A methods review of posttrial follow-up studies of cardiovascular prevention finds potential biases in estimating legacy effects.
The objective of the study was to assess the methods used, and potential for bias, in posttrial studies of cardiovascular disease (CVD) where legacy effects may be estimated. We undertook a methods review of posttrial studies after randomized controlled trials (RCTs) of interventions to prevent CVD. For each included article, we extracted information on important aspects of the design and analysis of the study, and on the reporting of legacy effects. Of 2,622 retrieved articles, 46 were included in the review: 13 on blood glucose control, 13 on blood pressure control, and 20 on blood lipid control. The median duration for the RCT and posttrial follow-up studies was 5.0 and 5.7 years, respectively. At least 80% of initial RCT participants were enrolled in the posttrial study in 32 of the reports. Most reports used both linkage to routine administrative data sources and active data collection for the posttrial study. Of the 46 included articles, the authors assessed and reported posttrial covariate balance in 29 and made statistical adjustments in the analysis for potential confounding in 25. Posttrial results were reported separately to overall results (from time of randomization) in 21 articles. Legacy effects were claimed in 19 reports, of which 16 could be justified on the basis of the posttrial results. Posttrial studies may provide valuable information for investigating legacy effects, but better reporting of results is needed to realize their full potential. Robust methods of data collection and analysis may address the risk of selection and confounding biases in posttrial studies.


Antroscopic study of the maxillary antrum in lepromatous leprosy.
The technique of antroscopy affords an accurate assessment of chronic sinus disease. It was performed in twelve patients suffering from lepromatous leprosy in order to determine the type, nature and site of the lesion. Antral involvement with lepromatous leprosy may begin with a localized area of erythema progressing to granuloma formation or ulceration. The antero-inferior part of the antrum is the most commonly affected site.


Phenotypic and Genetic Analysis of KPC-49, a KPC-2 Variant Conferring Resistance to Ceftazidime-Avibactam and Maintaining Resistance to Imipenem and Meropenem.
Klebsiella pneumoniae, a gram-negative bacterium, poses a severe hazard to public health, with many bacterial hosts having developed resistance to most antibiotics in clinical use. The goal of this study was to look into the development of resistance to both ceftazidime-avibactam and carbapenems, including imipenem and meropenem, in a K. pneumonia strain expressing a novel K. pneumoniae carbapenemase-2 (KPC-2) variant, referred to as KPC-49. After 1 day of incubation of K1 on agar containing ceftazidime-avibactam (MIC = 16/4 mg/L), a second KPC-producing K. pneumoniae strain (K2) was recovered. Antimicrobial susceptibility assays, cloning assays, and whole genome sequencing were performed to analyse and evaluate antibiotic resistance phenotypes and genotypes. K. pneumoniae strain (K1), that produced KPC-2, was susceptible to ceftazidime-avibactam but resistant to carbapenems. The K2 isolate harboured a novel bla KPC-49 variant, which differs from bla KPC-2 by a single nucleotide (C487A), and results in an arginine-serine substitution at amino acid position 163 (R163S). The mutant K2 strain was resistant to both ceftazidime-avibactam and carbapenems. We demonstrated the ability of KPC-49 to hydrolyse carbapenems, which may be attributed to high KPC-49 expression or presence of an efflux pump and/or absence of membrane pore proteins in K2. Furthermore, blaKPC-like was carried on an IncFII (pHN7A8)/IncR-type plasmid within a TnAs1-orf-orf-orf-orf-orf-orf-ISKpn6-bla KPC-ISKpn27 structure. The bla KPC-like gene was flanked by various insertion sequences and transposon elements, including the Tn3 family transposon, such as TnAs1, TnAs3, IS26, and IS481-ISKpn27. New KPC variants are emerging owing to sustained exposure to antimicrobials and modifications in their amino acid sequences. We demonstrated the drug resistance mechanisms of the new mutant strains through experimental whole genome sequencing combined with bioinformatics analysis. Enhanced understanding of laboratory and clinical features of infections due to K. pneumoniae of the new KPC subtype is key to early and accurate anti-infective therapy.


Physical health after childbirth and maternal depression in the first 12 months post partum: results of an Australian nulliparous pregnancy cohort study.
to investigate the relationship between maternal physical health problems and depressive symptoms in the first year after childbirth. prospective pregnancy cohort study. Melbourne, Victoria, Australia. 1507 nulliparous women. women were recruited from six public hospitals between six and 24 weeks gestation. Written questionnaires were completed at recruitment and at three, six and 12 months post partum. Edinburgh Postnatal Depression Scale (EPDS); standardised measures of urinary and faecal incontinence, a checklist of symptoms for other physical health problems. overall, 16.1% of women reported depressive symptoms during the first 12 months post partum, with point prevalence at three, six and 12 months post partum of 6.9%, 8.8% and 7.8% respectively. The most commonly reported physical health problems in the first three months were tiredness (67%), back pain (47%), breast problems (37%), painful perineum (30%), and urinary incontinence (29%). Compared with women reporting 0-2 health problems in the first three months post partum, women reporting 5 or more health problems had a six-fold increase in likelihood of reporting concurrent depressive symptoms at three months post partum (Adjusted OR=6.69, 95% CI=3.0-15.0) and a three-fold increase in likelihood of reporting subsequent depressive symptoms at 6-12 months post partum (Adjusted OR=3.43, 95% CI 2.1-5.5). poor physical health in the early postnatal period is associated with poorer mental health throughout the first 12 months post partum. Early intervention to promote maternal mental health should incorporate assessment and intervention to address common postnatal physical health problems.


Crystal-facet and microstructure engineering in ZnO for photocatalytic NO oxidation.
Photocatalysis is believed to be an important way of reducing NO pollutant in air and the facet engineering of semiconducting oxides could enhance the efficiency of the photocatalysis. ZnO nanoparticles with different exposed crystalline facets were successfully synthesized using a hydrothermal method and their photocatalytic degradation towards NO was investigated. The crystals from ZnCl2 precursor were hexagonal mesoporous ones with exposed (0002) facet, while those from zinc acetate were in the form of flakes or wheat ears with enhanced exposure of (101(-)1) facet. Calcination in air imparted an enhanced the textural coefficient of the orientated facets as well as the oxygen defects. The nanocrystals with enhanced (0002) facet and lower flat-band energy did better in photoelectrochemical water-oxidation than those with exposed (101(-)1) facet that showed superior photocatalytic activity (approaching 76.7 ± 0.6% under 365 nm photons) for NO oxidation. According to theoretical calculations, (101(-)1) facet with O termination showed much higher affinity to NO molecules than other configurations, and the oxygen vacancy in ZnO played an minor role in the photocatalytic oxidation of NO. A high quantum efficiency approaching 97.5 ± 1.4% under 275 nm photons was obtained for the ZnO crystals from zinc acetate with mixed (0002) and (101(-)1) facets. This research explores the special characteristics of ZnO with different exposed facets and is important for the future design of highly efficient photocatalyst for hazardous material removal.


[Sclerosing angiomatoid nodular transformation of the spleen (SANT): a case report].
We report a case of sclerosing angiomatoid nodular transformation of the spleen incidently discovered in a 41-year-old man. The macroscopic examination showed the presence of a reddish brown, well delineated but not encapsulated, multinodular lesion being histologically characterized by nodules made up of complex vascular structures lined by monomorphous but non atypical endothelial cells, surrounded by fibrin and a collagen stroma rich in spumous macrophages and hemosiderophages. The immunohistochemical markers carried out showed the presence of capillaries, veins and sinusoids normally found within the splenic parenchyma, but adopting an unusual configuration. This distinct entity, recently described and completely benign, must be included in the differential diagnosis of the vascular lesions of the spleen, which includes, among others, the hemangioma, the littoral cell angioma, the hemangioendothelioma and the inflammatory myofibroblastic tumor.


Allogenous vein graft as vascular access for hemodialysis--lost battle?
The purpose of this paper is to assess a long-term outcome of allogenous vein grafts (ALVG) as vascular access for hemodialysis. For nearly eight years (between 9/2002 and 9/2011) a total of 78 patients with 112 ALVGs were involved in the study. The register included 46 women and 32 men, mean age 66.1 ± 11.2 years; range 20-88 years. The patient database was retrospectively reviewed and statistical processing was performed. Almost all ALVGs were treated by PTA or surgically, very often repeatedly. The number of radiologic interventions was 316, the number of surgical procedures 31. Mean follow-up time was 795 days, range 28-3522 days. Thirty-five patients died of unrelated causes, nineteen with functional graft, fourteen patients were lost to follow-up. Forty ALVGs failed for various reasons, mostly because of occlusion. Only one patient underwent successful renal transplantation, no patient converted to peritoneal dialysis. Thirty-seven ALVGs remain correctly functioning. Primary patency rates at 6, 12, and 24 months were 81 ± 5%, 63 ± 5%, and 34 ± 2% respectively. Secondary patency rates at 6, 12, and 24 months were 96 ± 2%, 82 ± 4%, and 65 ± 5% respectively. Allogenous vein grafts, in spite of the high number of necessary radiologic and surgical interventions and reinterventions, show acceptable clinical usability and durability, comparable with other types of prosthetic grafts.


The role of cost-effectiveness for vascular surgery service provision in the United Kingdom.
The cost of health care is increasingly becoming an international issue, with many health care systems requiring evaluation of cost when agreeing to fund health care. In the United Kingdom (UK), for example, the National Institute for Health and Care Excellence highlights the importance of using cost-effectiveness analyses to facilitate the effective use of resources. This study evaluates the use of cost-effectiveness analyses and the provision of vascular surgery. A systematic review of published literature was performed. UK-based studies assessing cost-effectiveness or cost-utility of superficial venous interventions, abdominal aortic aneurysm (AAA) repair, and carotid endarterectomy (CEA) were included. All included studies were quality assessed to determine the overall strength of UK economic evidence for each intervention. Four superficial venous, six AAA, and two CEA studies met the inclusion criteria. After quality assessment, the UK evidence supporting the cost-effectiveness of superficial venous intervention was graded strong. The economic evidence for asymptomatic and symptomatic CEA was graded limited and insufficient, respectively, owing to a paucity of UK literature in this field. There was strong UK economic evidence affirming that endovascular aneurysm repair (EVAR) is unlikely to be a cost-effective alternative to open repair. There is strong economic evidence for symptomatic superficial venous intervention. However, funding for varicose vein treatments remains controversial. Future economic analyses are required for symptomatic and asymptomatic CEA to better advise national policy. Despite strong economic evidence, current UK guidance is for EVAR over open repair in the elective setting, with the majority of elective AAA repairs being EVAR.


