Positive remediation on sedimentary P by combination of capping with calcium hydroxide and oxidation with perhydrol.
The capping is called passive remediation because the sedimentary P was released and then immobilized by the capping materials. However, the release depends on the environmental conditions. Therefore, a hypothesis was proposed that the oxidant was used to accelerate sedimentary P release and the capping material was used to capture those released P. It is positive remediation to reduce sedimentary P amount. The results show that soluble reactive phosphorus (SRP) concentration in the overlying water and pore water increased and then decreased gradually under the combination of sodium percarbonate (SPC) and Ca(OH)2, similar as that under the capping with single Ca(OH)2. The sedimentary P amount was reduced considerably and P concentration in the capping layer increased obviously after 60 days, compared with the capping with single Ca(OH)2. All these indicated that oxidation improved the sedimentary P release and the released P was captured and immobilized by the capping material of Ca(OH)2. However, the acceleration of sedimentary P release due to the oxidation is obviously different from the traditional mechanism that the oxic condition in the sediment is favor of the immobilization on sedimentary P. It is attributed to the oxidizability of ·OH from SPC. The reduction of mobile-P and the increase of Ca-P under the combined use are observed. This is similar as traditional mechanism of oxic condition. It is sure that positive remediation reduced sedimentary P amount, resulting in the decrease of P release risk in a long time.


The Possibility of Applying the Vitamin D Brief Food Frequency Questionnaire as a Tool for a Country with No Vitamin D Data in Food Composition Tables.
Although the role of vitamin D is well known, the possibility of assessing its intake may be constricted in countries with no vitamin D data in food composition tables, as in the case of Croatia. The aim of the presented study was to adjust the VIDEO-FFQ (Vitamin D Estimation Only-Food Frequency Questionnaire), previously validated in Poland, to the Croatian population and to assess the validity and reproducibility of the adjusted Cro-VIDEO-FFQ (Croatian-VIDEO-FFQ). The study involved a group of Croatian women aged 20⁻30 and the Polish questionnaire was adjusted for a population due to similarities of the nutritional habits between countries. 106 individuals were recruited and 63 completed all the stages of the study. Participants conducted a 3-day dietary record and filled out the Cro-VIDEO-FFQ1 (first stage), as well as the same questionnaire (Cro-VIDEO-FFQ2) 6 weeks after (second stage). The following vitamin D intakes were observed in the studied group: 1.9 µg (0.2⁻8.0 µg) for 3-day dietary record, 3.3 µg (1.1⁻10.6 µg) for Cro-VIDEO-FFQ1, 3.6 µg (1.4⁻7.8 µg) for Cro-VIDEO-FFQ2. The Bland-Altman indexes in assessment of validity and reproducibility were 4.8% and 6.3%, respectively, with mean differences of 0.55 µg and 0.12 µg, as well as limits of agreement -0.91⁻2.01 µg and -0.44⁻0.69 µg. The kappa coefficient indicated a fair agreement for validity (0.21) and substantial for reproducibility (0.62), while correlations were significant (p = 0.0027, r = 0.37 for validity; p < 0.0001, r = 0.80 for reproducibility). It was observed that VIDEO-FFQ may be adjusted as a simple tool to assess vitamin D intake in a population with no vitamin D data in food composition tables, while Cro-VIDEO-FFQ may be a valid tool for nutritional assessment in Croatia.


Echogenic intracardiac foci and fetal cardiac anomalies: A review of cases from a tertiary care center in China.
To investigate the relationship between the location of echogenic intracardiac foci (EIFs) and fetal cardiac anomalies in our patient population. We performed a retrospective study of the clinical files of fetuses who underwent an echocardiographic examination at our fetal cardiac medical center from August 2010 to August 2016. Fetuses were grouped by EIF location (left ventricle [LV], right ventricle [RV], or bilateral ventricles [BVs]). The maternal age, reason for referral, and cardiac anomalies in the three groups were analyzed. We enrolled 2647 fetuses with an EIF. Of these, 2498 (94.4%) were in the LV group, while 45 (1.7%) and 104 (3.9%) were in the RV and BV groups, respectively. Aneuploidy was found in 3 fetuses, and all of these had a left-sided EIF. Cardiac anomalies were found in 93/2498 (3.7%) fetuses with a left-sided EIF, 5/45 (11.1%) of those with a right-sided EIF, and 3/104 (2.9%) of those with bilateral EIFs. The prevalence of congenital heart disease was significantly higher in fetuses with a right-sided EIF than in those with left-sided or bilateral EIFs (P < .05). Right-sided EIFs were more frequently associated with fetal cardiac anomalies than were left-sided or bilateral EIFs.


Diagnostic assessment of diabetic microangiopathy by tcPO2 stimulation tests.
Transcutaneous PO2 measurements at 37 degrees C can recognize and quantify diabetic microangiopathy if suitable stimulation tests are used. The following parameters are of practical importance: resting PO2, postocclusive PO2, rubefacient-induced PO2 and 45 degrees C heating PO2. Patients with diabetic microangiopathy show diminished PO2 values in rubefacient-induced PO2 and 45 degrees C heating PO2. The former ist probably related to endothelial-cell function disturbances and the letter to organic vessel wall changes. Thus, a quantitative and differentiated picture of microangiopathy can be obtained in each individual patient.


P2X4 receptor stimulation enhances MrgprB2-mediated mast cell activation and pseudoallergic reactions in mice.
Pseudoallergies caused by drugs make disease treatment difficult. Mas-relate G protein-coupled receptor X2 (MRGPRX2), which is specifically expressed in mast cells (MCs), has been implicated in pseudoallergies. High concentrations of therapeutic agents are typically required to stimulate MRGPRX2. Although regulatory mechanisms may enhance this response, the factors involved in this regulation are not well-understood. In this study, the effects of extracellular ATP on MC activation induced by MrgprB2, the mouse ortholog of human MRGPRX2, were examined in mouse peritoneal MCs (PMCs). ATP alone induced minimal PMC degranulation but markedly enhanced degranulation induced by the MrgprB2 agonist compound 48/80 (CP48/80), substance P, PAMP-12, and vancomycin. ATP promoted CP48/80-induced increase in intracellular Ca2+ in PMCs. This enhancement effect of ATP was absent in PMCs prepared from P2X4 receptor (P2X4R)-deficient mice and inhibited by the PI3K inhibitor wortmannin. In addition, P2X4R deficiency reduced the skin-specific and systemic anaphylactic responses to CP48/80 in vivo. In MC-deficient KitW-sh/W-sh mice, reconstitution with MCs obtained from wild-type mice led to a more severe anaphylactic response to CP48/80 compared to that from P2X4R-deficient mice. P2X4R-mediated effect may be involved in MrgprB2-mediated MC activation in vivo and is a potential target for alleviating pseudoallergic reactions.


Decision time and response accuracy in a conditional motor learning task are impaired independently in unilateral temporal lobe-resected patients.
Learning and memory of declarative knowledge and relational information are dependent on the integrity of medial temporal lobe (MTL). Numerous studies suggest that left lobectomy impairs verbal memory while right lobectomy impairs non-verbal memory. In order to instrumentally quantify material-specific memory impairment after temporal lobe excision, we compared, using a computerized conditional motor associative learning task, patients with surgically treated drug-resistant temporal lobe epilepsy to age-matched controls. We enrolled seven epileptic patients with left (LTR), seven with right (RTR) temporal lobe resection and fourteen controls. During the task, abstract visual stimuli had to be associated, by trial and error, with a spatially oriented joystick motor response. Response and decision time were analyzed. Statistical analysis disclosed that the learning curve slopes of both RTR and LTR patients were significantly shallower compared to controls, LTR patients needed a number of test trials significantly increased compared to RTR patients and controls, the average probability of success in the test trials was significantly lower in LTR patients compared to RTR patients and controls, and RTR patients' decision times were significantly longer than LTR patients and controls. The results suggest that RTR patients, using the preserved verbalization strategy, achieved higher learning scores than LTR patients, which were forced to use a visuo-spatial representation of the stimuli-response association. Accordingly, RTR patients were significantly slower, compared to LTR patients and controls, indicating that processes involving recall were partially impaired, and non-canonical networks for executing a non-verbal task could be in action.


Intermittent Administration of Nitroglycerin Sublingual Powder Compared with Placebo in Outpatients with Peripheral Artery Disease: Results of a Randomised Proof of Concept Study.
Treatment of peripheral artery disease (PAD), Fontaine Stage IIb with vasoactive substances is of limited efficacy and does not last beyond the active treatment. Glyceryl trinitrate (GTN) is a vasodilating agent that relaxes vascular smooth muscle cells. The aim was to prove the concept that GTN sublingual powder has sustained clinical efficacy and adequate safety in these patients. This was a multicentre, randomised, double blind, placebo controlled, forced titration, proof of concept study (phase IIa). Patients had a treadmill test at baseline, after 12 weeks of GTN/placebo administration, and at 19 and 26 weeks (without treatment). Primary objectives were an increase in initial claudication distance (ICD) and absolute claudication distance (ACD) at 12 weeks. Ninety-five patients were screened and 73 randomised, of which 53 patients completed the 12 week treatment phase (GTN 26, placebo 27). At a baseline ICD of 59.2 ± 32.8 m (GTN) and 57.5 ± 39.7 m (placebo), GTN led to a placebo corrected ICD increase of 23.2% vs. baseline (p = .35). Baseline ACD was 105.3 ± 52.9 m (GTN) and 106.1 ± 95.0 m (placebo), and GTN led to a placebo corrected increase of 3.6% (p = .44), with substantial interindividual variation. The change in claudication distance was greater in patients with an ICD of ≥50 m at baseline (ΔICD 29.3%; p = .19), and an ACD ≥ 100 m (ΔACD 8.5%; p = .40). The effect lasted beyond the active treatment period as shown by a 49.3% increase in ICD (p = .31) and a 20.6% increase in ACD (p = .21) by week 26. GTN sublingual powder was well tolerated. Intermittent treatment with nitroglycerin sublingual powder may represent a potential treatment option for patients with PAD stage Fontaine IIb, with an immediate and a sustained effect. The observed increases in ACD and ICD were however not statistically significant in this phase IIa proof of concept study. Further studies are required.


