Cloning and functional expression of the luteinizing hormone receptor complementary deoxyribonucleic acid from the marmoset monkey testis: absence of sequences encoding exon 10 in other species.
Based on sequence homologies among the human, porcine, rat, and mouse genes for the LH receptor (LHR), overlapping partial fragments of LHR complementary DNAs (cDNAs) were multiplied from marmoset monkey testicular RNA using reverse transcription-PCR. Ligations of the individual cDNA fragments generated a full-length monkey LHR cDNA (2031 bp) containing the complete amino acid-coding sequence (676 amino acids). Northern hybridization analysis of monkey testicular RNA, using a complementary RNA probe corresponding to the full-length cDNA, demonstrated major transcripts of 5.5 and 1.4 kilobases and minor ones of 4.0, 2.7, and 1.9 kilobases. Sequence analysis of the monkey LHR cDNA revealed a striking feature, i.e. the absence of an 81-bp nucleotide sequence corresponding to exon 10, present in the LHR cDNAs of all other species studied to date. The monkey LHR cDNA displayed 83-94% overall sequence homology with the other mammalian LHR cDNAs. Reverse transcription-PCR with human exon 10-specific primers demonstrated the total absence of this sequence from the monkey LHR messenger RNA. Southern hybridization of monkey genomic DNA using a human exon 10 probe demonstrated its presence in the monkey gene and that it is totally spliced out from the primary transcript. COS cells transfected with the monkey LHR cDNA showed similar high affinity (Kd = 0.25 nmol/liter) of [125I]iodo-hCG binding as those transfected with human LHR cDNA (Kd = 0.20 nmol/liter). The cells expressing the recombinant monkey and human LHR displayed similar responses of extracellular cAMP and inositol trisphosphate to hCG. In conclusion, marmoset monkey LHR seems to lack the sequence corresponding to exon 10 of the LHR gene in other mammalian species. The truncation does not alter LHR function, as the monkey receptor protein bound hCG and evoked cAMP and inositol trisphosphate responses comparable to those of the human LHR containing the exon 10-encoded structure. As the sequence homologous to exon 10 is missing in the other two glycoprotein receptors, i.e. those of FSH and TSH, this extra exon is apparently inserted into the LHR messenger RNA of some species during evolution from intronic sequences by a change in alternative splicing.


Exploring the ring-opening pathways in the reaction of morpholinyl radicals with oxygen molecule.
Quantum chemistry calculations using hybrid density functional theory and the coupled-cluster method have been performed to investigate the ring-opening pathways in the oxidation of morpholine (1-oxa-4-aza-cyclohexane). Hydrogen abstraction can form two different carbon-centered radicals, morpholin-2-yl or morpholin-3-yl, or the nitrogen-centered radical, morpholin-4-yl, none of which are found to have low-energy pathways to ring-opening. Extensive exploration of multiple reaction pathways following molecular oxygen addition to these three radicals revealed two competitive low energy pathways to ring-opening. Addition of O(2) to either carbon-centered radical, followed by a 1,4-H shifting mechanism can yield a long-lived cyclic epoxy intermediate, susceptible to ring-opening, following further radical attack. In particular, the second pathway begins with O(2) attack on morpholin-2-yl, followed by a 1,5-H shift and a unimolecular ring-opening without having to overcome a high barrier, releasing a significant amount of heat in the overall ring-opening reaction. The calculations provide valuable context for the development of mechanisms for the low temperature combustion chemistry of nitrogen and oxygen-containing fuels.


Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.
Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical suspicion of a possible connective tissue disorder when we encounter cases with atypical presentation and/or unique chest radiologic findings especially in young patients.


Community-acquired acute meningitis and encephalitis: a narrative review.
Meningitis and encephalitis are medical emergencies. Patients need prompt evaluation and immediate empiric therapy to reduce the likelihood of fatal outcomes and chronic neurological sequelae. Conjugate bacterial vaccines have significantly reduced the incidence of bacterial meningitis, especially in children. As the results of changes in patterns of bacterial drug sensitivity, ceftriaxone is now part of the recommended empiric treatment for bacterial meningitis and should be administered as early as possible. Neuroimaging delays the treatment of meningitis and is not needed in most cases. Adjunctive corticosteroid therapy is of benefit for many patients with meningitis and should be initiated in most adults before antibiotic therapy. Molecular testing can assist the specific diagnosis of encephalitis and should be based on the exposure history and geographic risk factors relevant to the patient, but non-infectious causes of encephalitis are also common. Empiric therapy for encephalitis should be directed at the most frequently identified infectious pathogen, herpes simplex virus type 1 (ie, intravenous aciclovir). Vaccines can protect against the major pathogens of childhood infections (measles, mumps, rubella, polio, varicella viruses), influenza viruses, and exotic pathogens that cause meningitis and encephalitis (rabies, Japanese encephalitis, dengue, yellow fever, tick-borne encephalitis viruses, Mycobacterium tuberculosis).


Explanations pertaining to the hip joint flexor moment during the stance phase of human walking.
A hip joint flexor moment in the last half of the stance phase during walking has repeatedly been reported. However, the purpose of this moment remains uncertain and it is unknown how it is generated. Nine male subjects were instructed to walk at 4.5 km/h with their upper body in three different positions: normal, inclined and reclined. Net joint moments were calculated about the hip, knee and ankle joint. The peak hip joint flexor moment during late stance was significantly lower during inclined walking than in the two other conditions. During normal walking the iliacus muscle showed no or very weak activity and first at the transition from stance to swing. When walking reclined, a clear but rather low activity level of the iliacus muscle was seen in the first half of the stance phase, which could contribute to the hip moment. In the inclined condition the iliacus showed much increased activity but only in the swing phase. It is concluded that the hip flexor moment in question is largely generated by passive structures in the form of ligaments resisting hip joint extension.


Glycopeptide Nanofiber Platform for Aβ-Sialic Acid Interaction Analysis and Highly Sensitive Detection of Aβ.
The variation of amyloid β peptide (Aβ) concentration and Aβ aggregation are closely associated with the etiology of Alzheimer's diseases (AD). The interaction of Aβ with the monosialoganglioside-rich neuronal cell membrane has been suggested to influence Aβ aggregation. Therefore, studies on the mechanism of Aβ and sialic acids (SA) interaction would greatly contribute to better understanding the pathogenesis of AD. Herein, we report a novel approach for Aβ-SA interaction analysis and highly sensitive Aβ detection by mimicing the cell surface presentation of SA clusters through engineering of SA-modified peptide nanofiber (SANF). The SANF displayed well-ordered 1D nanostructure with high density of SA on surface. Using FAM-labeled Aβ fragments of Aβ1-16, Aβ16-23, and Aβ24-40, the interaction between Aβ and SA was evaluated by the fluorescence titration experiments. It was found that the order of the SA-binding affinity was Aβ1-16 > Aβ24-40 > Aβ16-23. Importantly, the presence of full-length Aβ1-40 monomer triggered a significant fluorescence enhancement due to the multivalent binding of Aβ1-40 to the nanofiber. This fluorescent turn-on response showed high selectivity and sensitivity for Aβ1-40 detection and the method was further used for Aβ aggregation process monitoring and inhibitor screening. The results suggest the proposed strategy is promising to serve as a tool for mechanism study and the early diagnosis of Alzheimer's disease.


Increased plasma levels of adipokines and inflammatory markers in older women with persistent HPV infection.
We observed diminished lymphoproliferation to multiple stimuli in older women with persistent cervical human papillomavirus (HPV) infection. Adipokines are a class of inflammatory cytokines that are altered in some persistent infections. The objective was to compare the level of adipokines and inflammatory cytokines in heparinized plasma from women with persistent HPV cervical infection (Cases, N=50, oversampled for their weak lymphoproliferation responses) with women with no evidence of persistent HPV cervical infection (Controls, N=50, oversampled for their strong lymphoproliferation responses). Plasma samples were analyzed with multiplex assays for adipokines and inflammatory cytokines. Cases had significantly elevated plasma levels of resistin (p<0.0001) and sFas (p=0.0038) as compared to controls. Risk of persistent HPV infection increased significantly with increasing levels of resistin and 8Fas. This is the first study to demonstrate elevated levels of resistin and sFas in HPV persistently infected, older women with decreased immune function expanding the understanding of the systemic inflammation and immune alterations in individuals persistently infected with HPV. Further studies within a larger cohort are needed to define the generalities of these findings and any role adipokines have in persistent HPV infection.


Cytotoxicity of a series of ferrocene-containing beta-diketones.
Oxidised ferrocenium compounds often possess antineoplastic activity. In contrast, reduced ferrocene derivatives frequently only show activity if cell components can oxidise them inside cells to the ferrocenium species. Ferrocene compounds having the lowest formal reduction potential are normally expected to be the most cytotoxic. Here we demonstrate this is not always the case. Some of the structure-related and physical properties that enhance ferrocenyl antineoplastic activity have been investigated. Ferrocene-containing beta-diketones of the type FcCOCH2COR with Fc=ferrocenyl and R=CF3, CCl3, CH3, Ph(=C6H5, phenyl) and Fc, were tested for cytotoxicity against HeLa (human cervix epitheloid), COR L23 (human large cell lung carcinoma) and platinum resistant CoLo320DM (human colorectal) and COR L23/CPR cancer cell lines. Cell survival was measured by means of the colorometric 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay. The mean drug concentration from 3 experiments causing 50% cell growth inhibition, (IC50) values, varied between 4.5 and 85.0 micromol dm(-3'), with the CF3(-) containing beta-diketone being the most active. Drug activity was inversely proportional to the formal reduction potential, Eo', of the ferrocenyl group, and dependent on the R group in the general beta-diketone structure. The CF3 complex was more cytotocic than cisplatin inter alia against platinum-resistant cell lines, and at least eight times more reactive against cancer cell lines than against PHA (phytohaemagglutinin)-stimulated lymphocyte cultures. A drug activity-structural relationship exists in that ferrocenyl drugs with halogen substituents chains are more cytotoxic. Compounds with higher ferrocenyl group formal reduction potential and stronger acid strength (i.e. smaller pKa value) are more cytotoxic.


