and renal function). In crude models, polyphenol intake was associated with TPE corrected by 24-h volume (r=0.211; P<0.001), but not with creatinine normalization (r=0.014; P=0.692). However, urinary TPE expressed by creatinine correction was significantly correlated with dietary polyphenols after adjusting for covariates (pr=0.113; P=0.002). We conclude that urinary TPE expressed by 24-h volume is a better biomarker of polyphenol dietary intake than by urinary creatinine normalization. After covariate adjustment, both can be used for studying the relationships between polyphenol intake and health in large-scale epidemiological studies.


Indole-3-Acetic Acid Produced by Burkholderia heleia Acts as a Phenylacetic Acid Antagonist to Disrupt Tropolone Biosynthesis in Burkholderia plantarii.
Burkholderia heleia PAK1-2 is a potent biocontrol agent isolated from rice rhizosphere, as it prevents bacterial rice seedling blight disease caused by Burkholderia plantarii. Here, we isolated a non-antibacterial metabolite from the culture fluid of B. heleia PAK1-2 that was able to suppress B. plantarii virulence and subsequently identified as indole-3-acetic acid (IAA). IAA suppressed the production of tropolone in B. plantarii in a dose-dependent manner without any antibacterial and quorum quenching activity, suggesting that IAA inhibited steps of tropolone biosynthesis. Consistent with this, supplementing cultures of B. plantarii with either L-[ring-(2)H5]phenylalanine or [ring-(2)H2~5]phenylacetic acid revealed that phenylacetic acid (PAA), which is the dominant metabolite during the early growth stage, is a direct precursor of tropolone. Exposure of B. plantarii to IAA suppressed production of both PAA and tropolone. These data particularly showed that IAA produced by B. heleia PAK1-2 disrupts tropolone production during bioconversion of PAA to tropolone via the ring-rearrangement on the phenyl group of the precursor to attenuate the virulence of B. plantarii. B. heleia PAK1-2 is thus likely a microbial community coordinating bacterium in rhizosphere ecosystems, which never eliminates phytopathogens but only represses production of phytotoxins or bacteriocidal substances.


Education and psychological distress among older Chinese.
The goal of this research is to see if more highly educated older Chinese have lower levels of distress than do their poorly educated counterparts and whether engaging in cognitively stimulating activities such as reading and playing mahjong explains the association. Using the Chinese Healthy Longevity Survey, the authors find a significant negative association between education and psychological distress. Much of the association is mediated by activities, but not all in the ways expected. Reading, playing mahjong, and watching television all negatively correlate with distress. Better-educated older Chinese have lower levels of distress than do their less-well-educated counterparts in part because they engage in cognitively stimulating activities, have better economic circumstances, and engage in more physical activity.


Evaluating helicopter emergency medical missions: a reliability study of the HEMS benefit and NACA scores.
The benefits of the Helicopter Emergency Medical Service (HEMS) and dispatch accuracy are continuously debated, and a widely accepted score to measure the benefits of the mission is lacking. The HEMS Benefit Score (HBS) has been used in Finnish helicopter emergency medical services, but studies are lacking. The National Advisory Committee for Aeronautics (NACA) score is widely used to measure the severity of illness or injury in the pre-hospital setting, but it has many critics due to its subjectivity. We investigated the inter-rater and rater-against-reference reliability of these scores. Twenty-five fictional HEMS missions were created by an expert panel. A total of 22 pre-hospital physicians were recruited to participate in the study from two different HEMS bases. The participants received written instructions on the use of the scores. Intraclass correlation coefficients (ICCs) and mean differences between rater-against-reference values were calculated. A total of 17 physicians participated in the study. The ICC was 0.70 (95% CI 0.57-0.83) for the HBS and 0.65 (95% CI 0.51-0.79) for the NACA score. Mean differences between references and raters were -0.09 (SD 0.72) for the HBS and 0.28 (SD 0.61) for the NACA score, indicating that raters scored some lower NACA values than reference values formed by an expert panel. The HBS and NACA score had substantial inter-rater reliability. In addition, the rater-against-reference values were acceptable, though large differences were observed between individual raters and references in some clinical cases.