Sensory experience modulates the reorganization of auditory regions for executive processing.
Crossmodal plasticity refers to the reorganization of sensory cortices in the absence of their typical main sensory input. Understanding this phenomenon provides insights into brain function and its potential for change and enhancement. Using functional MRI, we investigated how early deafness influences crossmodal plasticity and the organization of executive functions in the adult human brain. Deaf (n = 25; age: mean = 41.68, range = 19-66, SD = 14.38; 16 female, 9 male) and hearing (n = 20; age: mean = 37.50, range = 18-66, SD = 16.85; 15 female, 5 male) participants performed four visual tasks tapping into different components of executive processing: task switching, working memory, planning and inhibition. Our results show that deaf individuals specifically recruit 'auditory' regions during task switching. Neural activity in superior temporal regions, most significantly in the right hemisphere, are good predictors of behavioural performance during task switching in the group of deaf individuals, highlighting the functional relevance of the observed cortical reorganization. Our results show executive processing in typically sensory regions, suggesting that the development and ultimate role of brain regions are influenced by perceptual environmental experience.


Feline immunodeficiency virus infection of cats as a model to test the effect of certain in vitro selection pressures on the infectivity and virulence of resultant lentivirus variants.
Three groups of specific pathogen-free (SPF) domestic cats, each containing 5 animals, were infected with one of three closely related FIV variants and monitored for 36 weeks. A fourth group of 5 cats was sham-infected and served as uninfected controls. FIV variants included: (1) a fully virulent animal passaged FIV-Petaluma; (2) a Crandell feline kidney (CrFK) cell-adapted FIV-Petaluma (FIV-CrFK); and (3) a variant of FIV-CrFK (FIV-CrFKAZT) that had been selected in vitro for resistance to azidothymidine. Cats infected with fully virulent FIV-Petaluma strongly seroconverted, became persistently viremic, and exhibited lymphadenopathy, neutropenia, and inversion of the CD4+:CD8+ T cell ratio. Cats infected with FIV-CrFK seroconverted but the antibody responses were much weaker and more variable; two of the cats became transiently viremic and no hematologic abnormalities or clinical signs of illness other than a very mild lymphadenopathy were observed. None of the five cats inoculated with FIV-CrFKAZT seroconverted, became viremic, or exhibited any gross or hematologic signs of disease, even though proviral DNA was transiently detected in tissue following inoculation. This study demonstrates that the FIV infection model can be used to assess differences in the virulence of FIV variants, including variants selected for antiretroviral drug resistance.


CCL3-CCR5 axis promotes cell migration and invasion of colon adenocarcinoma via Akt signaling pathway.
Infiltration of tumor-associated macrophages (TAMs) can promote tumorigenesis and development. C-C motif chemokine ligand 3 (CCL3) was reported to be derived from TAMs and tumor cells and facilitate the progression of several cancers. Nevertheless, whether CCL3 can be derived from TAMs and tumor cells of colon adenocarcinoma (COAD) is unclarified. Peripheral blood monocytes-derived macrophages were polarized by the conditioned medium from COAD cells to establish TAM-like macrophages (TAM1/2). RT-qPCR and western blotting were used for detection of expression levels of CCL3 and its receptors C-C motif chemokine receptor 1 (CCR1) and CCR5 in TAM1/2 and COAD cells. Immunofluorescence staining was utilized for evaluating CCL3, CD163 and CCR5 expression. The Akt signaling pathway-associated protein levels were measured by western blotting. Transwell assays were used for assessing cell migration and invasiveness. CCL3 displayed a high level in TAMs and cancer cells of COAD. CCL3 activated the Akt signaling pathway by binding to CCR5. CCL3-CCR5 axis facilitated COAD cell migration and invasiveness by activating the Akt signaling. CCL3 derived from both TAMs and cancer cells contributed to the malignant behaviors of COAD cells. High expression of CCL3/CCR5 was closely associated with poor prognoses of COAD patients. CCL3-CCR5 interaction promotes cell migration and invasiveness, and functions as a prognostic biomarker for COAD.


In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction.
Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.


Association of subjective cognitive complaints with poor sleep quality: A cross-sectional study among Chinese elderly.
Subjective cognitive complaints (SCC) are the earliest symptom of Alzheimer's disease (AD) progression. Increasing evidence shows an association between poor sleep quality and SCC, but the current conclusions regarding the association between poor sleep quality and SCC in older adults are contradictory. Here, we aimed to explore the correlation of SCC with poor sleep quality among older adults without dementia living in nursing home and community in China. A cross-sectional survey on sleep and psychosomatic health of older adults was conducted in Guangdong, China, between November 2020 and March 2021. Socio-demographic, health-related information, psychological factors, sleep quality and SCC of participants were evaluated through a face-to-face interview. A 9-item Subjective Cognitive Decline Questionnaire (SCD-Q9) was used to measure SCC; SCD-Q9 > 3 was defined as SCC. The Chinese version of the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality; PSQI > 7 was defined as poor sleep quality. The relationship between SCC and sleep quality was evaluated using logistics regression analysis. The study involved 730 participants (mean age 74.14 ± 8.246 years). The total SCC prevalence was 59.59%. The SCC group had poor sleep quality than the reference group (p < 0.05). Adjusted multiple logistic regression analysis revealed an association of poor sleep quality with SCC (OR = 1.841; 95% CI, 1.267-2.647; p = 0.001) after controlling for age, sex, residence, education level, marital status, income, smoking, alcohol consumption, tea drinking, multimorbidity, waist circumference, napping duration, anxiety symptoms, and depression symptoms. Hierarchical logistics regression analysis showed an association between sleep quality and SCC among community older adults (OR = 2.872; 95% CI: 1.787-4.615; p < 0.001), but not in nursing home residents (OR = 0.845; 95% CI: 0.437-1.637; p = 0.619). Poor sleep quality is associated with SCC in community older adults. Therefore, medical staff should take measures, such as earlier cognitive intervention, to postpone cognitive decline in older adults, in the meantime, earlier management and treatment of sleep disorders should be taken into consideration.


Mass gathering medicine: the Melbourne 2006 Commonwealth Games experience.
To investigate the nature and acuity of medical presentations of patrons and staff attending the Melbourne 2006 Commonwealth Games (M2006) venues and festival live sites. Retrospective case series chart audit of patients who were managed by St John Ambulance during the M2006. Patients who presented requiring first-aid review or treatment at any of the 21 designated event venues or 16 live sites during their prescribed operating hours between 15 March 2006 and 26 March 2006. Provisional diagnosis and ambulance transport to hospital. A total of 3514 presentations occurred during the study period, of which 2279 (64.9%, 95% CI, 63.3%-66.4%) occurred at event venues. Headaches, soft tissue injuries, blisters and other wounds accounted for 64.1% (95% CI, 62.5%-65.73%) of presentations. A total of 303 patients were referred for further medical care, including 69 patients (1.96%, 95% CI, 1.54%-2.49%) who required transport to hospital via ambulance. Traumatic injuries accounted for 42.0% (95% CI, 30.5%-54.5%) of patients transported by ambulance to hospital. The patient presentation rate across all venues was 0.857 per 1000 patrons. The transport to hospital rate was 0.0186 per 1000 patrons. The majority of first-aid presentations during the M2006 were of low acuity and treatment resulted in return of patrons to the event, with only a small number requiring ambulance transport to hospital.


Optimal dosing regimen of biapenem based on population pharmacokinetic/pharmacodynamic modelling and Monte Carlo simulation in patients with febrile neutropenia and haematological malignancies.
In the current study, a population pharmacokinetic (PPK) model was developed for biapenem in patients with febrile neutropenia (FN) and haematological malignancies. Through Monte Carlo simulation, optimal administration regimens were suggested based on the developed PPK model. In a prospective, single-centre, open-label study, 174 plasma samples from 120 Chinese patients with FN and haematological malignancies were analysed by chromatography, and PK parameters were analysed by NONMEM. The drug clearance process was influenced by crucial covariates, namely creatinine clearance (CLCR) and concomitant posaconazole (POS). The ultimate PPK model was as follows: CL (L/h)=29.81 × (CLCR/121.38)0.806 × (1-POS × 0.297); volume of distribution (L)=114. For the target of ≥40% fT>minimum inhibitory concentration (MIC) (duration that the plasma level exceeds the MIC of the causative pathogen) and achieving the probability of target attainment ≥90%, the PK/pharmacodynamic breakpoint was 2 mg/L for the 2.4 g/day dosing regimen consisting of 600 mg q6h and 800 mg q8h. The breakpoint was 1 mg/L for the 1.2 g/day dosing regimen consisting of 300 mg q6h and 600 mg q12h. Empirical therapy would benefit from utilizing higher dosages and extended infusion durations. Therefore, it is suggested that patients with symptoms that are strongly suggestive of Pseudomonas aeruginosa or Acinetobacter baumannii infection may be suitable for combined treatment with other antibacterial drugs.


Effects of food supplementation on a tropical bird.
Tropical birds typically exhibit a 'slow pace of life' relative to higher latitude species. This is often manifested as slow development, low fecundity, and high survival. Following from this, it is predicted that tropical birds may be more likely to trade current reproductive effort to favor self-maintenance, thus supporting survival and future reproduction. To test this idea, we conducted two food supplementation experiments on tropical rufous-collared sparrows (Zonotrichia capensis) in the eastern Andes of Ecuador. In the first experiment, we food-supplemented pairs during the non-breeding life-history stage, and in the second experiment, we food-supplemented pairs that were provisioning fledglings. In both experiments, a larger proportion of food-supplemented birds exhibited pre-basic molt (replacement of feathers) than in a control group. To our knowledge, this is the first study to experimentally demonstrate that a food-supplemented bird invests extra resources into molt, a form of self-maintenance, and contrasts with the majority of food supplementation studies in high latitude birds that show they typically advance the initiation of, or extend the period of, reproduction. Our results are consistent with the syndrome of the slow pace of life in the tropics and support the concept of fundamental differences between temperate-zone and tropical birds.


Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10.
Activation of hepatic stellate cells (HSCs) is the central event in the development of liver fibrosis and cirrhosis. The transdifferentiation process of quiescent into activated HSCs requires a complete reprogramming in gene expression, which is governed by modulation of transcriptional activators or repressors. Using microarray analysis to identify genes differentially expressed during the activation process of human HSCs, zinc finger protein 267 (ZNF267) mRNA was up-regulated in activated HSCs and in cirrhotic human liver. ZNF267 belongs to the family of Kruppel-like zinc fingers and contains a conserved KRAB (Kruppel associated box) A and B domain in the N-terminal part outside the C-terminal region of zinc fingers. ZNF267 constructs containing enhanced cyan fluorescence protein were constitutively localized in the nucleus. When fused to GAL4 DNA binding domain, full-length ZNF267 and all constructs encompassing KRAB A domain showed transcriptional repressor activity. Microarray analysis and RNase protection assays showed that ZNF267 represses MMP-10 gene expression, which was confirmed by reporter gene assays. Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis through alteration of matrix degradation in vivo.


Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency.
Pyruvate dehydrogenase deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. Most cases are caused by mutations in the X-linked gene for the E1alpha subunit of the complex. Mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 core component of the complex, have not been described previously. We report two unrelated patients with pyruvate dehydrogenase deficiency caused by defects in the E2 subunit. Both patients are less severely affected than typical patients with E1alpha mutations and both have survived well into childhood. Episodic dystonia was the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent. The patients had neuroradiological evidence of discrete lesions restricted to the globus pallidus, and both are homozygous for different mutations in the DLAT gene. The clinical presentation and neuroradiological findings are not typical of pyruvate dehydrogenase deficiency and extend the clinical and mutational spectrum of this condition.


Influenza virus infection of hamsters. A model for evaluating antiviral drugs.
Inoculation of hamsters with influenza virus [A/PR/8/34 HON 1] produces an inapparent infection which can be monitored by virus titrations of nasal washes or of homogenates prepared from trachea or lung. Antibody can be detected in the serum within 7 days following virus inoculation. Hamsters previously infected were found to be resistant to challenge with the same virus. The utility of this model for evaluating anti-influenza drugs was demonstrated with two compounds. Calcium elenolate, a virucidal agent, reduced the virus titers of nasal washes when the drug was given as nose drops near the time of virus inoculation so as to affect high drug concentrations in the nasal passages. Virazole, an inhibitor of virus replication, reduced the virus titers of the nasal washes when multiple drug treatments were given as nose drops in an effort to provide drug during the time of virus replication. The model described may provide a useful means of evaluating potential antiviral during candidates inasmuch as the drug can be delivered directly into the nasal passages in a non-fatal influenza infection in a convenient laboratory animal.


Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation.
Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation.


Characterization of the taxol binding site on the microtubule. 2-(m-Azidobenzoyl)taxol photolabels a peptide (amino acids 217-231) of beta-tubulin.
Photoaffinity labeling methods are being used to define the molecular contacts between taxol and its target protein, tubulin. Our laboratory has demonstrated previously that [3H]3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin (Rao, S., Krauss, N.E., Heerding, J.M., Swindell, C.S., Ringel, I., Orr, G.A., and Horwitz, S.B. (1994) J. Biol. Chem. 269, 3132-3134). The interaction of a second photoaffinity analogue of taxol, [3H]2-(m-azidobenzoyl)taxol, with tubulin has been investigated. This analogue specifically photolabels beta-tubulin and the photolabeling is completed by both taxol and unlabeled 2-(m-azidobenzoyl)-taxol indicating a common binding domain. To identify the site(s) of photoincorporation, [3H]2-(m-azidobenzoyl)taxol-photolabeled beta-tubulin was subjected to sequential cyanogen bromide and tryptic digestions. Radiolabeled peptides were purified by reverse phase high performance liquid chromatography, and amino acid sequencing studies identified a peptide containing amino acid residues 217-231 of beta-tubulin as the major photolabeled domain.


In vivo validation of near-infrared light transillumination for interproximal dentin caries detection.
The aims of this clinical study were to investigate the diagnostic accuracy of near-infrared light transillumination (NILT) as a novel X-ray-free method for proximal dentin caries detection and to compare this method to established diagnostic methods. A total of 127 interproximal dentin caries lesions without any cavity within visible dentin in posterior teeth from 85 consecutively selected patients were included. Visual and radiographic diagnoses and laser fluorescence measurements were available. NILT images were obtained, and a dentin lesion was predicted if a demineralisation involved the enamel-dentin junction (NILT-EDJ) or a shadow in dentin was detectable (NILT-dentin). Included lesions were opened and validated (reference standard). The statistical analyses included descriptive analyses and calculations of sensitivity, specificity and Az values. The diagnostic accuracy with respect to the reference standard was 1.6% for visual inspection, 66.7% for laser fluorescence, 96.1% for digital radiography, 29.1% for NILT-dentin and 99.2% for NILT-EDJ. Bitewings (Az 0.984) and NILT-EDJ (Az 0.992) performed equally. Given the lack of true negatives in the study, the diagnostic accuracy of NILT achieved the same level as bitewings for the detection of proximal dentin caries. This study might indicate that NILT could reduce the usage of bitewings.


Equilibrium and kinetic analysis of phosphorus adsorption from aqueous solution using waste alum sludge.
Excess phosphorus (P) in wastewaters promotes eutrophication in receiving waterways. A cost-effective method such as use of novel low-cost adsorbents for its adsorptive removal would significantly reduce such impacts. Using batch experiments, the intrinsic dynamics of P adsorption by waste alum sludge (an inevitable by-product of drinking water treatment plants) was examined. Different models of adsorption were used to describe equilibrium and kinetic data, calculate rate constants and determine the adsorption capacity. Results indicate that the intraparticle rate constant increased from 0.0075 mg g(-1)min(-1) at 5 mg L(-1) to 0.1795 mg g(-1)min(-1) at 60 mg L(-1) indicating that more phosphate is adsorbed per g min at higher P concentration. Further analyses indicate involvement of film and particle diffusion mechanisms as rate controlling steps at lower and higher concentrations, respectively. Mass transfer coefficient obtained ranged from 1.7 × 10(-6) to 1.8 × 10(-8) indicating a rapid transportation of phosphate molecules onto the alum sludge. These results further demonstrates that alum sludge-hitherto thought of as undesirable waste, can be used as novel adsorbent for P removal from wastewater through various applications, thus offsetting a portion of the disposal costs while at the same time improving water quality in sensitive watersheds.


Niche shifts in Greater Antillean Anolis communities: effects of niche metric and biological resolution on null model tests.
Using published data, a Monte Carlo approach was used to determine if niche shifts in communities of Anolis lizards have occurred within two islands in the Greater Antilles. Communities at 4 sites on Puerto Rico and 4 sites on Jamaica were randomly assembled using resource-use data from any of the 4 sites with the constraint that the species list of the random community was identical to that observed for each site. The observed niche structure and that of the randomly assembled community were compared at each site. The null hypothesis tested was that one of several functions of niche overlap did not produce lower values in the observed communities compared to those randomly assembled. The sensitivity of this method to details of the analysis was investigated by using 5 variations on the procedure for quantifying the niche structure of the communities. I investigated the effects of (1) using Pianka's versus Levins' metric of niche overlap, (2) using complete resource-use data versus the marginals of the distributions, (3) asymmetric responses to overlap due to size differences between overlapping species, (4) using estimated electivities versus the observed proportional use of resource states, and (5) methods of niche analysis based on different degrees of biological resolution (e.g., community-wide statistics versus individual species responses). The results of the simulations and statistical comparisons did not provide a clear, unambiguous answer to the question of the occurrence of niche shifts. Statistical evidence for niche shifts was more frequently detected using Levins' metric compared to Pianka's, and shifts were easier to detect using high biological resolution (examination of individual species) compared to community-wide measures of niche structure response.


Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats.
Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear. Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI. ESCS also significantly increased the myelinated area at 28 days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase, an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rhBMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI, and rhBMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.


Rescaling pain intensity measures for meta-analyses of analgesic medicines for low back pain appears justified: an empirical examination from randomised trials.
Meta-analyses of analgesic medicines for low back pain often rescale measures of pain intensity to use mean difference (MD) instead of standardised mean difference for pooled estimates. Although this improves clinical interpretability, it is not clear whether this method is justified. Our study evaluated the justification for this method. We identified randomised clinical trials of analgesic medicines for adults with low back pain that used two scales with different ranges to measure the same construct of pain intensity. We transformed all data to a 0-100 scale, then compared between-group estimates across pairs of scales with different ranges. Twelve trials were included. Overall, differences in means between pain intensity measures that were rescaled to a common 0-100 scale appeared to be small and randomly distributed. For one study that measured pain intensity on a 0-100 scale and a 0-10 scale; when rescaled to 0-100, the difference in MD between the scales was 0.8 points out of 100. For three studies that measured pain intensity on a 0-10 scale and 0-3 scale; when rescaled to 0-100, the average difference in MD between the scales was 0.2 points out of 100 (range 5.5 points lower to 2.7 points higher). For two studies that measured pain intensity on a 0-100 scale and a 0-3 scale; when rescaled to 0-100, the average difference in MD between the scales was 0.7 points out of 100 (range 6.2 points lower to 12.1 points higher). Finally, for six studies that measured pain intensity on a 0-100 scale and a 0-4 scale; when rescaled to 0-100, the average difference in MD between the scales was 0.7 points (range 5.4 points lower to 8.3 points higher). Rescaling pain intensity measures may be justified in meta-analyses of analgesic medicines for low back pain. Systematic reviewers may consider this method to improve clinical interpretability and enable more data to be included. Open Science Framework (osf.io/8rq7f).