Knowledge of the patient as decision-making power: staff members' perceptions of interprofessional collaboration in challenging situations in psychiatric inpatient care.
Challenging situations in psychiatric inpatient settings call for interprofessional collaboration, but the roles and responsibilities held by members of different professions is unclear. The aim of this study was to describe staff members' perceptions of interprofessional collaboration in the context of challenging situations in psychiatric inpatient care. Prior to the study taking place, ethical approval was granted. Focus group interviews were conducted with 26 physicians, ward managers, psychiatric nurses, and nursing assistants. These interviews were then transcribed and analysed using qualitative content analysis. Results described participants' perceptions of shared responsibilities, profession-specific responsibilities and professional approaches. In this, recognising knowledge of the patient as decision-making power was understood to be a recurring theme. This is a delimited qualitative study that reflects the specific working conditions of the participants at the time the study was conducted. The findings suggest that nursing assistants are the most influential professionals due to their closeness to and first-hand knowledge of patients. The results also point to the possibility of other professionals gaining influence by getting closer to patients and utilising their professional knowledge, thus contributing to a more person-centred care.


Micro-receiver guided transcranial beam steering.
A new method for focusing ultrasound energy in brain tissue through the skull is investigated. The procedure is designed for use with a therapeutic transducer array and a small catheter-inserted hydrophone receiver placed in the brain to guide the array's focus. When performed at high-intensity, a focal intensity on the order of several hundred watts per centimeter-squared is achieved, and cells within a target volume are destroyed. The present study tests the feasibility and range of the method using an ex vivo human skull. Acoustic phase information is obtained from the stationary receiver and used to electrically shift the beam to new locations as well as correct for aberrations due to the skull. The method is applied to a 104-element 1.1 MHz array and a 120-element 0.81 MHz array. Using these array configurations, it is determined that the method can reconstruct and steer a focus over a distance of 50 mm. Application of this minimally invasive technique for ultrasound brain therapy and surgery also is investigated in vitro with a 64-element 0.664 MHz hemisphere array designed for transskull surgery. Tissue is placed inside of a skull and a catheter-inserted receiver is inserted into the tissue. A focus intense enough to coagulate the tissue is achieved at a predetermined location 10 mm from the receiver, the maximum distance that this large element array can electronically steer the focus.


[Methodological specifications on the Todd method and preliminary results].
In order to measure the potentiality and kinetics tissue fibrinolysis we have modified Todd's histochemical method preparing at least six sections taken from same sample tissue, by infraoperatory biopsy, esponing them to a fibrin film at a constant concentration; we have also chosen to incubate the section at 10, 20, 30, 45, 60 min. The measurement of the areas of fibrin, of tissue and fibrinolysis, at the above mentioned times, has been effected at standard magnification (15 X) by an image analyser (Videoplan) scale 1:8. For each sample we suggest to elaborate an Index of the Potentiality of Fibrinolysis (formula; see text) and an Index of the Kinetics of the Fibrinolysis (formula; see text). Applying this method to two different groups of thyroid disease (struma and adenoma) we have not pointed out any statistically significant difference.


In vitro inhibition of lipopolysaccharide and mycobacterium bovis bacillus Calmette Guérin-induced inflammatory cytokines and in vivo protection from D-galactosamine/LPS -mediated liver injury by the medicinal plant Sclerocarya birrea.
Sclerocarya birrea is a medicinal plant used for the treatment of inflammatory- and bacterial-related diseases. The present study investigated in vitro and in vivo the effects of the stem bark methanol extract of S. birrea. Nitrite, TNF, IL-1beta, IL-6 and IL-12p40 production by bone marrow-derived macrophages (BMDM) pre-incubated with or without S. birrea, and stimulated with Lipopolysaccharide (LPS) or infected with live Mycobacterium bovis Bacillus Calmette Guérin (BCG) was evaluated. S. birrea extract inhibited, in a concentration-dependent manner, nitrite, TNF, IL-1beta, IL-6 and IL-12p40 production by BMDM stimulated with LPS or infected with live BCG. The iNOS expression was reduced by S. birrea after stimulation of BMDM with LPS. In addition, S. birrea inhibited the nuclear factor kB (NF-kB) activation by both LPS and BCG. The effects of the plant extract were also evaluated in an in vivo model of liver injury induced by D-galactosamine/LPS (D-GalN/LPS) administration in mice. S. birrea limited D-GalN/LPS-liver injury as assessed by a reduction in transaminases and TNF, IL-1beta, IL-6 serum levels, and translocation of NF-kB to the nucleus. Taken together, our data indicate that stem bark methanol extract of S. birrea possesses anti-inflammatory properties by inhibiting NF-kB activation and cytokine release induced by inflammatory or infectious stimuli.


Dissociation of stimulus relevance and saliency factors during shifts of visuospatial attention.
The control of visuospatial attention entails multiple processes, including both voluntary (endogenous) factors and stimulus-driven (exogenous) factors. Exogenous processes can be triggered by visual targets presented at a previously unattended location, thus capturing attention in a stimulus-driven manner. However, little is known about the relative role of stimulus salience and behavioral relevance for this type of spatial reorienting. Here, we directly assessed how salience and relevance affect activation of the frontoparietal attentional system, using either low-salience but task-relevant target stimuli or salient but task-irrelevant flickering checkerboards. We compared event-related functional magnetic resonance imaging responses for stimuli presented at the unattended versus attended side (invalid minus valid trials), separately for the 2 categories of visual stimuli. We found that task-relevant invalid targets activated the frontoparietal attentional network, demonstrating that this system engages when target stimuli are presented at an unattended location, even when these have a low perceptual salience. Conversely, the presentation of high-salience checkerboards in one hemifield while endogenous attention was engaged elsewhere did not activate the attentional network. These findings indicate that task relevance is critical for stimulus-driven engagement of the attentional network when attentional resources are endogenously allocated somewhere else.


Ethical considerations of phone-based interviews from three studies of COVID-19 impact in Bihar, India.
Phone-based interviews present a range of ethical challenges, including how to ensure informed consent and privacy and maintain confidentiality. Our paper presents conceptual and practical ethical considerations taken into account across three telephone studies on the impact of COVID-19 conducted following India's nationwide lockdown imposed in March 2020. Two studies captured COVID-19 response impact on primary-level Reproductive Maternal Neonatal and Child Health (RMNCH) services and on provider wellness, respectively. The third study focused on how the gendered experience of COVID-19 and the state's response to control transmission impacted women's lives, focusing on health services, livelihood, entitlements and social change, by interviewing individual women. The ethical challenges as well as the advantages of digital data collection are presented with recommendations for low-resource settings. Ethical considerations included the above challenges as well as avoiding posing unreasonable time burden on the respondents, framing questions with a gendered lens, considering emotional states given contagion concerns and economic uncertainties, and redressing pandemic-induced distress. Using scripted Hindi was challenging in consent-taking, as was protecting household respondents' privacy and confidentiality during lockdown. Unanticipated positive ethical implications of using a telephone approach included providing respondents privacy and catharsis, respondents choosing convenient interview times and affording health providers more privacy than institutional inperson interviews. Internalising empathy, respect and appreciative enquiry are key to establishing rapport in the absence of prior relationships. Institutional Review Board (IRB) time limits on call duration need to be flexible to allow for 'active listening' and empathetic enquiry in surveys on the impact of COVID-19.


Focus on Prevention: Peripheral Arterial Disease and the Central Role of the Cardiologist.
Peripheral artery disease (PAD) is a manifestation of systemic atherosclerotic disease. PAD patients have a poor prognosis with an increased risk of cardiovascular (CV) events, including myocardial infarction (MI), stroke, limb ischemia and CV death; therefore, it is important to detect and treat PAD early. PAD and coronary artery disease (CAD) share a common pathogenesis and risk factors for development; therefore, cardiologists are in a unique position to screen, diagnosis and treat PAD. Moreover, PAD and CAD also share some treatment goals, including an aggressive modification of risk factors to reduce the risk of CV events. However, PAD remains an underdiagnosed and undertreated disease with medico-legal implications. As the role of cardiologists is expanding, the purpose of this review was to awaken the clinicians to the significance of PAD.


Concurrent beau lines, onychomadesis, and retronychia following scurvy.
Beau lines, onychomadesis, and retronychia are nail conditions with their own characteristic clinical findings. It has been hypothesized that these 3 disorders may share a common pathophysiologic mechanism of slowing and/or halting nail plate production at the nail matrix. We report the case of a 41-year-old woman who presented with concurrent Beau lines, onychomadesis, and retronychia 6 months following a diagnosis of scurvy. Simultaneous presentation of these 3 nail conditions is not commonly reported, and our case supports a shared pathophysiologic basis.


Irradiation for bronchial carcinoma: reasons for failure. I. Analysis of local control as a function of dose, time, and fractionation.
Radiation therapy is the only potentially curative form of therapy for patients with carcinoma of the lung who are not surgical candidates. Previous studies have evaluated response by evaluating survival. Evaluation of local control of disease is essential if one is to understand and modify therapeutic approaches in an effort to increase survival. Clinical data are presented on 197 patients with primary epithelial tumors of the lung. An analysis of local control data is presented using the concept of nomial standard dose (NSD). If local failure is to occur, it is manifest by 15 months. Survival is affected by the ability or inability to achieve local control. Above a dose of 1450 ret, no correlation between increasing ret dose and increasing local control is observed.