A life cycle assessment of distributed energy production from organic waste: Two case studies in Europe.
By means of the life cycle assessment methodology, the purpose of this study is to assess the environmental impact when biomethane from organic waste produced at residential level is used to supply energy to a group of dwellings in the distributed generation paradigm. Three different Combined Heat and Power systems, such as fuel cells, Stirling engine and micro gas turbine, installed at household level are assessed in two different settings: one in Northern Europe (UK) and one in Southern Europe (Italy). Different operating strategies are investigated for each technology. Moreover, marginal electricity production technologies are analysed to assess their influence on the results. This study has demonstrated that the type of bio-methane fed micro-CHP technology employed has a significantly different environmental impact: fuel cells are the most environmentally friendly solution in every category analysed; Stirling engines, although can supply heat to the largest number of dwellings are the least environmentally friendly technology. However, key factors investigated in the model presented in this paper influence the decision making on the type of technology adopted and the operating strategy to be implemented.


Evaluation of quantitative sulfur speciation in gas oils by Fourier transform ion cyclotron resonance mass spectrometry: validation by comprehensive two-dimensional gas chromatography.
Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been applied for the quantitative speciation of sulfur containing compounds in gas oil (GO). For this purpose, ionization and mass spectrometric parameters have been studied and optimized with a set of standard compounds and GO samples. Comprehensive two-dimensional gas chromatography (GCxGC) was used as the reference method. To allow a quantitative comparison between FT-ICR MS and GCxGC results for GO samples, FT-ICR MS parameters were optimized and data obtained by both techniques were standardized. Response factors were established for two ionization modes: atmospheric pressure photo ionization (APPI) and electrospray after selective derivatization of sulfur compounds (MeESI). To test the validity of the developed MS methods, a third GO was analyzed and response factors were applied. Comparison with GCxGC results showed good agreement for sulfur families (deviation within 5% and 15% for MeESI and APPI data, respectively). Abundances of individual isomer groups match within 40% in most cases. These results principally demonstrate the suitability of FT-ICR MS for a quantitative analysis of sulfur compounds (by DBE and carbon number distribution pattern) in petroleum middle distillates. This approach has the potential to be extended to higher- and non-boiling petroleum fractions where quantitative speciation is presently not available.


Science, politics, and the regulation of dietary supplements: it's time to repeal DSHEA.
Since the turn of the century, resourceful entrepreneurs have advertised a wide variety of purportedly simple and painless cures for cancer, including liniments of turpentine, mustard, oil, eggs, and ammonia; peat moss; arrangements of colored floodlamps; pastes made from glycerine and limburger cheese . . . [T]his historical experience does suggest why Congress could reasonably have determined to protect the terminally ill, no less than other patients, from the vast range of self-styled panaceas that inventive minds can devise. [Individuals have] the right to be treated by a health care practitioner with any medical treatment (including a treatment that is not approved, certified, or licensed by the Secretary of Health and Human Services) that such individual desires or the legal representative of such individual desires. The makers of our Constitution undertook to secure conditions favorable to the pursuit of happiness. They recognized the significance of man's spiritual nature, of his feelings and of his intellect. They knew that only a part of the pain, pleasure and satisfactions of life are to be found in material things. They sought to protect Americans in their beliefs, their thoughts, their emotions and their sensations. They conferred, as against the Government, the right to be left alone--the most comprehensive of rights and the right most valued by civilized men.


Association between the reactivity of local cerebral oxygen saturation after hypo-to-hypercapnic tests and delirium after abdominal surgery in older adults: A prospective study.
This study aimed to investigate the correlation between changes in regional cerebral oxygen saturation (rSO2) and postoperative delirium in older adults undergoing major abdominal surgery. This prospective study enrolled older adults scheduled for elective major abdominal surgery at the Second Affiliated Hospital of Anhui Medical University from August 2021 to January 2022. The change in rSO2 from baseline was determined using the hypo-to-hypercapnic test. The main study outcome was the occurrence of postoperative delirium. A total of 101 participants were included for analysis, of whom 16 (15.8%) developed postoperative delirium. Compared with non-delirium participants, the mean arterial pressure and heart rate were not significantly different in the postoperative delirium group at T0, T1, T2, T3, T4, and T6 (all Pinteraction > 0.05), but the delirium group had lower pH, lower PaO2, and higher lactate levels at T4, T5, and T6 (all Pinteraction < 0.05). rSO2 at T0, T1, T2, T3, T4, and T6 was 69.0 (63.2-75.2), 70.7 ± 7.3, 68.2 ± 7.5, 72.1 ± 8.0, 69.9 ± 7.8, 67.4 ± 7.2, and 71.7 ± 8.1, respectively. The postoperative change in rSO2 during the hypercapnia test (TΔrSO2%) was 6.62 (5.31-9.36). Multivariable analysis showed that the Cumulative Illness Rating Scale (odd ratio, OR = 1.89, 95% confidence interval, CI: 1.10-3.25, P = 0.021), preoperative albumin levels (OR = 0.67, 95% CI: 0.48-0.94, P = 0.022), rSO2 at T4 (OR = 0.61, 95% CI: 0.41-0.89, P = 0.010), and postoperative TΔrSO2% (OR = 0.80, 95% CI: 0.66-0.98, P = 0.028) were independently associated with postoperative delirium in older adults undergoing elective abdominal surgery. The rSO2 measured at T4 and postoperative TΔrSO2% were independently associated with postoperative delirium in older adults undergoing elective abdominal surgery.


Go/no-go discriminated avoidance learning in prenatally x-irradiated rats.
Male Fischer344 rats were exposed to x-irradiation at a dose of 200 rad on Day 17 of gestation. Irradiated and control rats were tested at 10-13 weeks of age with the paradigm of go/no-go (active-passive) discriminated avoidance conditioning for three consecutive daily sessions. During the first conditioning session, they learned only active avoidance responses to two different warning signals. During the second and third sessions, they learned active and passive avoidance responses: in response to one warning signal, rats were required to make an active response to avoid a shock, but not to run in response to the other signal in order to avoid a shock. Prenatally irradiated rats made more active avoidance responses to both warning signals than controls (first session). In the early training phase of the go/no-go task, irradiated rats performed significantly higher active and lower passive avoidance responses than controls. Irradiated rats established a strong tendency to respond actively to the no-go signal, but eventually learned to respond to it.


Ascorbic acid enhances nitric oxide production in trabecular meshwork cells.
This study investigated the role of ascorbic acid on the production of nitric oxide (NO) in the trabecular meshwork (TM) cells. After primarily cultured human TM cells were exposed to 1, 10, and 100 microM of L-ascorbic acid (LAA), with or without co-administration of 1 mM sodium nitroprusside or 100 microM hydrogen peroxide for 48 hr, cellular survival and NO production were measured with MTT and Griess assay, respectively. LAA significantly potentiated NO production in a dose-dependent manner (p<0.05) without affecting cell viability. LAA increased cell viability after hydrogen peroxide-induced oxidative stress in a dose-dependent manner. LAA enhanced NO production in TM cells and showed a cytoprotective effect against hydrogen peroxide-induced oxidative stress. LAA might be involved in the regulation of trabecular outflow by enhancing NO production in TM cells.


Mucoepidermoid carcinoma of parotid gland as a subsequent neoplasm in children treated for acute lymphoblastic leukemia.
We report two cases of mucoepidermoid carcinoma occurring as a second neoplasm following treatment for acute lymphoblastic leukemia. Both patients underwent parotidectomy as the primary treatment. One of them received irradiation in addition to surgery. We discuss the risk of developing MEC as a second malignancy, prognosis, and treatment options.


An introduction to body composition models used in nutritional studies.
Chemical analysis of cadavers has led to the definition of 'reference' man but diseases may result in significant changes in body composition. By measuring body composition in patient groups the nature of disease progression can be followed and management regimens evaluated. Various techniques are available which attempt to measure body composition in vivo. Several models of body composition have evolved with the introduction of new measurement techniques. A description of these models is presented. The limitations of the models and the techniques adopted for their measurement are discussed.


A family service unit's approach to working with child abuse.
The staff of Brent Family Service Unit, a voluntary social work agency operating in London, has developed a range of broadly based services to bring about real changes in the behaviour of families who suffer child abuse. The paper argues that integrated teams of workers containing a variety of roles, experiences and approaches is essential in responding to families who experience varying constellations of interrelated problems. Some basic principles underlying the team's work are described. Contract work with individuals, families and groups embodies some of the above principles. This approach is invaluable in bringing both structure to the work process plus enabling specific observable change goals to be negotiated. The creative use of games, exercises and materials are used to bring about changes in behaviour and attitudes. Observations that can be made regarding the value and effectiveness of this approach include a reduction in the incidence and frequency of injuries and the social isolation of families. Fewer children are received into care. Parents learn to have much more realistic expectations of their children's behaviour.