Trans-potassium effects on the chloride/proton symporter activity of guinea-pig ileal brush-border membrane vesicles.
To investigate the inhibitory effect of trans potassium on the Cl-/H+ symporter activity of brush-border membrane vesicles from guinea pig ileum, we measured both 36Cl uptake and, by the pyranine fluorescence method, proton fluxes, in the presence of appropriate H+ and K+ gradients. In the absence of valinomycin, a time-dependent inhibitory effect of chloride uptake by trans K+ was demonstrated. This inhibition was independent of the presence or absence of any K+ gradient. Electrical effects cannot be involved to explain these inhibitions because the intrinsic permeability of these vesicles to Cl- and K+ is negligibly small. Rather, our results show that, in the absence of valinomycin, the inhibitory effect of intravesicular K+ involves an acceleration of the rate of dissipation of the proton gradient through an electroneutral exchange of trans K+ for cis H+, catalyzed by the K+/H+ antiporter also present in these membranes. Valinomycin can further accelerate the rate of pH gradient dissipation by facilitating an electrically-coupled exchange between K+ and H+. To evaluate the apparent rate of pH-dissipating, downhill proton influx, we measured chloride uptake by vesicles preincubated in the presence of alkaline-inside pH gradients (pHout/pHin = 5.0/7.5), charged or not with K+. In the absence of intravesicular K+, proton influx exhibited monoexponential kinetics with a time constant k = 11 s-1. Presence of 100 mM K+ within the vesicles significantly increased the rate of pH gradient dissipation which, furthermore, became bi-exponential and revealed the appearance of an additional, faster proton influx component with k = 71 s-1. This new component we interpret as representing the sum of the electroneutral and the electrically-coupled exchange of trans K+ for cis H+, mentioned above. Finally, by using the pH-sensitive fluorophore, pyranine, we demonstrate that, independent of the absence or presence of a pH gradient, either vesicle acidification or alkalinisation can be generated by adding, respectively, Cl- or K+ to the extravesicular medium. Such results confirm the independent existence of both Cl-/H+ symporter and K+/H+ antiporter activities in our vesicle preparations, the relative activity of the former being larger under the conditions of the present experiments. The possible interplay of these two proton-transfer mechanisms in the regulation of the intracellular pH is discussed.


Enhanced Surface Properties of Light-Trapping Si Nanowires Using Synergetic Effects of Metal-Assisted and Anisotropic Chemical Etchings.
Metal-assisted chemical etching (MACE) has been widely explored for developing silicon (Si)-based energy and optical devices with its benefits for low-cost and large-area fabrication of Si nanostructures of high aspect ratios. Surface structures and properties of Si nanostructures fabricated through MACE are significantly affected by experimental and environmental conditions of etchings. Herein, we showed that surfaces and interfacial energy states of fabricated Si nanowires can be critically affected by oxidants of MACE etching solutions. Surfaces of fabricated Si nanowires are porous and their tips are fully covered with lots of Si nano-sized grains. Strongly increased photoluminescence (PL) intensities, compared to that of the crystalline Si substrate, are observed for MACE-fabricated Si nanowires due to interfacial energy states of Si and SiOx of Si nano-sized grains. These Si grains can be completely removed from the nanowires by an additional etching process of the anisotropic chemical etching (ACE) of Si to taper the nanowires and enhance light trapping of the nanowires. Compared with the MACE-fabricated Si nanowires, ACE-fabricated tapered Si nanowires have similar Raman and PL spectra to those of the crystalline Si substrate, indicating the successful removal of Si grains from the nanowire surfaces by the ACE process.


Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant.
Children with advanced chronic kidney disease (CKD) frequently develop left ventricular (LV) hypertrophy. The extent of hypertrophy that results in cardiac dysfunction is unknown. Systolic function, routinely determined by ejection fraction (EF), is usually preserved in these patients. However, a decrease in EF represents an advanced cardiac dysfunction. We used cardiac magnetic resonance (CMR) and phosphorus-31 MR spectroscopy (31P MRS) to assess markers of cardiac dysfunction in young CKD patients. Ten dialysis and ten post-transplant patients completed the study. The outcomes were peak LV myocardial circumferential strain (Ecc); myocardial T2 relaxation time and full width at half maximum (FWHM) of T2 distribution; and phosphocreatinine/adenosine triphosphate (PCr/ATP) to measure muscle energy metabolism. Healthy controls were used for comparison. All patients had normal EF; nine (45%) had low Ecc. Ecc was lower in dialysis versus transplant (p<0.0001) patients and inversely correlated with LV mass index, r= -0.47, p=0.04. Patients had higher T2 (p=0.056) and FWHM (p=0.01) than controls. T2 levels were positively correlated with LVM index (r=0.46, p=0.04). PCr/ATP was lower in patients than in controls (p=0.02). Young patients with advanced CKD and normal EF have early cardiac changes. Association of these abnormalities with increased left ventricular mass (LVM) index suggests development of maladaptive hypertrophy.


A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide, ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours.
We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide. We used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week in unselected patients with solid tumours. Twenty (8 male, 12 female) patients with various solid tumours were treated (18 evaluable for toxicity) over eight planned dose levels (10-300 mg). ALM201 was well-tolerated at all dose levels without CTCAE grade 4 toxicities. Adverse events were predominantly grades 1-2, most commonly, localised injection-site reactions (44.4%), vomiting (11%), fatigue (16.7%), arthralgia (5.6%) and headache (11%). Thrombosis occurred in two patients at the 100 mg and 10 mg dose levels. The MTD was not reached, and a recommended Phase II dose (RP2D) based on feasibility was declared. Plasma exposure increased with dose (less than dose-proportional at the two highest dose levels). No peptide accumulation was evident. The median treatment duration was 11.1 (range 3-18) weeks. Four of 18 evaluable patients (22%) had stable disease. Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers.


Development of an eco-friendly and fast HPLC method for quantitative analysis of four nucleosides in Cordyceps and related products.
An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min-1. The detection wavelength was 260 nm. The developed HPLC method showed good linearity with correlation coefficients of 1.0000 in the test range. Good precision, repeatability and stability of this method were also observed (RSD ≤ 2.81%). The recovery ranged from 91.84%-105.19% (RSD ≤ 2.59%). Compared with reported methods, the current method did not use harmful organic solvent and took only 10.5 min. It obtained a high eco-score of 91 by the "Analytical Eco-Scale" tool. The developed method is eco-friendly and fast, which is suitable for the quality evaluation of Cordyceps and related products.


A cell cycle regulatory network controlling NF-kappaB subunit activity and function.
Aberrantly active NF-kappaB complexes can contribute to tumorigenesis by regulating genes that promote the growth and survival of cancer cells. We have investigated NF-kappaB during the cell cycle and find that its ability to regulate the G1-phase expression of key proto-oncogenes is subject to regulation by the integrated activity of IkappaB kinase (IKK)alpha, IKKbeta, Akt and Chk1. The coordinated binding of NF-kappaB subunits to the Cyclin D1, c-Myc and Skp2 promoters is dynamic with distinct changes in promoter occupancy and RelA(p65) phosphorylation occurring through G1, S and G2 phases, concomitant with a switch from coactivator to corepressor recruitment. Akt activity is required for IKK-dependent phosphorylation of NF-kappaB subunits in G1 and G2 phases, where Chk1 is inactive. However, in S-phase, Akt is inactivated, while Chk1 phosphorylates RelA and associates with IKKalpha, inhibiting the processing of the p100 (NF-kappaB2) subunit, which also plays a critical role in the regulation of these genes. These data reveal a complex regulatory network integrating NF-kappaB with the DNA-replication checkpoint and the expression of critical regulators of cell proliferation.