The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role.
Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic effects of ethanol but does not account for the tolerance. This fact, as well as the discovery of the proliferation of the smooth endoplasmic reticulum (SER) after chronic alcohol consumption, suggested the existence of an additional pathway which was then described by Lieber and DeCarli, namely the microsomal ethanol oxidizing system (MEOS), involving cytochrome P450. The existence of this system was initially challenged but the effect of ethanol on liver microsomes was confirmed by Remmer and his group. After chronic ethanol consumption, the activity of the MEOS increases, with an associated rise in cytochrome P450, especially CYP2E1, most conclusively shown in alcohol dehydrogenase negative deer mice. There is also cross-induction of the metabolism of other drugs, resulting in drug tolerance. Furthermore, the conversion of hepatotoxic agents to toxic metabolites increases, which explains the enhanced susceptibility of alcoholics to the adverse effects of various xenobiotics, including industrial solvents. CYP2E1 also activates some commonly used drugs (such as acetaminophen) to their toxic metabolites, and promotes carcinogenesis. In addition, catabolism of retinol is accelerated resulting in its depletion. Contrasting with the stimulating effects of chronic consumption, acute ethanol intake inhibits the metabolism of other drugs. Moreover, metabolism by CYP2E1 results in a significant release of free radicals which, in turn, diminishes reduced glutathione (GSH) and other defense systems against oxidative stress which plays a major pathogenic role in alcoholic liver disease. CYP1A2 and CYP3A4, two other perivenular P450s, also sustain the metabolism of ethanol, thereby contributing to MEOS activity and possibly liver injury. CYP2E1 has also a physiologic role which comprises gluconeogenesis from ketones, oxidation of fatty acids, and detoxification of xenobiotics other than ethanol. Excess of these physiological substrates (such as seen in obesity and diabetes) also leads to CYP2E1 induction and nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), with pathological lesions similar to those observed in alcoholic steatohepatitis. Increases of CYP2E1 and its mRNA prevail in the perivenular zone, the area of maximal liver damage. CYP2E1 up-regulation was also demonstrated in obese patients as well as in rat models of obesity and NASH. Furthermore, NASH is increasingly recognized as a precursor to more severe liver disease, sometimes evolving into "cryptogenic" cirrhosis. The prevalence of NAFLD averages 20% and that of NASH 2% to 3% in the general population, making these conditions the most common liver diseases in the United States. Considering the pathogenic role that up-regulation of CYP2E1 also plays in alcoholic liver disease (vide supra), it is apparent that a major therapeutic challenge is now to find a way to control this toxic process. CYP2E1 inhibitors oppose alcohol-induced liver damage, but heretofore available compounds are too toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an innocuous mixture of polyunsaturated phosphatidylcholines extracted from soybeans (and its active component dilinoleoylphosphatidylcholine), were discovered to decrease CYP2E1 activity. PPC also opposes hepatic oxidative stress and fibrosis. It is now being tested clinically.


Two different anionic manganese(II) coordination polymers constructed through dicyanamide coordination bridges.
In order to explore new metal coordination polymers and to search for new types of ferroelectrics among hybrid coordination polymers, two manganese dicyanamide complexes, poly[tetramethylammonium [di-μ3-dicyanamido-κ(6)N(1):N(3):N(5)-tri-μ2-dicyanamido-κ(6)N(1):N(5)-dimanganese(II)]], {[(CH3)4N][Mn2(NCNCN)5]}n, (I), and catena-poly[bis(butyltriphenylphosphonium) [[(dicyanamido-κN(1))manganese(II)]-di-μ2-dicyanamido-κ(4)N(1):N(5)]], {[(C4H9)(C6H5)3P]2[Mn(NCNCN)4]}n, (II), were synthesized in aqueous solution. In (I), one Mn(II) cation is octahedrally coordinated by six nitrile N atoms from six anionic dicyanamide (dca) ligands, while the second Mn(II) cation is coordinated by four nitrile N atoms and two amide N atoms from six anionic dca ligands. Neighbouring Mn(II) cations are linked together by μ-1,5- and μ-1,3,5-bridging dca anions to form a three-dimensional polymeric structure. The anionic framework exhibits a solvent-accessible void of 289.8 Å(3), amounting to 28.0% of the total unit-cell volume. Each of the cavities in the network is occupied by only one tetramethylammonium cation. In (II), each Mn(II) cation is octahedrally coordinated by six nitrile N atoms from six dca ligands. Neighbouring Mn(II) cations are linked together by double dca bridges to form a one-dimensional polymeric chain, and C-H...N hydrogen-bonding interactions are involved in the formation of the one-dimensional layer structure.


Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment.
Immature contractile cardiomyocytes proliferate to rapidly increase cell number, establishing cardiomyocyte endowment in the perinatal period. Developmental changes in cellular maturation, size and attrition further contribute to cardiac anatomy. These physiological processes occur concomitant with a changing hormonal environment as the fetus prepares itself for the transition to extrauterine life. There are complex interactions between endocrine, hemodynamic and nutritional regulators of cardiac development. Birth has been long assumed to be the trigger for major differences between the fetal and postnatal cardiomyocyte growth patterns, but investigations in normally growing sheep and rodents suggest this may not be entirely true; in sheep, these differences are initiated before birth, while in rodents they occur after birth. The aim of this review is to draw together our understanding of the temporal regulation of these signals and cardiomyocyte responses relative to birth. Further, we consider how these dynamics are altered in stressed and suboptimal intrauterine environments.


Stimuli-responsive hybrid materials: breathing in magnetic layered double hydroxides induced by a thermoresponsive molecule.
A hybrid magnetic multilayer material of micrometric size, with highly crystalline hexagonal crystals consisting of CoAl-LDH ferromagnetic layers intercalated with thermoresponsive 4-(4-anilinophenylazo)benzenesulfonate (AO5) molecules diluted (ratio 9 : 1) with a flexible sodium dodecylsulphate (SDS) surfactant has been obtained. The resulting material exhibits thermochromism attributable to the isomerization between the azo (prevalent at room temperature) and the hydrazone (favoured at higher temperatures) tautomers, leading to a thermomechanical response. In fact, these crystals exhibited thermally induced motion triggering remarkable changes in the crystal morphology and volume. In situ variable temperature XRD of these thin hybrids shows that the reversible change into the two tautomers is reflected in a shift of the position of the diffraction peaks at high temperatures towards lower interlayer spacing for the hydrazone form, as well as a broadening of the peaks reflecting lower crystallinity and ordering due to non-uniform spacing between the layers. These structural variations between room temperature (basal spacing (BS) = 25.91 Å) and 100 °C (BS = 25.05 Å) are also reflected in the magnetic properties of the layered double hydroxide (LDH) due to the variation of the magnetic coupling between the layers. Overall, our study constitutes one of the few examples showing fully reversible thermo-responsive breathing in a 2D hybrid material. In addition, the magnetic response of the hybrid can be modulated due to the thermotropism of the organic component that, by influencing the distance and in-plane correlation of the inorganic LDH, modulates the magnetism of the CoAl-LDH sheets in a certain range.


Rapid measurement of blood ethanol concentrations using the alcohol oxidase membrane technique.
The alcohol oxidase membrane technique is available for measurement of ethanol in commercial fluids. In this paper we examined its usefulness for cat and human blood in comparison with gas-liquid chromatography (GLC). The membrane method proved to be simple, reproducible, accurate, and inexpensive. Analysis took 1-2 min per sample and required only 25 microL of whole blood for measurement of concentrations between 0.05 and 1.0 mM (0.25-5 mg/dL) and 10 microL of whole blood for measurement of concentrations between 1.0 and 40 mM (5-190 mg/dL). Background concentrations were undetectable in cats after extraneous sources of alcohols were removed. The alcohol oxidase membrane technique is less specific than GLC, but it may be useful when ethanol is administered after background samples have shown an absence of other nonspecific reactants. Its high sensitivity is useful for kinetic studies where blood ethanol concentrations are below or close to those required for maximal hepatic ethanol metabolism.


Body mass index and mortality in heart failure: a meta-analysis.
In patients with chronic heart failure (CHF), previous studies have reported reduced mortality rates in patients with increased body mass index (BMI). The potentially protective effect of increased BMI in CHF has been termed the obesity paradox or reverse epidemiology. This meta-analysis was conducted to examine the relationship between increased BMI and mortality in patients with CHF. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science to identify studies with contemporaneous control groups (cohort, case-control, or randomized controlled trials) that examined the effect of obesity on all-cause and cardiovascular mortality. Two reviewers independently assessed studies for inclusion and performed data extraction. Nine observational studies met final inclusion criteria (total n = 28,209). Mean length of follow-up was 2.7 years. Compared to individuals without elevated BMI levels, both overweight (BMI approximately 25.0-29.9 kg/m(2), RR 0.84, 95% CI 0.79-0.90) and obesity (BMI approximately > or =30 kg/m(2), RR 0.67, 95% CI 0.62-0.73) were associated with lower all-cause mortality. Overweight (RR 0.81, 95% CI 0.72-0.92) and obesity (RR 0.60, 95% CI 0.53-0.69) were also associated with lower cardiovascular mortality. In a risk-adjusted sensitivity analysis, both obesity (adjusted HR 0.88, 95% CI 0.83-0.93) and overweight (adjusted HR 0.93, 95% CI 0.89-0.97) remained protective against mortality. Overweight and obesity were associated with lower all-cause and cardiovascular mortality rates in patients with CHF and were not associated with increased mortality in any study. There is a need for prospective studies to elucidate mechanisms for this relationship.


