Anterior capsule tear after laser iridotomy complicating phacoemulsification.
A 70-year-old Indian lady had a history of bilateral laser peripheral iridotomy (LPI) for primary angle closure. Subsequently she developed cataract in both the eyes. Right eye cataract surgery was complicated by an anterior capsule rupture, which was discovered intra-operatively at the site of the LPI. Trypan blue was used to stain the anterior capsule to delineate the anterior capsule defect. An attempt at continuous curvilinear capsulorhexis was unsuccessful, and the anterior capsulotomy was completed with scissors. To the best of our knowledge the surgical management of cataract in the presence of anterior capsule rupture as a result of LPI has not been reported. Awareness of this potential complication of LPI will aid in planning for successful phacoemulsification cataract surgery.


The influence of polyunsaturated fatty acids on spermine inhibition of lipoperoxidation. Studies on liposomes prepared with microsomal and mitochondrial phospholipids of sea bass (Dicentrarchus labrax L.) and rat liver.
1. Composition of phospholipids extracted from different organelles of European sea bass liver was determined and compared with that of phospholipids extracted from the same organelles of rat liver. 2. Spermine binding to the vesicles prepared from microsomal and mitochondrial phospholipids and their aggregation was studied: these parameters indicate that only the presence of acidic phospholipids and not their unsaturation was essential for polyamine action. 3. No correlation exists between polyunsaturated fatty acid and spermine inhibition of lipid peroxidation. In fact microsomal phospholipids, which have a low content of acidic phospholipids, and a prevalent presence of phosphatidylinositol, are not protected by spermine. 4. Mitochondrial phospholipids, which have high content of cardiolipin, elicit the capability of spermine to inhibit lipid peroxidation.


Implications of biological activated carbon filters for micropollutant removal in wastewater treatment.
Granulated Activated Carbon (GAC) filtration is a common process for advanced wastewater treatment. In such filters, the removal of organic substances results from adsorptive as well as biological processes. This work investigated the potential of biological processes and their influence on GAC-filter performance. During 32 months, the removal of micropollutants,Dissolved Organic Carbon (DOC) and the spectral absorption coefficient was monitored in six GAC-filters. The effects of pre-treatment (cloth- and/or membrane-filtration), EBCT (from 6 - 35 min) and GAC-type were evaluated. Likewise, the impact of the influent´s fluctuations in temperature, flow and concentration (ammonia, nitrate, and soluble reactive phosphorus (sRP)) were analysed. Biological processes were tracked by the frequency of backwashing, oxygen consumption, removal of poorly absorbable micropollutants and production of transformation products. Pre-treatment influenced biofilm growth significantly. Membrane filtration delayed the first backwashing event by 122 d in comparison to cloth-filtration, where the first backwash was conducted after only 21 d. Removal of poorly absorbable substances was observed early on (40 - 50 d). Parallel operation contributed to a better utilisation of the GAC-capacity and the biological removal potential. Influent nitrogen species > 0.5 mg N/L promoted biofilm growth, whereas sRP seemed to have no effect. The developed biofilm and optimal operating conditions led to longer life spans of the GAC-filters, making carbon usage rates comparable to those from PAC applications. The results suggest that biological processes accounted for about 25 - 42% of the totally removed DOC at the end of the operation.


Perception of precocious puberty among school-aged children in South Korea with the experience of treatment for precocious puberty: a Q methodological approach.
This study aimed to investigate the perceptions of precocious puberty and elucidate the distinct characteristics of each type of perception related to precocious puberty among school-aged children who had undergone treatment for the condition. This study applied the Q methodology to identify and classify the perceptions of precocious puberty among school-aged children who had undergone treatment for the condition. The analysis involved 34 questions from the Q sample and data from 35 individuals in the P sample, using the PC-QUANL Program for analysis. The perceptions of precocious puberty among school-aged children who had undergone precocious puberty treatment were classified into the following four types: "shyness - passive self-management," "resentment - suppression," "anxiety - fear," and "adaptation - acceptance." This study investigated the experiences and perceptions of children who have undergone treatment for precocious puberty. Through the identification of four types of perceptions, we can see that there is a need to develop an intervention program for nursing that is tailored to the specific type of precocious puberty.


LncRNA NORAD accelerates the progression and doxorubicin resistance of neuroblastoma through up-regulating HDAC8 via sponging miR-144-3p.
The dysregulation of non-coding RNAs (ncRNAs) often caused aberrant cell behaviors. In the present study, we focused on the role of long noncoding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in the development of neuroblastoma (NB). The enrichment of NORAD, miRNA-144-3p (miR-144-3p) and histone deacetylase 8 (HDAC8) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, chemoresistance, apoptosis, metastasis and autophagy of NB cells were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell migration and invasion assays and Western blot assay, respectively. The target relationship between miR-144-3p and NORAD or HDAC8 was predicted by Starbase software and validated through dual-luciferase reporter assay, RIP and RNA-pull down assays. The protein expression of HDAC8 was measured by Western blot assay. Murine xenograft model was used to verify the function of NORAD in vivo. We found that the level of NORAD was up-regulated in NB tissues and cells, and the level of NORAD was negatively correlated with the prognosis of NB patients. NORAD promoted the proliferation, metastasis and doxorubicin (DOX) resistance while inhibited the apoptosis and autophagy of NB cells. MiR-144-3p was a target of NORAD in NB cells, and NORAD accelerated the progression and DOX resistance of NB through sponging miR-144-3p. HDAC8 was a direct target of miR-144-3p in NB cells, and miR-144-3p suppressed the progression of NB through down-regulating HDAC8. NORAD up-regulated the expression of HDAC8 through sponging miR-144-3p in NB cells. NORAD accelerated the growth of NB tumors at least partly through miR-144-3p/HDAC8 signaling in vivo. In conclusion, NORAD promoted the progression and DOX resistance of NB through miR-144-3p/HDAC8 axis in vivo and in vitro.


Lack of influence of histamine antagonists on digitalis cardiotoxicity.
Experiments were carried out in order to study the interaction between cardioactive glycosides and histamine or histamine H1- AND/OR H2-receptor antagonists in anaesthetized cats or guinea pigs. The toxicity of ouabain or digoxin was tested by infusing the glycosides until idioventricular rhythm or death occurred. Histamine increased the toxicity of ouabain, but the histamine H1- and/or H2-receptor antagonists (metiamide and mepyramine)did not influence the toxicity of digitalis. In cats the increase in pulmonary arterial blood pressure caused by digoxin was not affectedby histamine H1- and/or H2-receptor antagonism in spite of the fact that the increase of pulmonary blood pressure caused by histamine could be abolished by H1-receptor antagonists. Our results indicate that histamine is not involved in the toxic effect of cardiac glycosides.


The Great East Japan Earthquake, tsunami, and Fukushima Daiichi nuclear power plant accident: a triple disaster affecting the mental health of the country.
The Great East Japan Earthquake in 2011 caused 2 other serious disasters: a tsunami and a nuclear power plant accident. A chronic shortage of mental health resources had been previously reported in the Tohoku region, and the triple disaster worsened the situation. Eventually a public health approach was implemented by providing a common room in temporary housing developments to build a sense of community and to approach evacuees so that they could be triaged and referred to mental health teams. Japan now advocates using psychological first aid to educate first responders. This article extracts key lessons from relevant literature.


Solarium Use and Risk for Malignant Melanoma: Many Open Questions, Not the Time to Close the Debate.
To shed further light on the ongoing debate whether sunbed use may increase melanoma risk, we have critically assessed the scientific literature that is at present available, focussing on a meta-analysis that we published recently. Our literature search identified several meta-analyses that report a weak association for ever-exposure to UV radiation from a solarium with melanoma risk. However, the quality of studies included in these meta-analyses and the resulting evidence levels and grades of recommendation were very low due to the lack of interventional trials and because of severe limitations of many of the observational studies. The results of cohort and case-control studies published until today do not prove causality, not even by the Hill criteria. The overall quality of these observational studies and the resulting evidence levels are low due to severe limitations (including unobserved or unrecorded confounding), which leads to bias. It must be recognized that in the majority of studies, published to date, many of the confounding factors, including sun exposure, sunburns and skin type, have not been adequately and systematically recorded and adjusted for. We conclude that the many limitations of the individual studies and the resulting low levels of evidence and grades of recommendation do at present not allow postulation of a causal relationship between solarium use and melanoma risk. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk.


Plasticity- and neurodegeneration-linked cyclic-AMP responsive element modulator/inducible cyclic-AMP early repressor messenger RNA expression in the rat brain.
In order to explore the role of CREM (cyclic-AMP responsive element modulator) gene expression in the function of the central nervous system, the gene transcripts were investigated in the rat brain in several conditions linked to increased neuronal activity. Up-regulation of CREM messenger RNA levels in the hippocampus was found to follow intraperitoneal administration of kainate (10 mg/kg). This increase was observed in both the dentate gyrus and hippocampus proper (CA subfields) and reached its maximum at 6 h after the treatment. Intrahippocampal injection of N-methyl-D-aspartate (200 nmol) resulted in elevated CREM messenger RNA expression as well. A similar increase of the messenger RNA abundance was also observed in the retrosplenial cortex after treating the female rats with a high dose (5 mg/kg) of dizocilpine maleate, an N-methyl-D-aspartate receptor antagonist. All these conditions are linked to neuronal excitation and neurodegeneration. However, an increase in CREM messenger RNA accumulation was also observed in the visual cortex after exposure of dark-adapted animals to the light, a procedure linked to neuronal plasticity. In the latter condition, it was found that CREM messenger RNA reached its highest levels at 6 h, i.e. later than the maximal increase of expression of immediate early genes such as c-fos, jun B and zif268, observed 45 min following the onset of visual stimulation. The ICER (inducible cyclic-AMP early repressor) form of CREM messenger RNA was identified to be induced by the light exposure. Finally, it was also found that cycloheximide, an inhibitor of protein synthesis, overinduces CREM/ICER gene expression. Together, these data suggest that CREM/ICER may be responsive to neuronal activation. Furthermore, given that CREM products have been shown previously to down-regulate expression of immediate early genes in vitro, they suggest that ICER may function as a molecular switch involved in down-regulation of immediate early gene expression in the rat brain.