Human papillomavirus epidemiology in populations with normal or abnormal cervical cytology or cervical cancer in the Middle East and North Africa: A systematic review and meta-analysis.
Human papillomavirus (HPV), one of the most common sexually transmitted viral infections worldwide, is the leading cause of cervical cancer. In Middle East and North Africa (MENA) Region HPV data is at scarce, and most of the countries haven't implemented any vaccination programs. This present meta-analysis and systematic review aimed to describe human papillomavirus (HPV) epidemiology by clinical subgroups in the (MENA) region. Studies assessing HPV prevalence rates were systematically reviewed, and the selected articles were reported following the PRISMA guideline. Random-effects meta-analyses and meta-regression were used to estimate HPV pooled mean prevalence rates and their association with other factors. For the cervical cancer population in the MENA region, the pooled HPV prevalence rate was 81% (95% CI, 70%-90%). HPV detected in cervical cancer samples was most prevalent in the Maghreb countries (88%; 95% CI, 78%-96%) and least prevalent in Iran (73%; 95% CI, 62%-83%).For the subgroup with abnormal-cervical cytology in the MENA region, the pooled HPV prevalence rate was 54% (95% CI, 41%-67%), with the highest prevalence reported in Northeast Africa (94%; 95% CI, 91%-96%), and the lowest prevalence in the Levant region (31%; 95 CI, 16%-49%). In the general population subgroup in the MENA region, the pooled HPV prevalence rate was 16% (95% CI, 14%-17%), HPV was most prevalent in the Northeast Africa region (21%; 95 CI, 7%-40%) and least prevalent in the Levant region (7%; 95 CI, 2%-14%). The present meta-analysis comprehensively described the current HPV prevalence rates in the MENA region and found that the rates have continued to increase with time, especially in African regions. Designing personalized awareness and vaccination programs that respect the various cultural and religious values remains the main challenge in prevention of cervical cancer in the MENA region.


Training paraprofessionals in the treatment of alcoholism. Effects on knowledge, attitudes and therapeutic techniques.
Participation in a training program for paraprofessional alcoholism counselors increased the trainees' knowledge of alcoholism, modified their attitudes toward alcoholism and affected their therapeutic techniques.


An Online Resident-as-Teacher Curriculum Improves First-Year Residents' Self-Confidence Teaching in the Clinical Learning Environment.
We implemented an online Resident-as-Teacher curriculum for all incoming residents (PGY1s) to provide them with a basic foundation for effective teaching in the clinical learning environment. The curriculum consisted of 5 asynchronous modules delivered via the web from 2017-2021. Prior to starting the course, the PGY1s completed a self-assessment of their teaching ability (pre-test) and then again 7-8 months after completing the course (post-test). Analysis of the paired data from 421 PGY1s showed a statistically significant improvement in the self-ratings of their teaching from pre-test to post-test (p < 0.001). Our findings suggest that an online Resident-as-Teacher curriculum can produce lasting benefits in new residents' self-confidence as educators.


Grazing incidence-X-ray fluorescence spectrometry for the compositional analysis of nanometer-thin high-kappa dielectric HfO2 layers.
In future microelectronic devices, SiO2 as a gate dielectric material will be replaced by materials with a higher dielectric constant. One such candidate material is HfO2. Thin layers are typically deposited from ligand-containing precursors in chemical vapor deposition (CVD) processes. In the atomic layer deposition (ALD) of HfO2, these precursors are often HfCl4 and H2O. Obviously, the material properties of the deposited films will be affected by residual ligands from the precursors. In this paper, we evaluate the use of grazing incidence--and total reflection-X-ray fluorescence spectrometry (GI-XRF and TXRF) for Cl trace analysis in nanometer-thin HfO2 films deposited using ALD. First, the results from different X-ray analysis approaches for the determination of Hf coverage are compared with the results from Rutherford backscattering spectrometry (RBS). Next, we discuss the selection of an appropriate X-ray excitation source for the analysis of traces within the high-kappa: layers. Finally, we combine both in a study on the accuracy of Cl determinations in HfO2 layers.


Improving the accuracy of estimates of the pulse sequence period using the methodology of complete sufficient statistics.
This paper is devoted to the synthesis of new signal processing algorithms based on the methodology of complete sufficient statistics and the possibility of using the Lehmann-Scheffe theorem. Using the example of a sequence of quasi-rectangular pulses, an approach to estimating their period was illustrated, taking into account the duty-off factor and the pulse squareness coefficient. A mathematical model was developed, on the basis of which, estimates of the potential accuracy of the methods were carried out. It is established that for the sample size value (n > 8), the relative root-mean-square error of estimating the repetition period using the methodology of complete sufficient statistics is lower than that of the traditional estimate. In addition to theoretical calculations, simulation results confirming the achieved effect are presented. The results obtained have a wide range of applicability and can be used in the design of control and measuring equipment in the oil and gas industry, in the development of medical equipment, in the field of telecommunications, in the design of pulse-Doppler radars, etc.