Coronary endothelial dysfunction from ischemia and reperfusion: effect of reactive oxygen metabolite scavengers.
Using anesthetized mongrel dogs exposed to 60 min of ligation of the left anterior descending coronary artery followed by 60 min of reperfusion, we examined the effect of superoxide dismutase (SOD) and dimethylthiourea (DMTU) on evidence of endothelial injury in coronary rings studied in vitro. In 13 dogs treated with saline rings from the normal left circumflex coronary artery (LCF) relaxed by 98 +/- 4% when exposed to 10(-5) M acetylcholine whereas rings from the left anterior descending coronary artery (LAD) relaxed by 79 +/- 7% (p less than 0.05). In the same rings maximum relaxation with the ionophore A23187 was 107 +/- 5% versus 87 +/- 8% (p less than 0.05) for the LCF and the LAD, respectively. Comparisons of concentration-response curves through a range of doses of both acetylcholine and A23187 revealed significant differences for both vasodilators between the LCF and the LAD (p less than 0.01 for each). Nine dogs were treated with bovine SOD infused in the left atrium the last 20 min of ligation and throughout reperfusion (140 units/kg/min) and six other dogs were treated with DMTU 500 mg/kg i.v. given the last 30 min of the ligation period. Neither SOD nor DMTU prevented endothelial injury in the LAD. Despite pretreatment with these agents, there were significant reductions in maximum relaxation and in total concentration-response curves in the LAD as compared with the results in rings from the LCF with both acetylcholine and A23187. There were normal responses to nitroprusside in both the LCF and LAD in all three experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Apoptosis, the heat shock response, hyperthermia, birth defects, disease and cancer. Where are the common links?
Many cells die during normal prenatal development. Throughout postnatal life, production of new cells is balanced by death of older cells to maintain the normal mass of organs and tissues. In these situations, cell death is usually in the form of apoptosis, characterized morphologically by shrinkage of cellular contents within their membranes, condensation and margination of chromatin against the nuclear membrane and phagocytic removal by macrophages or adjacent cells of the organ. It is initiated and controlled by a complex set of gene-directed activities. The process is tidy and avoids the inflammatory effects of degenerating cellular contents on other tissues. The capacity to undergo this form of cell death is lost in neoplastic cell lines. In embryos the normal process of apoptosis has been termed programmed cell death, and in prenatal and mature animals a number of toxic agents can also cause morphologically typical forms of apoptosis. The heat shock (HS) response occurs in a wide range of plants and animals as a basic reaction that assists survival and recovery from the effects of heat and other toxic agents. It appears to be an extension of the cellular mechanism by which newly synthesized proteins are received by other ('chaperone') proteins to be transported within cells and folded into their functional configurations. Chaperone proteins adhere to hydrophobic sites on newly synthesized proteins, preventing the formation of functionless aggregates by random adhesion to hydrophobic sites on other proteins. After disengagement, the new protein can assume its proper configuration. Chaperone proteins are normally present in embryos, the genes encoding for their synthesis becoming activated particularly at inductive and rapid growth stages of organ formation. Hyperthermia and some other toxic agents also activate a set of inducible heat shock genes to synthesize induced HS proteins that adhere to uncovered hydrophobic sites on the heat denatured proteins, preventing random associations and allowing reconstitution or assisting degradation of irreparably damaged proteins. Irreparable damage usually results in a morphologically typical form of apoptotic cell death. Knowledge of signals initiating the response is incomplete but includes prostaglandin release, amplification by kinase cascades of mitogen and stress-activated protein signals, binding of the HS factor to the HS element on the HS gene. Maternal hyperthermia is a proven teratogen in all species studied. The HS response is inducible in early embryonic life but it fails to protect embryos against damage at certain stages of development. An embryo must absorb a threshold 'dose' of heat if defects are to be caused, the dose being the product of the level and the duration of elevation above the normal maternal temperature. The lowest elevation causing damage is 2-2.5 degrees C. Low elevations require longer durations and as the elevation increases, the time required is reduced logarithmically. Heat-induced defects are most common in the central nervous system (CNS) and include open neural tube, microencephaly, microphthalmia and neurogenic contractures. Apoptotic cells are found in these organs soon after threshold doses of heat. The periods of high susceptibility are brief, occurring at the time of organ induction and, paradoxically, at this stage, chaperone protein synthesis is at high levels, presumably to protect this process. Susceptibility might be due to gene activity being concentrated into organ induction with chaperone proteins being unavailable for repair of heat-denatured proteins. With activation of the HS response, normal protein synthesis is suspended (perhaps including those controlling induction of organs) and protective HS proteins are produced which rescue the embryo, but survival is achieved at the expense of normal development.


The enigma of coproporphyrinogen oxidase: how does this unusual enzyme carry out oxidative decarboxylations to afford vinyl groups?
A new mechanism is proposed to explain how coproporphyrinogen oxidase performs two oxidative decarboxylations on a porphyrinogen substrate without the aid of cofactors or metal ions in the presence of molecular oxygen.


Are viral infections the cause of leukocytospermia?
Leukocytospermia is defined as a leukocyte count of more than 1 x 106 ml-1 ejaculate. It may be a symptom of male accessory gland infection, but is also observed in up to 10% of asymptomatic patients presenting for infertility work-up. Pathogenic bacteria are not present in all of these semen samples. We attempted to find evidence for infection with cytomegalovirus, Epstein-Barr virus and herpes simplex virus by determining antibodies in serum in 130 patients with, and 80 patients without, leukocytospermia and by polymerase chain reaction in 50 further patients and controls. All semen samples with or without leukocytospermia were free from clinically significant concentrations of pathogenic bacteria. Only IgM antibodies against HSV were found more frequently in patients with leukocytospermia than in the controls (10.8 and 1.25%, respectively). All other virus antibody findings showed an equal frequency in both groups. The determination of HSV DNA in 50 further semen samples with, and 50 samples without, leukocytospermia revealed no positive results. Although our study indicates an association of herpes virus infection and leukocytospermia in 10% of cases, the mechanism of association is to be clarified.


Expression of human immunodeficiency virus type 1 Nef antigen on the surface of acutely and persistently infected human T cells.
The authors have previously shown the role of human immunodeficiency virus type 1 (HIV-1) Nef protein as a growth inhibitor to CD4+ T lymphocytes. We now report that the Nef antigen is partly expressed on both acutely and persistently infected human T cells. To investigate the cell surface expression of the Nef antigen, murine monoclonal antibodies (mAbs) were prepared by immunization with a recombinant Nef protein. The recombinant Nef was expressed by a baculovirus expression system as a truncated Nef protein with 22 kDa containing the middle to the C-terminus. Three clones were found to produce mAbs with IgM isotype against Nef protein by ELISA with the same truncated Nef. All these mAbs reacted on immunoblotting with two forms of Nef, 25 kDa and 27 kDa, in an HIV-1-infected human T-cell line and with the 27 kDa Nef in retroviral vector-infected mouse fibroblasts expressing a full-length Nef protein. Membrane immunofluorescence and flow cytometry with these mAbs revealed the Nef antigen to be expressed, at least in part, on the surface of these cells. Thus, the cell-surface form of Nef might play an important role in the selective depletion of CD4+ cells in HIV-1 infection.


Engineered nanomaterials for (waste)water treatment - A scientometric assessment and sustainability aspects.
Application of nanomaterials for the treatment of effluents originated from various industrial and non-industrial sources, has been rapidly developed in recent decades. In this situation, there is a need for conclusive studies to identify the current status of the knowledge in this field and to promote the commercialization of such technologies by providing recommendations for future studies. In the present manuscript, a scientometric assessment on the progress made in this field has been performed and the results have been organized and discussed in terms of science statistics, research hotspots and trends, as well as the relevant sustainability aspects. Based on a set of keywords, identified through a pre-literature analysis, a total of 6539 documents were retrieved from the Web of Science (WoS) database and analyzed to achieve the main goals of this study. The results demonstrate that the studies in this field have been initiated since the beginning of the 2000s but were mainly performed in lab and pilot scales. Also, China and Iran were identified as the most contributing countries in this scientific area in terms of the number of publications. Among various types of engineered nanomaterials (ENMs), there has been especial attention for the application of iron-based nanomaterials as well as carbonaceous structures (such as graphene oxide and biochar). Besides, there are not still strong collaborations formed among researchers in this area worldwide. Regarding the research hotspots, the synthesis of green and sustainable nanomaterials (e.g., biosynthesis approaches) has received attention in recent years. The results can also demonstrate that the most widely studied pathway for the removal of pollutants from (waste)waters involves the adsorption of the pollutants using ENMs. Treatment of contaminants of emerging concern (CECs) as well as exploring the mechanisms involved in the treatment of contaminated (waste)waters using ENMs and the possible by-products are considered the current trends in the literature. Regarding the sustainability aspects of ENMs for (waste)water treatment, the results achieved in this study calls for in-depth sustainability studies, which consider parameters such as economic, environmental, and social aspects of nanomaterials utilization for (waste)water treatment purposes, besides the technical parameters, to push transferring such technologies from lab and pilot scales to large and real-scale applications.


Serum isocitrate dehydrogenase activity in Reye's syndrome.
Serum levels of isocitrate dehydrogenase was determined in 12 Reye's syndrome patients and the enzyme levels were compared with serum ornithine carbamyl phosphate, glutamic oxaloacetic transaminase (aspartate aminotransferase), ammonia, and the stages of the disorder. Isocitrate dehydrogenase was elevated in 8 of the 12 patients and there was no direct correlation between elevated serum isocitrate dehydrogenase level and other clinical parameters.


Novel, single-dose microsphere formulation of azithromycin versus 7-day levofloxacin therapy for treatment of mild to moderate community-acquired Pneumonia in adults.
This randomized, double-blind, noninferiority study was designed to demonstrate that a single 2.0-g oral dose of a novel microsphere formulation of azithromycin was at least as effective as 7 days of levofloxacin, 500 mg/day, in the treatment of adult patients with mild to moderate community-acquired pneumonia (Fine classes I, II, and III). In total, 427 subjects were randomly assigned to receive either a single 2.0-g dose of azithromycin microspheres (n = 213) or a 7-day regimen of levofloxacin (n = 214). At baseline, 219 of 423 (51.8%) treated subjects had at least one pathogen identified by culture, PCR, or serology. The primary end point was the clinical response (cure or failure) in the "clinical per protocol" population at test of cure (days 13 to 24). Clinical cure rates were 89.7% (156 of 174) for azithromycin microspheres and 93.7% (177 of 189) for levofloxacin (treatment difference, -4.0%; 95% confidence interval, -9.7%, 1.7%). Bacteriologic success at test of cure in the "bacteriologic per protocol" population was 90.7% (97 of 107) for azithromycin microspheres and 92.3% (120 of 130) for levofloxacin (treatment difference, -1.7%; 95% confidence interval, -8.8%, 5.5%). Both treatment regimens were well tolerated; the incidence of treatment-related adverse events was 19.9% and 12.3% for azithromycin and levofloxacin, respectively. A single 2.0-g dose of azithromycin microspheres was at least as effective as a 7-day course of levofloxacin in the treatment of mild to moderate community-acquired pneumonia in adult outpatients.