Longitudinal monitoring of individual infection progression in Drosophila melanogaster.
The innate immune system is critical for infection survival. Drosophila melanogaster is a key model for understanding the evolution and dynamics of innate immunity. Current toolsets for fly infection studies are limited in throughput and, because of their destructive nature, cannot generate longitudinal measurements in individual animals. We report a bioluminescent imaging strategy enabling non-invasive characterization of pathogen load. By using Escherichia coli expressing the ilux operon, we demonstrate that photon flux from autobioluminescent bacteria can be used to monitor pathogen loads in individual, living flies. Because animal sacrifice is not necessary to estimate pathogen load, stochastic responses to infection can be characterized in individuals over time. The high temporal resolution of bioluminescence imaging enables visualization of the dynamics of microbial clearance on the hours time-scale. This non-invasive imaging strategy provides a simple and scalable platform to observe changes in pathogen load in vivo over time.


Immunotherapies Targeting α-Synuclein in Parkinson Disease.
Parkinson disease (PD) is a progressive neurodegenerative disorder. Pathologic diagnosis of PD relies on loss of dopamine neurons in the substantia nigra and accumulation of the abnormal protein α-synuclein in the form of Lewy bodies and Lewy neurites. Alteration in aggregation properties of this protein is believed to play a central role in the pathogenesis of PD. Huge interest has developed in antibody-based therapies for PD. Several studies have tested immunotherapies in PD animal models with the aim of targeting α-synuclein. Immunotherapies can be instituted in 2 ways: active immunization in which the immune system is stimulated to produce antibodies against α-synuclein or passive immunization in which antibodies against α-synuclein are directly administered. Immunotherapy against α-synuclein has provided a new therapeutic avenue in neuroprotection. Results from the first human clinical trial are promising, but despite these results, more work is needed to clarify the role of α-synuclein in the pathogenesis of PD in humans.


Histopathological and genetic features of mismatch repair-deficient high-grade prostate cancer.
Mismatch repair (MMR) deficiency is commonly caused by functional inactivation of MLH1, PMS2, MSH2 or MSH6. The morphological and molecular correlates of MMR deficiency have been extensively characterized in certain tumour types such as colorectal and endometrial adenocarcinoma. In contrast, the histological and molecular features of MMR-deficient prostate cancer remain incompletely described. In this study, we evaluated 19 MMR-deficient prostate cancers, including 11 cases without prior systemic treatment. All treatment-naive cases (11 of 11, 100%) were grade group 4-5 and had predominant cribriform and/or solid growth patterns. Solid components (any amount) and tumour infiltrating lymphocytes were 7 cases each (7 of 11, 64%). In 68 MMR-proficient grade group 5 prostate cancers, predominant cribriform or solid growth patterns, solid components (any amount) and tumour infiltrating lymphocytes were seen at significantly lower frequencies (31 of 68, 46%; 9 of 68, 13% and 6 of 62, 9%, respectively; P < 0.001 for all comparisons). Molecular evaluation of 19 cases demonstrated that MMR-deficiency was secondary to functional loss of MSH2/MSH6 and MLH1/PMS2 in 15 (79%) and 4 cases (21%), respectively. Definite or probable germline mutations were present in 4 cases (4 of 19, 21%). TMPRSS2::ERG rearrangements were identified in 2 cases (2 of 19, 11%). Recurrent cancer-relevant somatic mutations included (but were not limited to) ATM, TP53, FOXA1, RB1, BRCA2 and PTEN. MMR deficiency was most commonly secondary to inactivation of MSH2/MSH6 in this study. Importantly, MMR-deficient high-grade prostatic adenocarcinomas had morphological features that might be useful to identify selected cases for MMR immunohistochemistry.


Development and characterization of nanostructured mists with potential for actively targeting poorly water-soluble compounds into the lungs.
To formulate nanoemulsions (NE) with potential for delivering poorly water-soluble drugs to the lungs. A self nanoemulsifying composition consisting of cremophor RH 40, PEG 400 and labrafil M 2125 CS was selected after screening potential excipients. The solubility of carbamazepine, a poorly water-soluble drug, was tested in the formulation components. Oil-in-water (o/w) NEs were characterized using dynamic light scattering, electrophoretic light scattering, transmission electron microscopy (TEM) and differential scanning calorimetry. NEs were nebulized into a mist using a commercial nebulizer and characterized using laser diffraction and TEM. An aseptic method was developed for preparing sterile NEs. Biocompatibility of the formulation was evaluated on NIH3T3 cells using MTT assay. In vitro permeability of the formulation was tested in zebra fish eggs, HeLa cells, and porcine lung tissue. NEs had neutrally charged droplets of less than 20 nm size. Nebulized NEs demonstrated an o/w nanostructure. The mist droplets were of size less than 5 μm. Sterility testing and cytotoxicity results validated that the NE was biocompatible and sterile. In vitro tests indicated oil nanodroplets penetrating intracellularly through biological membranes. The nanoemulsion mist has the potential for use as a pulmonary delivery system for poorly water-soluble drugs.


Methyl 2-{2-[(2-methyl-phen-oxy)meth-yl]phen-yl}-2-oxoacetate.
In the title compound, C17H16O4, the dihedral angle between the benzene rings is 4.4 (2)°. In the crystal, weak C-H⋯O hydrogen bonds connect mol-ecules along [001].


A novel null HLA allele, HLA-DRB1*15:115N, identified in a Chinese family.
The novel allele HLA-DRB1*15:115N differs from HLA-B*15:80N by a nucleotide substitution at position 227 T > A.


Metagenomic next-generation sequencing for Mycobacterium tuberculosis complex detection: a meta-analysis.
Metagenomic next-generation sequencing (mNGS) has been gradually applied to the diagnosis of tuberculosis (TB) due to its rapid and highly sensitive characteristics. Despite numerous studies on this subject, their results vary significantly. Thus, the current meta-analysis was performed to assess the performance of the mNGS on tuberculosis. PubMed, Embase, Web of Science, and The Cochrane Library were searched up to June 21, 2023. Studies utilizing the mNGS for tuberculosis detection were included. The risk of bias was assessed by QUADAS-2, and a meta-analysis was performed with STATA14.0 software. Seventeen studies comprising 3,205 specimens were included. The combined sensitivity and specificity of mNGS for clinical specimens were 0.69[0.58-0.79] and 1.00[0.99-1.00], respectively. Subgroup analysis identified sequencing platform, diagnostic criteria, study type, sample size, and sample types as potential sources of heterogeneity. Cerebrospinal Fluid (CSF) has a lower sensitivity of 0.58 (0.39-0.75). In a population with a 10% prevalence rate, the accuracy of sensitivity reached 94%. Metagenomic next-generation sequencing technology exhibits high sensitivity and speed in diagnosing Mycobacterium tuberculosis. Its application in mono and mixed infections peoples shows promise, and mNGS is likely to be increasingly used to address challenges posed by Mycobacterium tuberculosis complexes in the future.


In vitro evaluation and crystallographic analysis of a new class of selective, non-amide-based thrombin inhibitors.
We describe the in vitro evaluation and crystallographic analysis of a new class of potent and selective, non-amino acid-based, small-molecule thrombin inhibitors, exemplified by 14. This class of achiral inhibitors lacks an amide-based backbone, exhibits nM inhibition of thrombin, and is selective for thrombin. Compound 14 does not interact with the active-site catalytic apparatus and is anchored to the enzyme via a single network of hydrogen bonds to Asp189 of the S1 pocket.


Gait analysis in children with haemophilia: first Italian experience at the Turin Haemophilia Centre.
To investigate the functional status in haemophilia patients referred to an Italian paediatric haemophilia centre using gait analysis, verifying any differences between mild, moderate or severe haemophilia at a functional level. Forty-two patients (age 4-18) presenting to the Turin Paediatric Haemophilia Centre who could walk independently were included. Therapy included prophylaxis (n = 21), on-demand (n = 17) or immune tolerance induction + inhibitor (n = 4). Patients performed a test of gait analysis. Temporal, spatial and kinematic parameters were calculated for patient subgroups by disease severity and background treatment, and compared with normal values. Moderate (35.7%) or severe (64.3%) haemophilia patients showed obvious variations from normal across a variety of temporal and spatial gait analysis parameters, including step speed and length, double support, swing phase, load asymmetry, stance phase, swing phase and speed. Kinematic parameters were characterized by frequent foot external rotation with deficient plantar flexion during the stance phase, retropelvic tilt, impaired power generation distally and reduced ground reaction forces. Both Gait Deviation Index and Gait Profile Score values for severe haemophilia patients indicated abnormal gait parameters, which were worst in patients with a history of past or current use of inhibitors and those receiving on-demand therapy. Functional evaluation identified changes in gait pattern in patients with severe and moderate haemophilia, compared with normal values. Gait analysis may be a useful tool to facilitate early diagnosis of joint damage, prevent haemophilic arthropathy, design a personalized rehabilitative treatment and monitor functional status over time.