Prevalence of extended spectrum beta lactamases in Salmonella species isolated from patients with acute gastroenteritis.
Extended-spectrum β-lactamases (ESBLs) continue to be a major problem world wide, conferring resistance to the expanded-spectrum cephalosporins. They are increasingly associated with genus Salmonella. This study aimed to determine the prevalence of ESBLs in Salmonella isolates in our region by phenotypic methods. One thousand stool samples of acute gastroenteritis patients were screened and 42 strains of Salmonella (19 S. typhimurium, 14 S. enteritidis, 5 S. typhi, 3 S. paratyphi B 3 and 1 S. infantis) were detected. In the 3rd generation cephalosporin resistant Salmonella stains, ESBL was detected by double disc synergy test in ten isolates and by phenotypic confirmatory test in eight isolates of Salmonella. Drug resistance to various antibiotics was noted both among ESBL producers and non-ESBL producers. Resistance to chloramphenicol, nalidixic acid, norfloxacin and ciprofloxacin was noted in ESBL producers (n=4, 3, 8 and 8 of eight cases respectively) and in non-ESBL producers (n=10, 9, 16 and 13 of 34 cases, respectively). Quinolone resistance was significantly higher in ESBL producers while imipenem and cotrimoxazole resistance was significantly higher in non-ESBL producers. ESBL positive Salmonella isolates were found to be sensitive to amikacin and amoxyclav. The proper and regular monitoring of drug resistance ESBL production among Salmonella strains were necessary for the effective therapeutic outcome.


Sparstolonin B suppresses free fatty acid palmitate-induced chondrocyte inflammation and mitigates post-traumatic arthritis in obese mice.
Abnormal lipid metabolism, such as systemic increased free fatty acid, results in overproduction of pro-inflammatory enzymes and cytokines, which is crucial in the development of obesity-related osteoarthritis (OA). However, there are only a few drugs that target the lipotoxicity of OA. Recent researches have documented that the traditional Chinese medicine, Sparstolonin B (Ssn B), exerted anti-inflammatory effects in various diseases, but not yet in OA. On the basis of this evidence, our works purposed to evaluate the effect of Ssn B on free fatty acid (FFA) palmitate (PA)-stimulated human osteoarthritic chondrocytes and obesity-associated mouse OA model. We found that Ssn B suppressed PA-triggered inflammatory response and extracellular matrix catabolism in a concentration-dependent approach. In vivo, Ssn B treatment inhibited cartilage degeneration and subchondral bone calcification caused by joint mechanical imbalance and alleviated metabolic inflammation in obesity. Mechanistically, co-immunoprecipitine and molecular docking analysis showed that the formation of toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) complex caused by PA was blocked by Ssn B. Subsequently, it leads to inactivation of PA-caused myeloid differentiation factor 88 (MyD88)-dependent nuclear factor-kappaB (NF-κB) cascade. Together, these findings demonstrated that Ssn B is a potential treatment agent for joint degenerative diseases in obese individuals.


Glucocorticoids drive human CD8(+) T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production.
Glucocorticoids are highly effective in the treatment of allergy and asthma and inhibit the synthesis of IL-4, IL-5 and IL-13 by disease-promoting CD4(+) Th2 cells. CD8(+) T cells also synthesize these cytokines, and the aim of this study was to investigate how glucocorticoids effect cytokine production by these cells. When CD8(+) T cells are stimulated with anti-CD3 and IL-2 plus IL-4 or dexamethasone, production of the anti-inflammatory cytokine IL-10 is low in both primary and secondary cultures restimulated with anti-CD3 and IL-2 alone. However, when both are present, a synergistic effect on IL-10 synthesis is observed. The additional presence of antigen-presenting cells (APC) in the priming culture maintains IL-10 levels, but inhibits IL-4 and IL-5 production. CD4(+) T cells develop a similar glucocorticoid-induced phenotype. These cells demonstrate regulatory activity and inhibit CD4(+) T cell activation in an IL-10-dependent manner. Earlier reports show glucocorticoids promote a Th2 phenotype by effects on purified naive T cells or pretreatment of APC. This study demonstrates, more critically, that when APC are present, glucocorticoids induce CD4 and CD8 T cell populations synthesizing high levels of IL-10, but greatly reduced amounts of disease-promoting IL-4 and IL-5.


