Double-blinded, placebo-controlled trial of green tea extracts in the clinical and histologic appearance of photoaging skin.
Green tea extracts have gained popularity as ingredients in topical skin care preparations to treat aging skin. Green tea polyphenolic compounds have significant antioxidant and anti-inflammatory activities, and studies suggest that these extracts help mediate ultraviolet radiation damage. To evaluate the effects of a combination regimen of topical and oral green tea supplementation on the clinical and histologic characteristics of photoaging. Forty women with moderate photoaging were randomized to either a combination regimen of 10% green tea cream and 300 mg twice-daily green tea oral supplementation or a placebo regimen for 8 weeks. No significant differences in clinical grading were found between the green tea-treated and placebo groups, other than higher subjective scores of irritation in the green tea-treated group. Histologic grading of skin biopsies did show significant improvement in the elastic tissue content of treated specimens (p<.05). Participants treated with a combination regimen of topical and oral green tea showed histologic improvement in elastic tissue content. Green tea polyphenols have been postulated to protect human skin from the cutaneous signs of photoaging, but clinically significant changes could not be detected. Longer supplementation may be required for clinically observable improvements.


Disulfide bond isomerization in prokaryotes.
Proteins with multiple cysteine residues often require disulfide isomerization reactions before they attain their correct conformation. In prokaryotes this reaction is catalyzed mainly by DsbC, a protein that shares many similarities in structure and mechanism to the eukaryotic protein disulfide isomerase. This review discusses the current knowledge about disulfide isomerization in prokaryotes.


Massive data analyses show negative impact of type 1 and 2 diabetes on the outcome of periodontal treatment.
The aim was to evaluate the impact of diabetes on the outcome of periodontal treatment based on massive data analyses. Data originated from the database of a major German National Health Insurance. Patients who underwent periodontal treatment were allocated to four groups according to their medical condition: type 1 diabetes (D1), type 2 diabetes with the intake of oral anti-diabetics (D2M), type 2 diabetes without the intake of oral anti-diabetics (D2), and a control group without diabetes (ND). Four-year Kaplan-Meier survival analyses on the patient level and multivariate regression analyses were conducted for tooth extraction. Of 415,718 patients, 4139 matched the criteria for D1, 22,430 for D2M, and 23,576 for D2. At 4 years, the cumulative survival rate (no extraction) was 51.7% in the D1 group, 54.0% in the D2M group, and 57.7% in the D2 group. The ND control group had a significantly higher survival rate of 65.9% (P < 0.0001). In the multivariate analyses, both diabetes types were significantly associated with further tooth loss after periodontal treatment. The diagnosis of diabetes type 1 or 2 seems to be associated with a higher risk of tooth loss after periodontal treatment. The long-term prognosis of teeth in diabetes patients should be judged carefully.


Phosphorylation of JNK Increases in the Cortex of Rat Subjected to Diabetic Cerebral Ischemia.
Previous studies have demonstrated that the c-Jun N-terminal kinase (JNK) pathway plays an important role in inducing neuronal apoptosis following cerebral ischemic injury. JNK signaling pathway in activated during cerebral ischemic injury. It participates in ischemia-induced neuronal apoptosis. However, whether JNK signaling is involved in the process of neuronal apoptosis of diabetes-induced cerebral ischemia is largely unknown. This study was undertaken to evaluate the influence of cerebral ischemia-reperfusion injury on phosphorylation of JNK in diabetic rats. Twenty-four adult streptozotocin induced diabetic and 24 adult non-diabetic rats were randomly subjected to 15 min of forebrain ischemia followed by reperfusion for 0, 1, 3, and 6 h. Sixteen sham-operated diabetic and non-diabetic rats were used as controls. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Protein expression of phospho-JNK was examined by immunohistochemistry and Western blot. The numbers of TUNEL-positive cells and phospho-JNK protein expression in the cerebral cortices after 1, 3 and 6 h reperfusion was significantly higher in diabetic rats compared to non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). Western blot analysis showed significantly higher phospho-JNK protein expression in the cerebral cortices of the diabetic rats after 1 and 3 h reperfusion than that was presented in non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). These findings suggest that increased phosphorylation of JNK may be associated with diabetes-enhanced ischemic brain damage.


Expression of modified gene encoding functional human alpha-1-antitrypsin protein in transgenic tomato plants.
Transgenic plants offer promising alternative for large scale, sustainable production of safe, functional, recombinant proteins of therapeutic and industrial importance. Here, we report the expression of biologically active human alpha-1-antitrypsin in transgenic tomato plants. The 1,182 bp cDNA sequence of human AAT was strategically designed, modified and synthesized to adopt codon usage pattern of dicot plants, elimination of mRNA destabilizing sequences and modifications around 5' and 3' flanking regions of the gene to achieve high-level regulated expression in dicot plants. The native signal peptide sequence was substituted with modified signal peptide sequence of tobacco (Nicotiana tabacum) pathogenesis related protein PR1a, sweet potato (Ipomoea batatas) sporamineA and with dicot-preferred native signal peptide sequence of AAT gene. A dicot preferred translation initiation context sequence, 38 bp alfalfa mosaic virus untranslated region were incorporated at 5' while an endoplasmic reticulum retention signal (KDEL) was incorporated at 3' end of the gene. The modified gene was synthesized by PCR based method using overlapping oligonucleotides. Tomato plants were genetically engineered by nuclear transformation with Agrobacterium tumefaciens harbouring three different constructs pPAK, pSAK and pNAK having modified AAT gene with different signal peptide sequences under the control of CaMV35S duplicated enhancer promoter. Promising transgenic plants expressing recombinant AAT protein upto 1.55% of total soluble leaf protein has been developed and characterized. Plant-expressed recombinant AAT protein with molecular mass of around approximately 50 kDa was biologically active, showing high specific activity and efficient inhibition of elastase activity. The enzymatic deglycosylation established proper glycosylation of the plant-expressed recombinant AAT protein in contrast to unglycosylated rAAT expressed in E. coli ( approximately 45 kDa). Our results demonstrate feasibility for high-level expression of biologically active, glycosylated human alpha-1-antitrypsin in transgenic tomato plants.


Synthesis, structure, and biological active evaluation of a new cyclic tetranuclear copper(II) complex bridged both by oxamido and carboxylate groups.
A new tetracopper(II) complex bridged both by oxamido and carboxylato groups, namely [Cu4 (dmaepox)2 (bpy)2 ](NO3 )2 ·2H2 O, where H3 dmaepox and bpy represent N-benzoato-N'- (3-methylaminopropyl)oxamide and 2,2'-bipyridine, was synthesized, and its structure reveals the presence of a centrosymmetric cyclic tetracopper(II) cation assembled by a pair of cis-dmaepox3- - bridged dicopper(II) units through the carboxylato groups, in which the endo- and exo-copper(II) ions bridged by the oxamido group have a square-planar and a square-pyramidal coordination geometries, respectively. The aromatic packing interactions assemble the complex molecules to a two-dimensional supramolecular structure. The reactivity toward DNA and protein bovine serum albumin (BSA) indicates that the complex can interact with herring sperm DNA through the intercalation mode and the binding affinity is dominated by the hydrophobicity and chelate ring arrangement around copper(II) ions and quenches the intrinsic fluorescence of BSA via a static process. The cytotoxicity of the complex shows selective cancer cell antiproliferative activity.


Hippocampal intracerebral evoked potentials as a marker of its functionality in drug-resistant epilepsy.
To assess hippocampal function during stereoelectroencephalography (SEEG) investigations through the study of the medial temporal lobe event-related potential (ERP) MTL-P300. We recorded the MTL-P300 during a visual oddball task, using hippocampal electrodes implanted for SEEG in 71 patients, in a preoperative epilepsy investigation. The presence of an MTL-P300 and its amplitude were correlated with hippocampal involvement during seizures and memory function. Analysis using ROC curves revealed that an MTL-P300 amplitude below -46 µV, has a specificity of 93.3% in detecting the epileptogenic zone, and absence of the MTL-P300 in the left hippocampus of patients with typical language organization was associated with marked alteration of verbal memory scores. There was a significant correlation between performance in non-verbal memory tests and the amplitude of the MTL-P300 in the right hippocampus of patients with left hemispheric seizures (immediate visual recall: r = 0.67, p = 0.005; delayed visual recall: r = 0.56, p = 0.025). Using a linear regression, we confirmed that the absence of the MTL-P300 in the left hippocampus, the involvement of the left hippocampus during seizures, and the duration of epilepsy were predictors of verbal memory deficits. Analysis of the MTL-P300 during SEEG recording provides relevant information for the analysis of hippocampal functionality and can help to localize the epileptogenic zone.


Membrane interactions of mastoparan analogues related to their differential effects on protein kinase C, Na, K-ATPase and HL60 cells.
Membrane interactions of tetradecapeptide toxin mastoparan (MP) and analogues (MP-3, MP-X and polistes MP), as indicated by inhibition of various enzymatic and cellular activities, were investigated. MP-3 was found to be the least active in inhibiting protein kinase C (PKC; activated by phosphatidylserine vesicles, synaptosomal membranes or phorbol ester), synaptosomal membrane Na,K-ATPase and proliferation and viability of leukemia HL60 cells. MP-3, however, was as active as others in inhibiting PKC activated by arachidonate monomers and phorbol ester binding. The unique properties of MP-3, the [des-Ile1-Asn2]-analogue of MP, might be related to its low functional amphiphilicity compared to others and useful in further delineating biological activities associated with or regulated by membranes.


Positive abundance and negative distribution effects of a gastropod on an intertidal hermit crab.
Field experiments were used to determine the effect of a common intertidal snail (Nerita funiculata) on the use of space for foraging by the hermit crab Clibanarius digueti. Removals of Nerita resulted in an increased density of foraging Clibanarius, while additions of the gastropod had the opposite effect. The observed negative effect of the gastropod on individual hermit crabs appears to be food-related. Field surveys, however, suggested that the hermit crab population is limited by shell number, rather than food. Because Nerita contributes to the shell resource, its effect on the hermit crab population is positive. Nerita, therefore, has a negative effect on the distribution of foraging hermit crabs, but a positive effect on their abundance. Such decouplings of distribution and abundance effects are rare.