A data calibration method for micro air quality detectors based on a LASSO regression and NARX neural network combined model.
Studies have shown that there is a certain correlation between air pollution and various human diseases, especially lung diseases, so it is very meaningful to monitor the concentration of pollutants in the air. Compared with the national air quality monitoring station (national control point), the micro air quality detector has the advantage that it can monitor the concentration of pollutants in real time and grid, but its measurement accuracy needs to be improved. This paper proposes a model combining the least absolute selection and shrinkage operator (LASSO) regression and nonlinear autoregressive models with exogenous inputs (NARX) to calibrate the data measured by the micro air quality detector. Before establishing the LASSO-NARX model, correlation analysis is used to test whether the correlation between the concentration of air pollutants and its influencing factors is significant, and to find out the main factors that affect the concentration of pollutants. Due to the multicollinearity between various influencing factors, LASSO regression is used to further screen the influencing factors and give the quantitative relationship between the pollutant concentration and various influencing factors. In order to improve the prediction accuracy of pollutant concentration, the predicted value of each pollutant concentration in the LASSO regression model and the measurement data of the micro air quality detector are used as input variables, and the LASSO-NARX model is constructed using the NARX neural network. Several indicators such as goodness of fit, root mean square error, mean absolute error and relative mean absolute percent error are used to compare various air quality models. The results show that the prediction results of the LASSO-NARX model are not only better than the LASSO model alone and the NARX model alone, but also better than the commonly used multilayer perceptron and radial basis function neural network. Using this model to calibrate the measurement data of the micro air quality detector can increase the accuracy by 61.3-91.7%.


Creating therapeutic relationships through communication: a qualitative metasynthesis from the perspectives of people with communication impairment after stroke.
Communication between patients and clinicians influences the development of therapeutic relationships. Communication is disrupted when the patient has communication impairments after stroke. However, how these communication disruptions influence therapeutic relationships is not well-understood. This qualitative metasynthesis explores the perspectives of people with communication impairment to understand how interpersonal communication influences therapeutic relationships. Four databases were searched for qualitative studies which discussed how communication influenced therapeutic relationships from the perspectives of people with aphasia, dysarthria or apraxia of speech. Additional papers were identified through citation searching and subject experts. Nineteen eligible papers were included and analysed using thematic analysis. Four themes were constructed from the analysis: (1) Relationships provide the foundation for rehabilitation; (2) Different relational possibilities arise from "reading" the clinician; (3) Creating therapeutic relationships through validating interactions and connections; and (4) Creating therapeutic disconnections through invalidating, exclusionary interactions. A therapeutic relationship develops, at least in part, in response to the clinician's communication and how this is received and experienced by the patient. Understanding the characteristics of relationship-fostering communication and knowing how communication influences relationships can help clinicians critically reflect on their communication and better develop therapeutic relationships with people with communication impairment.IMPLICATIONS FOR REHABILITATIONPractitioner-patient communication can facilitate therapeutic relationships or create therapeutic disconnections.Communication patterns that are commonly evident when a patient has communication impairments can impede therapeutic relationships.Clinicians need to attend to how their communication is received and how it influences people's sense of self.Communication partner training should address the existential and relational needs of people with communication impairment after stroke.


Erythropoietic response after intravenous iron in patients with heart failure and reduced ejection fraction with and without background treatment with sodium-glucose cotransporter 2 inhibitors.
Intravenous (IV) iron increases haemoglobin/haematocrit and improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also increase haemoglobin/haematocrit and improve outcomes in heart failure by mechanisms linked to nutrient deprivation signalling and reduction of inflammation and oxidative stress. The effect of IV iron among patients using SGLT2i has not yet been studied. The aim of this study was to evaluate the changes in haemoglobin, haematocrit, and iron biomarkers in HFrEF patients treated with IV iron with and without background SGLT2i treatment. Secondary outcomes included changes in natriuretic peptides, kidney function and heart failure-associated outcomes. Retrospective, single-centre analysis of HFrEF patients with iron deficiency treated with IV iron using (n = 60) and not using (n = 60) SGLT2i, matched for age and sex. Mean age was 73 ± 12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anaemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in haemoglobin and haematocrit compared to SGLT2i non-users: haemoglobin +0.57 g/dl (95% confidence interval [CI] 0.04-1.10, p = 0.036) and haematocrit +1.64% (95% CI 0.18-3.11, p = 0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes. Combined treatment with IV iron and background SGLT2i was associated with a greater increase in haemoglobin and haematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response. Further studies are needed to ascertain the potential benefit or harm of combining these two treatments in heart failure patients.


The impact of three related emission industries on regional atmospheric chlorinated paraffins pollution.
Identifying the contributions of various chlorinated paraffins (CPs) sources in the environment plays an important practical role in the prevention and control of the CPs contamination. However, little is known about how main CP-related emission industries affect the regional atmospheric characteristics of CPs, including CP products industry, metal working industry, and polyvinyl chloride (PVC) industry. In this study, 60 passive air samples were collected from five typical cities in Henan Province, China, which had serious CP pollution and different structures of CP-related emission industry. Short chain CPs (SCCPs) and medium chain CPs (MCCPs) were detected in all samples in concentrations ranging of 2.6-7.7 × 102 and 2.1-4.3 × 102 ng m-3, respectively, which were higher than those in most reports. Moreover, Luoyang (LY) is different from other cities, showing a relatively severe MCCP contaminations. The CP pollution characteristics between different cities are obviously affected by the proportion of local CP-related industries. According to the results of cluster heatmaps, the local CP-related emission industrial structure had a greater impact on MCCPs pollution than SCCPs. Additionally, the contribution of metal working industry was beyond that of PVC production industry and CP products industry.


Optimal delivery of dose in cancer chemotherapy with the support of haematopoietic growth factors.
The delivery of cancer chemotherapy is often non-optimal because of dose reductions and delays related to various toxic effects. These result in a decrease of the dose intensity as well as of the relative dose intensity of a given regimen compared to a reference protocol. In retrospective studies, such modifications have been shown to negatively influence the therapeutic results in many clinical situations. The ability of haematopoietic growth factors to reduce chemotherapy-related neutropenia and its associated infectious complications allows better dose-on-time delivery of the chemotherapeutic drugs. The potential therapeutic impact of this effect remains to be determined in prospective studies.


Advancements and Dilemmas in the Management of Allergy.
Recent advances in the diagnosis and management of allergic disease also lead to new clinical decisions for providers. Advances in component (or molecular) diagnostic testing for allergy continue to build in the literature, but diagnosing inhalant allergy remains largely unchanged clinically. Prevention of allergy has been demonstrated by preventing peanut allergy in high-risk infants by intentional oral exposure to promote tolerance. Immunotherapy options have increased, with literature supporting sublingual drops, sublingual tablets, and subcutaneous immunotherapy. Expanded options create clinical questions such as the role of monotherapy in polysensitized patients. This article explores recent advances and their clinical implications.


A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis.
To determine whether a single dose of dexamethasone (0.6 mg/kg) is useful in the treatment of acute laryngotracheitis (croup), 29 hospitalized patients with acute laryngotracheitis were randomly assigned in a double-blind fashion to receive either parenterally administered dexamethasone (n = 16) or a saline placebo (n = 13). Severity of the illness was assessed by a clinical croup score based on retractions, stridor, air entry, cyanosis, and level of consciousness. Twelve hours from the time of injection, the patients receiving the dexamethasone had a statistically significant decline in median croup score from 4.5 to 1.0 (p less than 0.001), whereas the patients receiving the placebo did not. By 24 hours, a decline of two or more points in the total croup score was noted in 85% of the patients in the dexamethasone group compared with 33% of the patients in the placebo group (p = 0.027). During this same period, only 19% of patients receiving dexamethasone required two or more racemic epinephrine treatments in comparison with 62% of patients who received the placebo (p less than 0.05). There was no statistical difference between the two groups in improvement in oxygen saturation, respiratory rates, or duration of hospitalization. We conclude that dexamethasone is beneficial in reducing the overall severity of moderate to severe acute laryngotracheitis during the first 24 hours after injection.


Isotype-specific antibody-secreting cells in systemic and mucosal associated lymphoid tissues and antibody responses in serum of conventional pigs inoculated with PEDV.
An enzyme-linked immunospot (ELISPOT) has been developed to detect porcine epidemic diarrhea virus (PEDV)-specific antibody secreting cells (ASC) in gut associated lymphoid tissues (duodenum and ileum lamina propria and mesenteric lymph nodes) and systemic locations (spleen and blood) of conventional pigs so as to characterise the mucosal and systemic antibody response generated by the infection with PEDV. A total number of 28 eleven-day-old conventional pigs were orally inoculated with the field isolate of the PEDV strain CV-777. Diarrhea was observed in 32% of the pigs and virus shedding was demonstrated in 100% between postinoculation day (PID) 1 and 8. Serum IgG and IgA antibodies to PEDV were detected by isotype ELISA from PID 12 and 15, respectively, reaching maximum values at PID 32 (IgG) and 21 (IgA). PEDV specific IgM ASC occurred in all the tissues between PID 4 and 7, with the strongest response in the intestinal lamina propria. IgA and IgG ASC responses were evident in the intestinal lymphoid tissues from PID 21, the highest number of specific ASC corresponded to the duodenum lamina propria. In the systemic lymphoid tissues the number of IgG and IgA ASC detected were lower than in the mucosal tissues, however, in the blood, presence of IgA ASC was constantly detected from PID 14 until the end of the experiment. Memory antibody response to the PEDV was also studied by secondary in vitro stimulation of the mononuclear cells (MNC) isolated from mesenteric lymph nodes, spleen and blood. The memory B cell response was prominent at PID 21 and 25 and consisted in IgG and IgA ASC. To our knowledge, this is the first report to research into the presence and distribution of specific ASC in different locations of the systemic and the gut associated lymphoid tissues after a PEDV infection as well as the presence of memory B cells.