Labile products of vascular endothelium as mediators and modulators of the functions of the central nervous system.
A rapid development of the knowledge about vascular endothelial cell function as an "endocrine gland" releasing the labile, highly biologically active products, caused a major reapprisal of our concepts concerning the pathophysiology of our body. The publication summarizes the present understanding of the involvement of nitric oxide (NO), endothelins (ETs) and arachidonic acid products in the mechanisms underlying the regulation of the tonus of vessels supplying blood to the CNS, their known modulatory and mediatory role in CNS functions such as a development and memory, peripheral nonadrenergic noncholinergic, or sensory neurotransmission. The regulation intracellular Ca+ +ion levels as a proposed mechanism for the neuroprotective, as well as the neurotoxic effect of the described endothelial products is presented. The supposed therapeutical usefullness of compounds which can modulate their biosynthesis, substitute their activity, or modify its degradation are also summarized.


Protein phosphatase 2A (PP2A) regulatory subunits ParA and PabA orchestrate septation and conidiation and are essential for PP2A activity in Aspergillus nidulans.
Protein phosphatase 2A (PP2A) is a major intracellular protein phosphatase that regulates multiple aspects of cell growth and metabolism. Different activities of PP2A and subcellular localization are determined by its regulatory subunits. Here we identified and characterized the functions of two protein phosphatase regulatory subunit homologs, ParA and PabA, in Aspergillus nidulans. Our results demonstrate that ParA localizes to the septum site and that deletion of parA causes hyperseptation, while overexpression of parA abolishes septum formation; this suggests that ParA may function as a negative regulator of septation. In comparison, PabA displays a clear colocalization pattern with 4',6-diamidino-2-phenylindole (DAPI)-stained nuclei, and deletion of pabA induces a remarkable delayed-septation phenotype. Both parA and pabA are required for hyphal growth, conidiation, and self-fertilization, likely to maintain normal levels of PP2A activity. Most interestingly, parA deletion is capable of suppressing septation defects in pabA mutants, suggesting that ParA counteracts PabA during the septation process. In contrast, double mutants of parA and pabA led to synthetic defects in colony growth, indicating that ParA functions synthetically with PabA during hyphal growth. Moreover, unlike the case for PP2A-Par1 and PP2A-Pab1 in yeast (which are negative regulators that inactivate the septation initiation network [SIN]), loss of ParA or PabA fails to suppress defects of temperature-sensitive mutants of the SEPH kinase of the SIN. Thus, our findings support the previously unrealized evidence that the B-family subunits of PP2A have comprehensive functions as partners of heterotrimeric enzyme complexes of PP2A, both spatially and temporally, in A. nidulans.


COVID-19 Isolation and Risk of Death in Cyprus Elderly People.
Social isolation is associated with a higher risk of morbidity and death in older people. The quarantine and social distancing measures due to Covid-19 imposed in most countries and particularly in Cyprus, aim to isolate individuals from direct contact with others. This has resulted in vulnerable older people being isolated at their places of residence for several months, while the recommendations for continuing lockdowns do not appear to be ending. The risk of death from causes other than those related to Covid-19 increases in such individuals and it is due to the effects of social isolation. We estimate that in the next years, there will be a significant increase in the death numbers of such older people in Cyprus. The health authorities must develop a program of support for these older individuals to include medical, social, physical, and psychological elements. Examples of such support are given here.


Identification of a 24-kDa polypeptide processed from the coronavirus infectious bronchitis virus 1a polyprotein by the 3C-like proteinase and determination of its cleavage sites.
We report here the identification of a 24-kDa polypeptide in IBV-infected Vero cells by immunoprecipitation with a region-specific antiserum raised in rabbits against the IBV sequence encoded between nucleotides 10,928 and 11,493. Coexpression, deletion, and mutagenesis studies have demonstrated that this protein is encoded by ORF 1a from nucleotide 10,915 to 11,544 and is released from the 1a polyprotein by the 3C-like proteinase-mediated proteolysis. A previously predicted Q-S (Q3462S3463) dipeptide bond encoded by the IBV sequence from nucleotide 10,912 to 10,917 is identified as the N-terminal cleavage site, and a Q-N (Q3672N3673) dipeptide bond encoded by the IBV sequence between nucleotides 11,542 and 11,547 is identified as the C-terminal cleavage site of the 24-kDa polypeptide.


[Pre-menopausal dysfunctional menometrorrhagia: therapeutic approach].
Approximately 10% of premenopausal women suffer from dysfunctional menometrorrhagia. The correct therapeutic approach to this pathology above all requires a precise diagnostic framework. For this purpose the doctor can employ a number of laboratory and instrumental tests, both invasive and non-invasive, in order to differentiate the dysfunctional forms from those supported by organic pathologies or non-gynecological diseases. Once the diagnostic iter has been completed, the choice of therapy can be directed towards surgical or medical treatment; the latter may be symptomatic or causal. This review focuses on the most commonly used treatments for dysfunctional menometrorrhagia in premenopausal women and proposes clinical protocols for a correct diagnostic and therapeutic approach.


Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs.
Veterinary hemp products containing cannabidiol (CBD) and negligible psychoactive (THC) have increased popularity since hemp (with <0.3% THC) was removed from schedule 1 substances under the Controlled Substances Act in 2018. This was accompanied by increased CBD research, mostly on the short-term safety and efficacy for inflammatory and neurological conditions. It is imperative to understand how CBD is metabolized or accumulated in the body long-term, thus the goal of the present work was to determine monthly plasma CBD concentrations, as well as changes in pharmacokinetic (PK) parameters in chronically dosed dogs. The study was a masked, placebo-controlled, randomized design. Six adult beagles were assigned to placebo, 5 and 10 mg/kg/day CBD treatment groups. Dogs received oral oil treatment once daily for 36 weeks. Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h). Pharmacokinetics were conducted at 0, 18 and 36 weeks. Pharmacokinetics and monthly CBD plasma data of dogs who received CBD were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05. Average plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively. PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints. Cmax and AUC were dose proportional. Half-life demonstrated large inter-individual variations and increased (p < 0.05) at weeks 18 and 36 compared to baseline. Volume of distribution was not affected by time or treatment, while MRT increased, and clearance decreased over time (p < 0.05). Chronic administration of CBD to healthy adult dogs led to a dose-proportional accumulation in the body for 36 weeks, which was confirmed by an increased half-life, total exposure, mean residence time and plasma peak. Our data also suggests that CBD plasma levels may have less daily variation if administered twice daily.


"I prefer to take pills when I plan to have sex": Perceptions of on-demand versus daily oral pre-exposure prophylaxis among adolescents in Kampala, Uganda.
There is limited information about the use of on-demand and daily pre-exposure prophylaxis (PrEP) among adolescents and young people (AYP) in sub-Saharan Africa. We explored perceptions of both regimens among 14- to 19-year-olds perceived to be at high risk of HIV infection in Kampala, Uganda, using qualitative data collection methods. Data were analysed by theme and interpreted based on constructs from the framework of acceptability. Although there were no noticeable gender differences in preferences for a particular regimen, acceptability of PrEP depended on individual AYP sexual behaviour at the time of the study. Those who perceived themselves to be at increased risk of acquiring HIV preferred using daily PrEP, citing the consistency that comes from taking a pill daily and which they considered to be efficacious and safe. AYP who had less frequent sex preferred on-demand PrEP because it would enable them to "plan for sex". However, both groups perceived taking daily PrEP to be a burden, which was an impediment to acceptance of this form of PrEP. AYP anticipated that daily pill taking would be very stressful, requiring a lot of effort and would interrupt their daily routine. Therefore, while both on-demand and daily PrEP were acceptable and beneficial to these AYP, preferences for either regimen depended on self-perceived risk. Thus, oral PrEP use should be tailored to end-user preferences and risk profiles.


Characterization of a sialyl alpha 2-3 transferase and a sialyl alpha 2-6 transferase from human platelets occurring in the sialylation of the N-glycosylproteins.
Two sialyltransferases (EC 2.4.99.-) are extracted with Triton X-100 from human platelets and characterized with asialo 3H-labelled alpha 1-acid glycoprotein, an N-glycosylprotein. Methylation analysis of their specificities indicates that the enzymes transfer selectively sialic acid in a 3 or 6 position to oligosaccharides possessing Gal(beta 1-4)GlcNAc structure. The sialyl alpha 2-3 transferase was separated from the sialyl alpha 2-6 transferase by Ultrogel AcA34 column chromatography. Through affinity chromatography on CDPethanolamine-Sepharose, the two sialyltransferases are partly purified (5- and 20-fold enrichment of their specific activity, respectively, for sialyl alpha 2-3 transferase and alpha 2-6 transferase) and appear to be structurally heterogeneous.


Reported bruxism and biopsychosocial symptoms: a longitudinal study.
In this follow-up study of 30-50-year-old employees (n = 211) of the Finnish Broadcasting Company (YLE), respondents completed questionnaires in both 1999 and 2000 containing items on demographic data, tobacco use, levels of perceived bruxism, affective disturbance, sleep disturbance, somatic symptoms, pain symptoms and temporomandibular disorder (TMD) symptoms. Bruxism was significantly more prevalent among smokers (P = 0.005). Age, marital status, and gender were not associated with bruxism. Subjects in the frequent bruxism group (n = 74) reported the TMD-related painless symptoms, affective disturbance and early insomnia significantly more often than average. In the multivariate analyses, clustered pain symptoms (P = 0.001), TMD-related painless symptoms (P = 0.004) and smoking (P = 0.012) were significantly positively associated with frequent bruxism, when the independent effects of age and gender were controlled for. It was concluded that successful management of TMD necessitates smoking cessation, as tobacco use may both amplify the patient's pain response and provoke bruxism. Psychosocial factors and perceived stress should not be ignored, however.