Risk factors for the rupture of mirror middle cerebral artery aneurysm using computer-assisted semiautomated measurement and hemodynamic analysis.
To identify the morphologic and hemodynamic risk factor of mirror middle cerebral artery (MCA) aneurysms. We conducted a retrospective analysis of 40 paired mirror MCA aneurysms. Aneurysms were divided into ruptured and unruptured groups. Seventeen morphological and nine hemodynamic parameters were measured using computer-assisted semiautomated measurement (CASAM) and computer flow dynamic (CFD) simulation. We performed a paired t-test (for normally distributed data) or a paired Wilcoxon rank-sum (for non-normally distributed data) to analyze all parameters between the groups. Multivariate conditional logistic regression analysis identified independent risk factors. The receiver operating characteristic curve was analyzed to acquire the area under the curve (AUC) and the cutoff values of the independent risk factors. There were significant differences in morphological and hemodynamic parameters between the ruptured and unruptured mirror aneurysms. The multivariate logistic analysis showed that the greater size (odds ratio [OR] = 9.807, p = 0.003), smaller neck diameter (OR = 0.285, p = 0.018) and maximum oscillatory shear index (OSI) (OR = 0.000001, p = 0.046) were independently correlated with aneurysm rupture. AUCs for size, N. and maximum OSI were 0.794, 0.695, and 0.701, respectively. The cutoff values of the size, neck diameter, and maximum OSI were 6.30, 5.07, and 0.356437, respectively. Morphology and hemodynamics can help predict aneurysm rupture risks. The more significant size, smaller neck diameter and maximum OSI were independent risk factors for the rupture of MCA aneurysms. The variables could aid practical risk evaluation.


[Generalized chromomycosis caused by Phialophora verrucosa].
Chromomycosis is a chronic fungal skin infection that generally presents in the form of verrucous or vegetative lesions on uncovered areas of skin. We report an unusual case of generalised chromomycosis due to Phialophora verrucosa. A 42-year-old town-dwelling housewife was hospitalised for erythematous keratotic nodules on the arm showing sporotrichoid distribution, associated with a crusted ulcerative lesion on the homolateral index finger, as well as subcutaneous papulonodular lesions. In places, the lesions on the patient's back presented an umbilical and molluscoid appearance. The patient had suffered no previous injuries and had not visited any areas in which leishmaniasis is endemic. Her history included insulin-dependent diabetes. Screening for Leishman bodies was negative. Histopathological analysis of the skin biopsy revealed an epithelioid giant-cell granuloma with no caseous necrosis. The mycological study demonstrated the presence of fumagoid bodies and P. verrucosa was isolated. Treatment with terbinafine was initially given, followed by clarithromycin, but in the absence of any improvement, the patient was readmitted to hospital and is currently on itraconazole and amphotericin B. The novel features of our case comprise the clinical aspect of chromomycosis, the extent of the lesions, their unusual site on the back and upper limbs, and the isolation of a rare species, P. verrucosa (only the second observation in Morocco). It also highlights the therapeutic difficulties posed by this type of chromomycosis.


Hemorheological aspects in the microvasculature of several pathologies.
We evaluated morphological changes in several pathologies using computerized videocapillaroscopy, and related hemorheological patterns using the laser assisted optical rotational red cell analyzer (LORCA). In addition, tissue oxygenation was measured using two oximeters with Combi sensors (Periflux 5000, Perimed). The study included four groups of patients (pts) that were compared with a control group. Group A Controls (n=25: 15 males [M] and 10 females [F] aged 36 +/- 3 years); Group B Diabetic pts n=32 (IDDM pts n=20: 12 M and 8 F aged 43 +/- 4 years; NIDDM pts n=12: 6 M and 6 F aged 45 +/- 3 years); Group C Glaucoma pts n=30 (16 M and 14 F aged 42 +/- 5 years); Group D Liver failure pts n=6 (3 M and 3 F aged 44 +/- 5 years); Group E Hypertensive pts n=50 (smokers n=28: 12 M and 16 F aged 40 +/- 4 years, and nonsmokers n=22: 12 M and 10 F aged 38 +/- 3 years). In all patients hemorheological measurements were made using the LORCA (including red blood cell [RBC] deformability and aggregability), morphology was evaluated using computerized videocapillaroscopy (magnification 200 x), and transcutaneous oxygen partial pressure measurements (TcpO2) were made with the Periflux 5000. In patients with diabetic microangiopathy: the capillary loops in 50% (16/32) of these pts showed formations such as 'deer horns', 72% (23/32) showed formations such as 'elephant nose', and in 45% (14/32) formations such as a 'cork screw'; in diabetics with POAD an important capillary rarefaction was found in 26% (9/32) of the pts. In glaucoma patients, in 84% (25/30) we observed 'capillary meandering' and images such as 'a comb'. In patients with more complicated pathology capillary rarefaction was found in 70% (21/30) of the patients. An improvement in the perfusion of non-functional loops was found in deceased patients who had suffered liver failure one week after liver transplantation in 90% (5/6) of the studied cadavers. In non-smoking hypertensives morphological changes were found in 25% (6/22) of the patients, and in hypertensive smokers in 47% (13/28). RBC deformability was detected using LORCA and expressed as the Elongation Index (EI), and RBC aggregability was detected using LORCA and expressed in t 1/2 (seconds) indicating the RBC aggregability peak. Group A controls: EI 0.59 +/- 0.02; t 1/2 3 +/- 1 sec; Group B: IDDM EI 0.55 +/- 0.01; t 1/2 : 2 +/- 0.5 sec p < 0.05; NIDDM EI 0.56 +/- 0.01; t 1/2 2 +/- 0.2 sec p < 0.04; Group C glaucoma: EI 0.56 +/- 0.01; t 1/2 2 +/- 0.3 sec p < 0.05; Group D liver failure: EI 0.56 0.02; t 1/2 2 +/- 0.4 sec p < 0.03; Group E hypertensives: smokers EI 0.56 +/- 0.02; t 1/2 2 +/- 0.6 sec p < 0.04; non-smokers EI 0.57 +/- 0.02; t 1/2 2 +/- 0.6 sec p < 0.04 compared with controls. We also measured the TcpO2 at the dorsum of the right foot as a standard site representing peripheral control of microvasculature perfusion. Group A 96 +/- 11 mmHg; Group B IDDM 74 +/- 9 mmHg p < 0.05; NIDDM 76 +/- 8 mmHg p < 0.05; Group C glaucoma 75 +/- 9 mmHg p < 0.05; Group D liver failure 69 +/- 6 mmHg p < 0.05; Group E hypertensives: smokers 70 +/- 5 mmHg p < 0.05, non-smokers 77 +/- 9 mmHg p < 0.05 compared with controls. This study presents an interesting and complete methodology to evaluate the microcirculation in different pathologies that induce changes in the microvasculature.


Clinical results with the Tachylog antitachycardia pacemaker.
Tachylog is an implantable automatic multi-function device with several antitachycardia modes including "intelligent" search which is not preodained. Twenty-five patients have received Tachylog stimulators in England since December, 1982. Sixteen had supraventricular tachycardia with a mean rate of 220/minute and nine had ventricular tachycardia with mean rate in excess of 180/minute. Four patients with ventricular tachycardia died of poor coronary artery disease and two patients with WPW underwent bypass tract division because of very rapid atrial fibrillation on effort. Clinical control of all arrhythmias has been achieved in the remaining 19 patients. Eighty per cent of those with SVT and two out of five of those with VT need no drug therapy. Problems have been confined to sensing difficulties with early units.


Effect of cyclic AMP and cyclic GMP on the activity of interferon against herpes simplex virus types 1 and 2, and vesicular stomatitis virus.
The antiviral action of interferon (IFN) on herpes simplex virus (HSV) types 1 and 2, and vesicular stomatitis virus (VSV) was examined with respect to the intracellular levels of cyclic adenosine monophosphate (CAMP) and cyclic guanosine monophosphate (CGMP) in human fibroblast (HF) cultures. Interferon by itself increased the intracellular levels of CAMP, but had no effect on the CGMP levels. Inoculation of HF with HSV, however, decreased the CAMP levels. Also, HSV inoculation elevated the CGMP levels, but VSV did not alter the CGMP levels. When HSV and IFN were added to the HF cultures in various combinations, HSV inhibited the IFN-induced elevation of CAMP and increased the CGMP levels to that characteristically observed with HSV inoculation in the absence of IFN. In contrast, IFN antagonized the VSV-associated decrease in CAMP levels. Although the yields of VSV were unaltered by the presence of CAMP- or CGMP-enhancing compounds, the yields of HSV were decreased with CAMP enhancers and increased with CGMP enhancers. the combination of IFN and CAMP enhancers had an additive effect in reducing the yields of HSV. Neither the CAMP or CGMP enhancers affected the action of IFN on VSV. These studies suggest that the interactions observed between HSV and cyclic nucleotides might account for the relatively refractive nature of HSV, as compared to VSV, toward the antiviral activity of IFN.


Study of the temperature effect on the surface area of model organic molecules, the dispersive surface energy and the surface properties of solids by inverse gas chromatography.
This paper demonstrated the non-validity of Schultz et al. method by proving that the surface areas of n-alkanes and polar molecules strongly depend of the temperature. Consequently, the results of surface properties obtained by this method are inaccurate. Inverse gas chromatography (IGC) at infinite dilution and the dynamic contact angle (DCA) technique were used on the polytetrafluoroethylene (PTFE) fibers. DCA measurements led to the determination of the surface energy γs(T) of PTFE fibers as a function of the temperature T (Relation 6). The variations of the surface areas of n-alkanes and polar molecules versus the temperature were determined by studying the same PTFE fibers by IGC at infinite dilution. We proved that the product of the surface area a(T, Cn) (in Å2) of an alkane by the dispersive component of the surface energyγsd(T)of the solid is constant at any temperature: [Formula: see text] , where b(Cn) is a constant only depending on the carbon atom number n of n-alkane Cn. An analytical relation of the surface area of n-alkanes as a function of the temperature was obtained (equation 18). Our results highlighted the failure of Dorris-Gray method that was largely used to determine γsd of solids. This method considered the surface area a-CH2- of methylene group equal to 6 Å2 and constant for any used temperature. The obtained results proved the non-validity of Dorris-Gray method and gave the expression of a-CH2- as a function of the temperature T (Equation 20) proved the non-validity of Dorris-Gray method. The calculations of the thermal expansion coefficients of the surface area a and radius R represented by the respective derivatives da/dT and dR/dT, showed their important variations as a function of the temperature. The general expression of the surface area aX(T) of polar molecules was given as a function of the temperature (Expression 48). The large effect of the temperature on surface areas and radii of molecules was highlighted, except for toluene. The surface area of toluene was proved to remain constant whatever the temperature. Our results showed, in general, non-linear variations of the radius rX(T) of polar molecules adsorbed on PTFE fibers. However, except for chloroform, dichloromethane and diethyl ether where their thermal expansion coefficient depends on the temperature, the linearity of rX(T) was verified in the temperature interval [293 K, 353 K].