A rapid bioassay for chemicals that induce pro-oxidant states.
A new bioassay has been developed that allows rapid, sensitive detection of chemicals such as paraquat and adriamycin, which manifest their acute toxicity, mutagenicity or carcinogenicity by inducing a pro-oxidant state in vivo. Submitochondrial particles isolated from bovine myocardium are used to catalyze NADH-dependent enzymatic reduction of these chemicals to free radicals. The highly reactive species generated in this system reduce molecular dioxygen to the superoxide anion radical, which is detected spectrophotometrically using the adrenochrome reaction. The anticancer drug adriamycin, the herbicides paraquat and diquat, the analytical dye sulfonazo III, and the experimental carcinogen 4-nitroquinoline-N-oxide have been used to test the sensitivity of this new method. This assay can be used to screen fresh water samples for the presence of pollutants that can generate oxygen-centered free radicals in vivo, or to test newly synthesized chemicals for this activity, and may therefore be valuable for environmental monitoring and preliminary toxicity evaluation of industrial or pharmaceutical products.


Template-induced macrocycle diversity through large ring-forming alkylations of tryptophan.
Macrocyclic peptidomimetics are valuable in research and serve as lead compounds in drug discovery efforts. New methods to prepare such structures are of considerable interest. In this pilot study, we show that an organic template harboring a latent cinnamyl cation participates in novel Friedel-Crafts macrocyclization reactions with tryptophan. Upon joining the template to Trp-Trp-Tyr, a single operation efficiently generates eight unique macrocycles. Each has been isolated and thoroughly characterized. Product distribution as a function of Brønsted and/or Lewis acidic conditions was explored, and outcomes were compared to rearrangements induced within a corresponding tyrosine-linked cyclic ether. The solution structure of a new macrocyclic pyrroloindoline was solved using a combination of two-dimensional NMR methods and molecular mechanics simulations. Template-induced structural diversification of peptide sequences harboring aromatic residues has potential to create myriad macrocycles that target surfaces involved in protein-protein interactions.


Subclinical hypothyroidism and cardiovascular risk: a reason to treat?
Subclinical hypothyroidism (SH), defined by elevated serum levels of thyroid stimulating hormone (TSH) with normal levels of free thyroid hormones, is common in adults, especially in women over 60 years of age. Among individuals with this condition, up to two-thirds have serum TSH levels between 5-10 mU/L and thyroid autoantibodies; almost half of them may progress to overt thyroid failure, the annual percent risk increasing with serum TSH level. There is evidence that elevated TSH levels in patients with SH do not reflect pituitary compensation to maintain euthyroidism, but a mild tissue hypothyroidism sensu strictu. When lasting more than 6-12 months, SH may be associated with an atherogenic lipid profile, a hypercoagulable state, a subtle cardiac defect with mainly diastolic dysfunction, impaired vascular function, and reduced submaximal exercise capacity. The deviation from normality usually increases with serum TSH level ('dosage effect' phenomenon). Restoration of euthyroidism by levothyroxine (LT4) treatment may correct the lipid profile and cardiac abnormalities, especially in patients with an initially higher deviation from normality and higher serum TSH levels. Importantly, a strong association between SH and atherosclerotic cardiovascular disease, independent of the traditional risk factors, has been recently reported in a large cross-sectional survey (the Rotterdam Study). However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy. Therefore, until randomized, controlled, prospective, and adequately powered trials provide unequivocal answers to these critical questions, it is advisable to prescribe LT4 therapy on a case-by-case basis, taking into account the risk of progressive thyroid failure and the risk of cardiovascular events.


Distributed processing techniques: interface design for interactive information sharing.
The Information Systems Division of the University of Iowa Hospitals and Clinics has successfully designed and implemented a set of generalized interface data-handling routines that control message traffic between a satellite minicomputer in a clinical laboratory and a large main-frame computer. A special queue status inquiry transaction has also been developed that displays the current message-processing backlog and other system performance information. The design and operation of these programs are discussed in detail, with special emphasis on the message-queuing and verification techniques required in a distributed processing environment.


Multiple transcription factors co-regulate the Mycobacterium tuberculosis adaptation response to vitamin C.
Latent tuberculosis infection is attributed in part to the existence of Mycobacterium tuberculosis in a persistent non-replicating dormant state that is associated with tolerance to host defence mechanisms and antibiotics. We have recently reported that vitamin C treatment of M. tuberculosis triggers the rapid development of bacterial dormancy. Temporal genome-wide transcriptome analysis has revealed that vitamin C-induced dormancy is associated with a large-scale modulation of gene expression in M. tuberculosis. An updated transcriptional regulatory network of M.tuberculosis (Mtb-TRN) consisting of 178 regulators and 3432 target genes was constructed. The temporal transcriptome data generated in response to vitamin C was overlaid on the Mtb-TRN (vitamin C Mtb-TRN) to derive insights into the transcriptional regulatory features in vitamin C-adapted bacteria. Statistical analysis using Fisher's exact test predicted that 56 regulators play a central role in modulating genes which are involved in growth, respiration, metabolism and repair functions. Rv0348, DevR, MprA and RegX3 participate in a core temporal regulatory response during 0.25 h to 8 h of vitamin C treatment. Temporal network analysis further revealed Rv0348 to be the most prominent hub regulator with maximum interactions in the vitamin C Mtb-TRN. Experimental analysis revealed that Rv0348 and DevR proteins interact with each other, and this interaction results in an enhanced binding of DevR to its target promoter. These findings, together with the enhanced expression of devR and Rv0348 transcriptional regulators, indicate a second-level regulation of target genes through transcription factor- transcription factor interactions. Temporal regulatory analysis of the vitamin C Mtb-TRN revealed that there is involvement of multiple regulators during bacterial adaptation to dormancy. Our findings suggest that Rv0348 is a prominent hub regulator in the vitamin C model and large-scale modulation of gene expression is achieved through interactions of Rv0348 with other transcriptional regulators.


Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha.
Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2-4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2-4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2-4) by fusing the variable region of mouse mAb 2-4 to the constant region of feline antibody. The chimeric mAb 2-4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2-4 and chimeric mAb 2-4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2-4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2-4 was reduced. In contrast, in cats treated with chimeric mAb 2-4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2-4-treated cats.


Parenting Strategies Used by Parents of Children with ASD: Differential Links with Child Problem Behaviour.
Here, we explored the structure of the 'Parenting Strategies Questionnaire', a new scale designed to measure parenting strategies for problem behaviour in ASD. We then examined links between child behaviour and parenting in a sample of 222 predominantly-UK parents of ASD children exhibiting behaviour found difficult or challenging. Analysis revealed three parenting subscales: Accommodation, Reinforcement Approaches and Reducing Uncertainty. Both Accommodation and Reducing Uncertainty were linked to child problem behaviour. Child factors explained up to 29% of the variance in Accommodation, with Socially Inflexible Non-compliance the strongest predictor, and up to 24% of the variance in Reducing Uncertainty, with Intolerance of Uncertainty the strongest predictor. Child factors were not related to Reinforcement Approaches. Longitudinal studies investigating these relationships are needed.


Incretins and cardiovascular disease: to the heart of type 2 diabetes?
Major cardiovascular outcome trials and real-life observations have proven that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), regardless of structural GLP-1 homology, exert clinically relevant cardiovascular protection. GLP-1RAs provide cardioprotective benefits through glycaemic and non-glycaemic effects, including improved insulin secretion and action, body-weight loss, blood-pressure lowering and improved lipid profile, as well as via direct effects on the heart and vasculature. These actions are likely combined with anti-inflammatory and antioxidant properties that translate into robust and consistent reductions in atherothrombotic events, particularly in people with type 2 diabetes and established atherosclerotic CVD. GLP-1RAs may also have an impact on obesity and chronic kidney disease, conditions for which cardiovascular risk-reducing options are limited. The available evidence has prompted professional and medical societies to recommend GLP-1RAs for mitigation of the cardiovascular risk in people with type 2 diabetes. This review summarises the clinical evidence for cardiovascular protection with use of GLP-1RAs and the main mechanisms underlying this effect. Moreover, it looks into how the availability of upcoming dual and triple incretin receptor agonists might expand the possibility for cardiovascular protection in people with type 2 diabetes.


Sensitivity of neural stem cell survival, differentiation and neurite outgrowth within 3D hydrogels to environmental heavy metals.
We investigated the sensitivity of embryonic murine neural stem cells exposed to 10 pM-10 μM concentrations of three heavy metals (Cd, Hg, Pb), continuously for 14 days within 3D collagen hydrogels. Critical endpoints for neurogenesis such as survival, differentiation and neurite outgrowth were assessed. Results suggest significant compromise in cell viability within the first four days at concentrations ≥10 nM, while lower concentrations induced a more delayed effect. Mercury and lead suppressed neural differentiation at as low as 10 pM concentration within 7 days, while all three metals inhibited neural and glial differentiation by day 14. Neurite outgrowth remained unaffected at lower cadmium or mercury concentrations (≤100 pM), but was completely repressed beyond day 1 at higher concentrations. Higher metal concentrations (≥100 pM) suppressed NSC differentiation to motor or dopaminergic neurons. Cytokines and chemokines released by NSCs, and the sub-cellular mechanisms by which metals induce damage to NSCs have been quantified and correlated to phenotypic data. The observed degree of toxicity in NSC cultures is in the order: lead>mercury>cadmium. Results point to the use of biomimetic 3D culture models to screen the toxic effects of heavy metals during developmental stages, and investigate their underlying mechanistic pathways.