Leptin induces osteoblast differentiation of human valvular interstitial cells via the Akt and ERK pathways.
Calcific aortic valve disease (CAVD) affects 2-6% of the population over 65 years, and age, gender, smoking, overweight, dyslipidemia, diabetes contribute to the development of this disease. CAVD results, in part, from the osteoblast differentiation of human valvular interstitial cells (VICs). This study aims to elucidate the effects of leptin on osteoblast phenotype of VICs and the signalling pathways involved. Patients who underwent aortic valve replacement for CAVD (n = 43) were included in this study. Patients with coronary artery disease (CAD) without CAVD (n = 129) were used as controls. Patients with CAVD had higher serum leptin concentrations than CAD patients (p = 0.002). Leptin was found in calcific aortic valves, with higher concentrations in calcified versus non-calcified zones (p = 0.01). Chronic leptin stimulation of human VICs enhanced alkaline phosphatase (ALP) activity and ALP, BMP-2 and RUNX2 expression and decreased osteopontin expression. Moreover, inhibiting Akt or ERK during leptin stimulation lowered the expression of osteoblast markers in VIC. Taken together, these findings indicate that leptin plays a critical role in CAVD development by promoting osteoblast differentiation of human aortic VICs in an Akt- and ERK-dependent manner. This study highlights the role of leptin in CAVD development, and further studies are needed to determine whether reducing circulating leptin levels or blocking leptin actions on VICs is efficient to slow CAVD progression.


Impact of bilateral motion control shoes with outsole adjustment on gait asymmetry in individuals with mild leg length discrepancy.
Footwear adjustment is recommended in the management plan of leg length discrepancy. However, it is not clear how the outsole of motion control shoe adjustment influences trunk symmetry and walking performance. Does bilateral adjustment of the outsole affect trunk and pelvis symmetry and ground reaction force during walking in individuals with leg length discrepancy? 20 mild leg length discrepancy participants were recruited into a cross-sectional study. All subjects performed a walking trial with their habitual shoes to determine the outsole adjustment. Four trials of walking were carried out in the order of unadjusted and bilateral adjusted motion control air-cushion shoes. Shoulder level differences and trunk and pelvic motion were assessed, while the ground reaction force at the heel strike was reported. A paired t-test was performed to compare the differences between the conditions with a significance level at p < 0.05. During walking trials, mild leg length discrepancy participants with the adjusted shoe displayed lower variations in the maximum shoulder height differences (p = 0.001) and trunk rotation angle (p = 0.002) than those with the unadjusted shoe. Also, there was a significant reduction in the vertical ground reaction force (p = 0.030), but not in the anteroposterior or mediolateral directions, during walking in the adjusted shoe condition compared to the unadjusted shoe condition. The outsole adjustment of the bilateral motion control shoes can improve trunk symmetry while decreasing the ground impact at the heel strike. The study provides additional information to prescribe or recommend footwear adjustment to improve walking symmetry in leg length discrepancy participants.


Susceptibility of aging human bone to mixed-mode fracture increases bone fragility.
Since bone-mass-based measurements have demonstrated limited success in predicting age-related increase in fracture incidence, recent emphasis has been placed on quantification of bone quality. Specifically, material parameters such as strength, stiffness, and toughness have been quantified to characterize bone quality through mechanical testing. This study is the first one to report multiaxial failure characteristics of bone (quality) by conducting fatigue tests on human cortical bone specimens under physiologically relevant loading involving simultaneous application of axial and torsional loading to produce previously reported in vivo shear/normal stress ratios. Our results show that, compared to uniaxial tests, multiaxial fatigue tests show up to a 20-fold reduction in the fatigue life of human cortical bone. More significantly, the susceptibility of mixed-mode failure increases bone fragility in aging human bone. Furthermore, since the magnitude of mixed-mode loading varies with physiological activities, results of this study also suggest that a reduction in the activities involving significant mixed-mode loading may lower the overall fracture incidence among older individuals.


Electromagnetic and modeling analyses of an implanted device at 3 and 7 Tesla.
To study the specific absorption rates (SAR) associated with implantable devices at 3T and 7 T. Studies were carried out utilizing a finite difference time domain (FDTD) model that treats the radio frequency (RF) coil and an anatomically detailed human head mesh as a single system. Analyses were performed at 3 T and 7 T for different orientations and positions of an implanted (in the brain) aneurysm clip. Studies were also performed for two different types of FDTD mesh of the same aneurysm clip. The results showed that: 1) the electromagnetic effects of implanting the aneurysm clip (in the brain) is mostly local on SARs; and 2) orientations of the implanted aneurysm clip have considerable effect on the local SARs near the implanted clip; the level of such an effect can also vary significantly between 3 T and 7 T. In general, the presented study shows that the local SARs (in 1 g and in 10 g of tissue) near the implanted aneurysm clip are lower than the peak SARs (due to the standard RF coil operation) in other regions of the human head mesh/brain. For specific orientations, however, if the aneurysm clip is implanted in a region in which the brain peak-SAR occurs due the standard RF coil operation, the brain peak SAR increases further. This is more prevalent at 7T compared to 3T. Additionally, it was also found that basic structured and Cartesian FDTD modeling produces relatively higher local SARs than that obtained with simple non-Cartesian FDTD modeling.


Protein solubilising and stabilising ionic liquids.
We report a family of biocompatible ionic liquids (ILs) which are able to dissolve significant amounts of proteins such as cytochrome c and in which ATR-FTIR spectroscopy results show retention of secondary structure to extreme temperatures.


The effect of carbidopa on the pharmacokinetics and metabolism of intravenously administered levodopa in blood plasma and skeletal muscle.
The effect of carbidopa on the pharmacokinetics and metabolism of levodopa (L-dopa) in blood plasma and skeletal muscle extracellular fluid (ECF) has been studied by repeated measurements in one beagle dog. The administration of a single dose of L-dopa (25 mg/kg i.v.) without carbidopa pretreatment (controls) resulted in an increase in the concentrations of L-dopa and 3-O-methyldopa (3-OMD) in blood plasma and skeletal muscle ECF dialysates. This effect was clearly potentiated for L-dopa in blood plasma (186% increase in AUC) and 3-OMD in skeletal muscle dialysates (108% increase in AUC) after pretreatment with carbidopa (100 mg/day). In addition, carbidopa prolonged the half-life of the elimination of L-dopa in blood plasma by 48% and in skeletal muscle ECF by 66% but did not influence its blood plasma distribution half-life (t 1/2 alpha = 0.17 h). The elimination half-life of L-dopa in the controls was higher in muscle (t 1/2 beta = 1.76 h) than in blood plasma (t 1/2 beta = 0.50 h). Carbidopa pretreatment resulted in a relatively small increase (29%) in the L-dopa content of skeletal muscle ECF as indicated by the AUC. The accumulation of 3-OMD in muscle dialysates, in contrast to that in plasma, was significantly enhanced after the administration of L-dopa following treatment with carbidopa. In the control experiments, dopamine (DA) was detectable only in the dialysates from muscle ECF.(ABSTRACT TRUNCATED AT 250 WORDS)


Significance of the vertebral venous (Batson's) plexus in metastatic spread in colorectal carcinoma.
Recently studies of bone metastases in colorectal carcinoma by radionuclide scanning are reviewed. A frequency of 33--61% has been reported using the more recently available bone scanning tests. The commonly accepted frequency of bone metastases from colorectal carcinoma by x-ray or anatomic studies is 5%. This much higher frequency currently being reported must still be established by additional studies. However, if the much high frequency currently being reported is firm, they suggest a much greater importance of the Vertebral Venous Plexus in tumor spread than heretofore suspected for colorectal carcinoma.


Lithium sorption properties of HMnO in seawater and wastewater.
The lithium concentration in seawater is 0.17 mg/L, which is very low, but the overall quantity is approximately 2.5 × 10(14) kg. Therefore, seawater, which contains a vast amount of lithium, could be a major alternative source that might supply the rising demand for lithium. This research was undertaken to evaluate the feasibility of a manganese oxide (HMnO) adsorbent, which was produced after leaching lithium from lithium manganese oxide, for lithium collection from seawater. The HMnO was synthesized and deformed to a plastic after wet blending of manganese oxide and lithium hydroxide, and subsequently, the influence of pH, sorption isotherms, sorption rates, sorption energies, and effects of the co-ions were measured. Thermodynamic parameters such as ΔG°, ΔH°, and ΔS° indicated that the nature of the lithium sorption was both spontaneous and endothermic. The used HMnO could be regenerated by washing it with an HCl solution. The results demonstrated that HMnO could be effectively used for the collection of lithium from seawater with good selectivity.


The first COVID-19 triadic (homicide!)-suicide pact: Do economic distress, disability, sickness, and treatment negligence matter?
Dyadic suicide-pact is rare but possible incidence in the COVID-19 time. No prior evidences available on triadic suicide-pact, which is presented herein for the first-time. An Indian family consisting of three members, committed suicide. There is no evidence of homicide-suicide, which suggests the cases to be mutual suicide-pact. However, the suicide risk factors can be evidently noted as (i) economic distress, (ii) feeling burden of disability and sick people, and (iii) being stubborn as of not getting hospital treatment. Poisoning is reported for the suicide method; besides, the victims left a suicide note. The present case highlights the possibilities of further suicide-pacts in economically unprivileged family, whereas having disabled and/or sick people may add extra burdens in taking such extreme decision.


Investigating the trends in patient-reported outcomes pre-treatment and implications to efficacy analyses: A post-hoc analysis of a cancer clinical trial.
Uncertainty around key elements of an appropriate patient-reported outcome (PRO) baseline assessment introduces trial-specific variation in oncology clinical trials with a poorly understood consequence on drug evaluation decisions. This research investigated the impact of multiple pre-treatment PRO assessments and timing of assessments in a clinical trial. A post-hoc analysis of a completed phase 3, open-label, randomized, parallel arm clinical trial in non-small cell lung cancer with two pre-treatment PRO assessments (screening and Week 1 Day 1 [W1D1]). Descriptive analyses, mixed models for repeated measures and time until definitive deterioration analyses were performed to estimate differences between treatment arms. Through model adjustments, different baseline specifications and assessment timing (pre/post-randomization) on W1D1 PROs were evaluated. Patients with both pre-treatment PRO assessments were included in the analysis (N = 535). Numerically small average change scores were observed between screening and W1D1 (mean change, 0-100 scale ranges): Chest pain (-0.94), Cough (-0.94), Dyspnea (1.27), Physical functioning (-1.19). Both pre-treatment assessments were moderately-highly correlated (r: 0.55-0.78) and no trend was found for deterioration or improvement during this period. Varying baseline definitions in the models produced slight differences in model fit but no impact on the between treatment group effect estimate. W1D1 PRO scores were not statistically influenced by assessment timing pre/post-randomization (p-values: 0.142-0.628). Findings from this study question the need for multiple pre-treatment PRO assessments in oncology drug development trials and the degree of bias thought to be introduced through patient knowledge of treatment assignment. Implications for researchers are presented.