A study of oxaliplatin-nucleobase interactions using ion trap electrospray mass spectrometry.
Oxaliplatin is an important anti-cancer drug that has been approved for the treatment of colorectal cancer. It is known that oxaliplatin, like other Pt-based drugs, interacts with DNA to form cytotoxic Pt-DNA adducts that disrupt important biological processes such as DNA replication and protein synthesis. Linear ion trap electrospray ionisation mass spectrometry (ESI-MS) was employed to study the interaction of oxaliplatin with DNA nucleobases. It was shown that oxaliplatin formed adducts with all four DNA nucleobases when present individually and in combination in solution. Multiple-stage tandem mass spectrometry (MS(n)) enabled the fragmentation pathways of each adduct to be established. In addition, proposed structures for each product ion were obtained from the MS data. When all four bases were present together with the drug at near-equal molar concentrations, adducts containing predominantly adenine and guanine were formed, confirming that the drug preferentially binds to these nucleobases. A large molar excess of drug was required to ensure the formation of cytosine and thymine adducts in the presence of adenine and guanine. Even with a large excess of oxaliplatin, only mono-adducts of these nucleobases were observed when all four nucleobases were present.


Effects of Carotid Endarterectomy on Cerebral Reperfusion and Cognitive Function in Patients with High Grade Carotid Stenosis: A Perfusion Weighted Magnetic Resonance Imaging Study.
To investigate the influence of carotid endarterectomy (CEA) on cerebral perfusion and cognitive function in patients with internal carotid artery stenosis (ICA). Patients were prospectively enrolled in this study. Shunted patients were excluded. Cerebral perfusion was measured by magnetic resonance (MR) perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI) in 46 patients with >65% ICA (31 males, 64.5 ± 6.7 years) 1 week before and 6 weeks after CEA. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) 1 week before and 6 weeks after CEA. After CEA, perfusion parameters from PWI decreased, including mean transit time (MTT) (21.07 ± 7.36 vs. 14.27 ± 6.22, p < .0001), time to peak (TTP) (28.69 ± 8.54 vs. 23.45 ± 4.25, p = .001), arrive time (T0) (19.89 ± 7.32 vs. 15.20 ± 3.51, p = .001), and relative cerebral blood volume (rCBV) (11.48 ± 3.50 vs. 7.53 ± 3.17, p < .0001). A significant improvement was observed in MoCA (20.48 ± 1.70 vs. 22.04 ± 1.48, p = .001). Spearman's rank correlation analysis between TTP and MoCA scores demonstrated a linear relationship with an excellent correlation coefficient (R = -.893, p < .001). Linear regression indicated that diabetes was a risk factor for cognitive improvement in patients with ICA (p = .014). Further analysis showed that patients with DM performed worse in MoCA after the procedure (with-DM 21.15 ± 1.28 vs. non-DM 22.4 ± 1.46, p = .010) while the baselines were similar (non-DM: 20.3 ± 1.8 vs. with-DM: 20.9 ± 1.4, p = .362). CEA could improve the cerebral perfusion and the cognitive function in un-shunted ICA patients. Cerebral reperfusion was an important factor for cognitive improvement. Diabetes had a negative effect on cognitive improvement after CEA.


Early mortality after hip fracture surgery in COVID-19 patients: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to assess the risk of early mortality in hip fracture patients with COVID-19 infection who undergo surgical intervention. MEDLINE (PubMed) and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases. Studies were included in the systematic review if they reported postoperative mortality in patients with COVID-19 infection who underwent operative intervention for hip fracture. From this selection of studies, only investigations that reported postoperative mortality in a COVID-positive and a non-COVID group were included in the meta-analysis. Data regarding patient demographics, age, and sex were recorded. Additional data that was extracted included study location, data collection period, length of follow-up, COVID testing methodology, COVID testing results, and number of patients who underwent operative versus nonoperative management. The primary outcome of interest was postoperative mortality. Random effects meta-analyses were performed to assess the pooled relative risk of postoperative mortality according to COVID status. Odds ratios and 95% confidence intervals (CI) were calculated. The overall pooled mortality rate in the early postoperative period for hip fracture patients with concomitant COVID-19 infection was 32.6%. The relative risk for postoperative mortality in COVID-positive patients compared to non-COVID patients was 5.66 (95% CI 4.01-7.98; p < 0.001). The currently available literature demonstrates that COVID-19 infection represents a substantial risk factor for early postoperative mortality in the already susceptible hip fracture population. Further investigations will be needed to assess longer-term morbidity and mortality in this patient population. Therapeutic Level IV.


Synthesis of glucosinolate precursors and investigations into the biosynthesis of phenylalkyl- and methylthioalkylglucosinolates.
The alkenyl and aromatic glucosinolates in oilseed rape (Brassica napus) are biosynthesized from chain-extended homologues of protein amino acids, including methionine and phenylalanine. Homologues of these two amino acids, homophenylalanine (2-amino-4-phenylbutyric acid) and dihomomethionine (2-amino-6-methylthiohexanoic acid) were synthesized both with and without a 1-14C label. Microsomal preparations from oilseed rape leaves were shown to contain enzyme systems which metabolize these compounds, with loss of 14CO2, and produce the aldoxime intermediates possible in the biosynthetic pathway utilizing homophenylalanine. These were characterized by comparison with authenticated synthetic compounds. Potential intermediates on the pathway between homophenylalanine and its corresponding aldoxime, the N-hydroxyamino- and the oximino acids, were synthesized and their possible role in the pathway investigated.


Infratemporal fossa meningioma: CT and MR findings.
We report an unusual case of an extracranial meningioma presenting as a large facial mass. The CT and magnetic resonance findings and a brief review of extracranial meningiomas are presented.


miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization.
Tumor microenvironment (TME) is a complex environment containing tumor cells, tumor-associated macrophages (TAMs), interstitial cells, and non-cellular components. Epithelial-mesenchymal transition (EMT), as a major actor in cancer tumorigenicity and metastasis, was involved in the interaction between TAMs and tumor cells. However, the potential mechanisms of EMT and how EMT-programmed tumor cells affect M2-like TAMs still need further exploration. An integrated analysis of nine CRC miRNA expression datasets was performed. Functional assays, including the EdU, clone formation, wound healing, and transwell assays, were used to determine the anticancer role of miR-195-5p in human CRC progression. Furthermore, RNA immunoprecipitation, RNA decay, and dual-luciferase reporter assays were used to determine the mechanism of miR-195-p CRC progression. Then co-culture, migration, and ELISA assays were applied to determine the role of miR-195-5p in macrophage recruitment and alternative polarization. Xenograft mouse models were used to determine the role of miR-195-5p in CRC tumorigenicity and TAM polarization in vivo. An integrated analysis confirmed that miR-195-5p was significantly downregulated in CRC tissues, and patients with a low level of miR-195-5p had significantly shortened overall survival as revealed by the TCGA-COAD dataset. Altered miR-195-5p in colon cancer cells led to distinct changes of proliferation, migration, invasion, and EMT. Mechanistically, miR-195-5p regulated NOTCH2 expression in a post-transcriptional manner by directly binding to 3'-UTR of the Notch2 mRNA. Subsequently, miR-195-5p/NOTCH2 suppressed GATA3-mediated IL-4 secretion in CRC cells and ultimately inhibited M2-like TAM polarization. miR-195-5p may play a vital role in regulating NOTCH2-mediated tumor cell EMT, thereby affecting IL-4-related M2-like TAM polarization in CRC.


cis/trans Carotenoid Extraction, Purification, Detection, Quantification, and Profiling in Plant Tissues.
Reverse phase high-performance liquid chromatography (HPLC) is the method of choice used in biological, health, and food research to identify, quantify, and profile carotenoid species. The identification and quantification of cis- and/or trans-carotene and xanthophyll isomers in plant tissues can be affected by the method of sample preparation and extraction, as well as the HPLC column chemistry and the solvent gradient. There is a high degree of heterogeneity in existing methods in terms of their ease, efficiency, and accuracy. We describe a simple carotenoid extraction method and two different optimised HPLC methods utilizing C18 or C30 reverse-phase columns. We outline applications, advantages, and disadvantages for using these reverse phase columns to detect xanthophylls and cis-carotenes in wild-type photosynthetic leaves and mutant dark-grown etiolated seedlings, respectively. Resources are provided to profile individual species based upon their spectral properties and retention time, as well as quantify carotenoids by their composition and absolute levels in different plant tissues.


Bilirubin inhibits calcium carbonate precipitation in gallbladder bile.
Previous studies have shown that human bile contains one or more factors that inhibit the precipitation of calcium carbonate from supersaturated solutions of calcium chloride and sodium bicarbonate. Lower concentrations of this factor have been observed in the gallbladder bile of patients with calcified gallstones. We hypothesized that gallbladder bile contains factors that inhibit calcium carbonate and these factors are present in varying concentrations in normal persons and in patients with cholesterol gallstones with and without calcium carbonate. Gallbladder bile of patients without gallstones (n = 8) and of patients with cholesterol gallstones containing either calcium carbonate (n = 8) or other calcium salts (n = 8) was assayed for calcium carbonate inhibition. Individual components of bile (bilirubin, phospholipid, bile salts, and albumin) were tested in different concentrations in the same assay system. In addition, samples of model bile were tested. An inhibitory factor for calcium carbonate precipitation was present within all human gallbladder bile, irrespective of the absence, presence, or type of gallstones. The addition of a bilirubin-albumin solution to a supersaturated solution of calcium chloride and sodium bicarbonate entirely blocked precipitation of calcium carbonate from solution. In addition, serial dilutions of bilirubin exhibited a linear response between bilirubin concentration and inhibitory effect. Model bile and phospholipid dissolved in sodium taurocholate also exhibited a modest inhibitory effect on calcium carbonate precipitation. We conclude that bilirubin, cholesterol, and phospholipids incrementally interfere with calcium carbonate precipitation in supersaturated solutions through the preferential formation of a soluble calcium complex.