θ power responses in mild Alzheimer's disease during an auditory oddball paradigm: lack of theta enhancement during stimulus processing.
There is evidence that theta responses reflect cognitive performance: good performances are associated with a decrease in tonic theta power as well as an increase in phasic theta power. In the present study, both tonic and phasic theta activity were analysed in 22 patients with mild Alzheimer's disease (AD), and 16 healthy elderly controls. Single-trial theta power responses were evaluated by an active auditory oddball paradigm along an early poststimulus window (0-250 ms) and a late time window (250-500 ms), and then compared to prestimulus theta power during both target tone and standard tone processing. The main findings were: (1) in AD patients, there was an increased prestimulus theta power, as well as no significant poststimulus theta power increase upon both target and non-target stimulus processing; (2) in healthy aged controls, only during target tone processing, an enhancement of both early and late theta responses relative to the prestimulus baseline was found. Moreover, healthy controls had a frontal dominance of theta power. The results might indicate that, during target processing, theta response is not functionally sensitive in AD and cannot be involved in processing demands as efficiently as in healthy controls. From a psychophysiological point of view, this might suggest an impairment of attentional allocation resources. The psychological implications might be related to selective attention/working-memory impairment from the early stage of the disease. Our data confirm that both tonic and phasic theta are relevant indicators of cognitive performance: the lack of a phasic theta and an increase in tonic theta are congruous findings in cognitive decline. Another factor worth noting is that in AD patients theta response is not dominant at the frontal site (as observed in healthy controls), indicating a weaker frontal lobe network reactivity during stimulus processing.


Dayton William Dix's Birth Story.
In this birth story, a young mother relates her experience of moving beyond fear of labor and birth and developing confidence in her ability to give birth without an epidural. Knowledge and support, including the support of a doula, during the last months of pregnancy helped this mother change her plans for the labor and birth. This story highlights the importance of continuous emotional and physical support and how knowledge and confidence set the stage for a satisfying, safe, and healthy birth.


Testis-enriched Asb15 is not required for spermatogenesis and male fertility in mice.
The function of Asb15, which encodes an ASB protein with ankyrin (ANK) repeats and a C-terminal suppressor of cytokine signaling (SOCS) box motif, in male germ cells is poorly understood. Because expression of Asb15 is enriched in mouse testis, it may have a role in spermatogenesis. We used a computer-assisted sperm analysis (CASA) system to analyze sperm from Asb15 gene knockout (KO) mice that we generated using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) technique. Histological staining and immunostaining were used to evaluate spermatogenesis in Asb15-KO mice. Asb15-KO and wild-type mice showed no differences in histology or in semen quality, fertility, or sperm apoptosis. Asb15- and Asb17-double KO (dKO) mice were generated to determine whether Asb17 compensated for the loss of Asb15. However, Asb15/17-dKO mice also showed normal fertility, except for an increase in giant cells in testicular tubules, suggesting a minor functional compensation between the two genes during spermatogenesis. Our study suggests that Asb15 was individually not required for spermatogenesis or for fertility in mice. However, further investigation might be needed to reach a firm conclusion. These findings can prevent redundant research by other scientists and provides new information for further studies on the genetics of fertility in humans.


Metabolic Effects of Fasting and Animal Source Food Avoidance in an Ethiopian Adult Cohort.
Fasting is a religious practice to which the faithful comply strictly. The longest period of fasting in Orthodox religion is the lent (in Ethiopia known as "Hudade"). According to the doctrine of Ethiopian Orthodox Christianity, fasters should strictly avoid all animal source foods (ASF) and skip breakfast at least up to lunch time. This can be taken as a well-controlled natural experiment to evaluate the effect of breakfast skipping and avoidance of ASF for 55 days. However, there is no study that evaluated the effect of ASF fasting (avoidance of animal source foods and breakfast skipping) on lipid profiles, fasting blood sugar and body composition in Ethiopian set up. A retrospective cohort study was carried out among 704 employees of Jimma University (253 fasters and 451 non-fasters) from February 2015 to April 2015. Data on socio-demographic, anthropometry, blood pressure and blood samples were collected according to WHO STEPS procedure. Descriptive statistics and multivariable linear regression models were used to compare the effect of fasting on outcome variables. There was a significant difference in the body fat percent (mean ± sd) between non-fasters (32.35 ± 11.12) and fasters (30.59 ± 11.22, P = 0.045). Similarly, the mean ± sd waist circumference was higher among non-fasters (84.96 ± 11.43 cm) compared to fasters (83.04 ± 11.43 cm, P < 0.033). High density lipoprotein was significantly (P = 0.001) high among fasters (68.29 mg/dl) compared to non-fasters (57.24 mg/dl). Total cholesterol (T.chol) was also higher among non- fasters (181.01 mg/dl) than fasters (173.80 mg/dl, P = 0.035). The mean Triglyceride level was significantly (P = 0.035) high among non-fasters (142.76 mg/dl) compared to fasters (129.39 mg/dl). Similarly, fasting blood sugar was high among non-fasters (100.14 mg/dl) compared to fasters (95.11 mg/dl), P = 0.009. On multivariable linear regression analyses after adjusting for different variables, fasters had a significantly high mean HDL and lower mean T.chol, Triglycerides, FBS and LDL levels. Similarly, fasters had a significantly low mean waist circumference and low mean body fat percent (P < 0.05). In conclusion, animal source food avoidanceand breakfast skipping has a significant desirable health effects on lipid profiles, fasting blood sugar and body composition. The findings imply the need for considering such a dietary practice as a basis for public health promotion. Future research should investigate the effect of ASF fasting and breakfast skipping on micronutrient intake and determine the minimum number of days of fasting required to generate clinically significant effects.


Space motion sickness medications: interference with biomedical parameters.
The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.


Reversed-phase systems for the analysis of catecholamines and related compounds by high-performance liquid chromatography.
Phase systems using alkyl-modified silica as an absorbent, used as much and as a support for dynamically coated ion exchangers, were investigated for their capability in separating catecholamines and related compounds. Simple reversed-phase adsorption chromatography with C8-bonded silica is not able to separate these compounds very well because of (i) the very small retention of the more basic compounds in circumstances where the acidic compounds are well separated, (ii) bad peak shapes and (iii) low column efficiences, although the last drawback can be circumvented by the addition of inorganic anions to the eluent. The addition of a dynamically coated cation exchanger, sodium dodecylsulphate (SDS), to the eluent not only brings about drastic changes in the selectivity, but also makes available an additional degree of freedom for influencing the selectivity. The retention of the basic solutes increases upon addition of SDS and the retention becomes inversely proportional to the counter ion (Na+) concentration. Further, it was found that columns previously loaded with SDS can be used with SDS-free eluents when a pre-column, loaded with SDS, is used or with eluents containing a very small amount of SDS (less than 0.001%, w/v). These SDS-coated phase systems behave similarly to phase systems containing SDS in the eluent and show a better column stability and UV background.


Effects of mebendazole, albendazole, and praziquantel on glutathione S-transferase and superoxide dismutase of Echinococcus granulosus cyst wall harbored in mice.
To explore the existence of glutathione S-transferase (GST) and superoxide dismutase (SOD) in Echinococcus granulosus cyst, and the effect of anthydatid drugs on these 2 enzymes, mice infected with E granulosus protoscoleces for 10-12 months were used. The activity of GST was measured by conjugation rate of 1-chloro-2,4-dinitrobenzene with glutathione (reduced form), while the activity of SOD was measured by a modified autoxidation of 1, 2, 3-trihydroxy-benzene method. Activities of both GST and SOD in the cyst wall were 12.3 +/- 4.3 to 13.5 +/- 4.8 mumol min-1/mg protein and 4.4 +/- 2.9 to 6.1 +/- 1.4 U min-1/mg protein, respectively. When infected mice were treated ig with mebendazole (Meb) 25 mg kg-1 d-1 for 14 d, the GST activity of both collapsed and full cyst walls were inhibited by 30.1% and 26.8%, respectively. Whereas SOD activity of the cyst walls were activated by 105%-163%. Albendazole 300 mg kg-1 d-1 for 14 d and praziquantel 500 mg kg-1 d-1 for 14 d had no apparent effect on both GST and SOD of E granulosus cyst wall. The results suggested that the inhibition of GST activity in the cyst wall induced by Meb might damage the defence system of the parasite.


Molecular dynamics simulation of temperature profile in partially hydrogenated graphene and graphene with grain boundary.
Temperature profile in graphene, graphene with grain boundary and vacancy defects and hydrogenated graphene with different percentage of H-atoms are determined using molecular dynamics simulation. We also obtained the temperature profile in a graphene nanoribbon containing two types of grain boundaries with different misorientation angles, θ=21.8° and θ=32.2°. We found that a temperature gap appears in the temperature profile of a graphene nanoribbon with a grain boundary at the middle. Moreover, we found that the temperature profile in the partially hydrogenated graphene varies with the percentage of hydrogens, i.e. the C:H ratio. Our results show that a grain boundary line in the graphene sheet can change the thermal transport through the system which might be useful for controlling thermal flow in nanostructured graphene.


Production of antitumoral retamycin during fed-batch fermentations of Streptomyces olindensis.
Fed-batch runs were performed in order to correlate the production of retamycin, an anthracycline antibiotic produced by Streptomyces olindensis in submerged cultures, with the specific growth rate. Maximum retamycin production was achieved with an exponential feed rate, controlling the specific growth rate at a low value (0.03 h-1, about 10% of the maximum specific growth rate). Control of the specific growth rate at higher values (0.10 and 0.17 h-1) caused a decrease in antibiotic production. Morphology, assessed by image analysis, was shown to be highly relevant in this process. Cell growth mainly in the form of clumps (90% clumps and 10% free filaments) led to better results than growth as clumps (75%) and free filaments (25%).