DNA repair genes play a variety of roles in the development of fish embryos.
Embryogenesis is one of the most important life stages because it determines an organism's healthy growth. However, embryos of externally fertilizing species, such as most fish, are directly exposed to the environment during development and may be threatened by DNA damaging factors (pollutants, UV, reactive oxygen species). To counteract the negative effects of DNA fragmentation, fish embryos evolved complex damage response pathways. DNA repair pathways have been extensively studied in some fish species, such as zebrafish (Danio rerio). Our literature review, on the other hand, revealed a paucity of knowledge about DNA damage response and repair in non-model aquaculture fish species. Further, several pieces of evidence underlie the additional role of DNA repair genes and proteins in organogenesis, spatiotemporal localization in different tissue, and its indispensability for normal embryo development. In this review, we will summarize features of different DNA repair pathways in course of fish embryo development. We describe how the expression of DNA repair genes and proteins is regulated during development, their organogenetic roles, and how the expression of DNA repair genes changes in response to genotoxic stress. This will aid in addressing the link between genotoxic stress and embryo phenotype. Furthermore, available data indicate that embryos can repair damaged DNA, but the effects of early-life stress may manifest later in life as behavioral changes, neoplasia, or neurodegeneration. Overall, we conclude that more research on DNA repair in fish embryos is needed.


Vitamin C status and physical working capacity in adolescents.
The effect of ascorbic acid supplementation on physical working capacity was studied in young adolescent boys in which the concomitant biochemical riboflavin and pyridoxin deficiencies were corrected by medicamentous prophylaxis. After daily administration for two months of 70 mg ascorbic acid, the mean plasma vitamin C in the experimental group (n = 49) rose from 0.33 to 1.49 mg/dl (p less than 0.001) and the prevalence of deficient plasma vitamin C values (less than 0.20 mg/dl) decreased from 52.3 percent to zero. The improvement in vitamin C biochemical status was also accompanied by a statistically significant increase in VO2 max. (p less than 0.01). There were no significant changes neither in the mean plasma vitamin C values nor in the mean VO2 max. in the control group subjects (n = 42). The increase in VO2 max. in the experimental group was primarily the result of an increase of VO2 max. in subjects with initially lower values. When data from both experimental and control groups were pooled together, a positive and significant association was found between VO2 max. and the increase of plasma vitamin C values below 1.0 mg/dl. No further increase in VO2 max. was observed when vitamin C plasma values reached 1.0 mg/dl or more. The two regression lines crossed at X = 0.86 mg/dl. This cut off point of plasma vitamin C level corresponds to a dietary intake of about 80 mg of ascorbic acid per day. The results of this study are in agreement with the suggested optimal ascorbic acid daily intake obtained by kinetic studies with (1-14C) ascorbic acid.


MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters.
To control the coronavirus disease 2019 (COVID-19) pandemic and the emergence of different variants of concern (VoCs), novel vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed. In this study, we report the potent immunogenicity and efficacy induced in hamsters by a vaccine candidate based on a modified vaccinia virus Ankara (MVA) vector expressing a human codon optimized full-length SARS-CoV-2 spike (S) protein (MVA-S). Immunization with one or two doses of MVA-S elicited high titers of S- and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against parental SARS-CoV-2 and VoC alpha, beta, gamma, delta, and omicron. After SARS-CoV-2 challenge, MVA-S-vaccinated hamsters showed a significantly strong reduction of viral RNA and infectious virus in the lungs compared to the MVA-WT control group. Moreover, a marked reduction in lung histopathology was also observed in MVA-S-vaccinated hamsters. These results favor the use of MVA-S as a potential vaccine candidate for SARS-CoV-2 in clinical trials.


Pharmacokinetics of low molecular weight heparin in patients with malignant tumors.
Cancer patients have an increased risk for venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is the mainstay of VTE treatment in these patients. Heparanase, which degrades heparin and LMWH, is an enzyme secreted from a variety of malignant tumors. The objective of this study was to elucidate the pharmacokinetics of LMWH in patients with locally advanced or metastatic cancer. A total of 10 cancer patients with VTE treated with the LMWH enoxaparin at a standard dose of 1 mg/kg every 12 h were enrolled. Blood samples were obtained before the injection of LMWH and at 1, 2, 3, 4, 6, and 8 h after LMWH administration, and they were tested for anti-factor Xa activity and heparanase levels. Peak anti-Xa activity was achieved 2-8 h after subcutaneous administration of LMWH. Six patients did not reach a therapeutic anti-Xa activity target (0.6-1.2 IU/ml) at 4 h after LMWH administration. Four patients did not reach anti-factor Xa values of 0.6 IU/ml throughout the trial. The median anti-Xa activity before LMWH injection was 0.24 IU/ml (range 0.07-0.7 IU/ml), as opposed to 0.52 IU/ml in historical controls. The median anti-Xa activity 4 h after LMWH injection was 0.58 IU/ml (range 0.22-1.23 IU/ml), as opposed to 1.2 IU/ml in historical controls. The blood level of heparanase in patients with malignancy and VTE was 6.24 ± 4.3 ng/ml, compared with 2.67 ± 1.09 ng/ml in cancer-free, age-matched, normal controls. In this pilot study, a substantial proportion of cancer patients suffering from VTE and treated with LMWH had subtherapeutic anti-Xa activity.


Dynamic Carboniferous tropical forests: new views of plant function and potential for physiological forcing of climate.
Contents 1333 I. 1334 II. 1335 III. 1339 IV. 1344 V. 1347 VI. 1347 1348 1348 References 1348 SUMMARY: The Carboniferous, the time of Earth's penultimate icehouse and widespread coal formation, was dominated by extinct lineages of early-diverging vascular plants. Studies of nearest living relatives of key Carboniferous plants suggest that their physiologies and growth forms differed substantially from most types of modern vegetation, particularly forests. It remains a matter of debate precisely how differently and to what degree these long-extinct plants influenced the environment. Integrating biophysical analysis of stomatal and vascular conductivity with geochemical analysis of fossilized tissues and process-based ecosystem-scale modeling yields a dynamic and unique perspective on these paleoforests. This integrated approach indicates that key Carboniferous plants were capable of growth and transpiration rates that approach values found in extant crown-group angiosperms, differing greatly from comparatively modest rates found in their closest living relatives. Ecosystem modeling suggests that divergent stomatal conductance, leaf sizes and stem life span between dominant clades would have shifted the balance of soil-atmosphere water fluxes, and thus surface runoff flux, during repeated, climate-driven, vegetation turnovers. This synthesis highlights the importance of 'whole plant' physiological reconstruction of extinct plants and the potential of vascular plants to have influenced the Earth system hundreds of millions of years ago through vegetation-climate feedbacks.


Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus.
Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response elementbinding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal-regulated kinases (MEK)/extracellular signal-regulated kinases (ERK) pathways in the hippocampus. Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.


Generation of Perfluoroalkyl Acids from Aerobic Biotransformation of Quaternary Ammonium Polyfluoroalkyl Surfactants.
The aerobic biotransformation over 180 days of two cationic quaternary ammonium compounds (QACs) with perfluoroalkyl chains was determined in soil microcosms, and biotransformation pathways were proposed. This is the first time that polyfluoroalkyl cationic surfactants used in aqueous film-forming foam (AFFF) formulations were studied for their environmental fate. The biotransformation of perfluorooctaneamido quaternary ammonium salt (PFOAAmS) was characterized by a DT50 value (time necessary to consume half of the initial mass) of 142 days and significant generation of perfluoroalkyl carboxylic acid (PFOA) at a yield of 30 mol % by day 180. The biotransformation of perfluorooctane sulfonamide quaternary ammonium salt (PFOSAmS) was very slow with unobservable change of the spiked mass; yet the generation of perfluorooctanesulfonate (PFOS) at a yield of 0.3 mol % confirmed the biotransformation of PFOSAmS. Three novel biotransformation intermediates were identified for PFOAAmS and three products including perfluorooctane sulfonamide (FOSA) for PFOSAmS through high-resolution mass spectrometry (MS) analysis and t-MS(2) fragmentation. The significantly slower PFOSAmS biotransformation is hypothesized to be due to its stronger sorption to soil owing to a longer perfluoroalkyl chain and a bulkier sulfonyl group, when compared to PFOAAmS. This study has demonstrated that despite overall high stability of QACs and their biocide nature, the ones with perfluoroalkyl chains can be substantially biotransformed into perfluoroalkyl acids in aerobic soil.


Proton-Regulated Catalytic Activity of Nanozymes for Dual-Modal Bioassay of Urease Activity.
Benefiting from the merits of high stability and superior activity, nanozymes are recognized as promising alternatives to natural enzymes. Despite the great leaps in the field of therapy and colorimetric sensing, the development of highly sensitive nanozyme-involved photoelectrochemical (PEC) biosensors is still in its infancy. Specifically, the investigation of multifunctional nanozymes facilitating different catalytic reactions remains largely unexplored due to the difficulty in synergistically amplifying the PEC signals. In this work, mesoporous trimetallic AuPtPd nanospheres were synthesized with both efficient oxidase and peroxidase-like activities, which can synergistically catalyze the oxidation of 4-chloro-1-naphthol to produce benzo-4-chlorohexadienone precipitation on the surface of photoactive materials, and thus lead to the decreased photocurrent as well as increased charge-transfer resistance. Inspired by the proton-dependent catalytic activity of nanozymes, a self-regulated dual-modal PEC and electrochemical bioassay of urease activity was innovatively established by in situ regulating the activity of AuPtPd nanozymes through urease-mediated proton-consuming enzymatic reactions, which can remarkably improve the accuracy of the assay. Meanwhile, the determination of urease activity in spiked human saliva samples was successfully realized, indicating the reliability of the biosensor and its application prospects in clinical diagnosis.