Preparation of branched cyclomaltoheptaose with 3-O-α-L-fucopyranosyl-α-D-mannopyranose and changes in fucosylation of HCT116 cells treated with the fucose-modified cyclomaltoheptaose.
From a mixture of 4-nitrophenyl α-L-fucopyranoside and D-mannopyranose, 3-O-α-L-fucopyranosyl-D-mannopyranose was synthesised through the transferring action of α-fucosidase (Sumizyme PHY). 6(I),6(IV)-Di-O-(3-O-α-L-fucopyranosyl-α-D-mannopyranosyl)-cyclomaltoheptaose {8, 6(I),6(IV)-di-O-[α-L-Fuc-(1→3)-α-D-Man]-βCD} was chemically synthesised using the trichloroacetimidate method. The structures were confirmed by MS and NMR spectroscopy. A cell-based assay using the fucosyl βCD derivatives, including the newly synthesised 8, showed that derivatives with two branches of the α-L-Fuc or α-L-Fuc-(1→3)-α-D-Man residues possessed slight growth-promoting effects and lower toxicity in HCT116 cells compared to those with one branch. These compounds may be useful as drug carriers in targeted drug delivery systems.


An influence of the copy number of biosynthetic gene clusters on the production level of antibiotics in a heterologous host.
Streptomyces albus J1074 is a well-known host for heterologous expression of secondary metabolites. To further increase its potential and to study the influence of cluster multiplication, additional φC31-attachment site was integrated into its genome using a system for transposon mutagenesis. Four secondary metabolite clusters were expressed in strains with different numbers of attachment sites, ranging from one to three copies of the site. Secondary metabolite production was examined and a new compound could be detected, purified and its structure was elucidated.


The ocular safety of hydroxychloroquine.
The insert currently supplied with hydroxychloroquine states that patients should have an initial ophthalmological assessment and then regular assessments every 3 months. The rheumatologist should expect a report from the ophthalmologist, which includes a corneal assessment of tissue dose, a reference to visual field defects if present on the Amsler grid, and a comment concerning the status of the patient's color vision. Daily dose is more important than duration of dose, regarding maculopathy. The visual prognosis of retinopathy is excellent if the diagnosis is made at an early stage of the disease. This report suggests that ophthalmological review need only occur initially and on a yearly basis if the daily dose of hydroxychloroquine is less than 6.5 mg/kg/d and the duration of therapy is less than 9 years.


Practices and Attitudes Regarding Pediatric Cholesterol Screening Recommendations Differ Between Pediatricians and Family Medicine Clinicians.
Pediatricians had higher rates of ordering pediatric cholesterol screening than family medicine (FM) clinicians. This study aims to compare knowledge, attitude, and practices of clinicians' pediatric cholesterol screening practices and attitudes between these two specialties. A 14-item electronic survey using Likert scales was sent to all clinicians in the institution's Departments of Pediatrics and FM between 2018 and 2019. Chi-square and t-tests were used to compare pediatricians and FM clinicians. 22 clinicians from Pediatrics and 111 from FM completed the survey. Compared to FM clinicians, pediatricians were more familiar with the National Heart, Lung, and Blood Institute guidelines, which are more vigorous in their recommendation of universal cholesterol screening. Pediatricians reported being more supportive of universal cholesterol screening in children (p < 0.05). In practice, pediatricians reported screening almost two thirds (64.8%) of eligible patients during the past year, while FM clinicians reported screening approximately one third (34.1%) of eligible patients (p < 0.001). Pediatricians were more likely to screen based on patient-specific risk factors and their practice decisions were more heavily influenced by published guidelines, institutional education, availability of non-fasting blood to be used for screening, and the availability of an institutional pediatric lipid clinic (p < 0.05). The differences in knowledge, attitudes, and practices of cholesterol screening may contribute to different screening rates among clinicians from FM and pediatrics. To improve patient care and reduce gaps, it is important to implement interventions at the institutional level as well as to adopt uniform guideline recommendations at the national level.


Non-enzymatic synthesis of ubiquitin chains: where chemistry makes a difference.
Ubiquitination is a highly important posttranslational modification in eukaryotic cells where a target protein is conjugated to ubiquitin or a chain of ubiquitins via an isopeptide bond to trigger various cellular events such as proteasomal degradation. Rigorous investigations of the ubiquitin signal at the molecular level require homogeneous samples of ubiquitin chains in their free form or as anchored to a protein substrate in adequate quantities. The complexity of ubiquitin chains in terms of linkage types (owing to presence of seven Lys in ubiquitin) makes them difficult to prepare via enzymatic methods. Even more challenging is the attachment of these chains to a protein target at a selected site. This dearth is being filled by the recent developments of novel chemical tools that offer atomic level control over the synthesis for structural and functional studies. These emerging chemical approaches are discussed in this mini-review with focus on the preparation of ubiquitin chains to aid the ongoing efforts in understanding their role in the ubiquitin signal.


Recent development of surface-enhanced Raman scattering for biosensing.
Surface-Enhanced Raman Scattering (SERS) technology, as a powerful tool to identify molecular species by collecting molecular spectral signals at the single-molecule level, has achieved substantial progresses in the fields of environmental science, medical diagnosis, food safety, and biological analysis. As deepening research is delved into SERS sensing, more and more high-performance or multifunctional SERS substrate materials emerge, which are expected to push Raman sensing into more application fields. Especially in the field of biological analysis, intrinsic and extrinsic SERS sensing schemes have been widely used and explored due to their fast, sensitive and reliable advantages. Herein, recent developments of SERS substrates and their applications in biomolecular detection (SARS-CoV-2 virus, tumor etc.), biological imaging and pesticide detection are summarized. The SERS concepts (including its basic theory and sensing mechanism) and the important strategies (extending from nanomaterials with tunable shapes and nanostructures to surface bio-functionalization by modifying affinity groups or specific biomolecules) for improving SERS biosensing performance are comprehensively discussed. For data analysis and identification, the applications of machine learning methods and software acquisition sources in SERS biosensing and diagnosing are discussed in detail. In conclusion, the challenges and perspectives of SERS biosensing in the future are presented.


Sexual dimorphism in bill morphology and feeding ecology in Cory's shearwater (Calonectris diomedea).
The bill is a sexually dimorphic structure in many bird species and implicated in numerous functions. Sexual differences may arise from sexual selection or ecological divergence. Here, we examined differences in bill size and shape between males and females and explored to what extent these relate to feeding ecology of each sex in Cory's shearwater (Calonectris diomedea). We applied linear measurements and geometric morphometric methods to examine sexual differences in bill size and shape. We investigated feeding ecology by tracking foraging movements during the breeding period and by analysing stable isotope signatures in blood during the breeding period and in feathers grown during the non-breeding period. Bill traits were all sexually dimorphic, both in absolute and relative terms, and scaled hypermetrically with body mass in several characters in males. However, males and females did not differ in their feeding areas or isotopic signatures and no significant correlation was observed between these traits and bill dimorphism. Therefore, we discard the foraging-niche divergence hypothesis, and suggest that sexual dimorphism in bill size in this species is more likely driven by sexual selection related to antagonistic interactions.


Contralateral C7 transfer in adult plexopathies.
In the current study, a retrospective review of 56 patients with posttraumatic root avulsion brachial plexus injuries who underwent contralateral C7 transfer using the selective contralateral C7 technique is presented. The intraoperative findings of the involved brachial plexus, the surgical technique of preparation of the donor C7 nerve root, and the various neurotization procedures are reported. The surgical outcomes as well as the potential adverse effects of the procedure are analyzed. We conclude from this study that the selective contralateral C7 technique is a safe procedure that can be applied successfully for simultaneous reconstruction of several different contralateral muscle targets or for neurotization of cross chest nerve grafts for future free muscle transplantation.


Muscarinic cholinergic receptors on intact human lymphocytes. Properties and subclass characterization.
Saturable specific binding of tritiated N-methyl-scopolamine (3H-NMS) can be demonstrated on intact circulating human lymphocytes, with an average KD of 7 nmol/liter and an average density of about 15 fmol/10(6) cells. Specific 3H-NMS binding can be inhibited by cholinergic antagonists and agonists, is highly stereospecific for the enantiomers of the cholinergic antagonist quinuclidinyl benzilate (QNB), and is modulated by the stable guanosine triphosphate (GTP) analog GppNHp in a fashion similar to the specific binding of the same radioligand to rat heart membranes. The results indicate the presence of muscarinic cholinergic receptors on intact human lymphocytes, with a predominance of the M2 subtype. As central muscarinic cholinergic receptors have been reported to play an important role in the pathogenesis of affective disorders, the lymphocyte might represent a suitable model for the study of muscarinic receptor functions in humans.


Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion.
Cartilage oligomeric matrix protein (COMP) is an emerging regulator of tumor progression. The aim of this study was to evaluate the expression of COMP in periampullary adenocarcinoma with respect to prognostic value for survival and relapse, levels of fibrosis and infiltrating immune cells. COMP expression was evaluated using immunohistochemistry in primary tumors and subsets of paired lymph node metastases in tissue microarrays including 175 patients with periampullary adenocarcinoma. Collagen content was assessed with Sirius Red-Fast Green staining. High COMP levels were detected in cancer cells and in stroma, in 46% and 57% of the patients, respectively. High COMP expression was strongly associated with more aggressive pancreatobiliary-type (PB-type) compared to intestinal-type tumors (p < .0001). Importantly, high expression of COMP correlated with the exclusion of cytotoxic T-cells from the cancer cell compartment of the tumors, particularly in PB-type tumors. Higher levels of fibrosis measured by the density of collagen fibers correlated with high COMP levels in both cancer cells and stroma. This in turn could lead to exclusion of cytotoxic T-cells from accessing the cancer cells, a recognized immunotherapy resistance mechanism. Targeting COMP could therefore be considered as a novel therapeutic strategy in PB-type periampullary adenocarcinoma.