High or low dose radioiodine ablation of thyroid remnants?
The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose 131I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiated pT2-3NoMo thyroid cancer were studied. The uptake was 5%-10% at 24 h. Ten patients received 100 mCi, the others 30 mCi 131I. Three months later all patients received a therapeutic dose of 150 mCi 131I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%-10%. Ten patients received 300 mCi and ten 30 mCi 131I as ablation dose. Three months later all received 300 mCi 131I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24 h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, N X M1 patients the ablation was effective in seven out of ten cases in both groups. If "effective" ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in N X M1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Alteration of contraction-to-rest ratio to optimize trabecular bone adaptation induced by dynamic muscle stimulation.
Disuse osteopenia has shown to decrease bone mineral density and compromise bone's integrity, i.e., in aging population and long-term functional disuse. The degree of attenuation of trabecular bone loss and deterioration of its microarchitecture is closely dependent on the mechanical loading parameters within the regimen. Dynamic muscle stimulation as a preventive countermeasure for disuse osteopenia has been shown to be effective. The objective of this study is to determine whether the contraction-to-rest ratio is a crucial parameter to affect the skeletal adaptive responses under a functional disuse environment. Fifty-six skeletally matured Sprague-Dawley rats were divided into seven groups for the 4-week experiment: baseline control, age-matched control, hindlimb suspended (HLS), and HLS plus muscle stimulation with a contraction-to-rest ratio of 1/4, 2/8, 4/6, and 2/28 s. Muscle stimulation was carried out for total of 10 min/day, 5 days/week, for 4 weeks. Trabecular bone in the distal femurs was analyzed with microcomputed tomography and histomorphometry. HLS alone for 4-week resulted in a 25-45% trabecular bone loss in the distal femur. Dynamic muscle stimulation, applied at 50 Hz frequency, with a 2/8 s contraction-to-rest ratio demonstrated significant attenuation of trabecular bone loss against the 4-week disuse, with up to +74% in bone volume fraction, +164% in connectivity, +20% in trabecular number, and -18% in spacing (p<0.05). Stimulation with 1/4 and 4/6 also showed similar effects but with lesser percentage differences when comparing to the HLS animals. Similarly, histomorphometric analysis showed partial enhancement in mineralizing surface and mineral apposition rate. The results suggested the potentials of dynamic muscle stimulation in regulating skeletal adaptive responses and illustrated the effects of optimized contraction-to-rest in mitigation of bone loss, in which 2/8 s has shown maximal adaptive response among all tested ratios.


Preparation of beta-cyclodextrin based nanocomposite for magnetic solid-phase extraction of organic ultraviolet filters.
A simple and efficient analytical method for organic UV filters (UV-Fs) in environmental samples has been established in this study. Taking advantage of the hydrophobicity on the inner cavity, hydrophilicity on the outer wall, and host-guest interaction provided by beta-cyclodextrin, a core-shell magnetic extraction material was firstly synthesized by using a facile method. The extractant was utilized in magnetic solid-phase extraction of UV-Fs in complex environmental samples, including beach sand, sediment and river water samples, followed by the quantitation using high-performance liquid chromatography. A series of factors affecting extraction efficiencies of seven UV-Fs were profoundly optimized. Under the optimal conditions, the linear ranges were at 5.0-5.0 × 102 ng mL-1 for the UV-Fs with regression coefficients (r) at 0.9984-0.9998. The limits of detection were from 0.12 to 1.4 ng mL-1. The recoveries were in the range of 84.2-109%. Furthermore, the molecular dynamics simulations and independent gradient model analysis were applied to reveal the adsorption configuration and interaction mechanisms between target analytes and the sorbent.


[Lung dose depending on exact patient positioning during total body irradiation (TBI). Isoeffectiveness considerations to assess the risk of interstitial pneumonia after TBI].
In this case report, we studied the effect of patient's movements on total lung dose during total body irradiation (TBI). The dose-effect relationship regarding the development of interstitial pneumonitis and the problem of defining a threshold value are discussed. Based on considerations about the isoeffects we calculated the pneumonitis risk in dependence of increasing lung dose. We calculated dose-volume histograms of the lung for defined lateral deviations (0-3 cm) from the isocenter. Total dose was 12 Gy, given in six fractions over 3 days. Lung shields were used after a total dose of 9 Gy. Lung shields were transferred into the Helax-TMS planning system to quantify the influence of lateral deviation to lung dose. The child's lateral deviation amounted up to 3 cm. Median dose of the whole lung amounted up to 11.64 Gy depending on lateral deviation. In TBI, the lung limits the total dose. To estimate the risk of radiation pneumonitis, we calculated the isoeffective lung dose of our TBI regime for a fractionation scheme of 2 Gy daily using a formalism of van Dyk. The increase of median lung dose from 9.76 to 11.64 Gy would isoeffectively correspond to the increase from 19 Gy (no deviation) to 20.9 Gy (3 cm lateral deviation) with conventional fractionation. According to Burman, a pneumonitis risk of approximately 20% could be expected. With an estimated pneumonitis risk of approximately 20%, in indication for irradiation in general anesthesia seems to be reasonable. This is practicable in cooperation with radiation oncologists, anesthesists and pediatricians and should be included into therapeutic concepts.


Spinal trauma: therapy--options and outcomes.
The management of patients with spinal trauma is based on the following goals: (1) the preservation of life; (2) preserving and maximising the neurological function; and (3) providing a stable, painless vertebral column. There have been advances in both non operative as well operative modalities of treatment of patients with spinal injuries. These advances have led to renewed interest in the management of a spinally injured patient. However, despite these advances controversies exist regarding the classification of these fractures, the use of pharmacological intervention, the timing of surgical intervention and indeed the use of surgical intervention itself in the management of these fractures. Most of these controversies surround the treatment of thoracic and lumbar fractures. The purpose of this article is to provide an over view of the therapy options available in the treatment of these fractures. The article shall also look at some of the controversies surrounding the management of these fractures.


Tat-P combined with GAPR1 releases Beclin1 to promote autophagy and improve Bronchopulmonary dysplasia model.
Long-term exposure to hyperoxia can leading to the bronchopulmonary dysplasia (BPD). The progression of BPD is primarily driven by the apoptosis of alveolar epithelial cells, and the regulation of autophagy has an impact on apoptosis. This study aims to investigate the therapeutic potential and underlying mechanism of an autophagy-promoting peptide (Tat-P) in ameliorating BPD. In vitro experiments demonstrated that Tat-P promoted autophagy and partially prevented apoptosis caused by exposure to hyperoxia. Further investigation into the mechanism revealed that Tat-P competitively binds to GAPR1, displacing the Beclin1 protein and thereby inhibiting the apoptosis. In vivo experiments conducted on Sprague-Dawley pups exposed to high oxygen levels demonstrated that Tat-P promoted autophagy and reduced apoptosis in lung tissues and ameliorated BPD-related phenotypes. Our findings elucidate the underlying mechanisms and effects of Tat-P in enhancing autophagy and preventing apoptosis. This study presents an approach for the prevention and treatment of BPD.


Dual-Site W-O-CoP Catalysts for Active and Selective Nitrate Conversion to Ammonia in a Broad Concentration Window.
Environmentally friendly electrochemical reduction of contaminated nitrate to ammonia (NO3 - RR) is a promising solution for large quantity ammonia (NH3 ) production, which, however, is a complex multi-reaction process involving coordination between different reaction intermediates of nitrate reduction and water decomposition-provided active hydrogen (Hads ) species. Here, a dual-site catalyst of [W-O] group-doped CoP nanosheets (0.6W-O-CoP@NF) has been designed to synergistically catalyze the NO3 - RR and water decomposition, especially the reactions between the intermediates of NO3 - RR and water decomposition-provided Hads species. This catalytic NO3 - RR exhibits an extremely high NH3 yield of 80.92 mg h-1 cm-2 and a Faradaic efficiency (FE) of 95.2% in 1 m KOH containing 0.1 m NO3 - . Significantly, 0.6W-O-CoP@NF presents greatly enhanced NH3 yield and FE in a wide NO3 - concentration ranges of 0.001-0.1 m compared to the reported. The excellent NO3 - RR performance is attributed to a synergistic catalytic effect between [W-O] and CoP active sites, in which the doped [W-O] group promotes the water decomposition to supply abundant Hads , and meanwhile modulates the electronic structure of Co for strengthened adsorption of Hads and the hydrogen (H2 ) release prevention, resultantly facilitating the NO3 - RR. Finally, a Zn-NO3 - battery has been assembled to simultaneously achieve three functions: electricity output, ammonia production, and nitrate treatment in wastewater.


Cavernous lymphohemangioendothelioma of the right atrium--a case report.
The authors report a successful resection of a rare cystic tumor in the right atrium, discovered in an asymptomatic patient with atrial fibrillation. The cystic nature of the tumor was characterized by two-dimensional echocardiogram preoperatively. The site of attachment and movement of the tumor were clearly shown by cine computed tomography preoperatively. The tumor contained numerous endothelium-lined cavernous channels and groups of red blood cells. These features are distinctly different from those of other cystic tumors.


Mediterranean Diet and Atherothrombosis Biomarkers: A Randomized Controlled Trial.
To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n = 120) or nuts (MedDiet-Nuts; n = 119) versus a low-fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1-year differences in biomarkers. Differences are observed between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in high-density lipoproteins (HDLs) (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1 -antitrypsin levels (-6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments are associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake are linked to enhancements in biomarkers. MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.