Roflumilast enhances the renal protective effects of retinoids in an HIV-1 transgenic mouse model of rapidly progressive renal failure.
Retinoic acid decreases proteinuria and glomerulosclerosis in several animal models of kidney disease by protecting podocytes from injury. Our recent in vitro studies suggest that all-trans retinoic acid induces podocyte differentiation by activating the retinoic acid receptor-α (RARα)/cAMP/PKA/CREB pathway. When used in combination with all-trans retinoic acid, an inhibitor of phosphodiesterase 4 further enhanced podocyte differentiation by increasing intracellular cAMP. Additionally, we found that Am580, a specific RARα agonist, has similar renal protective effects as all-trans retinoic acid in a rederived colony of HIV-1 transgenic mice with rapidly progressive renal failure (HIV-Tg) that mimics human HIV-associated nephropathy. Treatment with either the inhibitor of phosphodiesterase 4, roflumilast, or Am580 significantly reduced proteinuria, attenuated kidney injury, and improved podocyte differentiation in these HIV-Tg mice. Additional renal protective effects were found when roflumilast was combined with Am580. Consistent with the in vitro data, glomeruli from HIV-Tg mice treated with both Am580 and roflumilast had more active phosphorylated CREB than with either agent alone. Thus, phosphodiesterase 4 inhibitors could be used in combination with RARα agonists to provide additional renal protection.


Inhibition of the calcium store-operated calcium entry pathway by chemotactic peptide and by phorbol ester develops gradually and independently along differentiation of HL60 cells.
N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibited transiently the entry of Ca2+ and Mn2+ induced by emptying with thapsigargin the Ca2+ stores of HL60 cells differentiated toward granulocytes. Phorbol 12,13-dibutyrate (PDB) produced a permanent inhibition of this store-operated Ca2+ entry pathway (SOCP), suggesting that inhibition was due to protein phosphorylation mediated by protein kinase C (PKC). Inhibition by PDB was prevented by the PKC inhibitors staurosporin and chelerythrine. Inhibition by fMLP was prevented by chelerythrine but only partially by staurosporin. The characteristics of the inhibition were similar to those reported in human neutrophils (Montero, M., Alvarez, J., and García-Sancho, J. (1993) J. Biol. Chem. 268, 13055-13061). Neither fMLP nor PDB inhibited significantly SOCP in undifferentiated HL60 cells. Single-cell [Ca2+]i measurements at different stages of differentiation showed that inhibition by fMLP and PDB developed independently, suggesting different inhibitory mechanisms. The simplest explanation would be that inhibition by fMLP takes place through activation of a protein kinase distinct from PKC and that the PDB-activated PKC isoform necessary to phosphorylate and inhibit SOCP is expressed only along differentiation. Additionally, inhibition by both fMLP and PDB developed gradually. At intermediate stages of differentiation, PDB was able to produce a partial and maintained inhibition and fMLP a partial and short-lived inhibition of SOCP.


Contrasting allozyme and RAPD variation in spider populations from patchy forest habitats.
During the last 1000 years, massive deforestation events have occurred in Flanders (the northern part of Belgium) and the remaining forests have become very isolated patches. It is expected that organisms bound to these patchy forest habitats and with limited dispersal capacities will likely experience strong effects of genetic drift. One such organism is the spider Coelotes terrestris. Allozyme data suggested that 10 Flemish populations of this spider showed little genetic variation, as only one out of 20 loci was polymorphic (phosphoglucose isomerase). In view of this result, we used random amplified polymorphic DNA (RAPD) markers to test whether this lack of allozyme diversity is an inherent feature of the populations and/or species studied or whether it rather reflects a characteristic of the markers and/or methods used. Since the RAPD data revealed a substantial amount of genetic diversity in the same 10 populations, our results suggest that the latter is true. Furthermore, the RAPD data agree with the expectations for an organism with low dispersal capacities that has lived in isolated forest patches for at least 200 generations. Supplemented with the results of other techniques and studies, these findings might be of importance for the future conservation of this spider species in Flanders.


Re-thinking the environment in landscape genomics.
Detecting the extrinsic selective pressures shaping genomic variation is critical for a better understanding of adaptation and for forecasting evolutionary responses of natural populations to changing environmental conditions. With increasing availability of geo-referenced environmental data, landscape genomics provides unprecedented insights into how genomic variation and underlying gene functions affect traits potentially under selection. Yet, the robustness of genotype-environment associations used in landscape genomics remains tempered due to various limitations, including the characteristics of environmental data used, sampling designs employed, and statistical frameworks applied. Here, we argue that using complementary or new environmental data sources and well-informed sampling designs may help improve the detection of selective pressures underlying patterns of local adaptation in various organisms and environments.


Effects of a health screening on mortality and causes of death in middle-aged men. A prospective study from 1970 to 1974 of mean in Malmö, born 1914.
All men born in even-numbered months in 1914 and domiciled in Malmö were invited in 1969 to participate in an investigation regarding risk factors for cardiovascular disease. Individuals with a blood pressure of 165/110 and over were treated and a sub-sample of heavy smokers were later invited to take part in a quit-smoking project. During the following five year period total and cause-specific mortality in the examined group was compared with corresponding data for men born in uneven months in 1914. Mortality in the examined cohort was lower than among controls and differed significantly from that in the control group with regard to cardiovascular mortality.


Retraction: Hydrogen Peroxide as an Effective Disinfectant for Pasteurella multocida. Yonsei Med J 2014;55:1152-6.
[This retracts the article DOI: 10.3349/ymj.2014.55.4.1152.].


Transcriptome-wide N6-methyladenosine modification profiling of mRNAs during infection of Newcastle disease virus in chicken macrophages.
N6-methyladenosine (m6A) modification, the most prevalent post-transcriptional modification of eukaryotic mRNAs, is reported to play a crucial role in viral infection. However, the role of m6A modification during Newcastle disease virus (NDV) infection has remained unclear. In this study, we performed MeRIP-seq to investigate the transcriptome-wide m6A methylome and m6A-modified genes in NDV-infected chicken macrophages. A total of 9496 altered peaks were identified, of which 7015 peaks were significantly upregulated across 3320 genes, and 2481 peaks were significantly down-regulated across 1264 genes. Combined analysis of m6A peaks and mRNA expression showed that 1234 mRNAs had significantly altered levels of methylation and expression after NDV infection, and m6A modification tended to have a negative relationship with mRNA expression, suggesting that m6A modification may regulate the process of NDV infection by regulating gene expression, particularly of the genes important in the innate immune response. To the best of our knowledge, this is the first comprehensive characterization of m6A patterns in chicken macrophage mRNA after NDV infection, providing a valuable basis for further exploring the role of m6A modification mechanisms during the course of NDV infection.


Use of oxcarbazepine to treat a pediatric patient with resistant complex regional pain syndrome.
We describe a 12-year-old patient with severe, protracted complex regional pain syndrome type I. His pain did not respond to gabapentin, amitriptyline, physical therapy, opioids, or nonsteroidal drugs. Sympathetic or regional block was not attempted because of persistent bacteremia and severe local sepsis. His pain responded dramatically to the addition of oxcarbazepine, with rapid improvement in his symptoms and functional status. We suggest that oxcarbazepine might be a useful adjunct in the treatment of gabapentin-resistant complex regional pain syndrome type I in children and should be considered. Oxcarbazepine's antinociceptive effect is mediated via sodium channel inhibition in neuropathic models and by inhibition of substance P and prostaglandins in anti-inflammatory models. The efficacy of oxcarbazepine in this patient might be attributable to these mechanisms or possibly to synergism with either gabapentin or the anti-inflammatory effects produced by amitriptyline.


Doppler sonographic evaluation of resistive index of intra-renal arteries in acute ureteric obstruction.
Acute ureteric colic is one of the most commonly encountered acute abdominal conditions. Diagnosis of obstruction caused by ureteric calculus occasionally becomes challenging if there is inadequate dilation of the urinary tract proximal to obstruction. In such a situation, intra-renal artery Doppler parameters can be used as a diagnostic tool. Our study compared intra-renal arterial Doppler in patients with obstructed and non-obstructed kidneys presenting within 24 h of onset of symptoms of unilateral acute renal colic. The resistivity index (RI) in the segmental arteries of all 54 patients with obstructed kidneys was significantly higher than in those with non-obstructed kidney: 0.75 vs. 0.56, with a p value less than 0.001, a sensitivity of 85% and a specificity of 93%. Doppler ultrasound is a useful diagnostic tool in the evaluation of acute renal obstruction, thus enabling practitioners to avoid ordering unnecessary CT and exposing patients to ionizing radiation. An RI value > 0.7 has good sensitivity and specificity in our study. The results obtained in the study were comparable to those of pioneer studies conducted worldwide.


Cloning, expression and characterization of the murine Efemp1, a gene mutated in Doyne-Honeycomb retinal dystrophy.
Development of the bone and cartilage structures is one of the best-studied systems for epithelial-mesenchymal interaction as well as proliferation and differentiation. In a screen for genes differentially expressed in mice deficient for transcription factor AP-2alpha, we have identified a gene which, based on its homology to the human EFEMP-1 gene was designated Efemp1. It encodes for six repeats similar to the domain of the epidermal growth factor. Sequence comparison with EFEMP1 genes of human and rat revealed that the three proteins share a high amino acid identity (92%), suggesting a conserved function during vertebrate development. However, there is no EFEMP1ortholog annotated in sequence databases of other non-mammalian species indicating that it might have evolved in higher vertebrates only. Analysis of the murine genomic locus revealed that the gene is encoded by 11 exons, which are spread over 80 kb of distance on murine chromosome 11A4. The multidomain protein structure may indicate that Efemp1 protein interacts with extracellular matrix components and serves to connect and integrate the function of multiple partner molecules. The gene is expressed in the embryo proper starting from day 9.5 to day 18.5 of murine development. In situ analyses showed that Efemp1 is found in condensing mesenchyme, giving rise to bone and cartilage as well as in developing bone structures of the cranial and the axial skeleton. These results will help in further defining the role of Efemp1 during murine embryogenesis.