Pulse doublets generated by a frequency-shifting loop containing an electro-optic amplitude modulator.
We investigate theoretically and experimentally an all-fibered frequency-shifting loop which includes an electro-optic amplitude modulator (EOM) and an optical amplifier, and is seeded by a continuous-wave laser. At variance with frequency-shifted feedback lasers, or Talbot lasers, that contain an acousto-optic frequency shifter, the EOM creates at each round-trip two side-bands that recirculate inside the loop. Benefiting from the high modulation frequency of the EOM, a wide optical frequency comb up to 40 GHz is generated. We demonstrate an original double-pulse regime when the loop length is a multiple of the RF modulation wavelength applied to the modulator. The inter-pulse interval is governed by both the bias voltage and modulation depth of the EOM. Besides, some typical waveforms such as saw-tooth and rectangle are experimentally obtained by properly setting operating frequency, bias voltage and the RF power. The system is modeled by a linear interference model that takes the amplitude modulation function and loop delay into account. The model explains the formation of pulse doublets and reproduces well all the experimental waveforms. Furthermore, the un-seeded loop driven above threshold also generates mode-locked picosecond pulse doublets with a continuously adjustable delay up to the modulation period.


Prenatal diagnosis of transposition of great arteries with left anterior aorta (SDL-TGA).
We report a case with prenatal diagnosis of transposition of great arteries (TGA) with L-posed aorta (SDL-TGA) which was confirmed by postnatal echocardiography. The anatomic findings were confirmed during the successful arterial switch operation (ASO). The technical challenges of ASO in the L-posed aorta are also described.


The role of caries recognition: treatment decisions from bitewing radiographs.
To describe the effect of the ability to estimate caries depth from bitewing radiographs on restorative treatment decisions. A 10% random sample of Dutch dental practitioners (n = 444) was sent a two-part questionnaire based on an analytic approach to radiographic caries diagnosis and restorative treatment decision making. In the second part the dentists were asked to diagnose radiographs of 105 tooth surfaces with and without dentine caries and then to make a treatment decision for each surface. A regression analysis was carried out using the negative predictive value (TN/[TN + FN]) of the restorative treatment decision for dentine caries as the dependent variable. The mean negative predictive value for the dentists' proposals from radiographs to leave surfaces untreated was 0.77 (SD 0.05; min. 0.60, max 0.87). Nine significant (P < 0.05) variables explained 65% (R2 = 0.65) of the variation in decision making. One diagnostic ability variable explained 48% of the variation found. Dentists appear to take the seriousness of errors in restorative decisions into account when deciding on treatment. The ability of dental practitioners to identify and discriminate between lesions in the inner half of the enamel and the outer half of the dentine, however, plays a dominant role in their treatment decision making.


Access to the scholarly record of medicine by the osteopathic physicians of southeastern Michigan.
This paper is one part of a continuing study to determine the availability of library service to physicians in southeastern Michigan not associated with academic institutions. The institutional affiliations of the 800 osteopathic physician community of the area were identified. As the availability of library service at these institutions was known, the conclusion is patent that 60 percent of these physicians do not have dependable access to the library resources of the area. Further, it is apparent from the way the institutions are distributed and the responsibilities physicians have, that the only hope of providing library service to the practicing physician is through hospitals.


Stroke risk in multiple sclerosis: a critical appraisal of the literature.
Observational studies suggest that the occurrence of stroke on multiple sclerosis (MS) patients is higher compared to the general population. MS is a heterogeneous disease that involves an interplay of genetic, environmental and immune factors. The occurrence of stroke is subject to a wide range of both modifiable and non-modifiable, short- and long-term risk factors. Both MS and stroke share common risk factors. The immune mechanisms that underlie stroke are similar to neurodegenerative diseases and are attributed to neuroinflammation. The inflammation in autoimmune diseases may, therefore, predispose to an increased risk for stroke or potentiate the effect of conventional stroke risk factors. There are, however, additional determinants that contribute to a higher risk and incidence of stroke in MS. Due to the challenges that are associated with their differential diagnosis, the objective is to present an overview of the factors that may contribute to increased susceptibility or occurrence of stroke in MSpatients by performing a review of the available to date literature. As both MS and stroke can individually detrimentally affect the quality of life of afflicted patients, the identification of factors that contribute to an increased risk for stroke in MS is crucial for the prompt implementation of preventative therapeutic measures to limit the additive burden that stroke imposes.


Role of Indocyanine Green in Fluorescence Imaging with Near-Infrared Light to Identify Sentinel Lymph Nodes, Lymphatic Vessels and Pathways Prior to Surgery - A Critical Evaluation of Options.
Modern surgical strategies aim to reduce trauma by using functional imaging to improve surgical outcomes. This reviews considers and evaluates the importance of the fluorescent dye indocyanine green (ICG) to visualize lymph nodes, lymphatic pathways and vessels and tissue borders in an interdisciplinary setting. The work is based on a selective search of the literature in PubMed, Scopus, and Google Scholar and the authors' own clinical experience. Because of its simple, radiation-free and uncomplicated application, ICG has become an important clinical indicator in recent years. In oncologic surgery ICG is used extensively to identify sentinel lymph nodes with promising results. In some studies, the detection rates with ICG have been better than the rates obtained with established procedures. When ICG is used for visualization and the quantification of tissue perfusion, it can lead to fewer cases of anastomotic insufficiency or transplant necrosis. The use of ICG for the imaging of organ borders, flap plasty borders and postoperative vascularization has also been scientifically evaluated. Combining the easily applied ICG dye with technical options for intraoperative and interventional visualization has the potential to create new functional imaging procedures which, in future, could expand or even replace existing established surgical techniques, particularly the techniques used for sentinel lymph node and anastomosis imaging.


Sex, drugs and rock iguanas: testicular dynamics and plasma testosterone concentrations could predict optimal semen collection times in Cyclura.
Iguanas are the most endangered family of reptiles, with 77% categorised as threatened or near threatened. Further, Cyclura is the most endangered reptile genus, with all 12 species considered threatened. Therefore, it is vital that we develop assisted reproductive technologies for Cyclura spp. to enhance their conservation efforts. The goals of this study were to collect semen, and to measure testicle size and testosterone concentrations in Grand Cayman rock iguana hybrids (Cyclura lewisi ×nubila (CLN)) and rhinoceros rock iguanas (Cyclura cornuta (CC)). A prospective longitudinal study was performed in 9.0 CLN and 9.0 CC during their reproductive season in southern Florida (February-July). Serial testicle ultrasound measurements and plasma testosterone concentrations were collected monthly. Testicle measurements (length (L), width (W), height (H)) were collected and testicle volume (V ) was estimated using the equation V =0.52(LW 2 ). There were significant differences in testicle L, W, H and V for both species. Testicle size peaked for CLN and CC in April and May respectively. Plasma testosterone concentrations increased from baseline during February, March and April in CLN and in March, April and May in CC. Ultrasound testicle measurements could be used to predict when to collect semen in these seasonally monocyclic iguanas.


Temperature-dependent reproduction of Spodoptera eridania: developing an oviposition model for a novel invasive species.
Temperature plays a critical role in the development and reproductive process of insects, therefore understanding how insects respond to temperature is vital for comprehending and predicting their population dynamics, particularly when it comes to agricultural pests. Spodoptera eridania Stoll is a polyphagous pest that has recently expanded its distribution beyond its native range. In this study, we assessed the impact of temperature on the reproduction of S. eridania and used the obtained data to develop an oviposition model that could be used to predict egg-laying behavior under field conditions. The reproductive parameters were evaluated at temperatures of 15, 20, 25, 28, and 32 °C. Temperature had a significant impact on the reproductive parameters examined. Overall, as temperature increased, the pre-oviposition period, oviposition period, and longevity decreased. Total fecundity exhibited a bell-shaped response to temperature, with peak egg-laying observed at 20 and 25 °C. In line with the experimental data, our model predicted higher rates of oviposition between 20 and 26 °C, thus reinforcing that this temperature range may represent the optimal conditions for the reproduction of S. eridania. The findings from our study provide a significant contribution to the understanding of the ecology of an important agricultural pest. The information generated can have practical applications in developing control strategies by enabling the aligning of the timing of control measures with peaks of reproductive activity. © 2023 Society of Chemical Industry.


A rare complication of IgA vasculitis: renal and intestinal ischemia successfully treated with plasmapheresis.
IgA vasculitis (IgAV) is a multisystemic small vessel vasculitis and is the most common vasculitis in childhood. The characteristic findings of IgAV are palpable purpuric rash, abdominal pain, arthralgia or arthritis, and hematuria. Ischemic complications are very rare in IgAV. Thrombotic complications can be observed after a COVID-19 infection. Also in the presence of familial Mediterranean fever, IgAV may have an atypical or more severe course. We present a case of IgAV complicated with renal infarction and intestinal ischemia. There was no recent or distant history of COVID-19 in the patient or family members, but the patient`s COVID-19 antibody was positive. In addition, MEFV gene analysis of the patient showed homozygous M694V mutation. The patient did not respond to enoxaparin, pulse methylprednisolone, intravenous immunoglobulin (IVIG), iloprost, and cyclophosphamide treatments. She was successfully treated with six sessions of plasmapheresis. Plasmapheresis seems to be an effective treatment option in IgAV-related ischemic findings that do not respond to intensive immunosuppressive therapy.