Clinical use of ferric carboxymaltose in patients with solid tumours or haematological malignancies in France.
This study collected data on the use of ferric carboxymaltose (FCM) in a cancer patient population in France to evaluate the feasibility and the conditions of use of FCM in routine clinical practice beyond the limiting criteria of clinical trials. This observational, prospective study of patients with a solid tumour or a haematological malignancy who have received treatment with FCM after 01 July 2011 evaluated data about the circumstances of iron administration, concomitant medication and laboratory tests in the period from 3 months prior to the first FCM administration (baseline) until 3 months post-baseline. Data from 367 FCM-treated patients were analysed. FCM was mainly given as a single dose at baseline (69.2%) and without additional erythropoiesis-stimulating agent (ESA, 64.3%). The median total iron dose was 1000 mg per patient. Median haemoglobin (Hb) levels of FCM-treated patients improved from 10.3 g/dL (interquartile range 9.5, 11.1 g/dL) at baseline to 11.8 g/dL (11.1, 13.0 g/dL) until the end of the 3-month observational period. Patients treated with FCM alone or additional ESA achieved similar median Hb increase (1.3 [0.4, 2.1] g/dL and 1.4 [0.4, 2.5] g/dL, respectively). Patients with baseline Hb up to 11.0 g/dL and serum ferritin up to 500 ng/mL and beyond achieved stable median Hb levels ≥11.0 g/dL without signs of iron overload. No severe or serious adverse reaction and no hypersensitivity reactions were reported. The results of this observational study confirm the effectiveness and tolerability of FCM when given in clinical routine practice alone or in combination with an ESA.


Left main mycotic aneurysm causing myocardial infarction.
Mycotic coronary aneurysms are rare, and simultaneous involvement of the left main, left anterior descending and circumflex arteries has never been described. In the present case, multislice computed tomography was an invaluable tool to adequately delineate the aneurysm from the surrounding structures and to plan cardiac surgery accordingly.


A series of non-quinoline cysLT1 receptor antagonists: SAR study on pyridyl analogs of Singulair.
The structure-activity relationship of a series of styrylpyridine analogs of MK-0476 (montelukast, Singulair) is described. This work has led to the identification of a number of potent and orally active cysLT1 receptor (LTD4 receptor) antagonists including 2ab (L-733,321) as an optimized candidate.


A combination atmospheric pressure LC/MS:GC/MS ion source: advantages of dual AP-LC/MS:GC/MS instrumentation.
Modification of commercial LC/MS instrumentation to allow both atmospheric pressure (AP) LC/MS and GC/MS is described. Advantages of this additional capability versus LC/MS alone include higher chromatographic resolution in the GC versus LC mode, greater peak capacity for complex mixture analysis, higher sensitivity for a variety of volatile compounds, and the ability to observe compounds of low polarity that are not readily observed in LC/MS. Advantages over conventional GC/MS include the ability to use higher carrier gas flow and shorter columns for passing less volatile materials through the gas chromatograph, selective ionization, and rapid switching between positive and negative ion modes. Other advantages include application of the enhanced capabilities of LC/MS instrumentation to GC/MS analyses such as cone voltage fragmentation, MS(n), high mass resolution, and accurate mass measurement. Limitations of APGC/MS include the inability to observe saturated hydrocarbon and certain other highly nonpolar compounds and less odd-electron fragmentation for computer aided library searching. For some analyses, the limitation related to ionization of highly nonpolar compounds is advantageous, as is the simplified mass spectrum and easy molecular weight identification that results from less fragmentation observed in the AP ionization mode.


Discrimination of Neotropical Anopheles species based on molecular and wing geometric morphometric traits.
Morphological similarities among closely related Anopheles species that differ in biological traits and malaria transmission represent a challenge in medical entomology; therefore, new tools are constantly tested to bring solutions. Particularly, in this work, a geometric morphometric analysis of wing geometry variation, based on morphologically and molecularly identified specimens, was applied for the discrimination of fourteen Anopheles species belonging to the Nyssorhynchus, Anopheles and Kerteszia subgenera. DNA barcodes helped to confirm species assignation and the geometric morphometric approach revealed wing form differences not only at the subgenera but also at the species level. Each subgenus presented a particular wing size trend, possibly related to the evolutionary history of these lineages. Wing shape allowed species discrimination, except for some very closely related taxa. The current findings highlight the importance of using complementary approaches involving morphological and molecular data for Anopheles species discrimination.


Broadband achromatic optical metasurface devices.
Among various flat optical devices, metasurfaces have presented their great ability in efficient manipulation of light fields and have been proposed for variety of devices with specific functionalities. However, due to the high phase dispersion of their building blocks, metasurfaces significantly suffer from large chromatic aberration. Here we propose a design principle to realize achromatic metasurface devices which successfully eliminate the chromatic aberration over a continuous wavelength region from 1200 to 1680 nm for circularly-polarized incidences in a reflection scheme. For this proof-of-concept, we demonstrate broadband achromatic metalenses (with the efficiency on the order of ∼12%) which are capable of focusing light with arbitrary wavelength at the same focal plane. A broadband achromatic gradient metasurface is also implemented, which is able to deflect wide-band light by the same angle. Through this approach, various flat achromatic devices that were previously impossible can be realized, which will allow innovation in full-color detection and imaging.Metasurfaces suffer from large chromatic aberration due to the high phase dispersion of their building blocks, limiting their applications. Here, Wang et al. design achromatic metasurface devices which eliminate the chromatic aberration over a continuous region from 1200 to 1680 nm in a reflection schleme.


Hypnotic consumption in the Portuguese population: data from the National Health Survey 1998-1999.
To assess the prevalence and factors related to hypnotic intake in Portugal. Data from the National Health Survey conducted in 1998-1999 in a representative sample of 39 640 subjects aged > 18 years. Subjects were asked if they took hypnotics, for how long and also for how many days they had taken them the previous 2 weeks. Overall, 13% of subjects reported taking hypnotics, and this frequency was higher for women (19%) than for men (7.4%, p < 0.001) and increased from 1.5% among age group [18-25[ to 26.2% among subjects aged > 75 years (p < 0.001). In both genders, the Lisbon region had the higher prevalence (15.4%) and Algarve the lowest (10%, p < 0.001); also ex-smokers the highest (15.4%), and current smokers the lowest prevalence (6.8%, p < 0.001). Women took hypnotics continuously during the previous 2 weeks more frequently than men (75 vs. 70%, p < 0.001), and the main reason for intake also differed between genders (p < 0.001). Finally, 69% of the subjects reported taking hypnotics for more than 3 years, and this prevalence was higher in women (71.6%) than in men (62.0%, p < 0.001). Multivariate analysis showed hypnotic intake to be positively related with age and inversely related with a sedentary lifestyle in both genders, and positively related with smoking and negatively related with obesity in men. A significant percentage of the Portuguese population takes hypnotics in an almost continuous manner, and the intake is related to gender, age, obesity, and physical activity status.


Evaluation of five commercially available direct radio-immunoassays for the determination of 17 beta-estradiol in serum for the hormonal monitoring of ovarian stimulation.
Five direct radio-immunoassay kits for the dosage of 17 beta-estradiol were assessed for their usefulness to monitor the serum values of 17 beta-estradiol in stimulated and natural ovarian cycles. Prerequisites included a turn-around time of 4 hours for an assay of 100 tubes and a range extended to at least 2,000 ng/l. The following parameters were evaluated: characteristics of the standard curve, sensitivity, precision profile, within- and between-assay precision, analytical drift and linearity. We found that the five tested methods are technically suitable to monitor serum 17 beta-estradiol in stimulated cycles but they all lack precision for low 17 beta-estradiol levels as seen in the early follicular phase of natural cycles.


Organisation of the thalamofugal visual projections in chick embryos, and a sex difference in light-stimulated development.
The organisation of the thalamofugal visual projections to the forebrain has been determined in chick embryos by injecting retrograde tracers (true blue and either fluorogold or diamidino yellow) into the left or right hyperstriatum. The embryos were injected on day 19 of incubation and allowed to survive for a further 4 days. Unlike chicks posthatching, the embryos were found to have no asymmetry of the thalamofugal visual projections, irrespective of whether they had received 24 h of light exposure prior to injecting the tracer dyes or had been kept in darkness. The light exposure did, however, lead to a significant increase in the ratio of the number of cell bodies in the thalamus labelled contralaterally to the injection site to the number labelled ipsilaterally (CI ratio) in male embryos. The elevation of the CI ratio appeared to be due to an increase in the number of contralateral projections from each side of the thalamus to the hyperstriatum on the other side of the forebrain. Thus, growth of these visual projections is promoted by light experience during the later stages of embryonic development. Most likely, light stimulation promotes increased arborisation of end-terminals in the hyperstriatum. Development of the thalamofugal visual projections in female embryos was not influenced by exposure to light, a finding consistent with earlier studies demonstrating that circulating oestrogen either inhibits or over-rides the sensitivity of these developing neurones to light stimulation.