[Identifying ostomized patients' needs throughout their healthcare program].
Few studies address the needs of ostomized patients throughout their healthcare program. A better understanding of these needs would contribute to a significant improvement of patient management and would allow better patient adjustment. Acknowledging these needs and identifying their time of onset would strengthen the patient-caregivers relationship.


The maternal distribution and placental transfer of cadmium in zinc deficient rats.
Although a transitory maternal zinc deficiency has been shown to result in an increased cadmium-induced fetotoxicity, the results of the present investigation indicated that a maternal zinc deficiency apparently did not affect the placental transfer of cadmium. However, a zinc deficiency did alter the maternal distribution of cadmium. The increased cadmium fetotoxicity associated with a maternal zinc deficiency may be caused by a maternal alteration rather than a direct effect on the fetus. Further study is necessary prior to any definitive statement concerning the effects of a maternal zinc deficiency on cadmium fetotoxicity.


Nanowires of metal-organic complex by photocrystallization: a system to achieve addressable electrically bistable devices and memory elements.
A new method has been achieved to form a Cu:benzoquinone derivative (DDQ) charge-transfer complex by the photoexcitation of [Cu(DDQ)2(CH 3COO)2] ( 1) that has been synthesized by the reaction of DDQ and hydrated cupric acetate in acetonitrile. Photoexcitation of coordinated complex 1 leads to the formation of charge-transfer complex Cu2+(DDQ(.-)2 ( 2). The charge transfer complex 2, when spun on solid substrates, forms nanowires. Sandwich structures of 2 exhibit electrical bistability associated with memory phenomenon. Read-only and random-access memory phenomena are evidenced in nanowires of 2 providing a route to attend the issues pertaining to the addressibility of organic memory devices.


Examining the evidence for anxiety-related cognitive biases in obsessive-compulsive disorder.
In light of current concerns about the diagnostic classification of obsessive-compulsive disorder (OCD), this article critically examines recent experimental research on anxiety-related cognitive biases in OCD in order to determine whether it provides grounds for OCD's differentiation from other anxiety disorders. This small body of work is found to be fraught with defects, anomalies, and inconsistencies. These findings contrast dramatically with the robust results obtained with other clinical anxiety disorders. When biases are in evidence it tends to be with a select group of subjects, that is, those with contamination concerns. It is suggested that only this subtype of OCD, or some core characteristic underlying it, may be associated with cognitive tendencies comparable to those found in other anxiety disorders (i.e., biases at the attentional level associated with the emotional tone, or content, of information). Cognitive tendencies in other subtypes likely require different explanatory frameworks. This review provides evidence for the partial uniqueness of OCD from other anxiety disorders.


Dexmedetomidine implementation in pain management in the immediate postoperative period of cardiac surgery.
This study arose from the need to improve all tasks related to monitoring pain in post cardiac surgery patients. Checking and quantifying the pain suffered by patients undergoing cardiac surgery in the first 24hours of their stay in the intensive care unit (ICU), treated with Dexmedetomidine (Dex) as analgesic adjuvant, as well as their degree of sedation and the need for opiates such as rescue analgesia. Unicentric study, observational, descriptive, from April 2016 to September 2017. Both genders, all adult, undergoing cardiac surgery, operating theatre-extubated and Dex continuous infusion carriers. Pain degree level was evaluated by the Visual analogue Scale of Pain (VAS), from immediately post-surgery until 24hours from ICU entry and sedation degree, by the Richmond Sedation Agitation Scale (RASS), only while the Dex infusion lasted. 109 patients were included. The results obtained showed that the average pain suffered by patients during the first 24hours was .47 with standard deviation (SD) of 1.25; the average maximum pain experienced was 3.58 with a range of 0 to 8 and the RASS average was -.68 (SD: 0,80). In addition, 44.04% of the patients needed rescue opiates, although only 7.32% showed severe pain greater than 6. The Dex infusion patients showed mild levels of pain, however, a small percentage, who must be taken into account, suffered severe pain.


A pre-post study of stressors and burnout affecting breast radiologists before and during the COVID-19 pandemic.
To compare burnout and stressors of breast radiologists prior to and during the COVID-19 pandemic. Members of the Society of Breast Imaging were emailed an IRB-approved survey in January 2021 during the COVID-19 pandemic. Survey included questions from the Maslach Burnout Inventory and specific stressors including work pace, work-life balance, care of dependents, and financial strain. Data were compared to previous surveys prior to the pandemic. The response rate was 25% (261/1061) for those who opened the email. Of the respondents, 74% (194/261) were female, 82% (214/261) were white, 73% (191/261) were full time, 71% (185/261) were fellowship trained, 41% (106/261) had more than 20 years of experience, and 30% (79/261) were in academic practice.Respondents in 2021 reported frequent levels of depersonalization (2.2) and emotional exhaustion (3.4) while reporting frequent levels of personal accomplishment (5.3), a protective factor. These values were nearly identical before the pandemic in 2020: (2.2, 3.5, 5.3, respectively, p = .9). Respondents rated practicing faster than they would like as the highest stressor; however, 5 of the 6 stressors improved after the pandemic onset (p < .05). Conversely, participants perceived these stresses had gotten slightly worse since the pandemic (p < .01). Almost 50% of respondents reported they were considering leaving their practice; the most common reason was work/life balance. Burnout in breast radiologists remains frequent but unchanged during the COVID-19 pandemic. While participants perceived that some stressors were worse during the pandemic, there was slight improvement in most stressors between the pre-pandemic and pandemic cohorts.


Clinical significance of long non-coding RNA DUXAP8 and its protein coding genes in hepatocellular carcinoma.
Backgrounds: Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide that is difficult to diagnose during the early stages and its tumors are recurrent. Long non-coding RNAs (lncRNAs) have increasingly been associated with tumor biomarkers for diagnosis and prognosis. This study attempts to explore the potential clinical significance of lncRNA DUXAP8 and its co-expression related protein coding genes (PCGs) for HCC. Method: Data from a total of 370 HCC patients from The Cancer Genome Atlas were utilized for the analysis. DUXAP8 and its top 10 PCGs were explored for their diagnostic and prognostic implications for HCC. A risk score model and nomogram were constructed for prognosis prediction using prognosis-related genes and DUXAP8. Molecular mechanisms of DUXAP8 and its PCGs involved in HCC initiation and progression were investigated. Then, potential target drugs were identified using genome-wide DUXAP8-related differentially expressed genes in a Connectivity Map database. Results: The top 10 PCGs were identified as: RNF2, MAGEA1, GABRA3, MKRN3, FAM133A, MAGEA3, CNTNAP4, MAGEA6, MALRD1, and DGKI. Diagnostic analysis indicated that DUXAP8, MEGEA1, MKRN3, and DGKI show diagnostic implications (all area under curves ≥0.7, p≤0.05). Prognostic analysis indicated that DUXAP8 and RNF2 had prognostic implications for HCC (adjusted p=0.014 and 0.008, respectively). The risk score model and nomogram showed an advantage for prognosis prediction. A total of 3 target drugs were determined: cinchonine, bumetanide and amiprilose and they may serve as potential therapeutic targets for HCC. Conclusion: Functioning as an oncogene, DUXAP8 is overexpressed in tumor tissue and may serve as both a diagnostic and prognosis biomarker for HCC. MEGEA1, MKRN3, and DGKI maybe potential diagnostic biomarkers and DGKI may also be potentially prognostic biomarkers for HCC.


An enzymatic cycling procedure for beta-NADP+ generated by 3'-phosphodiesterase, 2':3'-cyclic nucleotide.
An enzymatic cycling procedure for beta-NADP+ generated by the enzyme 3'-phosphodiesterase, 2':3'-cyclic nucleotide (EC 22.214.171.124) from its substrate 2':3'-cyclic NADP+ is described. The enzymes glucose-6-phosphate dehydrogenase (EC 22.214.171.124) and diaphorase (EC 220.127.116.11) are used to cycle the cofactor between its oxidized and reduced forms in the presence of glucose-6-phosphate and p-iodonitrotetrazolium violet (INT) with the concomitant production of colored INT-formazan, monitored at 492 nm. The amplification is about 400-fold per hour and is sensitive enough to detect 6 x 10(-13) mol of NADP(H). A simple procedure for the optimization of this cycling assay is also described. Conjugates to 3'-phosphodiesterase, 2':3'-cyclic nucleotide may be used in heterogeneous enzyme immunoassays for the detection of small quantities of haptens or proteins in biological fluids.


Atrial fibrillation in cancer survivors - a systematic review and meta-analysis.
Atrial fibrillation (AF) is a common cardiac complication during cancer treatment. It is unclear if cancer survivors have increased AF risk when compared to the population. AF screening is now recommended in patients ≥65 years, however there are no specific recommendations in the oncology population. We sought to compare the AF detection rate of cancer survivors compared to the general population. We searched the Pubmed, Embase and Web of Science databases using search terms related to AF and cancer mapped to subject headings. We included English language studies, limited to adults > 18 years who were > 12 months post completion of cancer treatment. Using a random-effects model we calculated the overall AF detection rate. Meta-regression analysis was performed to assess for potential causes for study heterogeneity. Sixteen studies were included in the study. The combined AF detection rate amongst all the studies was 4.7% (95% C.I 4.0-5.4%), which equated to a combined annualised AF rate of 0.7% (95% C.I 0.1-0.98%). There was significant heterogeneity between studies (I2 = 99.8%, p < 0.001). In the breast cancer cohort (n = 6 studies), the combined annualised AF rate was 0.9% (95% C.I 0.1-2.3%), with significant heterogeneity (I2 = 99.9%, p < 0.001). Whilst the results should be interpreted with caution due to study heterogeneity, AF rates in patients with cancer survival >12 months were not significantly increased compared to the general population. Open Science Framework - DOI: https://doi.org/10.17605/OSF.IO/APSYG .