Growth hormone-releasing pituitary microadenoma overshaded by a macroadenoma: a case of double pituitary adenomas and review of the literature.
Double pituitary adenoma is a rare entity that can pose a significant challenge. The incidence of double or multiple pituitary adenomas is ∼1% in autopsy cases and 0.4-1.3% in surgical series. Its definition varies, including 'double adenomas' in the literature in contrast to 'multiple adenomas', which is more specific and suitable. While some authors require separating topographically unique tumours, others have used a looser definition of separate immunohistochemistry. We presented the case of a 26-year-old patient with recurrent carpal tunnel syndrome symptoms, with double pituitary adenomas secreting growth hormone (GH) and thyroid-stimulating hormone (TSH). To date, 89 patients have been reported in the literature with symptomatic carpal tunnel syndrome, but only five had GH-TSH secretion. Double adenoma resection is of great importance for ensuring successful biochemical treatment. To ensure a successful operation, a careful preoperative 3T MRI examination is of great importance.


Lung lavage and surfactant replacement for hydrochloric acid aspiration in rabbits.
Hydrochloric acid (0.1 N, 5.0 ml.kg-1 in total) was administered intratracheally to 28 adult rabbits anesthetized with pentobarbital and mechanically ventilated with pure oxygen. When the PaO2 decreased to 14.1 +/- 2.8 kPa (mean +/- s.d.), the PaCO2 increased to 8.9 +/- 2.5 kPa, and the minute ventilation (VE) decreased to 51 +/- 8% of the baseline value, animals were divided into 4 groups. The deteriorated values did not improve in the non-treated (control) animals, whereas the animals treated with lung lavage and surfactant replacement showed a significant increase in PaO2 to 35.1 +/- 12.2 kPa, and maintained lower PaCO2 and larger VE than the controls. These parameters showed no significant improvement with surfactant replacement alone, and deteriorated further with lung lavage alone. The minimum surface tension (gamma min) of the edema fluid that accumulated in the airways after acid administration was 22.5 +/- 1.7 mN.m-1, and was not lowered by adding surfactant preparation (10 mg.ml-1) whose original gamma min was less than 2 mN.m-1. We concluded that surfactant inhibition by edema fluid was a cause of respiratory failure, and that lung lavage followed by surfactant replacement might be of therapeutic value for acid aspiration.


The extent of task-sharing implementation as a strategy to expand abortion services in Colombia.
To analyze the extent to which task-sharing to midlevel providers has been implemented as a strategy to increase access to abortion provision in Colombia, and examine the factors that have affected decentralization of services. We conducted a case study based on the World Health Organization's 2015 guideline: Health Worker Roles in Providing Safe Abortion Care and Post-abortion Contraception. Documentation was collected on the standard and epidemiological landscape of abortion in Colombia, followed by semistructured discussions with groups and individual stakeholders. Task-sharing as a distinct policy to increase access to abortion services has not been implemented in Colombia. However, role distribution toward nonspecialist physicians has been used as a strategy to ensure access. Other professionals, such as nurses, have limited tasks in abortion care despite evidence to support a more expanded role. The implementation of task-sharing as a strategy to increase access to safe abortion services in Colombia is influenced by a wide range of factors and, although it is not policy, nonspecialist and diverse healthcare professionals supervise abortion care. Knowing the evidence-based guidelines to safely and successfully include other healthcare professionals in abortion provision is a fundamental step in implementing this strategy.


Brain microdialysis in freely moving animals.
Brain microdialysis is an analytical technique used for the dynamic monitoring of brain neurochemistry in awake, freely moving animals. This technique requires the insertion of a small dialysis catheter, called a microdialysis probe, into a specific brain region, and its perfusion with an artificial extracellular fluid. The microdialysate samples, obtained from the probe outlet, can be analysed using high-performance liquid chromatography with electrochemical detection for the quantification of oxidizable molecules recovered from the extracellular space. In this chapter, we describe a protocol for performing a microdialysis setup and experiment in freely moving rats and mice. Furthermore, the high-performance liquid chromatographic determination of ascorbic acid, uric acid, catecholamines, indolamines and derivatives is described in detail.


Enhanced anaerobic digestion of waste activated sludge with periodate-based pretreatment.
The potential of periodate (PI) in sludge anaerobic digestion is not tapped, although it has recently attracted great research interest in organic contaminants removal and pathogens inactivation in wastewater treatment. This is the first work to demonstrate significant improvement in methane generation from waste activated sludge (WAS) with PI pretreatment and to provide underlying mechanisms. Biochemical methane potential tests indicated that methane yield enhanced from 100.2 to 146.3 L per kg VS (VS, volatile solids) with PI dosages from 0 to 100 mg per g TS (TS, total solids). Electron spin resonance showed PI could be activated without extra activator addition, which might be attributed to the native transition metals (e.g., Fe2+) in WAS, thereby generating hydroxyl radical (•OH), superoxide radicals (•O2 -), and singlet oxygen (1O2). Further scavenging tests demonstrated all of them synergistically promoted WAS disintegration, and their contributions were in the order of •O2 - > •OH > 1O2, leading to the release of substantial biodegradable substances (i.e., proteins and polysaccharides) into the liquid phase for subsequent biotransformation. Moreover, fluorescence and ultraviolet spectroscopy analyses indicated the recalcitrant organics (especially lignocellulose and humus) could be degraded by reducing their aromaticity under oxidative stress of PI, thus readily for methanogenesis. Microbial community analysis revealed some microorganisms participating in hydrolysis, acidogenesis, and acetoclastic methanogenesis were enriched after PI pretreatment. The improved key enzyme activities and up-regulated metabolic pathways further provided direct evidence for enhanced methane production. This research was expected to broaden the application scope of PI and provide more diverse pretreatment choices for energy recovery through anaerobic digestion.


COVID-19 susceptibility and outcomes among patients with neuromyelitis optica spectrum disorder (NMOSD): A systematic review and meta-analysis.
We conducted this systematic review and meta-analysis to assess the risk of coronavirus disease (COVID-19), clinical features and outcome among patients with neuromyelitis optica spectrum disorder (NMOSD). We systematically searched PubMed, Scopus, Web of Science, and Embase from December 1, 2019, to July 2, 2021. The gray literature including the references of original studies, review studies, conference abstracts, and WHO COVID-19 database was also searched. We included any type of studies that reported NMOSD patients with COVID-19, prevalence of COVID-19 among NMOSD patients or the infection outcome (hospitalization, intensive care unit [ICU] admission, or mortality). Out of 540 records, a total of 23 studies (19 published articles and 4 conference abstracts) including 112 NMOSD patients with COVID-19 met the inclusion criteria. Nine studies reporting risk of COVID-19 and nine studies on outcome were included in a quantitative synthesis. The pooled prevalence of COVID-19 was 1.2% (95% CI: 0.001%-0.030%; I2 = 92%, p< 0.001), with hospitalization of 33.7% (95% CI: 23.3-44.8%; I2 = 9.1%, p = 0.360) with 52.9% on rituximab treatment. ICU admission was 15.4% (95% CI: 7.6%-24.7%; I2 = 20.7%, p = 0.272) and mortality was 3.3% (95% CI: 0-9.7%; I2 = 21.3%, p = 0.253). Thirty-eight patients (48.7%) reported at least one comorbidity. The mean age of the included patients was 40.8 (10.63) years, female/male ratio was 3.35:1. The most common COVID-19 symptom was fever (54.5%), followed by fatigue/asthenia (42.9%), headache (41.6%), and cough (40.3%). Four patients developed neurological worsening. The Begg's and Egger's tests showed no evidence of publication bias. The analysis suggests that comorbidity and treatment with rituximab may be risk factors for COVID-19 infection in NMOSD patients.


Lifetime History of Suicide Attempts among Not Guilty by Reason of Insanity State Hospital Inpatients: The Roles of past Harmful Substance Use and Current Social Support.
This study tested current perceived social support (CPSS) as a moderator of the relation between previous substance use (PSU) and lifetime suicide attempt (SA) history among 200 NGRI inpatients. Results indicated no significant CPSS main effect. PSU was associated with greater odds of multiple prior lifetime SA. Moderation indicated those low in PSU but high in CPSS were least likely to report multiple prior lifetime SA. Conversely, NGRI inpatients with high CPSS and high PSU were most likely to report multiple lifetime SA. Our study suggests CPSS and PSU assessments may inform suicide risk assessments and interventions among NGRI inpatients.


Benefits of a hospital-based peer intervention program for violently injured youth.
Exposure to violence predisposes youths to future violent behavior. Breaking the cycle of violence in inner cities is the primary objective of hospital-based violence intervention and prevention programs. An evaluation was undertaken to determine if a hospital-based, peer intervention program, "Caught in the Crossfire," reduces the risk of criminal justice involvement, decreases hospitalizations from traumatic reinjury, diminishes death from intentional violent trauma, and is cost effective. We designed a retrospective cohort study conducted between January 1998 and June 2003 at a university-based urban trauma center. The duration of followup was 18 months. Patients were 12 to 20 years of age and were hospitalized for intentional violent trauma. The "enrolled" group had a minimum of five interactions with an intervention specialist. The control group was selected from the hospital database by matching age, gender, race or ethnicity, type of injury, and year of admission. All patients came from socioeconomically disadvantaged areas. The total sample size was 154 patients. Participation in the hospital-based peer intervention program lowered the risk of criminal justice involvement (relative risk=0.67; 95% CI, 0.45, 0.99; p=0.04). There was no effect on risks of reinjury and death. Subsequent violent criminal behavior was reduced by 7% (p=0.15). Logistic regression analysis showed age had a confounding effect on the association between program participation and criminal justice involvement (relative risk=0.71; p=0.043). When compared with juvenile detention center costs, the total cost reduction derived from the intervention program annually was $750,000 to $1.5 million. This hospital-based peer intervention program reduces the risk of criminal justice system involvement, is more effective with younger patients, and is cost effective. Any effect on reinjury and death will require a larger sample size and longer followup.


Escherichia coli hemolysin permeabilizes small unilamellar vesicles loaded with calcein by a single-hit mechanism.
Escherichia coli hemolysin produces small unilamellar lipid vesicles permeable to the fluorescent dye calcein by forming pores through their membrane. The process of permeabilization proceeds as a pseudo first-order reaction, indicating that the toxin is active as a monomer; consistently no evidence for cooperativity has been found in a dose-response titration. The rate of interaction increases on lowering the pH of the solution and by introducing negatively charged lipids into the vesicles. The overall pore formation mechanism resembles that of other toxins of bacterial origin such as colicins, diphtheria, tetanus and botulinum toxin.