Mass quarantine and mental health during COVID-19: A meta-analysis.
To reveal the complex relationships between quarantine and mental health during COVID-19, a meta-analysis was conducted involving 34 articles and a total sample size of 134,061. As the relationship between quarantine and mental health was found to be affected by the sampling objects and national factors, a random-effects model was applied for the meta-analysis. First, a heterogeneity test and sensitivity analysis were conducted to determine whether there was heterogeneity in the samples, after which a funnel chart, Rosenthal's Classic Fail-safe N test and Egger's test were applied to further determine whether there was publication bias in the included samples. Finally, a sub-group test was used to explore whether the sampling group and the country of origin had a moderating effect on the relationship between quarantine and mental health, which revealed that the relationship between quarantine and mental health was regulated and influenced by the sampled objects but was not affected by the country categories. The results indicated that: COVID-19 quarantine had varying impacts on individual anxiety, depression, and psychological stress; different groups had different regulatory effects on the relationship between quarantine and mental health; and country of origin had no moderating effect on quarantine and psychology. COVID-19 is the most important topic in 2020, and mass quarantine is the measures for pandemic prevention and control around the world since 2020. To explore the relationships between mass quarantine and mental health during COVID-19, a meta-analysis was conducted involving 28 articles and a total sample size of 134,061. As the relationship between mass quarantine and mental health was found to be affected by the sampling objects and national factors, a random-effects model was applied for the meta-analysis. First, a heterogeneity test and sensitivity analysis were conducted to determine whether there was heterogeneity in the samples, after which a funnel chart, Rosenthal's Classic Fail-safe N test and Egger's test were applied to further determine whether there was publication bias in the included samples. Finally, a sub-group test was used to explore whether the sampling group and the country of origin had a moderating effect on the relationship between mass quarantine and mental health. COVID-19 quarantine had varying impacts on individual anxiety, depression, and psychological stress; different groups had different regulatory effects on the relationship between quarantine and mental health; and country of origin had no moderating effect on quarantine and mental health. This study employed a meta-analysis to examine the relationships between the COVID-19 pandemic mass quarantine measures and mental health factors such as anxiety, depression and stress, from which it was found that influence of quarantine on anxiety was stronger, the relationship between quarantine and mental health was affected by the sampled object, and there was no significant relationship between quarantine and country of origin in the sample population.


The potential for eye donation from hospice and palliative care clinical settings in England: a retrospective case note review of deceased patients' records.
There is a need to identify additional routes of supply for ophthalmic tissue in the UK. This paper reports the findings from a national study exploring the potential for eye donation (ED) from three Hospice Care (HC) and three Hospital Palliative Care Services (HPC) in England. The objectives addressed in this paper are i.) to establish the size and describe the clinical characteristics of the potential eye donor population across six clinical sites; ii.) to identify challenges for clinicians in applying the standard ED criteria for assessing patient eligibility. Retrospective assessment of 1199 deceased patient case notes, 601 Hospice Care and 598 Hospital Palliative Care services, against current eye donation criteria. Clinicians' assessments were then evaluated against the same criteria. by specialists based at the National Health Service Blood and Transplant Tissue Services division (NHSBT-TS). Results of the assessment and evaluation are reported as descriptive statistics (numerical data). Free-text comment boxes facilitated clarification and/or justification of review and evaluation decisions. 46% (n = 553) of 1199 deceased patients' notes were agreed as eligible for eye donation (Hospice care settings = 56% (n = 337); Palliative care settings = 36% (n = 216). For all eligible cases (n = 553) the option of ED was recorded as being raised with family members in only 14 cases (3%). Significant potential exists for eye donation from the clinical sites in this study. This potential is not currently being realised.


Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast.
Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC. A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002). Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.


Approach to idiopathic recurrent pancreatitis.
Acute pancreatitis is caused by acute or chronic alcohol intake or choledocholithiasis in approximately 80% of cases. In the absence of alcohol abuse or gallstones, a variety of established and putative factors must be considered, any of which can cause a single or recurrent attacks of acute pancreatitis. When the underlying cause eludes detection following an initial thorough search and leads to a second attack, the term idiopathic acute recurrent pancreatitis (IARP) is applied. This article discusses IARP and its work-up.


Pulmonary metastases in men: primary tumor in an unusual location.
We report a case of breast cancer identified in a 72-year-old male as an accidental finding during the course of the investigation of a primary tumor and the search for pulmonary metastases. We address aspects related to the epidemiology, diagnosis, treatment and prognosis of this condition in males.


Impact of assuming a circular orifice on flow error through elliptical regurgitant orifices: computational fluid dynamics and in vitro analysis of proximal flow convergence.
Grounded in hydrodynamic theory, proximal isovelocity surface area (PISA) is a simplistic and practical technique widely used to quantify valvular regurgitation flow. PISA provides a relatively reasonable, though slightly underestimated flow rate for circular orifices. However, for elliptical orifices frequently seen in functional mitral regurgitation, PISA underestimates the flow rate. Based on data obtained with computational fluid dynamics (CFD) and in vitro experiments using systematically varied orifice parameters, we hypothesized that flow rate underestimation for elliptical orifices by PISA is predictable and within a clinically acceptable range. We performed 45 CFD simulations with varying orifice areas 0.1, 0.3 and 0.5 cm2, orifice aspect ratios 1:1, 2:1, 3:1, 5:1, and 10:1, and peak velocities (Vmax) 400, 500 and 600 cm/s. The ratio of computed effective regurgitant orifice area to true effective area (EROAC/EROA) against the ratio of aliasing velocity to peak velocity (VA/Vmax) was analyzed for orifice shape impact. Validation was conducted with in vitro imaging in round and 3:1 elliptical orifices. Plotting EROAC/EROA against VA/Vmax revealed marginal flow underestimation with 2:1 and 3:1 elliptical axis ratios against a circular orifice (< 10% for 8% VA/Vmax), rising to ≤ 35% for 10:1 ratio. In vitro modeling confirmed CFD findings; there was a 8.3% elliptical EROA underestimation compared to the circular orifice estimate. PISA quantification for regurgitant flow through elliptical orifices produces predictable, but generally small, underestimation deemed clinically acceptable for most regurgitant orifices.


Rod input to amacrine cells in dace retina.
Intracellular recordings in dace retina demonstrate a type of amacrine cell whose responses to flashes of light were characteristically a transient depolarization at the onset of light, followed by a slow decay toward the dark level, similar to rod-dominated, AII amacrine cells described in cat retina. Electron microscopy of HRP-filled dace AII-like amacrine cells suggested that they receive significant rod inputs through rod-dominated bipolar cells.


The Pooled Diagnostic Accuracy of Neuroimaging, General Movements, and Neurological Examination for Diagnosing Cerebral Palsy Early in High-Risk Infants: A Case Control Study.
Clinical guidelines recommend using neuroimaging, Prechtls' General Movements Assessment (GMA), and Hammersmith Infant Neurological Examination (HINE) to diagnose cerebral palsy (CP) in infancy. Previous studies provided excellent sensitivity and specificity for each test in isolation, but no study has examined the pooled predictive power for early diagnosis. We performed a retrospective case-control study of 441 high-risk infants born between 2003 and 2014, from three Italian hospitals. Infants with either a normal outcome, mild disability, or CP at two years, were matched for birth year, gender, and gestational age. Three-month HINE, GMA, and neuroimaging were retrieved from medical records. Logistic regression was conducted with log-likelihood and used to determine the model fit and Area Under the Curve (AUC) for accuracy. Sensitivity and specificity for detecting CP were 88% and 62% for three-month HINE, 95% and 97% for absent fidgety GMs, and 79% and 99% for neuroimaging. The combined predictive power of all three assessments gave sensitivity and specificity values of 97.86% and 99.22% (PPV 98.56%, NPV 98.84%). CP can be accurately detected in high-risk infants when these test findings triangulate. Clinical implementation of these tools is likely to reduce the average age when CP is diagnosed, and intervention is started.


Analysis of relation between placental lesions and perinatal outcome according to Amsterdam criteria: a comparative study.
To verify the correlation between histological examination of the placenta (HP), classifying the lesions according to the Amsterdam criteria (AC), and the main neonatal pathological patterns. This prospective study carried out at the University of Bari between May 2015 and May 2017,enrolled 350 pregnant women. Complete obstetric history and HP was collected. 380 newborns were also enrolled. The analysis was also carried out by comparing the incidence of the various placental pathologies in the sample of physiological pregnancies (PP), represented by 142 cases, with the incidence of the group with placental anomalies (PA). The statistical software used was STATA MP11. Respiratory disorders (61 cases) are significantly correlated with generic PA (p=0.006). Neonatal sepsis (15 cases) was significantly correlated with placental inflammation (p=0.035) and villitis of unknown origin (p=0.039).Twin pregnancies (50 cases) were correlated with generic PA (p=0.00001) and late maternal malperfusion (p=0.00001). Congenital cardiopathies (50 cases) were correlated with the villitis of unknown origin and PA (p=0.0000). Preterm birth (145 cases)was correlated with the premature malperfusion (p=0, 0011) and PA (p=0.0000); SGA (low weight in relation to the gestational age - 75 cases) neonates were correlated with the early malperfusion (p=0.00000) and the generic PA (p=0.00000). The present study has therefore verified whether in reality the HP can be of great help to the neonatologist in the nosological and therapeutic setting of the pathological newborn. The pathological examination of the placenta is nevertheless essential to clarify the causes of the stillbirths and that these causes are particularly important for the obstetric and neonatal outcome of subsequent pregnancies.


EE-Explorer: A Multimodal Artificial Intelligence System for Eye Emergency Triage and Primary Diagnosis.
To develop a multimodal artificial intelligence (AI) system, EE-Explorer, to triage eye emergencies and assist in primary diagnosis using metadata and ocular images. A diagnostic, cross-sectional, validity and reliability study. EE-Explorer consists of 2 models. The triage model was developed from metadata (events, symptoms, and medical history) and ocular surface images via smartphones from 2038 patients presenting to Zhongshan Ophthalmic Center (ZOC) to output 3 classifications: urgent, semiurgent, and nonurgent. The primary diagnostic model was developed from the paired metadata and slitlamp images of 2405 patients from ZOC. Both models were externally tested on 103 participants from 4 other hospitals. A pilot test was conducted in Guangzhou to evaluate the hierarchical referral service pattern assisted by EE-Explorer for unspecialized health care facilities. A high overall accuracy, as indicated by an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI, 0.966-0.998), was obtained using the triage model, which outperformed the triage nurses (P < .001). In the primary diagnostic model, the diagnostic classification accuracy (CA) and Hamming loss (HL) in the internal testing were 0.808 (95% CI 0.776-0.840) and 0.016 (95% CI 0.006-0.026), respectively. In the external testing, model performance was robust for both triage (average AUC, 0.988, 95% CI 0.967-1.000) and primary diagnosis (CA, 0.718, 95% CI 0.644-0.792; and HL, 0.023, 95% CI 0.000-0.048). In the pilot test in the hierarchical referral settings, EE-explorer demonstrated consistently robust performance and broad participant acceptance. The EE-Explorer system showed robust performance in both triage and primary diagnosis for ophthalmic emergency patients. EE-Explorer can provide patients with acute ophthalmic symptoms access to remote self-triage and assist in primary diagnosis in unspecialized health care facilities to achieve rapid and effective treatment strategies.