Bacterial sialic acid modulates activation of the alternative complement pathway of channel catfish (Ictalurus punctatus).
The alternative complement pathway (ACP) provides the non-immune channel catfish (Ictalurus punctatus) with protection against many Gram-negative bacteria. Very little serum bactericidal activity (0-13%) was found against 8 fish pathogens, but a strong bactericidal response (100%) was found against 7 non-pathogens. MgEGTA chelation of catfish serum did not essentially change the bactericidal results. Catfish serum heated at 56 degrees C and serum adsorbed with zymosan had no bactericidal activity. This demonstrated that the ACP was responsible for the bactericidal response. The molecular nature of the microbial surface determines whether or not the ACP will be activated. A relative lack of surface sialic acid has been found to be important for binding complement Factor B of the ACP by susceptible microbial surfaces. This study therefore examined the 15 Gram-negative bacterial fish pathogens and non-pathogens by determining their sialic acid content and their ability to elicit a bactericidal response by the catfish ACP. It was found that there was very little bactericidal activity against the fish pathogens that contained sialic acid but a very strong bactericidal response (100%) against the non-pathogens that lacked sialic acid (p = .0043). A relative lack of sialic acid or no sialic acid therefore correlated with a strong bactericidal response by the catfish ACP. Neuraminidase treatment of the bacterial fish pathogens to remove sialic acid greatly increased the bactericidal response against them by the catfish ACP when compared with untreated bacteria (p = .0431).


Morphometric evaluation of effects of two sex steroids on mammary gland of female rats.
The purpose of this study was to evaluate the effects of two sex hormones on normal mammary gland of female rats. Forty 250-day-old female rats, 20 of them with offspring and 20 not, were ovariectomized and, divided into 4 subgroups in order to receive one of the following subcutaneous treatment: estradiol benzoate (EB), medroxyprogesterone (MPA), EB+MPA or placebo, for 10 weeks. After treatment, mammary glands were studied with optical microscope. Whole gland, lobule, ductule and lumen compartments were evaluated by morphometric methods. Also a qualitative evaluation were performed seeking for secretion, microcalcification and trophic status. It was found that (a) MPA-only and placebo were similar for all parameters; (b) the same between EB and EB+MPA; (c) EB and EB+MPA increased lobule, ductule and lumen compartments significantly compared to MPA-only or placebo; (d) EB increased epithelium but without significance and EB+MPA increased it significantly compared to placebo or MPA; (e) EB and EB+MPA incremented secretion. In normal mammary gland of female rats: progestin action depends on estrogen presence. MPA does not revert estrogen-dependent proliferation, but it magnifies estradiol effect. Both EB and EB+MPA stimulate differentiation. Rats without offspring presented a greater epithelial proliferation under treatment with these sex hormones.


Hypoxia and panvascular diseases: exploring the role of hypoxia-inducible factors in vascular smooth muscle cells under panvascular pathologies.
As an emerging discipline, panvascular diseases are a set of vascular diseases with atherosclerosis as the common pathogenic hallmark, which mostly affect vital organs like the heart, brain, kidney, and limbs. As the major responser to the most common stressor in the vasculature (hypoxia)-hypoxia-inducible factors (HIFs), and the primary regulator of pressure and oxygen delivery in the vasculature-vascular smooth muscle cells (VSMCs), their own multifaceted nature and their interactions with each other are fascinating. Abnormally active VSMCs (e.g., atherosclerosis, pulmonary hypertension) or abnormally dysfunctional VSMCs (e.g., aneurysms, vascular calcification) are associated with HIFs. These widespread systemic diseases also reflect the interdisciplinary nature of panvascular medicine. Moreover, given the comparable proliferative characteristics exhibited by VSMCs and cancer cells, and the delicate equilibrium between angiogenesis and cancer progression, there is a pressing need for more accurate modulation targets or combination approaches to bolster the effectiveness of HIF targeting therapies. Based on the aforementioned content, this review primarily focused on the significance of integrating the overall and local perspectives, as well as temporal and spatial balance, in the context of the HIF signaling pathway in VSMC-related panvascular diseases. Furthermore, the review discussed the implications of HIF-targeting drugs on panvascular disorders, while considering the trade-offs involved.


Laparoscopic Right Hepatectomy for Cirrhotic Patients: Takasaki's Hilar Control and Caudal Approach.
Cirrhotic patients bearing hepatocellular carcinomas (HCC) derive benefits from laparoscopic hepatectomy1 - 6 such as reduced bleeding, less overall and liver-specific complications, and fewer adhesions in the case of future reoperation or transplantation.7 - 10 Bleeding is concerning in the setting of cirrhosis,11 - 15 and adequate inflow control reduces blood loss. The caudal approach is the laparoscopic counterpart of the anterior approach to open surgery. It implies in parenchymal transection initiated from the visceral surface of the liver after limited hepatic mobilization, reducing the risk of increased circulating tumoral cells.16 - 18 Venous outflow transection and completion of ligament mobilization are left as last steps. A 46 years-old-male with hepatitis C virus and alcoholic cirrhosis was diagnosed with a 4-cm HCC (right hepatic lobe). Expected future liver remnant was 45 % of his total liver volume. A totally laparoscopic right hepatectomy was performed using six ports, and the specimen was removed through a Pfannenstiel auxiliary incision. A 10-mm 30° scope was used. The pneumoperitoneum pressure was set to 12 mmHg. The right hepatic pedicle, the caudate lobe, and the major hepatic veins were managed with laparoscopic vascular staplers. Surgery was performed with limited liver mobilization and en bloc extrafascial right pedicle control (Takasaki's technique),19 followed by caudal parenchymal transection along the paracaval plane. The operative time was 450 min, and the estimated blood loss was 800 ml (no transfusion was required). The laparoscopic Takasaki technique and caudal approach are feasible procedures in the setting of cirrhosis, resulting in an oncologic adequate intervention with less morbidity.


Wave Patterns in Cell Membrane and Actin Cortex Uncoupled from Chemotactic Signals.
When cells of Dictyostelium discoideum orientate in a gradient of chemoattractant, they are polarized into a protruding front pointing toward the source of attractant, and into a retracting tail. Under the control of chemotactic signal inputs, Ras is activated and PIP3 is synthesized at the front, while the PIP3-degrading phosphatase PTEN decorates the tail region. As a result of signal transduction, actin filaments assemble at the front into dendritic structures associated with the Arp2/3 complex, in contrast to the tail region where a loose actin meshwork is associated with myosin-II and cortexillin, an antiparallel actin-bundling protein. In axenically growing strains of D. discoideum, wave patterns built by the same components evolve in the absence of any external signal input. Since these autonomously generated patterns are constrained to the plane of the substrate-attached cell surface, they are optimally suited to the optical analysis of state transitions between front-like and tail-like states of the membrane and the actin cortex. Here, we describe imaging techniques using fluorescent proteins to probe for the state of the membrane, the reorganization of the actin network, and the dynamics of wave patterns.


Behavioural access to short-term memory in bees.
Memory formation proceeds in temporal phases which differ in their effectiveness in controlling subsequent behavior and in their susceptibility to amnestic treatment. The initial phase of memory formation, frequently termed short-term memory, is generally considered a necessary precursor to long-term memory. However, the course of short-term memory differs widely between animal species and is dependent on experimental procedure. Information may even bypass the short-term phase en route to the long-term one. Experiments reported here using honey bees in a behavioural learning situation suggest that the greatest significance of short-term memory is its function as a mode of memory storage which may be altered effectively by new and contradictory information. Freely flying honey bees were presented two colour alternatives and rewarded on first one and then the other in a reversal learning paradigm. Subsequent colour preference was dependent on the interval between the two trials. Several new features of short-term memory are described. It is concluded that a single mechanisms of short- to long-term memory transfer cannot account for the observed bimodal interval dependent behaviour. Two mechanisms are proposed.


[Distraction in mouth, jaw and facial surgery].
Distraction osteogenesis is established worldwide as a new surgical technique. The former rule, not to osteotomize before the end of bone growth, is no longer valid. Today, distraction starts as early as infancy as well as in childhood and adolescence. This new method allows the gain of bone in the distraction gap so that bone grafting can be avoided. Distraction is indicated in hemifacial microsomias, multiple syndromes with mandibular malformations, mandibular retrognathia, posttraumatic jaw deficiencies, craniofacial malformations, alveolar ridge resorptions, and alveolar ridge resections. Distraction surgery started in the mandible and was continued in the maxilla and the craniofacial region. Alveolar ridge distraction followed. After using extraoral devices, the development of internal applicable distractors followed. Today, bi- or tridirectional internal devices are already available. The whole treatment concept includes the orthodontist. Distraction planning before surgery is of great importance. The literature presently includes methods, indications, and case reports but only few results, which we compare with our experiences.