Protooncogene expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus as an indicator of the disease activity.
In the present study, we examined the various protooncogene expressions in PBMC (peripheral blood mononuclear cell) of systemic lupus erythematosus (SLE) patients to determine if they could be an indicator for the disease activity. We divided SLE patients into "very active," "active," and "remitting" states according to the clinical symptoms in addition to the laboratory data peculiar to SLE. In addition, we determined the amount of circulating immune complex (IC) as one of the representative laboratory indicators for the disease activity. We found a positive correlation with either c-myc or c-myb expression and the amounts of IC and clinical disease activity. The degree of c-myc and c-myb expression was significantly reduced along with or prior to the amelioration of clinical symptoms and improvement as determined by laboratory data under treatment with prednisolone and/or azathioprine administration. The degree of c-myc and c-myb gene expression had no direct relation to the presence of particular clinical sign(s) or autoantibody. The expression of the c-raf gene was found in SLE and other systemic autoallergic patients although it showed no correlation with the disease activity. No significant expression of c-src, c-ras, c-fos, c-fgr, c-fps, c-fes, c-fms, c-yes, c-rel, c-abl, c-mos, c-sis, and c-erb B genes was found in the patients. c-myc and c-myb expression as having pathogenic and clinical significance is discussed.


Descemet's Stripping Automated Endothelial Keratoplasty versus Descemet's Membrane Endothelial Keratoplasty in the Fellow Eye for Fuchs Endothelial Dystrophy: A Retrospective Study.
To evaluate visual outcome and endothelial cell density (ECD) after Descemet's Membrane Endothelial Keratoplasty (DMEK) in comparison with Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) in the fellow eye for Fuchs endothelial dystrophy (FED). Single-centre, retrospective case series. 30 eyes of 30 patients undergoing DMEK, who completed a 1-year follow-up, were compared with 30 fellow eyes which underwent DSAEK for bilateral FED. Main outcome measures studied included Best Corrected Visual Acuity (BCVA) and ECD during a 1-year follow-up period. BCVA improved from 0.78 ± 0.35 logMAR, and 0.73 ± 0.31 logMAR before surgery to 0.22 ± 0.1 logMAR and 0.35 ± 0.12 logMAR 6 months after DMEK and DSEK, respectively (P < 0.001). At one year after surgery, the BCVA was maintained at 0.21 ± 0.12 logMAR and 0.34 ± 0.1 logMAR, respectively, after DMEK and DSAEK. A statistically better visual outcome was observed after DMEK compared to DSAEK (P < 0.05) in fellow eyes. DMEK provided better visual rehabilitation when compared to DSAEK. Nevertheless, there were no significant differences with regard to the ECD within a 1-year follow-up.


Nerve sprouting contributes to increased severity of ventricular tachyarrhythmias by upregulating iGluRs in rats with healed myocardial necrotic injury.
Sympathetic nerve sprouting in healed myocardial infarction (MI) has been associated with high incidences of lethal arrhythmias, but the underlying mechanisms are largely unknown. This study sought to test that sympathetic hyperinnervation and/or MI remodels the myocardial glutamate signaling and ultimately increases the severity of ventricular tachyarrhythmias. Myocardial necrotic injury (MNI) was created by liquid nitrogen freeze-thawing across an intact diaphragm to mimic MI. Cardiac sympathetic hyperinnervation was induced by chronic subcutaneous injection of 4-methylcatechol, a potent stimulator of nerve growth factor expression. The results showed that sympathetic hyperinnervation with or without MNI upregulated the myocardial expression of ionotropic glutamate receptors (iGluRs), including NMDA receptor (NMDAR) and AMPA receptor (AMPAR), and induced cardiomyocyte apoptosis. Intravenous infusion with either NMDA (12 mg/kg) or AMPA (15 mg/kg) triggered ventricular tachycardia and ventricular fibrillation in rats with healed MNI plus sympathetic hyperinnervation; these arrhythmias were prevented by respective antagonist of NMDAR or AMPAR. We conclude that MNI with sympathetic nerve sprouting upregulates the expression of NMDAR and AMPAR in the myocardium and this impact in turn enhances cardiac responses to stimulations of iGluRs and thus increases the incidence of ventricular tachyarrhythmias.


The kinaesthetic perception of Euclidean distance: a study of the detour effect.
An experiment investigated the mechanisms by which humans estimate Euclidean distances on the basis of kinaesthetic cues. Blindfolded participants followed straight and curvilinear paths with a hand-held stylus (encoding phase). Then, with a straight movement, they estimated the Euclidean distance between the start- and end-points of the path (response phase). The experiment contrasted an On-axis condition, in which encoding and response movements were spatially aligned, and an Off-axis condition, in which they were displaced laterally. Performances were slightly more accurate in the On-axis condition than in the Off-axis condition. In both conditions, however, errors were consistently smaller when the path covered a larger surface. The results showed that small paths yielded an overestimation of the Euclidean distance, the relative errors increasing with the length of curvilinear paths. The findings are compared with results of other studies in which distances were estimated on the basis of haptic cues.


Clinical impact of hepatic steatosis on chronic hepatitis B patients in Asia: A systematic review and meta-analysis.
Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.


Vestibular migraine: clinical and epidemiological aspects.
Vestibular migraine (VM) is one of the most often common diagnoses in neurotology, but only recently has been recognized as a disease. To analyze the clinical and epidemiological profile of patients with VM. This was a retrospective, observational, and descriptive study, with analysis of patients' records from an outpatient VM clinic. 94.1% of patients were females and 5.9% were males. The mean age was 46.1 years; 65.6% of patients had had headache for a longer period than dizziness. A correlation was detected between VM symptoms and the menstrual period. 61.53% of patients had auditory symptoms, with tinnitus the most common, although tonal audiometry was normal in 68.51%. Vectoelectronystagmography was normal in 67.34%, 10.20% had hyporeflexia, and 22.44% had vestibular hyperreflexia. Electrophysiological assessment showed no abnormalities in most patients. Fasting plasma glucose and glycemic curve were normal in most patients, while the insulin curve was abnormal in 75%. 82% of individuals with MV showed abnormalities on the metabolism of carbohydrates. VM affects predominantly middle-aged women, with migraine headache representing the first symptom, several years before vertigo. Physical, auditory, and vestibular evaluations are usually normal. The most frequent vestibular abnormality was hyperreflexia. Most individuals showed abnormality related to carbohydrate metabolism.


Label-free characterization of organoids with quantitative confocal Raman spectral imaging.
Stem cell-derived organoids have the potential to significantly improve the drug discovery process. However, a key challenge is monitoring the maturation process and drug response. In this issue of Cell Reports Methods, LaLone et al. have shown that quantitative confocal Raman spectral imaging, a label-free technique, can reliably monitor organoid development, drug accumulation, and drug metabolism.


[Genital actinomycosis and the intrauterine device. Apropos of 3 cases].
Three cases of actinomycosis are reported. In two of these three patients, both of whom had worn an intra-uterine device for several years, the actinomycosis probably followed secondary to previous appendicitis. In the third case, however, it was primary and directly linked to the presence of the I.U.D. From these observations and from studying the literature, this type of infection should be suspected in any women wearing an I.U.D. who has a tubo-ovarian abscess.


Gas-phase purification enables accurate, multiplexed proteome quantification with isobaric tagging.
We describe a mass spectrometry method, QuantMode, which improves accuracy of isobaric tag-based quantification by alleviating the pervasive problem of precursor interference, simultaneous isolation and fragmentation of impurities, through gas-phase purification. QuantMode analysis of a yeast sample 'contaminated' with interfering human peptides showed substantially improved quantitative accuracy compared to a standard scan, with a small loss of spectral identifications. This technique enables large-scale, multiplexed quantitative proteomics using isobaric tagging.


Estradiol regulation of astroglia and apolipoprotein E: an important role in neuronal regeneration.
The effects of ovarian hormone on neuronal growth and function are well known. However, equally important, but often neglected, are ovarian hormone effects on glia. Our in vivo and in vitro studies show that estradiol modifies both neuronal growth and glial activity and these effects are tightly linked. Estradiol stimulates neurite growth and the release of the glial apolipoprotein E (apoE) in culture studies. Estradiol-stimulated neurite growth in these cultures requires apoE. Estradiol replacement in ovariectomized mice transiently increases the expression of apoE, the low density lipoprotein receptor related protein (LRP) and synaptophysin throughout the brain. Continuous estradiol replacement over two months loses effect on apoE, LRP, and synaptophysin and suppresses reactive gliosis. Estrous cycle variation of glial activation (GFAP) and apoE are not identical. We propose that estradiol (and other ovarian hormones) functions as a zeitgeber to co-ordinate neuronal-glial interactions. Co-ordination assures temporally appropriate excitatory and inhibitory interactions between glia and neurons. With aging and the loss of ovarian cyclicity, some of this co-ordination must be diminished. These observations present significant clinical implications. Approaches to hormone therapy (HT), for diminishing the risk of chronic neurological diseases, need to consider the temporal nature of ovarian hormones in brain repair and plasticity. Moreover, approaches must consider apoE genotype. The neuroprotective effects of HT in numerous chronic age-related diseases may represent effective co-ordination of repair processes rather than direct disease-specific actions. Moreover, the role of glial-derived proteins in neuroprotection should not be ignored.


Coverage and Determinants of COVID-19 Vaccination Among Pregnant Women: An Experience From a Low-Income Country.
to determine COVID-19 vaccination coverage among pregnant women and investigate the factors affecting vaccine uptake. Analytical cross-sectional study. Palestinian health care facilities. Between October and November 2021 - eight months after the country's first COVID-19 vaccination. We needed 820 people to estimate vaccination coverage among pregnant women with a precision rate of 3%. Therefore, we invited 950 pregnant Palestinian women who were eligible and had a response rate of 91.6%. An interviewer-administered questionnaire examined vaccination uptake, attitudes, and concerns about the COVID-19 vaccine. Bivariable and multivariable analysis using SPSS. vaccination uptake was reported by 219 pregnant women [25.5%, 95% CI: 22.6% -28.5%]. Knowledge (aOR=2.0; 95% CI: 1.2-3.1), perceived benefits (aOR=1.1; 95% CI: 1.06-1.16), employment (aOR=5; 95% CI: 3.1-8.1), and underlying medical condition (aOR=2.1; 95% CI: 1.1-4.1) predicted uptake. Reporting vaccine barriers reduces vaccine uptake (aOR=.92; 95% CI: .89-95). Pregnant women's COVID-19 vaccination rates are low. Concerns regarding the COVID-19 vaccine for infants affected their decision. COVID-19 vaccination regulations and legislative nudges drove maternal vaccination. Vaccine fears and misconceptions among pregnant women should be addressed.