IL-4 is an endogenous inhibitor of neutrophil influx and subsequent pathology in acute antibody-mediated inflammation.
IL-4 is an immunoregulatory cytokine that has in vitro and in vivo anti-inflammatory actions. In this study we investigated whether endogenously produced IL-4 modulates inflammatory processes that occur after Abs bind to target tissue by comparing the severity of glomerulonephritis induced by heterologous anti-glomerular basement membrane Abs in wild-type (IL-4+/+) mice to that of glomerulonephritis induced in homozygous IL-4 gene knockout (IL-4-/-) mice. Two hours after Ab injection, IL-4-/- mice had significantly higher intrarenal intercellular adhesion molecule-1 mRNA expression and intraglomerular neutrophil accumulation than the IL-4+/+ group. Treatment of IL-4-/- mice with recombinant murine IL-4 at the time of disease induction reduced intercellular adhesion molecule-1 expression and neutrophil influx to levels observed in IL-4+/+ kidneys. Four days after Ab administration, untreated IL-4-/- mice developed significantly greater urinary protein excretion, intracapillary fibrinogen deposits, and glomerular hypercellularity than IL-4+/+ mice. These results demonstrate that endogenous IL-4 suppresses neutrophil influx and limits tissue damage in Ab-induced glomerulonephritis, suggesting that IL-4 is an important regulator of acute inflammatory processes.


Molecular and developmental mechanisms of anterior segment dysgenesis.
Anterior segment dysgenesis (ASD) is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, associated with an increased risk of glaucoma and corneal opacity. Several different gene mutations have been identified underlying these anomalies with the majority of ASD genes encoding transcriptional regulators. In this review, the role of the ASD genes, PITX2 and FOXC1, is considered in relation to the embryology of the anterior segment, the biochemical function of these proteins, and their role in development and disease aetiology. The emerging view is that these genes act in concert to specify a population of mesenchymal progenitor cells, mainly of neural crest origin, as they migrate anteriorly around the embryonic optic cup. These same genes then regulate mesenchymal cell differentiation to give rise to distinct anterior segment tissues. Development appears critically sensitive to gene dosage, and variation in the normal level of transcription factor activity causes a range of anterior segment anomalies. Interplay between PITX2 and FOXC1 in the development of different anterior segment tissues may partly explain the phenotypic variability and the genetic heterogeneity characteristic of ASD.


Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults.
In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of "biotics" or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.


A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy.
The favorable response rate of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication has been demonstrated. However, there are limited data available on the long-term outcomes. The aim of this retrospective study was to evaluate the long-term outcomes of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication. Thirty-four consecutive patients with localized gastric mucosa-associated lymphoid tissue lymphoma that were refractory to eradication were treated with radiotherapy (a total dose of 30 Gy). The response and adverse events of radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence-free, overall and disease-specific survival rates were calculated as long-term outcomes. Thirty-three (97.1%) patients achieved complete remission and radiotherapy was well tolerated. One patient underwent emergency gastrectomy due to severe hematemesis. Of the 34 patients during the median follow-up period of 7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one patient underwent surgery for bowel obstruction secondary to small bowel metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9 years. Pathologically, all three recurrences revealed mucosa-associated lymphoid tissue lymphoma without any transformation to high-grade lymphoma. None died of gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free survival rate was 97.0%. The 5-year overall survival rates and disease-specific survival rates were 97.0 and 100%, respectively. Radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication can achieve excellent overall survival. However, long-term surveillance is necessary to identify late recurrences.


Efficacy of Ultrasonography at the Ankle Level for Estimation of Pedal Microcirculation.
Chronic wounds due to diabetes mellitus (DM) and/or peripheral arterial disease (PAD) often occur in the pedal region peripheral to the ankle. To predict wound healing potential of limb ulcers, skin perfusion pressure (SPP) and transcutaneous oxygen tension (TcPO2) have recently become popular as the parameters that reflect skin microcirculation. On the other hand, ultrasonography for the macrocirculatory vessels has already prevailed widely as the standard vascular investigation. The skin microcirculation peripheral to the ankle probably depends on the macrocirculatory blood flow at the ankle level. Thus, this study aims to estimate whether the blood flow of the anterior tibial artery (ATA) and the posterior tibial artery, at the ankle level, reflect the values of SPP and TcPO2 on the foot. The protocol enrolled 88 patients (122 limbs) with foot ulcers due to DM and/or PAD. The statistical analysis revealed that the sum of blood flow of the ATA and the PTA (posterior tibial artery), at the ankle level, significantly correlated with SPP on the foot. The findings support the availability of conventional ultrasonographic investigation to estimate microcirculation of the foot crucial for wound healing. (This article is a translation of J Jpn Coll Angiol 2014; 54: 45-50.).


Plant genotype mediates the effects of nutrients on aphids.
Soil nutrients, and factors which influence their concentrations and bioavailability, form a basic component of bottom-up control of ecosystem processes, including plant-herbivore interactions. Increased nutrient levels are linked, through plant defence theory, with increased levels of herbivore susceptibility. The focal point of many ecological experiments examining this link is at the species level, where the response of single species is the average of many different genotypes. Here, we focus on the genetic basis of indirect ecological interactions. We investigated the effects of nutrient concentration on the population growth of an aphid herbivore across multiple genotypes of barley in relation to plant growth rate. In general, both aphid population size and plant growth rate increased with nutrient concentration. However, they were both dependent on the interaction between nutrient concentration and barley genotype. Our data raise the testable possibility of differential defense responses between genotypes of barley, for example divergent, fixed and inducible defences against aphids. We provide evidence that the indirect effects of soil nutrients on aphid population size are mediated by the genetics of the host plant.


Familial hemophagocytic lymphohistiocytosis: from autopsy to prenatal diagnosis. Report of a case.
Hemophagocytic lymphohistiocytosis is a rare immunologic disorder affecting small children. It is characterized by an excessive and injurious immune response which turns rapidly fatal unless promptly and effectively treated. The main clinical signs are prolonged fever, hepatosplenomegaly, bleeding and laboratory findings of pancytopenia, increased serum transaminases, hypertriglyceridemia and hypofibrinogenemia. Four genes responsible for familiar hemophagocytic lymphohistiocytosis, which is inherited in autosomal recessive manner, have been identified so far. This case report describes a fatal case of familiar hemophagocytic lymphohistiocytosis caused by compound heterozygote mutation for perforin. A previously healthy neonate, first child of noncosanguineous young healthy parents, presented with hypothermia and fulminant hepatic failure at 28 days of life and succumbed short after. The diagnosis was made at autopsy and confirmed by genetic testing postmortem. Five months later prenatal testing confirmed carrier status in the sibling to be born. This is to our knowledge only the second case of familiar hemophagocytic lymphohistiocytosis caused by perforin deficit in a Czech patient.


Diminishing returns or appropriate treatment strategy?--an analysis of short-term outcomes after pain clinic treatment.
In the United Kingdom patients with chronic pain are frequently managed in anaesthetist-led outpatient pain clinics. In many of these clinics the emphasis is on medical therapies (analgesics and psychotropic drugs, TENS, acupuncture and nerve blocks) with patients trying a series of different therapies until relief is achieved or further attempts at physical treatments are discontinued. The sequential trial of different treatment modalities presents clinicians with a problem. Patients who receive little benefit from (say) the first three treatments tried might be expected to be less likely to gain benefit from the next treatment modality. The presence or absence of such 'diminishing returns' from treatment will influence when therapeutic efforts based on the medical model of pain should be abandoned. This study examined basic outcome data on 1912 patients seen in a single Scottish pain clinic between 1987 and 1994. The data were analysed to assess whether the success of treatment modalities depended on whether they were used as a first-choice treatment or were given after previous therapeutic attempts had failed. Diminution in success rates was generally not large although this varied between therapies. No fall-off in success rates was seen for antidepressants, acupuncture or sympathetic nerve blocks. However, the other nerve blocks all showed falling success rates when they were used as fourth- or fifth-line treatments. That little diminution of success rates was seen warrants further investigation. Pain clinics need good information on the success or otherwise of late treatment so that they can devise rational pain management strategies covering multiple therapies and appropriate criteria for ending medical interventions. These findings suggest that allowing patients access to multiple pain therapies may well be an appropriate management strategy.


[Features of the distribution of HLA antigens in patients with neurologic manifestations of lumbar osteochondrosis].
Examinations of the HLA antigens (A and B loci) distribution in patients with neurologic manifestations of lumbar osteochondrosis (NMLO) has revealed a statistically more rare incidence of A11 antigens and a more frequent one, of B7 and B18 ones. A different distribution of the antigens in cases with the major clinical forms of lumbar osteochondrosis was noted. Patients with discogenic lumbosacral radiculitis differed from normal subjects by the same antigens as all NMLO patients. For patients with lumbar ischialgia increased concentrations of B7 and B18 antigens were characteristic, whereas in radicular ischialgias A11 and B15 antigens were less incident and B40 one, more incident. The findings confirm the polygenic nature of hereditary predisposition to NMLO.


Cancers in Australia in 2010 attributable to and prevented by the use of menopausal hormone therapy.
To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to menopausal hormone therapy (MHT) use. We estimated the population attributable fraction for cancers causally associated with MHT (breast, endometrium, ovary), and the proportion of colorectal cancers prevented by MHT. We used standard formulae incorporating Australian prevalence data, relative risks of cancer associated with MHT and cancer incidence. We also estimated potential change in cancer incidence under two hypothetical scenarios whereby 25% fewer Australian women used MHT, or women exclusively used oestrogen-only MHT. An estimated 539 cancers in Australia in 2010 were attributable to MHT: 453 breast, 67 endometrial and 19 ovarian cancers equating to 3.4%, 3.1% and 1.6% of each cancer type, respectively. In contrast, MHT may have prevented 52 colorectal cancers. If 25% fewer women used MHT, then 141 cancers may have been avoided. If women exclusively used oestrogen-only MHT then 240 cancers may have been avoided. MHT use caused more than 500 cancers in Australian women in 2010 and prevented ∼50 colorectal cancers. MHT use continues to cause an excess of cancers. The risks, benefits, regimen and treatment duration should be carefully considered for each woman before MHT is commenced.