Histones Acetylation and Cancer Stem Cells (CSCs).
Chromatin decondensation is a key mechanism that guarantees gene transcription and repair of the genome, regulated mainly by the acetylation of histones. Emerging evidence has pointed out to histones as a new controlling mechanism of stem cell maintenance and fate. In this chapter, we will focus on the methods used to enrich tumor cell lines for cancer stem cells, and in the methods to identify the status of the histone acetylation in cancer cells and stem cells using immunofluorescence, invasion, and adhesion assays and identification of nuclear size.


De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature.
Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form. Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found. These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population.


D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease.
To determine whether higher circulating levels of inflammatory and thrombotic markers are associated with greater decline in lower extremity performance. Prospective cohort. Academic medical center. Three hundred thirty-seven men and women with lower extremity peripheral arterial disease (PAD) and 215 without PAD. Objective measures of leg function, including the 6-minute walk and Short Physical Performance Battery (SPPB), were obtained at baseline and annually for 3 years. D-dimer, high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen levels were measured at baseline. Participants were categorized into one of three groups, ranging from low to high levels of inflammation, depending on the number of individual blood factors in the lowest and highest tertiles for each corresponding blood factor. Adjusting for age, sex, race, ankle brachial index, comorbidities, and other confounders, greater inflammation was associated with greater decline in the SPPB (P=.008). Results were similar when repeated in participants with and without PAD separately (P for trend=.04 for participants with PAD and .07 for participants without PAD). In fully adjusted analyses, there were no significant associations between inflammation group and decline in 6-minute walk performance. Higher baseline levels of inflammatory markers and D-dimer were associated with greater decline in the SPPB at 3-year follow-up in persons with and without PAD.


A historical review of the problem of mitogenetic radiation.
The 'miracle of caryokinesis' was the starting point that stimulated Alexander G. Gurwitsch to carry out his famous 'mitogenetic' experiments in 1923. The results obtained confirmed his hypothesis of a weak radiation from cells, which is able to trigger the growth of other cells. Extensive experimental work within the first two decades after this discovery indicated that the problem of mitogenetic radiation is generally related to the biological significance of UV-radiation. Both 'energetic' and 'informational' aspects have to be considered, namely radiation effective in activating molecules, and that involved in arranging them into larger units. The molecular organization of biological structures is evidently governed by nonequilibrium conditions needing the uptake or emission of radiation. These concepts of A. G. Gurwitsch can be linked with modern approaches based on hypotheses of coherence in biology, 'synergetics' and 'dissipative structures'. However, the question of causal interrelationships between this part of non-equilibrium radiation and biological matter on different levels of evolution has to be solved now.


[The study of color vision in children].
The paper analyses results after investigation of color perception in 520 children (264 boys and 256 girls), aged 3-5 years, by means of two simple tests: a "Pflüger-Trident Test" (Velhagen) and a "Simplified Test of Color Vision" (Fletcher). It is proved that in children of under school age color perception is already developed enough and can be investigated for detecting disturbances in color vision.


Sports doping: emerging designer and therapeutic β2-agonists.
Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future.


Interventions for improving childhood vaccination coverage in low- and middle-income countries.
'Cochrane Corner' in the November SAMJ highlights a Cochrane review that evaluated the effects of interventions for improving childhood vaccination coverage in low- and middle-income countries. Which interventions increase the uptake of childhood vaccines in low and middle-income countries? Health education, home visits, and reminders probably increase the uptake of childhood vaccines in low and middle-income countries.