Changing adolescent health behaviors: the healthy teens counseling approach.
Brief motivational interventions that have been provided in addition to routine primary care have changed adolescent health behaviors. Whether health screening and motivational-interviewing-based counseling provided by clinicians during routine care can change behaviors is unknown. Healthy Teens was a primary care, office-system intervention to support efficient, patient-centered counseling at well visits. Healthy Teens utilized a personal digital assistant (PDA)-based screener that provided the clinician with information about a teen's health risks and motivation to change. Changes in adolescent self-report of diet and activity health behaviors 6 months later were assessed in two cross-sectional samples of teens from five rural practices in 2005 and 2006. Usual-care subjects (N=148) were recruited at well visits prior to the intervention, and the Healthy Teens subjects (N=136) were recruited at well visits after the Healthy Teens system was well established. At 6-month follow-up, the Healthy Teens group had significantly increased self-reported exercise levels and milk-product intake. In the models exploring covariates, the only significant predictors for improvement in exercise levels were intervention-group status (p=0.009) and post-visit interest in making a change (p=0.015). Interest in changing predicted increased milk intake (p=0.028) in both groups. When teens planned an action related to nutrition, physical activity, or both after a well visit, Healthy Teens participants were more likely to report multiple planned actions (68% Healthy Teens vs 32% usual care, p<0.05). Changes in office systems using low-cost technology to screen adolescents and promote patient-centered counseling appear to influence teens to increase exercise and milk intake.


Epilepsy in 22q11.2 Deletion Syndrome: A Case Series and Literature Review.
The 22q11.2 deletion syndrome affects multiple organ systems, and the neurological manifestations are an important aspect of this disorder. Many are aware of cardiac anomalies associated with this uncommon genetic disorder. However, the different types of seizures, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) findings seen in this condition are not appreciated. Medical records of four patients with epilepsy due to 22q11.2 deletion syndrome were retrospectively reviewed for documentation of seizure types, EEG, and brain MRI findings. In addition, we also did a literature review of previously reported individuals with unprovoked seizures in this condition. A review of all published cases including our patients reveals that focal epilepsy (39 of 88, 44%) is the most common type followed by genetic generalized epilepsy (24 of 88, 27%). Diffuse cerebral atrophy and polymicrogyria were the most frequent MRI findings. Patients with structural brain abnormalities, especially polymicrogyria and associated epilepsy should have a chromosomal microarray (CMA) performed to screen for the 22q11.2 deletion syndrome. Focal epilepsy and genetic generalized epilepsy are the most frequent epilepsy types reported in this condition.


Building FAIR Functionality: Annotating Events in Time Series Data Using Hierarchical Event Descriptors (HED).
Human electrophysiological and related time series data are often acquired in complex, event-rich environments. However, the resulting recorded brain or other dynamics are often interpreted in relation to more sparsely recorded or subsequently-noted events. Currently a substantial gap exists between the level of event description required by current digital data archiving standards and the level of annotation required for successful analysis of event-related data across studies, environments, and laboratories. Manifold challenges must be addressed, most prominently ontological clarity, vocabulary extensibility, annotation tool availability, and overall usability, to allow and promote sharing of data with an effective level of descriptive detail for labeled events. Motivating data authors to perform the work needed to adequately annotate their data is a key challenge. This paper describes new developments in the Hierarchical Event Descriptor (HED) system for addressing these issues. We recap the evolution of HED and its acceptance by the Brain Imaging Data Structure (BIDS) movement, describe the recent release of HED-3G, a third generation HED tools and design framework, and discuss directions for future development. Given consistent, sufficiently detailed, tool-enabled, field-relevant annotation of the nature of recorded events, prospects are bright for large-scale analysis and modeling of aggregated time series data, both in behavioral and brain imaging sciences and beyond.


Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization: Therapeutic implications in bone defect repair.
Bone defects caused by diseases or surgery are a common clinical problem. Researchers are devoted to finding biological mechanisms that accelerate bone defect repair, which is a complex and continuous process controlled by many factors. As members of transcriptional costimulatory molecules, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play an important regulatory role in osteogenesis, and they affect cell function by regulating the expression of osteogenic genes in osteogenesis-related cells. Macrophages are an important group of cells whose function is regulated by YAP/TAZ. Currently, the relationship between YAP/TAZ and macrophage polarization has attracted increasing attention. In bone tissue, YAP/TAZ can realize diverse osteogenic regulation by mediating macrophage polarization. Macrophages polarize into M1 and M2 phenotypes under different stimuli. M1 macrophages dominate the inflammatory response by releasing a number of inflammatory mediators in the early phase of bone defect repair, while massive aggregation of M2 macrophages is beneficial for inflammation resolution and tissue repair, as they secrete many anti-inflammatory and osteogenesis-related cytokines. The mechanism of YAP/TAZ-mediated macrophage polarization during osteogenesis warrants further study and it is likely to be a promising strategy for bone defect repair. In this article, we review the effect of Hippo-YAP/TAZ signaling and macrophage polarization on bone defect repair, and highlight the regulation of macrophage polarization by YAP/TAZ.


DNA nanovehicles and the biological barriers.
DNA is emerging as a smart material to construct nanovehicles for targeted drug delivery. The programmability of Watson-Crick base paring enables construction of defined and dynamic DNA nanostructures of almost arbitrary shape and DNA can readily be functionalized with a variety of molecular modules. The applications of DNA nanostructures are still in its infancy, but one of the high expectations are to deliver solutions for targeted therapy. Nucleic acids, however, do not easily enter cells unassisted and biological barriers and harsh nucleolytic conditions in the human body must also be overcome. Here, we highlight recent strategies for DNA nanostructures in drug delivery, DNA nanovehicles, to facilitate targeting and crossing of the biological barriers. In light of this, we discuss future solutions and challenges for DNA nanovehicles to unravel their great potential to facilitate targeted drug delivery.


Sieving a living: a review of the biology, ecology and conservation status of the plankton-feeding basking shark Cetorhinus maximus.
The basking shark Cetorhinus maximus is the world's second largest fish reaching lengths up to 12 m and weighing up to 4 tonnes. It inhabits warm-temperate to boreal waters circumglobally and has been the subject of fisheries exploitation for at least 200 years. There is current concern over its population levels as a consequence of directed harpoon and net fisheries that in the north-east Atlantic Ocean alone took over 100,000 mature individuals between 1946 and 1997. As a consequence, it is not known whether populations are recovering or are at a fraction of their historical, pre-fishing biomass. They are currently Red-listed as vulnerable globally, and endangered in the north-east Atlantic. The basking shark is one of only three shark species that filter seawater for planktonic prey and this strategy dominates key aspects of its life history. Until recently, very little was known about the biology, ecology and behaviour of this elusive species. The advent of satellite-linked electronic tags for tracking has resulted in considerable progress in furthering our understanding of basking shark behaviour, foraging, activity patterns, horizontal and vertical movements, migrations and broader scale distributions. Genetic studies are also beginning to reveal important insights into aspects of their global population structure, behaviour and evolutionary history. This chapter reviews the taxonomy, distribution and habitat, bionomics and life history, behaviour, population structure, exploitation, management and conservation status of the basking shark. In doing so, it reveals that whilst important behavioural and ecological information has been gained, there are still considerable gaps in knowledge. In particular, these relate to the need to resolve population sizes, spatial dynamics such as population sub-structuring and sexual segregation, the critical habitats occupied by pregnant females, and the distribution and scale of fishery by-catch rates. Although challenging, it is arguable that without achieving these goals the conservation status of the basking shark will be difficult to assess accurately.


Phenotypic characterization of a mouse model of juvenile neuronal ceroid lipofuscinosis.
Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessively inherited neurodegenerative disorder that results from mutations in the CLN3 gene. JNCL is characterized by accumulation of autofluorescent lysosomal storage bodies, vision loss, seizures, progressive cognitive and motor decline, and premature death. Studies were undertaken to characterize the neuronal ceroid lipofuscinosis phenotype in a Cln3 knockout mouse model. Progressive accumulation of autofluorescent storage material was observed in brain and retina of affected mice. The Cln3(-/-) mice exhibited progressively impaired inner retinal function, altered pupillary light reflexes, losses of inner retinal neurons, and reduced brain mass. Behavioral changes included reduced spontaneous activity levels and impaired learning and memory. In addition, Cln3(-/-) mice had significantly shortened life spans. These phenotypic features indicate that the mouse model will be useful for investigating the mechanisms underlying the disease pathology in JNCL and provide quantitative markers of disease pathology that can be used for evaluating the efficacies of therapeutic interventions.


Gamma-tubulin in chicken erythrocytes: changes in localization during cell differentiation and characterization of cytoplasmic complexes.
The mechanism of marginal band (MB) formation in differentiating erythroid cells is not fully understood, and the proteins involved in nucleation of MB microtubules are largely unknown. To gain insights into the function of gamma-tubulin in MB formation, we have followed its distribution in developing chicken erythrocytes and characterized soluble forms of the protein. In early stages of erythroid cells differentiation, gamma-tubulin was present in microtubule-organizing centers, mitotic spindles, as well as on MB. Its subcellular localization changed in the course of differentiation, and in postnatal peripheral erythrocytes gamma-tubulin was found only in soluble forms. After cold-induced depolymerization gamma-tubulin in erythroid cells formed large clusters that were not observed in matured cells, and re-growth experiments demonstrated that gamma-tubulin was not present in distinct nucleation structures at the cell periphery. Soluble gamma-tubulin formed complexes of various size and large complexes were prone to dissociation in the presence of high salt concentration. Interaction of gamma-tubulin with tubulin dimers was revealed by precipitation experiments. gamma-Tubulin occurred in multiple charge variants whose number increased in the course of erythrocyte differentiation and corresponded with decreased binding to MB. The presented data demonstrate for the first time that gamma-tubulin is a substrate for developmentally regulated posttranslational modifications and that the binding properties of gamma-tubulin or its complexes change during differentiation events.


Visualization and quantification of carbon "rusty sink" by rice root iron plaque: Mechanisms, functions, and global implications.
Paddies contain 78% higher organic carbon (C) stocks than adjacent upland soils, and iron (Fe) plaque formation on rice roots is one of the mechanisms that traps C. The process sequence, extent and global relevance of this C stabilization mechanism under oxic/anoxic conditions remains unclear. We quantified and localized the contribution of Fe plaque to organic matter stabilization in a microoxic area (rice rhizosphere) and evaluated roles of this C trap for global C sequestration in paddy soils. Visualization and localization of pH by imaging with planar optodes, enzyme activities by zymography, and root exudation by 14 C imaging, as well as upscale modeling enabled linkage of three groups of rhizosphere processes that are responsible for C stabilization from the micro- (root) to the macro- (ecosystem) levels. The 14 C activity in soil (reflecting stabilization of rhizodeposits) with Fe2+ addition was 1.4-1.5 times higher than that in the control and phosphate addition soils. Perfect co-localization of the hotspots of β-glucosidase activity (by zymography) with root exudation (14 C) showed that labile C and high enzyme activities were localized within Fe plaques. Fe2+ addition to soil and its microbial oxidation to Fe3+ by radial oxygen release from rice roots increased Fe plaque (Fe3+ ) formation by 1.7-2.5 times. The C amounts trapped by Fe plaque increased by 1.1 times after Fe2+ addition. Therefore, Fe plaque formed from amorphous and complex Fe (oxyhydr)oxides on the root surface act as a "rusty sink" for organic matter. Considering the area of coverage of paddy soils globally, upscaling by model revealed the radial oxygen loss from roots and bacterial Fe oxidation may trap up to 130 Mg C in Fe plaques per rice season. This represents an important annual surplus of new and stable C to the existing C pool under long-term rice cropping.