Structural design of magnetic biosorbents for the removal of ciprofloxacin from water.
Magnetic biosorbents with specific morphological and molecular structure (PMCCs) were designed for the removal of ciprofloxacin (CIP) from water. Radical polymerization method was applied to immobilize the designed polymer brushes onto core-shell shaped magnetic microspheres to fabricate PMCCs. PMCCs exhibited a maximum adsorption capacity of 527.93 mg·g-1, which is much higher than reported adsorbents, owing to the complete stretch of polymer brushes and increased active sites as well as enhanced interaction. The investigation on the adsorption behavior of PMCCs for CIP manifested that CIP adsorption well fitted the Langmuir isotherm model and pseudo-second-order kinetic model. The calculated thermodynamic parameters suggested that CIP adsorption onto PMCCs was spontaneous and exothermic. Further recycling experiments showed a loss of less than 20% in the CIP adsorption capacity after five times, demonstrating the reusability of the as-designed biosorbents.


8-Piperazinyl-2,3-dihydropyrrolo[3,2-g]isoquinolines: potent, selective, orally bioavailable 5-HT1 receptor ligands.
The novel 8-piperazinyl-2,3-dihydropyrroloisoquinoline template was synthesized in nine steps. The template was N-substituted to give a series of compounds showing binding to human cloned 5-HT1A, 5-HT1B and 5-HT1D receptors with pKi's greater than 9 and selectivities up to 1000-fold against other serotonin, dopamine and adrenergic receptors. Several compounds were shown to possess weak partial agonist activity in cloned receptors, which translated to antagonism in in vitro studies.


Age and vitamin D affect the magnitude of the antibody response to the first dose of the SARS-CoV-2 BNT162b2 vaccine.
Most approved vaccines utilise a two-dose strategy. To enable larger groups of patients to receive the first dose, the UK government increased the gap between the two doses from three to twelve weeks. Here we report on the immunogenicity of the first dose, including effect of age and vitamin D status on these levels over an 8 week-period. Blood samples were collected from healthcare workers (HCW) receiving their first BNT162b2 vaccine dose between January and February 2021. Antibody (Ab) production was measured, prior to and weekly for 4 weeks post immunization, and a final measurement was performed at 8 weeks. Serum vitamin D concentrations were also measured at baseline. Immunization of 97 HCW induced an Ab response that peaked 3•2 weeks post immunization to decrease thereafter. Ab levels remained positive at 8 weeks. IgG peak concentration was negatively associated with age (β=-0•440, p<0.001). Response to immunization was also significantly affected by vitamin D status (p=0•022), on average 29•3% greater peak value in individuals with 25(OH)D>50nmol/L. No other variable showed significant effect. The first dose of BNT162b2 produced Ab levels that remained positive after 8 weeks. Peak was greater in younger subjects and 25(OH)D>50nmol/L was beneficial. Booster campaigns should take into consideration vitamin D status which is at its highest following a period of sunshine exposure or following oral supplementation (400-1000IU daily). Abbott Diagnostics Ltd supplied the kits used to quantify the anti-SARS -CoV-2 Spike IgG and technical support as well as provided financial support for sample collections.


Lessons from relatives: C4 photosynthesis enhances CO2 assimilation during the low-light phase of fluctuations.
Despite the global importance of species with C4 photosynthesis, there is a lack of consensus regarding C4 performance under fluctuating light. Contrasting hypotheses and experimental evidence suggest that C4 photosynthesis is either less or more efficient in fixing carbon under fluctuating light than the ancestral C3 form. Two main issues have been identified that may underly the lack of consensus: neglect of evolutionary distance between selected C3 and C4 species and use of contrasting fluctuating light treatments. To circumvent these issues, we measured photosynthetic responses to fluctuating light across 3 independent phylogenetically controlled comparisons between C3 and C4 species from Alloteropsis, Flaveria, and Cleome genera under 21% and 2% O2. Leaves were subjected to repetitive stepwise changes in light intensity (800 and 100 µmol m-2 s-1 photon flux density) with 3 contrasting durations: 6, 30, and 300 s. These experiments reconciled the opposing results found across previous studies and showed that (i) stimulation of CO2 assimilation in C4 species during the low-light phase was both stronger and more sustained than in C3 species; (ii) CO2 assimilation patterns during the high-light phase could be attributable to species or C4 subtype differences rather than photosynthetic pathway; and (iii) the duration of each light step in the fluctuation regime can strongly influence experimental outcomes.


Causes for revision surgery in total hip replacement. A retrospective epidemiological analysis.
To determine the impact of each cause of revision surgery in total hip arthroplasty during the period 2009-2013. To analyse the relationship between these causes with different variables. A study was conducted on 127 patients who had hip replacement revision surgery in our hospital during this period. Parameters, such as age, sex, date of primary arthroplasty, prosthetic replacement date, and main cause of the revision were recorded. Those revisions performed within 5 years after the primary arthroplasty were considered as early rescue. The most common cause of rescue was aseptic loosening in 38 (30%) followed by instability in 30 (24%). In terms of age at the time of rescue, statistically significant differences were found, with it being significantly higher in patients re-operated for a fracture. Differences in age at first surgery were found to be 7 years younger than those with late rescue (63.40) with respect to early (70.21). Similar results to ours have been observed in other published series, except for the higher incidence of instability in early rescue. This study demonstrates aseptic loosening and instability as the most frequent causes of revision surgery in our hospital. Age is a very influential factor in relation to longevity of primary arthroplasty. Complications were higher in when the primary hip replacement is implanted in older patients.


Glitazones in chronic kidney disease: potential and concerns.
Glitazones rank now among the most used hypoglycemic agents in patients with type-2 diabetes. This systematic review focuses on the cardiovascular and renal outcomes in chronic kidney disease (CKD) patients treated with these drugs. Data from randomized clinical trials and a meta-analysis indicate that glitazones (particularly rosiglitazone) may increase the risk of myocardial infarction, heart failure and cardiovascular death in type-2 diabetics. Observational studies looking at survival and cardiovascular outcomes in diabetic patients with kidney failure show controversial results. Studies in experimental models and clinical studies suggest that glitazones may have favorable effects on renal disease progression, because these drugs coherently reduce urinary albumin excretion and proteinuria in diabetic and non-diabetic nephropathies. No clinical trial based on clinical end-points like kidney failure has until now tested the effect of glitazones on the evolution of chronic renal failure in these patients. Whether the use of glitazones has a positive or a negative impact upon major cardiovascular and renal outcomes in diabetic patients remains an open, unanswered question. Specific studies are needed to assess the efficacy and safety of glitazones in a high risk population like type-2 diabetics with chronic kidney disease.


SSMD: a semi-supervised approach for a robust cell type identification and deconvolution of mouse transcriptomics data.
Deconvolution of mouse transcriptomic data is challenged by the fact that mouse models carry various genetic and physiological perturbations, making it questionable to assume fixed cell types and cell type marker genes for different data set scenarios. We developed a Semi-Supervised Mouse data Deconvolution (SSMD) method to study the mouse tissue microenvironment. SSMD is featured by (i) a novel nonparametric method to discover data set-specific cell type signature genes; (ii) a community detection approach for fixing cell types and their marker genes; (iii) a constrained matrix decomposition method to solve cell type relative proportions that is robust to diverse experimental platforms. In summary, SSMD addressed several key challenges in the deconvolution of mouse tissue data, including: (i) varied cell types and marker genes caused by highly divergent genotypic and phenotypic conditions of mouse experiment; (ii) diverse experimental platforms of mouse transcriptomics data; (iii) small sample size and limited training data source and (iv) capable to estimate the proportion of 35 cell types in blood, inflammatory, central nervous or hematopoietic systems. In silico and experimental validation of SSMD demonstrated its high sensitivity and accuracy in identifying (sub) cell types and predicting cell proportions comparing with state-of-the-arts methods. A user-friendly R package and a web server of SSMD are released via https://github.com/xiaoyulu95/SSMD.


Background-free in-vivo Imaging of Vitamin C using Time-gateable Responsive Probe.
Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its "off" state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background-free monitoring of cellular uptake or endogenous production of vitamin C, and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules.


Fecal lactoferrin as a noninvasive biomarker in inflammatory bowel diseases.
The diagnosis and management of inflammatory bowel diseases (IBD), i.e., Crohn's disease and ulcerative colitis, still present a number of challenges. The fecal biomarker lactoferrin has been shown to be useful in the diagnosis and management of these diseases. This review includes a discussion of the current literature on lactoferrin as a biomarker of intestinal disease, detection of disease activity in IBD, comparison of lactoferrin to endoscopy and histology, lactoferrin measurement in pediatric IBD and lactoferrin as a biomarker for monitoring medical treatment in IBD.