Reported adverse food reactions overestimate true food allergy in the community.
To determine the extent to which perceived adverse food reactions were associated with IgE mediated food allergy, as defined by skin prick testing (SPT). A cohort epidemiological study. Participants underwent SPT to five common food allergens (cow's milk, peanut mix, egg white, shrimp and whole grain wheat mix) and were asked whether they had ever suffered any food 'illness/trouble', and if so to list such food(s). A positive SPT was defined as wheal diameter of > or =3 mm. Cohen's kappa (kappa) was used to assess the agreement between SPT and self-reported reactions to food(s) which contained the allergen of interest. Randomly selected adults who took part in the follow-up of the European Community Respiratory Health Survey (ECRHS) in 1998. The subjects were 457 adults aged 26-50 y. Fifty-eight (13%) adults were sensitised to at least one food allergen whilst 99 adults (22%) reported illness to food(s) nearly always. However, only seven subjects who reported illness to a food also had a positive SPT to the same food. The prevalence of adverse food reactions associated with IgE mediated allergy in the adult general population would be less than 1.5% (7/457). The agreement between SPT and self-reported illness to food(s) was poor for cow's milk (kappa=0) and wheat (kappa=0), slight for shrimp (kappa=0.16) and egg white (kappa=0.09) and fair for peanut mix (kappa=0.37). There was little agreement between self-reported perceived illness to food(s) known to contain the food allergen of interest, and positive SPT, suggesting that most reactions are not due to IgE mediated food allergy.


Acute kidney injury after liver transplantation, perioperative risk factors, and outcome: prospective observational study of 1681 patients (OLTx Study).
Acute kidney injury (AKI) represents a frequent complication after orthotopic liver transplantation (OLT). This study aimed to evaluate early postoperative AKI incidence during the first 72 h after OLT, perioperative risk factors, and AKI impact on survival. From January 2011 to December 2013, 1681 patients underwent OLT in 19 centers and were enrolled in this prospective cohort study. According to RIFLE criteria, AKI occurred in 367 patients, 21.8% (R: 5.8%, I: 6.4%, F: 4.8%, L: 4.8%). Based on multivariate analysis, intraoperative risk factors for AKI were: administration of 5-10 RBCs (OR 1.8, 95% CI 1.3-2.7), dopamine use (OR 1.6, 95% CI 1.2-2.3), post-reperfusion syndrome (OR 1.5, 95% CI 1.0-2.3), surgical complications (OR 2.0, 95% CI 1.3-3.0), and cardiological complications (OR 2.2, 95% CI 1.2-4.0). Postoperative risk factors were: norepinephrine (OR 1.4, 95% CI 1.0-2.0), furosemide (OR 4.2, 95% CI 3.0-5.9), more than 10 RBCs transfusion, (OR 3.7, 95% CI 1.4-10.5), platelets administration (OR 1.6, 95% CI 1.1-2.4), fibrinogen administration (OR 3.0, 95% CI, 1.5-6.2), hepatic complications (OR 4.6, 95% CI 2.9-7.5), neurological complications (OR 2.4, 95% CI 1.5-3.7), and infectious complications (OR 2.7, 95% CI 1.8-4.3). NO-AKI patients' 5-year survival rate was higher than AKI patients (68.06, 95% CI 62.7-72.7 and 81.2, 95% CI 78.9-83.3, P<0.001). AKI still remains an important risk factor for morbidity and mortality after OLT. Further research to develop new strategies aimed at preventing or minimizing post-OLT AKI is needed.


Remogliflozin Etabonate Improves Fatty Liver Disease in Diet-Induced Obese Male Mice.
Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) are serious conditions and are being diagnosed at an increased rate. The etiology of these hepatic disorders is not clear but involves insulin resistance and oxidative stress. Remogliflozin etabonate (Remo) is an inhibitor of the sodium glucose-dependent renal transporter 2 (SGLT2), and improves insulin sensitivity in type 2 diabetics. In the current study, we examined the effects of Remo in a diet-induced obese mouse model of NAFLD. After 11-weeks on High-Fat-Diet 32 (HFD32), C57BL/6J mice were obese and displayed characteristics consistent with NAFLD. Cohorts of obese animals were continued on HFD32 for an additional 4-week treatment period with or without Remo. Treatment with Remo for 4 weeks markedly lowered both plasma alanine aminotransferase (76%) and aspartate aminotransferase (48%), and reduced both liver weight and hepatic triglyceride content by 42% and 40%, respectively. Remo also reduced hepatic mRNA content for tumor necrosis factor (TNF)-α (69%), and monocyte chemoattractant protein (MCP)-1 (69%). The diet-induced increase in thiobarbituric acid-reactive substances, a marker of oxidative stress, was reduced following treatment with Remo, as measured in both liver homogenates (22%) and serum (37%). Finally, the oxygen radical absorbance capacity (ORAC) in three different SGLT2 inhibitors was determined: remogliflozin, canagliflozin and dapagliflozin. Only remogliflozin had any significant ORAC activity. Remo significantly improved markers associated with NAFLD in this animal model, and may be an effective compound for the treatment of NASH and NAFLD due to its insulin-sensitizing and antioxidant properties.