Calculating Half Maximal Inhibitory Concentration (IC50) Values from Glycomics Microarray Data Using GraphPad Prism.
Half maximal inhibitory concentration (IC50) is a measurement often used to compare the efficiency of various carbohydrates and their derivatives for inhibition of lectin binding to particular ligands. IC50 values can be calculated using experimental data from various platforms including enzyme-linked immunosorbent assay- (ELISA-)type microtiter plate assays, isothermal titration calorimetry (ITC), or glycan microarrays. In this chapter, we describe methods to fluorescently label a lectin, to carry out a lectin binding inhibition experiment on glycan microarrays, and to calculate the IC50 value of a binding inhibitory molecule using GraphPad Prism software. In the example used to illustrate the method in this chapter, IC50 calculation is demonstrated for inhibition of Maackia amurensis agglutinin (MAA) binding to 3'sialyl-N-acetyllactosamine (3SLN) using free lactose.


SIRT2 inhibition attenuates the vasculopathy and vision impairment via Akt signaling in retinopathy of prematurity.
Despite decades of researches, the underlying mechanism of retinopathy of prematurity (ROP) remains unclear. The role of Sirt2, which is involved in both angiogenesis and inflammation, both pivotal in ROP, was investigated in an animal model of ROP known as oxygen-induced retinopathy (OIR). Our study found that Sirt2 was overexpressed and colocalized with microglia in OIR. Furthermore, it demonstrated that the level of Sirt2 was upregulated in hypoxia microglia BV-2 in vitro. Subsequently, our results elucidated that administration of the Sirt2 antagonist AGK2 attenuated the avascular and neovascular area and downregulated the expression of IGF-1. The phosphorylation of Akt and the expression of IGF-1 were upregulated in hypoxia BV-2 and conditional media collected from BV-2 under hypoxia promoted the migration and tube formation of retinal capillary endothelial cells, which were suppressed with AGK2. Notably, our findings are the first to demonstrate the deleterious role of Sirt2 in ROP, as Sirt2 inhibition led to the downregulation of Akt/IGF-1 and ameliorated vasculopathy, ultimately improving visual function. These results suggest that Sirt2 may be a promising therapeutic target for ROP.


Flight attendant occupational nutrition and lifestyle factors associated with COVID-19 incidence.
In the era of COVID-19, essential workers are plagued with unforeseen and obfuscated challenges. Flight attendants are a unique subgroup of essential workers who face a multitude of health risks attributed to occupational exposures that are accentuated by the COVID-19 pandemic. Such risks can be ameliorated with strategies that target factors which enhance COVID-19 risk, including modifiable factors of diet and lifestyle. The aim of this cross-sectional study is to detect occupational dietary and lifestyle factors which could increase COVID-19 incidence amongst flight attendants. To identify potential risk factors, a questionnaire was administered to eighty-four flight attendants and examined the participants' diet and lifestyle, and COVID-19 incidence. Descriptive statistics and logistic regression indicated that the participants' perceived dietary quality at work (p = 0.003), sleep disruptions which impacted their consumption of a healthy diet (p = 0.013), job tenure (OR: 0.67, 95% CI: 0.46:0.98) and frequency of reported cold/flu (OR: 1.49, 95% CI: 1.014-2.189) were all factors associated with confirmed/suspected COVID-19 incidence. This study also revealed that a lack of infrastructure for food storage and time limitations are considerable occupational barriers for flight attendants to consume healthy foods. Additional investigation can further elucidate these relationships and related solutions to mitigate COVID-19 risk in the future.


Cholesterol homeostasis in mononuclear leukocytes from patients with familial hypercholesterolemia treated with lovastatin.
We evaluated the effects of different doses of lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and the rate-limiting enzyme in cholesterol biosynthesis, on parameters of cholesterol homeostasis in freshly isolated mononuclear leukocytes from 19 patients with heterozygous familial hypercholesterolemia. Patients were treated with sequentially increasing doses of lovastatin (10 to 80 mg/day in a twice-daily regimen). The in vitro activity of HMG CoA reductase and cholesterol synthesis from 2-14C-acetate was determined in mononuclear cells obtained under steady-state conditions after patients had spent 6 weeks on doses of 20, 40, or 80 mg/day. The total and high affinity degradation of 125I-low density lipoprotein (LDL) was determined at baseline and on lovastatin at a dose of 80 mg/day. LDL cholesterol levels fell progressively on lovastatin (38% reduction on 80 mg daily, p less than 0.005). These changes were paralleled by a 121% increase in the activity of HMG CoA reductase (p less than 0.05) and a 39% increase in cholesterol synthesis from 2-14C-acetate (p less than 0.005). Total and high affinity degradation of 125I-LDL increased from 27 +/- 3.3 and 12.1 +/- 1.6 ng/4 x 10(6) cells/4 hours on the diet only to 69.7 +/- 7.2 and 32.9 +/- 3.6 ng/4 x 10(6) cells/4 hours, respectively, (mean +/- SEM) in mononuclear cells isolated from patients on 80 mg of lovastatin daily (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.
Longitudinal tau positron emission tomography (PET) is a relevant outcome in clinical trials evaluating disease-modifying therapies in Alzheimer disease (AD). A key unanswered question is whether the use of participant-specific (individualized) regions of interest (ROIs) is superior to conventional approaches where the same ROI (group-level) is used for each participant. To compare group- and participant-level ROIs in participants at different stages of the AD clinical continuum in terms of annual percentage change in tau-PET standardized uptake value ratio (SUVR) and sample size requirements. This was a longitudinal cohort study with consecutive participant enrollment between September 18, 2017, and November 15, 2021. Included in the analysis were participants with mild cognitive impairment and AD dementia from the prospective and longitudinal Swedish Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably 2 (BioFINDER-2) study; in addition, a validation sample (the AVID 05e, Expedition-3, Alzheimer's Disease Neuroimaging Initiative [ADNI], and BioFINDER-1 study cohorts) was also included. Tau PET (BioFINDER-2, [18F]RO948; validation sample, [18F]flortaucipir), 7 group-level (5 data-driven stages, meta-temporal, whole brain), and 5 individualized ROIs. Annual percentage change in tau-PET SUVR across ROIs. Sample size requirements in simulated clinical trials using tau PET as an outcome were also calculated. A total of 215 participants (mean [SD] age, 71.4 (7.5) years; 111 male [51.6%]) from the BioFINDER-2 study were included in this analysis: 97 amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals, 77 with Aβ-positive mild cognitive impairment (MCI), and 41 with AD dementia. In the validation sample were 137 Aβ-positive CU participants, 144 with Aβ-positive MCI, and 125 with AD dementia. Mean (SD) follow-up time was 1.8 (0.3) years. Using group-level ROIs, the largest annual percentage increase in tau-PET SUVR in Aβ-positive CU individuals was seen in a composite ROI combining the entorhinal cortex, hippocampus, and amygdala (4.29%; 95% CI, 3.42%-5.16%). In individuals with Aβ-positive MCI, the greatest change was seen in the temporal cortical regions (5.82%; 95% CI, 4.67%-6.97%), whereas in those with AD dementia, the greatest change was seen in the parietal regions (5.22%; 95% CI, 3.95%-6.49%). Significantly higher estimates of annual percentage change were found using several of the participant-specific ROIs. Importantly, the simplest participant-specific approach, where change in tau PET was calculated in an ROI that best matched the participant's data-driven disease stage, performed best in all 3 subgroups. For the power analysis, sample size reductions for the participant-specific ROIs ranged from 15.94% (95% CI, 8.14%-23.74%) to 72.10% (95% CI, 67.10%-77.20%) compared with the best-performing group-level ROIs. Findings were replicated using [18F]flortaucipir. Finding suggest that certain individualized ROIs carry an advantage over group-level ROIs for assessing longitudinal tau changes and increase the power to detect treatment effects in AD clinical trials using longitudinal tau PET as an outcome.


Large Optical Tunability from Charge Density Waves in 1T-TaS2 under Incoherent Illumination.
Strongly correlated materials possess a complex energy landscape and host many interesting physical phenomena, including charge density waves (CDWs). CDWs have been observed and extensively studied in many materials since their first discovery in 1972. Yet they present ample opportunities for discovery. Here, we report a large tunability in the optical response of a quasi-2D CDW material, 1T-TaS2, upon incoherent light illumination at room temperature. We hypothesize that the observed tunability is a consequence of light-induced rearrangement of CDW stacking across the layers of 1T-TaS2. Our model, based on this hypothesis, agrees reasonably well with experiments suggesting that the interdomain CDW interaction is a vital potentially knob to control the phase of strongly correlated materials.


The effect of indomethacin on plasma levels of prostaglandin F2alpha in women in labour.
Prostaglandin F2alpha was measured by means of radiommunoassay in the serum of women in the active phase of term labour before and after rectal indomethacin administration. Samples of blood were collected every 20 or 30 seconds, between and during contractions. There was a significant decrease of the level of PGF2alpha in plasma 30 to 30 minutes after indomethacin administration, but the pattern of rapid short-term fluctuations in prostaglandin levels was unaltered.