Influence of hydrogen sulfide on zymogen activation of homocysteine-induced matrix metalloproteinase-2 in H9C2 cardiocytes.
To observe the influence of different concentrations of homocysteine (Hcy) and hydrogen sulfide (H2S) on the secretion and activation of matrix metalloproteinase-2 (MMP-2) in cardiocytes so as to search for new ways to fight against myocardial tissue fibrosis. Cardiocytes H9C2 was cultured in vitro and different concentrations of Hcy and H2S were added for 6-h and 24-h cultivation. MTT cell proliferation assay was applied to test the activation change of cardiocytes H9C2 after affecting by different concentrations of Hcy and H2S. ELISA and MTT were employed to detect the expression and enzymatic activity of MMP-2. The H9C2 cell inhibition of activity was more significant with 1000 μmol/L of Hcy as compared with other concentrations (P < 0.001). With 2.5-100.0 μmol/L Hcy and 0.1, 1.0 and 10.0 mmol/L H2S, the activity of H9C2 did not change significantly (P > 0.05). Hcy with concentrations of 10, 50 and 100 μmol/L could increase the quantity of MMP-2 secreted by cardiocytes H9C2, and the interaction strength was concentration-dependent (P < 0.05). After interacting with 100 μmol/L of Hcy for 6 h, the zymogen activation effect of MMP-2 was stronger than that of the 2.5-25 μmol/L group (P < 0.05). After interacting with Hcy and H2S (1.0 mmol/L) for 6 h and 24 h, the activation effect of MMP-2 was stronger than those interacted with 10, 25, 50 and 100 μmol/L of Hcy (P < 0.05). Hcy can increase the production of MMP-2 secreted by H9C2 cell and improve its zymogen activation. Besides, the interaction strength is concentration-dependent; while H2S can up-regulate the activation of MMP-2 and co-promote the activation of MMP-2 with Hcy as well.


Expression and purification of cyto-insectotoxin (Cit1a) using silkworm larvae targeting for an antimicrobial therapeutic agent.
Antimicrobial peptides (AMPs), both synthetic and from natural sources, have raised interest recently as potential alternatives to antibiotics. Cyto-insectotoxin (Cit1a) is a 69-amino-acid antimicrobial peptide isolated from the venom of the central Asian spider Lachesana tarabaevi. The synthetic gene Cit1a fused with the enhanced green fluorescent protein (EGFP) gene was expressed as the EGFP-Cit1a fusion protein using a cysteine protease-deleted Bombyx mori nucleopolyhedrovirus (BmNPV-CP(-)) bacmid in silkworm larva and pupa. The antimicrobial effect of the purified protein was assayed using disk diffusion and broth microdilution methods. The minimum inhibitory concentration of EGFP-Cit1a was also measured against several bacterial strains and showed similar antimicrobial activity to that of the synthetic Cit1a reported earlier. The EGFP-Cit1a fusion protein showed antibiotic activity toward gram-positive and gram-negative bacteria at the micromolar concentration level. These results show that active Cit1a can be produced and purified in silkworm, although this peptide is insecticidal. This study demonstrates the potential of active Cit1a purified from silkworms to use as an antimicrobial agent.


Time course of auditory impairment in mice lacking the electroneutral sodium bicarbonate cotransporter NBC3 (slc4a7).
Mice with a targeted disruption of the gene encoding the stilbene-insensitive electroneutral sodium bicarbonate cotransporter (NBC3; slc4a7) exhibit cochlear and retinal degeneration. To establish the progressive nature of sensory cells loss in slc4a7-/- deficient mice, we studied the morphology of cochleas of slc4a7-/- and slc4a7+/+ mice from postnatal day two (P2) to ninety (P90). Cell death was evaluated in slc4a7-/- cochleas using the TUNEL technique and caspase-3 immunoreactivity. The time course of NBC3 expression in the cochlea was assessed by immunohistochemistry using an antibody against NBC3. Between P2 and P8, slc4a7-/- mice cochlea exhibit normal morphology. There was a normal complement of inner and outer hair cells from the hook to the apical region. At P15, slc4a7-/- mice cochlea inner and outer hair cells were still present at the hook region, and vacuoles were seen underneath Hensen's cells. At P21, inner and outer hair cells were degenerated in this region. Between P30 and P90, there was a pronounced loss of hair cells and spiral ganglia neurons. Morphological analysis of the spiral ligament showed a progressive loss of type II and IV fibrocytes beginning at day 21. Transmission electron microscopy observations at P30 and P90 revealed that type II and IV fibrocytes showed shrinkage and vacuolization. In addition, hair cells were deteriorated with evidence of shrinkage and picnotic nuclei. TUNEL staining showed apoptotic cells at P8 in the organ of Corti at the basal region of the cochlea. At P15, caspase-3 immunoreactivity was present in supporting cells of the organ of Corti. NBC3 mild immunoreactivity was detected in the organ of Corti at P11. There was an increase in the expression of NBC3 in the spiral ligament between P17 and P19. From P21 to P90, NBC3 expression was confined to the spiral ligament and inner and outer sulcus cells. The vestibular sensory epithelia from slc4a7-/- mice were normal from P2 to P90. Damage of the sensory epithelia at the high frequency zone of the cochlea suggests that NBC3 may play an important physiological role in this region.


Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants.
Plasmid-mediated resistance to polymyxins mediated by the MCR-1/2 determinants has been reported in Enterobacteriaceae worldwide. Using PCR-based and cloning strategies, a series of Moraxella spp. were screened for mcr-like genes. Moraxella spp. that are mainly animal pathogens but may also be human pathogens were identified as potential reservoirs of mcr-like genes.


[Change in the content of adenine nucleotides and creatine phosphate and in the activity of creatine kinase in the large intestine mucosa in chronic enterocolitis in relation to the severity of the disease].
Content of ATP, ADP, AMP, phosphocreatine and activity of creatine kinase were estimated in homogenates of biopsy material obtained from large intestine mucose of patients with chronic enterocolitis and of healthy persons. Impairments were observed in interrelations and transformations of adenine nucleotides and in creatine kinase reactions. Decrease in content of total adenine nucleotides and of ATP correlated with the degree of the disease severity. In severe cases the molar ratio ATP/ADP was distinctly decreased.


Development of 12 microsatellite markers for Bombina orientails based on RNA-Seq and their usefulness in population genetic diversity.
Bombina orientalis is widely used due to bombesin which isolated from its skin. But in recent years, the population of B. orientalis has become declining distinctly because of human activities, environmental pollution, drought climatic conditions and other factors. In order to provide the molecular basis for the proposal of biodiversity conservation, we report the development of 12 microsatellite markers for B. orientalis based on RNA-Seq. We test polymorphism against in 48 B. orientalis individuals which randomly selected from 182 individuals take advantage of polyacrylamide gel electrophoresis (PAGE). These markers will be useful in the research on the genetic diversity, population genetic structure and other studies. For B. orientalis, all of these loci showed polymorphism, and in line with the H-W equilibrium law. The number of alleles per locus ranged from 3 to 21. The observed and expected heterozygosities ranged from 0.0118 to 0.7795 and from 0.1612 to 0.8703, respectively. The polymorphism information content ranged from 0.153 to 0.857. And the genetic diversity of B. orientalis in Lushui Rivers is significantly higher than that in the Maoer Mountains.


Prokaryotic expression and action mechanism of antimicrobial LsGRP1C recombinant protein containing a fusion partner of small ubiquitin-like modifier.
Antimicrobial peptides (AMPs) are peptides exhibiting broad-spectrum antimicrobial activities and considered as potential therapeutic agents. LsGRP1C, a novel AMP derived from defense-related LsGRP1 protein of Lilium, was proven to inhibit kinds of bacteria and fungi via alteration of microbial membrane permeability and induction of fungal programmed cell death-like phenomena by in vitro assays using synthetic LsGRP1C. In this study, the prokaryotic production of LsGRP1C recombinant protein containing an N-terminal fusion partner of the yeast small ubiquitin-like modifier (SUMO) was achieved by using optimized Escherichia coli host and purification buffer system, which lead to a high yield of soluble SUMO-LsGRP1C fusion protein. In vitro assay revealed that E. coli-expressed SUMO-LsGRP1C exhibited even better antifungal activity as compared to synthetic LsGRP1C. Meanwhile, the ability of SUMO-LsGRP1C in conducting fungal membrane permeabilization and programmed cell death was verified by SYTOX Green staining and 4',6-diamidino-2-phenylindole staining/terminal deoxynucleotidyl transferase dUTP nick-end labeling assays, respectively, indicating that E. coli-expressed SUMO-LsGRP1C shares identical modes of action with synthetic LsGRP1C. Herein, this E. coli expression system enables the effective and convenient production of antimicrobial LsGRP1C in a form of SUMO-fused recombinant protein.


Haemodynamic response to crystalloids or colloids in shock: an exploratory subgroup analysis of a randomised controlled trial.
To compare the haemodynamic effect of crystalloids and colloids during acute severe hypovolaemic shock. Exploratory subgroup analysis of a multicentre randomised controlled trial (Colloids Versus Crystalloids for the Resuscitation of the Critically Ill, CRISTAL, ClinicalTrials.gov NCT00318942). CRISTAL was conducted in intensive care units in Europe, North Africa and Canada. Current analysis included all patients who had a pulmonary artery catheter in place at randomisation. 220 patients (117 received crystalloids vs 103 colloids) underwent pulmonary artery catheterisation. Crystalloids versus colloids for fluid resuscitation in hypovolaemic shock. Haemodynamic data were collected at the time of randomisation and subsequently on days 1, 2, 3, 4, 5, 6 and 7. Median cumulative volume of fluid administered during the first 7 days was higher in the crystalloids group than in the colloids group (3500 (2000-6000) vs 2500 (1000-4000) mL, p=0.01). Patients in the colloids arm exhibited a lower heart rate over time compared with those allocated to the crystalloids arm (p=0.014). There was no significant difference in Cardiac Index (p=0.053), mean blood pressure (p=0.4), arterial lactates (p=0.9) or global Sequential Organ Failure Assessment score (p=0.3) over time between arms. During acute severe hypovolaemic shock, patients monitored by a pulmonary artery catheter achieved broadly similar haemodynamic outcomes, using lower volumes of colloids than crystalloids. The heart rate was lower in the colloids arm.