Fabrication high toughness poly(butylene adipate-co-terephthalate)/thermoplastic starch composites via melt compounding with ethylene-methyl acrylate-glycidyl methacrylate.
The preparation of biodegradable composites with high toughness and low cost is of great significance for their application and promotion in the packaging field. As a renewable and biodegradable material with abundant sources, the inclusion of starch in biodegradable composites can significantly reduce costs. However, the poor compatibility between starch and matrix severely limits its large-scale practical application. In this work, the poly(butylene adipate-co-terephthalate)/thermoplastic starch/ethylene-methyl acrylate-glycidyl methacrylate (PBAT/TPS/EGMA) blends with high toughness were prepared by melt compounding. The elongation at break increased significantly from 533 ± 125 % for the PBAT/TPS(60/40) blend to 1188 ± 28 % for the PBAT/TPS/EGMA(60/40/2) blend. According to the analysis of Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscope (SEM), the toughness improvement brought about by the addition of EGMA can be attributed to the enhanced compatibility between PBAT and TPS and the refinement of TPS particle size. The knowledge obtained from this study provides a method to enhance the toughness of biodegradable polymer composites with high TPS loading, which will facilitate the practical application of starch in the packing field.


Reliable and cost effective design of intermetallic Ni2Si nanowires and direct characterization of its mechanical properties.
We report that a single crystal Ni2Si nanowire (NW) of intermetallic compound can be reliably designed using simple three-step processes: casting a ternary Cu-Ni-Si alloy, nucleate and growth of Ni2Si NWs as embedded in the alloy matrix via designing discontinuous precipitation (DP) of Ni2Si nanoparticles and thermal aging, and finally chemical etching to decouple the Ni2Si NWs from the alloy matrix. By direct application of uniaxial tensile tests to the Ni2Si NW we characterize its mechanical properties, which were rarely reported in previous literatures. Using integrated studies of first principles density functional theory (DFT) calculations, high-resolution transmission electron microscopy (HRTEM), and energy-dispersive X-ray spectroscopy (EDX) we accurately validate the experimental measurements. Our results indicate that our simple three-step method enables to design brittle Ni2Si NW with high tensile strength of 3.0 GPa and elastic modulus of 60.6 GPa. We propose that the systematic methodology pursued in this paper significantly contributes to opening innovative processes to design various kinds of low dimensional nanomaterials leading to advancement of frontiers in nanotechnology and related industry sectors.


Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition.
Non-central nervous system cancer in childhood (non-CNS CC) and its treatments pose a major threat to brain development, with implications for functional networks. Structural and functional alterations might underlie the cognitive late-effects identified in survivors of non-CNS CC. The present study evaluated resting-state functional networks and their associations with cognition in a mixed sample of non-CNS CC survivors (i.e., leukemia, lymphoma, and other non-CNS solid tumors). Forty-three patients (off-therapy for at least 1 year and aged 7-16 years) were compared with 43 healthy controls matched for age and sex. High-resolution T1-weighted structural magnetic resonance and resting-state functional magnetic resonance imaging were acquired. Executive functions, attention, processing speed, and memory were assessed outside the scanner. Cognitive performance was within the normal range for both groups; however, patients after CNS-directed therapy showed lower executive functions than controls. Seed-based connectivity analyses revealed that patients exhibited stronger functional connectivity between fronto- and temporo-parietal pathways and weaker connectivity between parietal-cerebellar and temporal-occipital pathways in the right hemisphere than controls. Functional hyperconnectivity was related to weaker memory performance in the patients' group. These data suggest that even in the absence of brain tumors, non-CNS CC and its treatment can lead to persistent cerebral alterations in resting-state network connectivity.