Benthic algal assessment of ecological status in European lakes and rivers: Challenges and opportunities.
This opinion paper introduces a special series of articles dedicated to freshwater benthic algae and their use in assessment and monitoring. This special series was inspired by talks presented at the 9th International Congress on the Use of Algae for Monitoring Rivers and Comparable Habitats (Trento, Italy, 2015), the latest of a series of meetings started in 1991. In this paper, we will first provide a brief overview of phytobenthos methods in Europe. Then, we will turn towards the 'dark side' of phytobenthos and describe four particular problems for phytobenthos assessment in the European Union: (1) over-reliance on a single group of algae (mostly diatoms) to the exclusion of other groups; (2) relatively low adoption of benthic algae for ecological assessments in lakes; (3) absence of measures of phytobenthos abundance; (4) approaches used to define boundaries between ecological classes. Following this, we evaluate the strengths and limitations of current phytobenthos assessment methods against 12 criteria for method evaluation addressing four areas: ecological rationale, performance, feasibility of implementation, and use in communication and management. Using these criteria, we identify and discuss three general challenges for those developing new methods for phytobenthos-based assessment: a weak ecological rationale and insufficient consideration of the role of phytobenthos as a diagnostic tool and for communicating ecosystem health beyond a narrow group of specialists. The papers in the special series allow a comparison with the situation and approaches in the USA, present new methods for the assessment of ecological status and acidification, provide tools for an improved management of headwaters and petrifying springs, discuss the utility of phytobenthos for lake assessments, and test the utility of functional measures (such as biofilm phosphorus uptake capacity, PUC).


Facile synthesis of ZIF-8-lignosulfonate microspheres with ultra-high adsorption capacity for Congo red and tetracycline removal from water.
Zeolitic imidazolate frameworks (ZIFs) can be used as adsorbent to efficiently adsorb organic pollutants. However, the hydrophobicity of the ZIFs may be easily to form ZIFs nanoparticles aggregates, hampering the effective and practical application in adsorption. In this study, novel spherical composites of ZIF-8 incorporated with lignosulfonate (LS) were synthesized by in-situ growth method. The effects of different mass ratios of LS and Zn in ZIF-8-LS composites were evaluated with respect to structural characteristics and adsorption properties. As an adsorbent for adsorptive removing Congo Red (CR) and tetracycline (TC) from water, the prepared ZIF-8-LS4 shows the best adsorption capacity of 31.5 mg g-1 and 48 mg g-1, respectively. The spherical structure facilitates the contact between the ZIF-8 and the adsorbed substance, in addition to the H-bonding, electrostatic and π-π stacking interactions also contribute to the improvement of the adsorption performance of the ZIF-8-LS4 composite. The outstanding adsorption capacity and good reusability of the ZIF-8-LS4 composite provide a good prospect for the effective removal of other contaminants from water.


Hepcidin deficiency in mice impairs white adipose tissue browning possibly due to a defect in de novo adipogenesis.
The role of iron in the two major sites of adaptive thermogenesis, namely the beige inguinal (iWAT) and brown adipose tissues (BAT) has not been fully understood yet. Body iron levels and distribution is controlled by the iron regulatory peptide hepcidin. Here, we explored iron homeostasis and thermogenic activity in brown and beige fat in wild-type and iron loaded Hepcidin KO mice. Hepcidin-deficient mice displayed iron overload in both iWAT and BAT, and preferential accumulation of ferritin in stromal cells compared to mature adipocytes. In contrast to BAT, the iWAT of Hepcidin KO animals featured with defective thermogenesis evidenced by an altered beige signature, including reduced UCP1 levels and decreased mitochondrial respiration. This thermogenic modification appeared cell autonomous and persisted after a 48 h-cold challenge, a potent trigger of thermogenesis, suggesting compromised de novo adipogenesis. Given that WAT browning occurs in both mice and humans, our results provide physiological results to interrogate the thermogenic capacity of patients with iron overload disorders.


Expression of the fragile site Xq27 in fibroblasts. II. Evidence for negative and positive clones from heterozygous females and possible relationship between frequency and phenotype.
An investigation of fibroblast clones from two females heterozygous for the Martin-Bell syndrome showed that the fibroblasts of these individuals consist of two sub-populations, one with cells expressing the fra(X)(q27) and another with cells in which this fragile site cannot be induced. This is to be expected and is in contrast to the fibroblast clones of hemizygous patients investigated earlier. The expression of fra(X)(q27) in females evidently depends on the presence of an X-linked defect with the normal allele inactivated on the other X chromosome. There may be a relationship between the mental status and the ratio of somatic cells with this defect on the active X and those cells with this defect on the inactive X chromosome in the heterozygotes. The divergence between the inactivation of the defective gene and expression of fra(X)(q27) on the late replicating X chromosome is discussed.


Selective purification of cardiac myosin by a high-performance salicylate affinity column.
The cardiac muscle proteins, myosin and actin, were purified in one step using a salicylate-silica affinity column. The affinity columns were prepared by coupling sodium salicylate via its hydroxyl group to an Altex Ultraffinity-EP column. Crude detergent extracts from guinea pig hearts were passed through the column and the myosin-actin complex was then eluted with excess free salicylate or high salt. The affinity of cardiac myosin for immobilized salicylate was unique as myosin heavy chain from guinea pig leg muscle detergent extracts could not be purified by this procedure. Commercially purified rabbit leg muscle myosin also appeared to have no interaction with the salicylate affinity column, suggesting that the column is specific for cardiac myosin.


Four types of adenine-related RNA modification writers -mediated molecular subtypes contribute to predicting clinical outcomes and treatment options in bladder cancer.
RNA modifications, containing m6A, m1A, alternative polyadenylation and adenosine-to-inosine RNA editing, involve in critical cancerous immunity and cancerous processes. However, the functional roles of RNA modification writers in bladder cancer (BLCA) are largely unknown. In this study, unsupervised clustering was used to identify novel RNA modification writers -mediated molecular subtypes in BLCA. A corresponding quantitative indicator called WriterScore was developed using univariate Cox and Least absolute shrinkage and selection operator (LASSO) analysis. Then, we systematically analyzed the correlation between RNA modification writer-related clusters (WriterScore) and immunological characteristics, classical molecular subtypes, clinicopathologic features and treatment options in BLCA. Finally, we validated the WriterScore in multiple other external BLCA datasets, clinical sample dataset in Shengjing Hospital and pancancer. Two RNA modification writer-related clusters and three DEGclusters were obtained. These RNA modification writer-related clusters (WriterScore) were strongly associated with immunological characteristics, classical molecular subtypes, clinicopathologic features of BLCA. Moreover, WriterScore can properly predict the clinical outcomes and immunotherapy of BLCA patients. Our study systematically investigated the role of RNA modification writers and developed a significant WriterScore to guide several treatment options in BLCA, which might bring some potential benefits for BLCA patients.


Self-reported severity measures as predictors of return-to-work outcomes in occupational back pain.
We test an array of biopsychosocial, cognitive-behavioral, and work-related factors to identify the best predictors of work disability following a back injury. We test the validity of alternative severity measures in predicting the likelihood of four distinct, mutually exclusive patterns of post-injury employment in the first year after onset of back pain. The study sample includes 959 participants in the ASU Healthy Back Study, a prospective cohort study of workers who filed claims for occupational back pain between 1999 and 2002. Self-reported severity measures include: NRS-101 measures of the intensity of back or leg pain, Roland-Morris scale of functional disability, and mental and physical components of the SF-12. All the severity measures have significant predictive power on return-to-work outcomes even after 1 year. Baseline physical functioning and overall mental and physical health status are more predictive of specific patterns of post-injury employment than pain intensity measures, possibly because there is considerable idiosyncratic variation in the pain intensity measures. The mental component of the SF-12, in particular, is relatively robust to alternate specifications, consistently statistically significant, and has the lowest probability significance level in explaining patterns of employment 1 year after injury.


CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer.
The CpG island methylator phenotype (CIMP) is observed in approximately 30% of colorectal cancer (CRC) cases and is characterized by the concurrent methylation of multiple CpG islands in tumor DNA. This phenotype (CIMP+) is more frequently observed in tumors with proximal location, microsatellite instability, and normal p53. Because it has previously been observed that each of these features is associated with a good survival benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy, we investigated in the present study whether CIMP+ has independent predictive value. CIMP+ status was evaluated in 103 stage III CRCs from patients treated with surgery alone and for an additional 103 cases from patients treated with surgery and adjuvant 5-FU-based chemotherapy. The two cohorts were randomly pair-matched for age, sex, and tumor site, and the median length of follow-up time was 39 months. CIMP+ status predicted survival benefit from 5-FU treatment independently of microsatellite instability and p53 mutation status (relative risk = 0.22; 95% confidence interval, 0.06-0.84; P = 0.027). Unmeasured, high-risk confounding factors could only account for this association if they were unequally distributed between the two patient cohorts by a factor of at least 2-fold. CIMP+ has independent predictive significance for the survival benefit from 5-FU chemotherapy in CRC. This molecular marker should be incorporated into prospective clinical trials of fluorouracil-based therapies to confirm its clinical value.


Antimicrobial susceptibility among E. faecalis and E. faecium from France, Germany, Italy, Spain and the UK (T.E.S.T. Surveillance Study, 2004-2009).
We report on antimicrobial activity against E. faecalis and E. faecium collected in France, Germany, Italy, Spain, and the UK between 2004 and 2009 as part of the Tigecycline Evaluation and Surveillance Trial (UK in vitro data not included due to low isolate numbers). Overall, 1.1% (n=23/2068) of E. faecalis and 11.5% (n=103/893) of E. faecium were vancomycin-resistant. High levels of minocycline-resistant E. faecalis were reported in Germany, Spain, France, and Italy (40.2-44.2%); levofloxacin resistance was high in Germany, Italy, and Spain (31.1-41.6%). Minocycline non-susceptibility increased significantly among E. faecalis in Spain and Italy (P<0.001). No tigecycline-resistant E. faecalis were reported. Among E. faecium, resistance ranged from 72.9% (France) to 93.3% (Germany) for ampicillin, from 56.1% (France) to 90.2% (Germany) for levofloxacin, and from 75.3% (Italy) to 94.7% (Germany) for penicillin. Levofloxacin non-susceptibility increased significantly among E. faecium in France and Spain (P<0.001). The lowest rates of antimicrobial resistance among E. faecium were reported for tigecycline (2/893; 0.2%) and linezolid (3/893; 0.3%).


Personal values and attitudes toward people living with HIV among health care providers in Kazakhstan.
Our study investigates the relationship between health care providers' personal value preferences and their attitudes toward people living with HIV (PLWH). The study was conducted among nurses (n = 38) and physicians (n = 87) working in HIV Centers in Kazakhstan. Significant relationships were found between the providers' personal value preferences and their attitudes toward PLWH: higher preferences for tradition and power values and lower preferences for benevolence values were associated with more negative attitudes toward PLWH. In addition, more years of experience working with PLWH was associated with more positive attitudes toward this population. Age, gender, family status, religiosity, occupation, and number of years working in health care were not related to the health care providers' attitudes toward PLWH. Theoretical and practical implications of the results obtained are discussed.