Copper levels and changes in pH induce oxidative stress in the tissue of curimbata (Prochilodus lineatus).
We analyzed the effect of exposure to 25% 96 h-LC50 of copper at low (24.5 μg L(-1) Cu, pH 4.5), neutral (7.25 μg L(-1) Cu, pH 7.0) and high pH (4.0 μg L(-1) Cu, pH 8.0) at 20 °C on antioxidant defenses and oxidative stress in the liver, gills and white muscle of the fish Prochilodus lineatus. Water at pH 4.5 and 8.0 affected the enzymatic and non-enzymatic antioxidant systems of the liver and gills, but not of the white muscles of P. lineatus, when compared to water at pH 7.0. After Cu exposure, SOD (superoxide dismutase), GPx (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) activities increased and CAT (catalase) activity decreased in the liver at water at pH 4.5 and 8.0. Meanwhile, the activities of SOD, CAT, GPx, GR and GST increased in the gills at these pHs. SOD and CAT activities increased in the white muscle after Cu exposure at pH 8.0 and GPx, GR and GST activities decreased after Cu exposure at pH 4.5 and 8.0. LPO levels decreased in the liver and gills of fish that were exposed to water at pH 4.5 and 8.0 and, after Cu exposure, the LPO level increased in the liver, gills and white muscle of fish that were exposed to water at pH 4.5 and 8.0, when compared to the control group at pH 7.0. The metallothionein (MT) concentration increased in the liver of fish in water at pH 4.5 and 8.0 and the gill of fish in water at pH 8.0. After Cu exposure, MT in the liver and gills was significantly elevated in fish exposed to water at pH 4.5 and 8.0, but remained at levels similar to the control group in the white muscle. These results indicate a differing sensitivity of fish organs and tissues to essential metals, such as copper, and that toxicity may be relevant at environmental concentrations. These results indicate that the effect of Cu on the response of antioxidant defense systems is determined by water pH.


Effector or target cell selection mediated by C3 bridges.
Potential effector cells (including stimulated lymphocytes and cultured monocytes) and potential target cells of NK and AK type cytotoxic reactions (including several lymphoblastoid cell lines) cleave the third complement component (C3). As a result of expression of C3bA sites such cells are able to bind covalently the activated C3b through its metastable binding site and thereby become "armed" by the C3b. This permits C3b-bridge formation between these cells and CR1-bearing cells. The "effector selection" (i.e. when C3b is bound covalently to potential target cells) or "target selection" (when C3b is covalently bound to C3bA sites on potential effector cells) mediated by C3b bridges results in enhanced killing capacity. Macrophages activate and bind C3b as well; but the covalent binding of C3b by these cells inhibits Fc receptor mediated ADCC type killing.


Periodic polarization of electroactive biofilms increases current density and charge carriers concentration while modifying biofilm structure.
Anodic electroactive biofilms (EABs) need to overcome low current densities for applications such as microbial fuel cells or biosensors. EABs can store charge in self-produced redox proteins when temporarily left in open circuit, and discharge them once the electrode is appropriately repolarized, thus behaving as pseudocapacitors. Here we investigated the effect of such periodic polarization on the intrinsic nature of the EABs during their entire growth (i.e. starting from inoculation and for 10 days) on glassy carbon electrodes. An optimal periodic polarization (half-period of 10 s) greatly increased the maximum steady-state current density delivered by the Geobacter-dominated EABs (up to 1.10 ± 0.02 mA cm-2, n = 3 electrodes) when compared to continuously polarized EABs (0.41 ± 0.04 mA cm-2); and increased the amount of electric charges produced per hour by 69 ± 17% even taking into account the half-periods of open circuit. This enhancement was highly correlated with a substantial increase in charge carriers concentration (10.6 ± 0.5 mMe- vs. 2.9 ± 0.6 mMe-), allowing higher charge storage capacity and higher electron mobility across the EABs. Our results suggest that appropriate periodic polarizations may upregulate the expression of heme-containing redox proteins associated with the matrix, such as c-type cytochromes. The EABs grown under periodic polarization presented mushroom-like structures on their top layers, while EABs grown under continuous polarization were flat.


The Removal of Airborne Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Other Microbial Bioaerosols by Air Filtration on Coronavirus Disease 2019 (COVID-19) Surge Units.
Airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in a coronavirus disease 19 (COVID-19) ward before activation of HEPA-air filtration but not during filter operation; SARS-CoV-2 was again detected following filter deactivation. Airborne SARS-CoV-2 was infrequently detected in a COVID-19 intensive care unit. Bioaerosol was also effectively filtered.


Effect of Ultraviolet-A and Riboflavin treatment on the architecture of the center and periphery of normal rat cornea: 7 days post treatment.
Corneal collagen cross-linking (CXL) is a treatment that is widely applied to halt the progression of ectatic diseases such as keratoconus by creating biomechanical strength in the cornea. Most of the studies assessed the effect of the CXL on the cornea without any differentiation of its effect between periphery and the center of the untreated control cornea especially after the 7 days of CXL application. We investigate the ultrastructural changes in the architecture of the center and periphery of rat corneas, 7 days after standard CXL application. Five Wistar rats (10 corneas) were used in the present study. The left eye corneas (5 mm area) were de-epithelialized and irradiated with standard CXL application using riboflavin and Ultraviolet-A (UVA) (3 mW/cm2 for 30 min). The right eye corneas were used as a control. The sclera-cornea button was removed and processed for electron microscopy. Digital images were captured with a bottom mounted Quemesa camera and analyzed using the iTEM software. The ultrastructure of epithelium, hemi-desmosomes, Bowman's layer and stroma were organized in both untreated control and CXL rat cornea in both untreated control and CXL rat cornea. Within the same CXL cornea, both the collagen fibril (CF) diameter and interfibrillar spacing at the center were significantly smaller compared to the peripheral diameter and spacing of the cornea. When comparing the untreated control and CXL cornea, the central interfibrillar spacing of the CXL cornea was significantly smaller than the central spacing the untreated control cornea. In the CXL cornea the peripheral spacing was significantly higher compared to the peripheral interfibrillar spacing of the untreated control cornea. Within the CXL cornea, the proteoglycans (PGs) area and density of the periphery was significantly higher compared to the area and density of the center of the cornea. It suggests that CXL was more effective at the periphery of the cornea. This could be due to the higher amount of leucine rich PG lumican and higher diffusion of oxygen and riboflavin at the periphery cornea.


Sonographic diagnosis of neurogenic heterotopic ossification in patients with severe acquired brain injury in a neurorehabilitation unit.
To illustrate the ultrasonographic (US) and power Doppler US (PDUS) features of neurogenic heterotopic ossification (NHO) in consecutive patients with severe acquired brain injury and to evaluate the role of bedside US in diagnosis of NHO. Ninety-two consecutive patients with severe acquired brain injury underwent clinical and laboratory screening for NHO. In 6 of 92 patients, bedside US confirmed the clinical suspicion of NHO. US diagnosis of NHO was then confirmed by other imaging methods. The incidence of clinical NHO was 7% (9/92) with one patient having multifocal involvement. In NHO of the hip, US demonstrated the classic pattern of zone phenomenon, and PDUS demonstrated vascular signal within mineralized NHO and in outer hypoechoic area. No vascular signal was observed in the central hypoechoic core. In NHO of the knee, a heterogeneously hypoechoic mass was seen and in the elbow a hyperechoic mineralized mass was visualized, with vascular signals seen within the lesions. Spectral wave analysis demonstrated low resistance vessels in NHO. Bedside US is a useful tool in the diagnosis of NHO. PDUS adds data regarding neoangiogenetic activity of NHO.


Structural insights into ABC transporter mechanism.
ATP-binding cassette (ABC) transporters utilize the energy from ATP hydrolysis to transport substances across the membrane. In recent years, crystal structures of several ABC transporters have become available. These structures show that both importers and exporters oscillate between two conformations: an inward-facing conformation with the substrate translocation pathway open to the cytoplasm and an outward-facing conformation with the translocation pathway facing the opposite side of the membrane. In this review, conformational differences found in the structures of homologous ABC transporters are analyzed to understand how alternating-access is achieved. It appears that rigid-body rotations of the transmembrane subunits, coinciding with the opening and closing of the nucleotide-binding subunits, couples ATP hydrolysis to substrate translocation.


Can pulsatile ocular blood flow distinguish between patients with and without diabetic retinopathy?
Our aim was to determine if pulsatile ocular blood flow (POBF) measurements could distinguish between type 2 diabetes mellitus (DM) subjects with and without diabetic retinopathy (DR). Ninety-eight DM subjects were recruited. POBF was measured using an Ocular Blood Flow tonometer and retinopathy was assessed using retinal digital photography. The duration of diabetes, blood pressure, glycosylated haemoglobin and plasma glucose level were also recorded. Seventy-two subjects had no DR and 26 subjects exhibited mild to moderate non-proliferative DR. POBF was higher in those subjects with non-proliferative DR but did not reach significance. Those subjects receiving insulin treatment had a significantly longer duration of DM, higher HbA1c and plasma glucose levels and greater incidence of non-proliferative DR compared to subjects receiving oral hypoglycaemic agents, who in turn demonstrated higher levels of these parameters than those who were controlled by diet alone (ANOVA p < 0.05 in all cases). POBF was found to increase with level of management but not significantly so. A single measurement of POBF does not distinguish between subjects with and without mild/moderate non-proliferative DR.


Dielectrophoresis and shear-enhanced sensitivity and selectivity of DNA hybridization for the rapid discrimination of Candida species.
We present a dielectrophoresis (DEP)-based microfluidic chip that is capable of enhancing the sensitivity and selectivity of DNA hybridization using an AC electric field and hydrodynamic shear in a continuous through-flow. Molecular DEP was employed to rapidly trap ssDNA molecules in a flowing solution to a cusp-shaped nanocolloid assembly on a microfluidic chip with a locally amplified AC electric field gradient. The detection time can be accelerated to sub-minute periods, and the sensitivity can reach the pico-molar level due to the AC DEP-enhanced molecule concentration (at an optimal AC frequency of 900 kHz) in a small region (∼100 μm(2)) instead of the broad area used in a tank reactor (∼10(6) μm(2)). Continuous flow in a microchannel provides a constant and high shear rate that can shear off most non-specific target-probe binding to promote the discriminating selectivity. On-chip multi-target discrimination of Candida species can be achieved within a few minutes under optimal conditions.