Paget's disease in an epidermal cyst.
A case of Paget's disease involving both the epidermis of the nipple and an adjacent epidermal cyst is reported. Immunohistochemistry showed similarity between the infiltrating cells in both sites and those of the underlying mammary adenocarcinoma. Epidermal cysts may be involved in a variety of disease processes which affect the epidermis in general and, unless they are subjected to careful histopathological examination, these diseases may be overlooked.


The DNA adenine methylase of Salmonella Enteritidis promotes their intracellular replication by inhibiting arachidonic acid metabolism pathway in macrophages.
Macrophages can participate in immune responses by altering their metabolism, and play important roles in controlling bacterial infections. However, Salmonella Enteritidis can survive and proliferate in macrophages. After the deletion of DNA adenine methylase (Dam), the proliferation of Salmonella Enteritidis in macrophages decreased, the molecular mechanism is still unclear. After infecting macrophages with Salmonella Enteritidis wild type and dam gene deletion strains, intracellular metabolites were extracted and detected by non-targeted metabolomics and fatty acid targeted metabolomics. We found Dam had significant effects on arachidonic acid and related metabolic pathways in macrophages. The dam gene can promote the proliferation of Salmonella Enteritidis in macrophages by inhibiting the metabolic pathway of cytosolic phospholipase A2-mediated arachidonic acid production and conversion to prostaglandin E2 in macrophages, reducing the secretion of the pro-inflammatory factors IL-1β and IL-6. In addition, inhibition of arachidonic acid-related pathways in macrophages by Arachidonyl trifluoromethyl ketone could restore the proliferation of dam gene deletion strains in macrophages. This study explored the role of Dam in the process of Salmonella Enteritidis invading host cells from the perspective of host cell metabolism, and provides new insights into the immune escape mechanism of Salmonella Enteritidis.


Analysis of hazard perception characteristics based on driving behavior considering overt and covert hazard scenarios.
The drivers' hazard perception plays an important role in preventing and reducing the occurrence of traffic accidents. In order to explore the drivers' hazard perception and their behavioral characteristics in overt and covert hazards, hazardous events of three traffic conflict types (vehicle to vehicle, vehicle to cyclist and vehicle to pedestrian) were designed for overt and covert hazards based on the UC-win/Road driving simulation software, respectively. 35 drivers were organized to conduct the driving simulation tests. The data of driving behavior was collected when they were driving. A comparative analysis of drivers' hazard perception ability and driving behavior characteristics was carried out for hazardous scenarios and traffic conflict types. The result has shown that drivers are more likely to take slowing measures or brake earlier in overt hazard scenarios to ensure safe driving. And drivers are more likely to be involved in collisions in covert hazard scenarios. The types of traffic conflict have a significant effect on the hazard perception ability of drivers (F = 5.92, p < 0.01). Drivers have the strongest hazard perception for cyclists and the weakest hazard perception for pedestrians. Traffic conflict types has a significant effect on drivers' average braking depth (F = 32.31, p < 0.01), average speed (F = 13.78, p < 0.01), and average acceleration (F = 9.26, p < 0.01).


Association between 25-hydroxyvitamin D deficiency and cardiovascular disease in type 2 diabetic patients with mild kidney dysfunction.
A potentially modifiable and underestimated risk factor for cardiovascular disease (CVD) in subjects with kidney dysfunction is 25-hydroxyvitamin D deficiency, although the relationship between inadequate vitamin D status and manifest CVD in type 2 diabetic subjects with mild kidney impairment has not been extensively examined. We evaluated the relationship between serum 25-hydroxyvitamin D concentrations, baseline kidney function (estimated using the modification of diet in renal disease equation) and manifest CVD (myocardial infarction, angina, ischaemic stroke, coronary revascularization or carotid endarterectomy) among 462 consecutive patients with type 2 diabetes. In the whole population, the mean age was 62+/-7 years, 64% were men, 76.3% had hypertension and the mean estimated glomerular filtration rate (GFR) was 94+/-33 ml/min/1.73 m(2). Kidney function was strongly and inversely associated with CVD. In multivariate logistic regression analysis, there was an inverse association between serum 25-hydroxyvitamin D concentrations and prevalent CVD [odds ratio 0.95 (95% CI 0.92-0.98; P=0.001)] in the whole population independent of baseline kidney function and other known risk factors. Additionally, the association between serum 25-hydroxyvitamin concentrations and CVD [odds ratio 0.97 (95% CI 0.94-0.99; P=0.045)] remained statistically significant in participants in the lowest estimated GFR tertile after adjustment for potential confounders. Decreased 25-hydroxyvitamin D concentrations are independently associated with prevalent CVD in type 2 diabetic patients with mild kidney dysfunction.


Toxicity of different industrial effluents in Taiwan: a comparison of the sensitivity of Daphnia similis and Microtox.
Industrial effluents are known to exhibit toxicity toward different aquatic organisms. In Taiwan management of these discharges still relies on chemical and physical and physical characteristics of water, although various standard method for assessing aquatic toxicity have been proposed by the Taiwan Environmental Protection Administration. In this study we examined the toxicity and compared the sensitivity of different types of industrial effluents using two proposed toxicity tests: the Daphnia similis acute toxicity test and the Microtox acute assay (Vibrio fischeri). Results showed that electroplating effluents were the most toxic of all the effluents tested, followed by acrylonitrile manufacturing, pulp/paper, and tannery effluents. The EC50 of an electroplating effluent for D. similis and V. fischeri (15 min) was as low as, respectively, 2.9% and 3.9% of the whole effluent. The other effluents were not acutely toxic to either organism tested. However, the tests exhibited different sensitivity toward various discharges. Only the electroplating and acrylonitrile manufacturing effluents had effects on both organisms. These results indicate the importance of the incorporation of aquatic toxicity tests into the management scheme for treated wastewaters.


Beyond Simple Differences: Moderators of Gender Differences in Heteronormativity.
Heteronormativity is a culturally embedded system defining acceptable identities and behaviors in romantic relationships. Recent literature has suggested that heteronormativity is strongly associated with political attitudes, personality characteristics such as tolerance of ambiguity, and key demographic variables such as gender and sexual orientation. However, interactions between gender and other factors have not been thoroughly explored as predictors of heteronormative attitude and beliefs. The current study (N = 306) expands the understanding of predictors of heteronormativity, particularly as they interact with gender. In the current study, higher education was associated with lower heteronormativity among women, but not among men, and expressiveness was associated with lower heteronormativity among men, but not among women. Finally, a 3-way interaction showed that the relationship between education and heteronormativity for men (but not women) depended on trait expressiveness. Future studies are recommended, including observation of changes in heteronormativity over time and exploration of mechanisms that reinforce or reduce heteronormativity.


Microbial glycoproteomics.
Mass spectrometry-based "-omics" technologies are important tools for global and detailed mapping of post-translational modifications. Protein glycosylation is an abundant and important post translational modification widespread throughout all domains of life. Characterization of glycoproteins, including identification of glycan structure and components, their attachment sites and protein carriers, remains challenging. However, recent advances in glycoproteomics, a subbranch that studies and categorizes protein glycosylations, have greatly expanded the known protein glycosylation space and research in this area is rapidly accelerating. Here, we review recent developments in glycoproteomic technologies with a special focus on microbial protein glycosylation.


Association between larger thymic size and higher thymic output in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.
To examine the impact of thymic size on immune recovery in patients with human immunodeficiency virus (HIV) infection, the thymus was visualized, using computed tomographic scans, in 25 HIV-infected patients who had received highly active antiretroviral therapy (HAART) for 6-18 months and had levels of viremia <500 copies/mL. For comparison, 10 control subjects were included in the study. Total and naive CD4+ cell counts were determined by flow cytometry. To determine thymic output, the number of CD4+ cells containing T cell receptor excision circles (TRECs) was measured. Qualitative immune recovery was evaluated by determination of CD4+ T cell receptor repertoire in 19 of the HIV-infected patients. Larger thymic size was associated with higher CD4+ cell counts (r=0.498; P=.011) and higher CD4+ TREC frequency (r=0.652; P<.001). Furthermore, patients with abundant thymic tissue seemed to have broader immunologic repertoires, compared with patients with minimal thymic tissue (P=.054). These findings suggest that thymopoiesis is ongoing in the adult thymus and contributes to immune reconstitution in HIV-infected patients receiving HAART.


'Green' on the ground but not in the air: Pro-environmental attitudes are related to household behaviours but not discretionary air travel.
The rise in greenhouse gas emissions from air travel could be reduced by individuals voluntarily abstaining from, or reducing, flights for leisure and recreational purposes. In theory, we might expect that people with pro-environmental value orientations and concerns about the risks of climate change, and those who engage in more pro-environmental household behaviours, would also be more likely to abstain from such voluntary air travel, or at least to fly less far. Analysis of two large datasets from the United Kingdom, weighted to be representative of the whole population, tested these associations. Using zero-inflated Poisson regression models, we found that, after accounting for potential confounders, there was no association between individuals' environmental attitudes, concern over climate change, or their routine pro-environmental household behaviours, and either their propensity to take non-work related flights, or the distances flown by those who do so. These findings contrasted with those for pro-environmental household behaviours, where associations with environmental attitudes and concern were observed. Our results offer little encouragement for policies aiming to reduce discretionary air travel through pro-environmental advocacy, or through 'spill-over' from interventions to improve environmental impacts of household routines.