Stress distribution in the transitional peri-implant bone in a single implant-supported prosthesis with platform-switching under different angulated loads.
A 3D finite element analysis was conducted to evaluate and compare the stress distribution in the peri-implant bone (transitional cortical and trabecular bone) of one single implant-supported crown with platform switching and another without platform switching, under a vertical and an oblique load. Two models were created, simulating an osseointegrated implant (4 × 13 mm, platform 4.1 mm) embedded in the jaw bone. One model simulated a 4.1-mm diameter abutment connection (conventional model) and the other a 3.8-mm diameter abutment connection (platform-switching model). A crown with a Co-Cr alloy framework and feldspathic porcelain veneering was applied over the titanium abutment. Static, vertical and oblique loads (0°, 15°, 30°, 45°) with a maximum value of 150 N were applied to the crown. For any inclination of the applied load, the stress values in the transitional cortical bone were lower in the platform-switching model than in the conventional model. However, the stress in the transitional trabecular bone was higher in the platform-switching model than in the conventional model. Stress values increased when the load was more oblique at the transitional cortical bone in both models and was slightly reduced at the transitional trabecular bone of the conventional model. The platform-switching technique reduces the stress at the transitional cortical bone. In both models, this stress gradually increases as the load becomes more inclined. The transitional trabecular bone shows lower stress values than the transitional cortical bone. The location of stress is similar in both models.


Glutathione regulates transcriptional activation of iron transporters via S-nitrosylation of bHLH factors to modulate subcellular iron homoeostasis.
Glutathione (GSH) is known to regulate iron (Fe) deficiency response in plants but its involvement in modulating subcellular Fe homoeostasis remains elusive. In this study, we report that the GSH-deficient mutants, cad2-1 and pad2-1 displayed increased sensitivity to Fe deficiency with significant downregulation of the vacuolar Fe exporters, AtNRAMP3 and AtNRAMP4, and the chloroplast Fe importer, AtPIC1. Moreover, the pad2-1 mutant accumulated higher Fe levels in vacuoles but lower Fe levels in chloroplasts compared to wild type (Columbia ecotype [Col-0]) under Fe limited conditions. Exogenous GSH treatment enhanced chloroplast Fe contents in Col-0 but failed to do so in the nramp3nramp4 double mutants demonstrating that GSH plays a role in modulating subcellular Fe homoeostasis. Pharmacological experiments, mutant analysis, and promoter assays revealed that this regulation involves the transcriptional activation of Fe transporter genes by a GSH-S-nitrosoglutathione (GSNO) module. The Fe responsive bHLH transcription factors (TFs), AtbHLH29, AtbHLH38, and AtbHLH101 were found to interact with the promoters of these genes, which were, in turn, activated via S-nitrosylation (SNO). Taken together, the present study highlights the role of the GSH-GSNO module in regulating subcellular Fe homoeostasis by transcriptional activation of the Fe transporters AtNRAMP3, AtNRAMP4, and AtPIC1 via SNO of bHLH TFs during Fe deficiency.


Structural homology among four nodaviruses as deduced by sequencing and X-ray crystallography.
The genomic RNA2s of nodaviruses encode a single gene, that of protein alpha, the precursor of virion proteins beta and gamma. We compared the sequences of the RNA2s of the nodaviruses, black beetle virus (BBV), flock house virus, boolarra virus and nodamura virus, with the objective of identifying homologies in the primary and secondary structure of these RNAs and in the structure of their encoded protein. The sequences of the four RNAs were found to be similar, so that homologous regions relating to translation and RNA replication were readily identified. However, the overall, secondary structures in solution, deduced from calculations of optimal Watson-Crick base-pairing configurations, were very different for the four RNAs. We conclude that a particular, overall, secondary structure in solution within host cells is not required for virus viability. The partially refined X-ray structure of BBV (R = 26.4% for the current model) was used as a framework for comparing the structure of the encoded proteins of the four viruses. Mapping of the four protein sequences onto the BBV capsid showed many amino acid differences on the outer surface, indicating that the exteriors of the four virions are substantially different. Mapping in the beta-barrel region showed an intermediate level of differences, indicating that some freedom in choice of amino acid residues is possible there although the basic framework of the capsids is evidently conserved. Mapping onto the interior surface of the BBV capsid showed a high degree of conservation of amino acid residues, particularly near the protein cleavage site, implying that that region is nearly identical in all four virions and has an essential role in virion maturation, and also suggests that all four capsid interior surfaces have similar surfaces exposed to the viral RNA. Apart from a small portion of the C promoter, the amino terminus of the BBV protein (residues 1 to 60) is crystallographically disordered and the amino acid residues in that region are not well conserved. The disordered portion of the BBV protein clearly projects from the capsid inner surface into the interior of the virion, the region occupied by the viral RNA. In all four viruses, residues 1 to 60 had a high proportion of basic residues, suggesting a virus-specific interaction of the amino terminus with the virion RNA.


A study of molecular dynamics and freezing phase transition in tissues by proton spin relaxation.
Muscle, spleen, and kidney tissues from 4-wk-old C57 black mice were studied by proton magnetic resonance. Spin-lattice relaxation times at high fields and in the rotating frame, as well as the spin-spin relaxation times, are reported as a function of temperature in the liquid and frozen phase. Motions of large molecules and of water molecules and their changes at the freezing phase transition are studied. The shortcomings of the two-state fast-exchange relaxation model are discussed.


Pediatric bilateral spontaneous pneumothoraces in monozygotic twins.
Primary spontaneous pneumothorax from subpleural bleb disease is an uncommon occurrence in pediatric patients. This is a rare case of monozygotic twins presenting at alternating intervals with a single-sided spontaneous pneumothorax, only to have it surgically corrected, and to present later with a subsequent contralateral pneumothorax. A review of familial spontaneous pneumothoraces occurring in children was queried for congenital or genetic syndromes. We concluded that a vast majority of pneumothoraces in children, like adults, are not spontaneous and not familial linked. While they are rare, some congenital syndromes have been identified. The HLA haplotype A2 B40, the gene encoding folliculin, Alph-1-antitrypsin, Marfan's syndrome, Ehlers-Danlos syndrome and Birt-Hogg-Dube syndrome have all been associated with familial spontaneous pneumothoraces. Physicians need to counsel family members to ensure appropriate observation and expedited treatment is not delayed.


Cadherin Combinations Recruit Dendrites of Distinct Retinal Neurons to a Shared Interneuronal Scaffold.
Distinct neuronal types connect in complex ways to generate functional neural circuits. The molecular diversity required to specify this connectivity could be supplied by multigene families of synaptic recognition molecules, but most studies to date have assessed just one or a few members at a time. Here, we analyze roles of cadherins (Cdhs) in formation of retinal circuits comprising eight neuronal types that inform the brain about motion in four directions. We show that at least 15 classical Cdhs are expressed by neurons in these circuits and at least 6 (Cdh6-10 and 18) act individually or in combinations to promote specific connectivity among the cells. They act in part by directing the processes of output neurons and excitatory interneurons to a cellular scaffold formed by inhibitory interneurons. Because Cdhs are expressed combinatorially by many central neurons, similar interactions could be involved in patterning circuits throughout the brain.


Adenoid cystic carcinoma of the antrum and epiphora.
Tearing was the initial symptom in two patients who subsequently developed a mass over the anterior lacrimal crest area caused by adenoid cystic carcinoma of the antrum. In a 76-year-old woman, a paranasal sinus X-ray film revealed an antral mass, and the histopathologic diagnosis was made by incisional biopsy. She refused further examination and treatment. In a 62-year-old woman, a paranasal sinus X-ray film and computed axial tomography examination revealed an antral mass. Epiphora caused by obstruction of the nasolacrimal sac was shown by dacryocystography. Bony destruction of the medial orbital floor was shown by paranasal sinus X-ray film, and confirmed at the time of initial biopsy. Orbital exenteration and radical maxillectomy and ethmoidectomy were performed, and the histopathologic diagnosis and primary site of the tumor were confirmed. There was no recurrence 24 months postoperatively.


A systematic review of randomized controlled trials for prevention or treatment of atopic dermatitis in dogs: 2008-2011 update.
The management of atopic dermatitis (AD) in dogs relies mainly on the use of interventions to reduce pruritus and skin lesions. To provide a critical analysis of recent clinical trials reporting the efficacy and safety of interventions for canine AD. Systematic review of randomized controlled trials (RCTs) published, presented or completed between 2008 and 2011, which enrolled dogs with AD. The search was done using electronic databases, reviewing published meeting abstracts and sending queries to professional email lists. Trials reporting the efficacy of interventions aimed at treating, preventing or reducing glucocorticoid usage in atopic dogs were selected. Twenty-one RCTs were included. We found further moderate-quality evidence of efficacy and safety of oral glucocorticoids and ciclosporin for treatment of canine AD. There was additional moderate-quality evidence of the efficacy of a topical glucocorticoid spray containing hydrocortisone aceponate. Low-quality evidence was found for the efficacy and safety of injectable recombinant interferons, a budesonide leave-on conditioner, a ciclosporin topical nano-emulsion and oral fexofenadine. There is low-quality evidence of efficacy of oral masitinib, with a need for monitoring for protein-losing nephropathy. Finally, we uncovered low-quality evidence of efficacy of a commercial diet as a glucocorticoid-sparing intervention and of a glucocorticoid spray as a flare-delaying measure. Very low-quality evidence was found for the efficacy of other interventions. Topical or oral glucocorticoids and oral ciclosporin remain the interventions with highest evidence for efficacy and relative safety for treatment of canine AD.


Heart Failure With Preserved Ejection Fraction.
Heart failure (HF) is one of the largest drivers of morbidity and health care expenditure in the world and continues to increase in prevalence at an alarming rate. Most of this increasing burden is related to the rapidly expanding population of HF with preserved ejection fraction (HFpEF), largely driven by the increasing rates of obesity, hypertension, and metabolic syndrome in western countries. In the last 3 decades, there have been tremendous advances in treating patients with HF with reduced ejection fraction (HFrEF), with essentially no change in outcomes for HFpEF. The lack of efficacy for established HFrEF therapies in HFpEF underscores the fundamental differences between both these phenotypically distinct forms of HF. In this review, we will summarize the current understanding of the pathophysiology of HFpEF, discuss diagnostic and therapeutic strategies, and provide future avenues to direct clinical investigation.