Lessons learned from the design of chemical space networks and opportunities for new applications.
The concept of chemical space is of fundamental relevance in chemical informatics and computer-aided drug discovery. In a series of articles published in the Journal of Computer-Aided Molecular Design, principles of chemical space design were evaluated, molecular networks proposed as an alternative to conventional coordinate-based chemical reference spaces, and different types of chemical space networks (CSNs) constructed and analyzed. Central to the generation of CSNs was the way in which molecular similarity relationships were assessed and a primary focal point was the network-based representation of biologically relevant chemical space. The design and comparison of CSNs based upon alternative similarity measures can be viewed as an evolutionary path with interesting lessons learned along the way. CSN design has matured to the point that such chemical space representations can be used in practice. In this contribution, highlights from the sequence of CSN design efforts are discussed in context, providing a perspective for future practical applications.


A cerium(III) selective polyvinyl chloride membrane sensor based on a Schiff base complex of N,N'-bis[2-(salicylideneamino)ethyl]ethane-1,2-diamine.
A polyvinyl chloride (PVC) based membrane sensor for cerium ions was prepared by employing N,N'-bis[2-(salicylideneamino)ethyl]ethane-1,2-diamine as an ionophore, oleic acid (OA) as anion excluder and o-nitrophenyloctyl ether (o-NPOE) as plasticizer. The plasticized membrane sensor exhibits a Nernstian response for Ce(III) ions over a wide concentration range (1.41 x 10(-7) to 1.0 x10 (-2) M) with a limit of detection as low as 8.91 x 10(-8) M. It has a fast response time (<10s) and can be used for 4 months. The sensor revealed a very good selectivity with respect to common alkali, alkaline earth and heavy metal ions. The response of the proposed sensor is independent of pH between 3.0 and 8.0. It was used as an indicator electrode in potentiometric titration of fluoride, carbonate and oxalate anions and determination of cerium in simulated mixtures.


The bZIP transcription factor FpAda1 is essential for fungal growth and conidiation in Fusarium pseudograminearum.
Fusarium pseudograminearum is an important pathogen of Fusarium crown rot and Fusarium head blight, which is able to infect wheat and barley worldwide, causing great economic losses. Transcription factors (TFs) of the basic leucine zipper (bZIP) protein family control important processes in all eukaryotes. In this study, we identified a gene, designated FpAda1, encoding a bZIP TF in F. pseudograminearum. The homolog of FpAda1 is also known to affect hyphal growth in Neurospora crassa. Deletion of FpAda1 in F. pseudograminearum resulted in defects in hyphal growth, mycelial branching and conidia formation. Pathogenicity assays showed that virulence of the Δfpada1 mutant was dramatically decreased on wheat coleoptiles and barley leaves. However, wheat coleoptile inoculation assay showed that Δfpada1 could penetrate and proliferate in wheat cells. Moreover, the FpAda1 was required for abnormal nuclear morphology in conidia and transcription of FpCdc2 and FpCdc42. Taken together, these results indicate that FpAda1 is an important transcription factor involved in growth and development in F. pseudograminearum.


Making a positive difference: Criticality in groups.
How critical are individual members perceived to be for their group's performance? In this paper, we show that judgments of criticality are intimately linked to considering responsibility. Prospective responsibility attributions in groups are relevant across many domains and situations, and have the potential to influence motivation, performance, and allocation of resources. We develop various models that differ in how the relationship between criticality and responsibility is conceptualized. To test our models, we experimentally vary the task structure (disjunctive, conjunctive, and mixed) and the abilities of the group members (which affects their probability of success). We show that both factors influence criticality judgments, and that a model which construes criticality as anticipated credit best explains participants' judgments. Unlike prior work that has defined criticality as anticipated responsibility for both success and failures, our results suggest that people only consider the possible outcomes in which an individual contributed to a group success, but disregard group failure.


Production of lactic acid and fungal biomass by Rhizopus fungi from food processing waste streams.
This study proposed a novel waste utilization bioprocess for production of lactic acid and fungal biomass from waste streams by fungal species of Rhizopus arrhizus 36017 and R. oryzae 2062. The lactic acid and fungal biomass were produced in a single-stage simultaneous saccharification and fermentation process using potato, corn, wheat and pineapple waste streams as production media. R. arrhizus 36017 gave a high lactic acid yield up to 0.94-0.97 g/g of starch or sugars associated with 4-5 g/l of fungal biomass produced, while 17-19 g/l fungal biomass with a lactic acid yield of 0.65-0.76 g/g was produced by the R. oryzae 2062 in 36-48 h fermentation. Supplementation of 2 g/l of ammonium sulfate, yeast extract and peptone stimulated an increase in 8-15% lactic acid yield and 10-20% fungal biomass.


In situ detection of exosomal RNAs for cancer diagnosis.
Exosomes are considered as biomarkers reflecting the physiological state of the human body. Studies have revealed that the expression levels of specific exosomal RNAs are closely associated with certain cancers. Thus, detection of exosomal RNA offers a new avenue for liquid biopsy of cancers. Many exosomal RNA detection methods based on various principles have been developed, and most of the methods detect the extracted RNAs after lysing exosomes. Besides complex and time-consuming extraction steps, a major drawback of this approach is the degradation of the extracted RNAs in the absence of plasma membrane and cytosol. In addition, there is considerable loss of RNAs during their extraction. In situ detection of exosomal RNAs can avoid these drawbacks, thus allowing higher diagnostic reliability. In this paper, in situ detection of exosomal RNAs was systematically reviewed from the perspectives of detection methods, transport methods of the probe systems, probe structures, signal amplification strategies, and involved functional materials. Furthermore, the limitations and possible improvements of the current in situ detection methods for exosomal RNAs towards the clinical diagnostic application are discussed. This review aims to provide a valuable reference for the development of in situ exosomal RNA detection strategies for non-invasive diagnosis of cancers. STATEMENT OF SIGNIFICANCE: Certain RNAs have been identified as valuable biomarkers for some cancers, and sensitive detection of cancer-related RNAs is expected to achieve better diagnostic efficacy. Currently, the detection of exosomal RNAs is receiving increasing attention due to their high stability and significant concentration differences between patients and healthy individuals. In situ detection of exosomal RNAs has greater diagnostic reliability due to the avoidance of RNA degradation and loss. However, this mode is still limited by some factors such as detection methods, transport methods of the probe systems, probe structures, signal amplification strategies, etc. This review focuses on the progress of in situ detection of exosomal RNAs and aims to promote the development of this field.


Neurocognitive performance in children and adolescents with bipolar disorder: a review.
A number of studies have reported the evidence of cognitive deficits in adult bipolar patients. Recently, there has been a shift in research on neurocognitive performance in bipolar disorder (BD) towards examining younger age groups. A review of the literature on neurocognitive impairments in BD in childhood and adolescence was conducted. We searched systematically for studies in samples of age groups younger than 18 years of age in average that included either a healthy control group or normative data for the cognitive tests used. Twenty-one original articles were found and reviewed. Children and adolescents with BD show deficits in a variety of cognitive areas. The most consistent results were found for impairments in verbal memory. A majority of studies also indicated impairments in working memory. Similar pattern of neurocognitive impairment was found in children and adolescents as compared to adults suffering from BD. The neurocognitive deficits need to be recognized and incorporated into individual treatment programs.


[Results of 3 years of screening of abnormal hemoglobins in the blood donors of Guadeloupe (French Antilles)].
A screening on qualitative abnormalities of hemoglobin for 10.559 blood-donors has been done in Guadeloupe. Results give 8,08% for sickle trait and 2,52% for C trait. Scarce hemoglobins such as S Korle Bu, J Broussais and N Baltimore have so been found.


How risk is perceived, constructed and interpreted by clients in clinical genetics, and the effects on decision making: systematic review.
As an individual's understanding of their genetic risk may influence risk management decisions, it is important to understand the ways in which risk is constructed and interpreted. We systematically reviewed the literature, undertaking a narrative synthesis of 59 studies presenting data on the ways in which individuals perceive, construct and interpret their risk, and the subsequent effects. While most studies assessed perceived risk quantitatively, the combined evidence suggests individuals find risk difficult to accurately quantify, with a tendency to overestimate. Rather than being a stand-alone concept, risk is something lived and experienced and the process of constructing risk is complex and influenced by many factors. While evidence of the effects of perceived risk is limited and inconsistent, there is some evidence to suggest high risk estimations may adversely affect health and lead to inappropriate uptake of medical surveillance and preventative measures by some individuals. A more focused approach to research is needed with greater exploration of the ways in which risk is constructed, along with the development of stronger theoretical models, to facilitate effective and patient-centered counseling strategies.


Medication-related problems in the elderly : defining the issues and identifying solutions.
The elderly population is at great risk for medication-related problems as a result of age-related physiological changes, the presence of multiple chronic diseases and conditions, and the types and numbers of prescription and nonprescription medications they consume.Medication-related problems have received international attention. In the US, as many as 200,000 people may die of medication-related problems each year. Studies from other developed nations where patients have access to medications have determined that various types of medication-related problems occur in the elderly population in health care environments ranging from nursing homes to community dwelling settings.A variety of initiatives have been developed in an attempt to reduce the likelihood of medication-related problems in the elderly. The role that a pharmacist can play in identifying and preventing the negative health outcomes and costs of medication-related problems is being increasingly recognised. Indeed, numerous studies have now documented the positive impact that pharmacists can have in this area, and ongoing research is being conducted. With the growing numbers of elderly, and the increase in the numbers and types of medications available, it is imperative that awareness of medication-related problems be increased and that further initiatives be developed to optimise the positive outcomes of drug therapy in the elderly.


Postoperative wound scoring.
Assessing postoperative wound sepsis rates is important from both an economic and an audit point of view. Most definitions of wound sepsis are too narrow and too subjective and wound scoring systems that have been developed to counteract these deficiencies suffer from a lack of objectivity, making valid comparisons between wound sepsis rates in different institutions impossible. The ASEPSIS scoring system is a definite advance in this area and its proven reproducibility makes it invaluable in multicentre trials assessing wound sepsis. However, it has limitations, mainly associated with the underlying assumption regarding the linearity of the ASEPSIS index. It is felt that by closely examining ASEPSIS wound scores from a large number of patients it may be possible to improve this scoring system.