Contrasting coral community structures between natural and artificial substrates at Koh Tao, Gulf of Thailand.
Concrete cubic frames and decommissioned steel naval vessels have been deployed in Thailand liberally to act as artificial substrates for coral restoration and marine recreation. We assessed recruitment at such substrate types at Koh Tao, Gulf of Thailand, and compared the community structure of scleractinian corals between artificial substrates and nearby natural reefs. Our results from a sample of 2677 recruits from nine sites highlighted significant differences in community structure between both reef types. Investigations of variables including time since deployment, distance from the natural reef, and seafloor depth revealed only the latter as a possible influencing factor. The diversity of recruits could not be explained by dynamics in coral spawning, and were found to represent groups with lower structural complexity. Our results suggest that coral community structure on artificial and natural reefs differs and supports distinct ecological and functional roles.


Fluoroscopy-Guided Suture Anchor Placement Yields Excellent Accuracy for Arthroscopic Acetabular Labral Repair: A Cadaveric Study.
To determine the accuracy of fluoroscopy-guided suture anchor placement for arthroscopic acetabular labral repair in cadaveric hip specimens. Two sports medicine fellowship-trained surgeons performed arthroscopic hip surgery on 6 cadaveric specimens each. Suture anchors were placed at the 11-, 12-, 1-, 2-, 3-, and 4-o'clock positions of the acetabulum in each specimen using a previously described fluoroscopically guided technique. Gross dissection and thin-cut computed tomography scans were performed to assess for accuracy. The insertion angle between the subchondral bone and the drill bit immediately prior to suture anchor insertion was measured, and fluoroscopic visualization of the subchondral bone at each clock-face position was qualitatively graded as good, fair, or poor by 2 independent reviewers. Overall, 90.3% of attempts (65 of 72) were entirely intraosseous, 5.5% (4 of 72) perforated the articular cartilage, and 4.2% (3 of 72) perforated the far cortex, rates that are comparable with those in previous cadaveric studies. There was no statistically significant difference in accuracy between the surgeons (P = .42) or between the various clock-face positions (P = .63). Neither the insertion angle (P = .26) nor visualization of the subchondral bone (P = .35) was significantly correlated with accuracy by gross dissection. In a cadaveric hip arthroscopy model, fluoroscopy-guided suture anchor placement yields excellent accuracy rates, similar to non-image-guided techniques. Intra-articular suture anchor placement and intrapelvic suture anchor placement are known complications of arthroscopic acetabular labral repair. Fluoroscopically guided suture anchor placement can be a useful tool for hip arthroscopy surgeons performing acetabular labral repair and reconstruction, potentially reducing the risk of these complications.


Identification of HESX1 mutations in Kallmann syndrome.
To determine whether HESX1 mutations are present in patients with idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS). Polymerase chain reaction-based DNA sequencing was performed on 217 well-characterized IHH/KS patients. Putative missense mutations were analyzed by sorting intolerant from tolerant (SIFT) and Clustal Ω. Academic medical center. Two hundred seventeen patients with IHH/KS and 192 controls. Deoxyribonucleic acid was extracted from patients and controls; genotype/phenotype comparisons were made. Deoxyribonucleic acid sequence of HESX1, SIFT analysis, and ortholog alignment. Two novel heterozygous missense mutations (p.H42Y and p.V75L) and previously reported heterozygous missense mutation p.Q6H in HESX1 were identified in 3 of 217 patients (1.4%). All were males with KS. Both p.Q6H and p.H42Y were predicted to be deleterious by SIFT, whereas p.V75L was conserved in 8 of 9 species. No other IHH/KS gene mutations were present. HESX1 mutations may cause KS in addition to more severe phenotypes. Our findings expand the phenotypic spectrum of HESX1 mutations in humans, thereby broadening its role in development.


Mercury and methylmercury in liver tissue from ringed herring gulls collected in three Danish localities.
In connection with a large scale reduction of herring gulls population, 119 ringed herring gulls were collected from Hirsholmene (Oresund), and Christiansø (Baltic Sea) in the spring of 1975 and 1976. The gulls had been ringed at the respective localities where they were later killed. An average of 0.65 mg Hg/kg liver (wet weight) was found with considerable differences between the three localities.


Emergency department visits in older people: pattern of use, contributing factors, geographical differences and outcomes.
To assess the pattern of use of Emergency Departments (EDs), factors contributing to the visits, geographical distribution and outcomes in people aged 65 years or more living in the Italian Lombardy Region in 2012. Based on an administrative database the study population was divided into groups according to the number of ED visits. A multinomial logistic regression model was performed to compare the characteristics of each group. The Getis-Ord's G statistic was used to evaluate the clusters of high and low visit prevalence odd ratios (OR) at district level. To estimate the severity of the disease leading to ED attendance, visits were stratified based on the level of emergency and outcome. About 2 million older people were included in the analyses: 78 % had no ED visit, 15 % only 1, 7 % 2 or more. Male sex, age 85 years or more, high number of drugs, ED visits and hospital admissions in the previous year and the location of an ED within 10 km from the patient's place were all factors associated with a higher risk to have more ED visits. Clusters of high and low prevalence of visits were found for occasional users. Overall, 83 % of ED visit with a low emergency triage code at admission had as visit outcome discharge at home. In older people several variables were associated with an increased risk to have a high number of ED visits. Most of the visits were done for non-urgent problems and significant geographic differences were observed for occasional users.


Characterizing the BCR repertoire during lymphocyte reduction and recovery mediated by cyclophosphamide and granulocyte-macrophage colony-stimulating factor.
Leukopenia is a common manifestation of many diseases, including global outbreak SAS-CoV-2 infection. Granulocyte-macrophage colony-stimulating factor (GM -CSF) has been proved to be effective in promoting lymphocyte regeneration, but adverse immunological effects have also emerged. This study aim to investigate the effect of GM -CSF on BCR heavy chain CDR3 repertoire while promoting lymphocyte regeneration. Cyclophosphamide (CTX) and GM -CSF were used to inhibit and stimulate bone marrow hematopoiesis, respectively. High throughput sequencing was applied to detect the characteristics of BCR CDR3 repertoire in controls, CTX group and GM -CSF group. The white blood cells (WBCs) were quickly reduced (P < 0.05) with lymphocytes decreasing causing by CTX, and the WBCs and lymphocytes returned to the level of controls after GM -CSF treatment. The diversity of BCR heavy chain CDR3 repertoire was also significantly decreased in CTX group. Although there is still a big gap from the controls, the diversity was picked up after GM -CSF treatment. The expression of IGHD01-01, IGHD02-14 and IGHJ04-01 with high-frequency usage regularly and significantly changed in three groups, and many genes with low-frequency usage lost in CTX group and did not reappear in GM -CSF group. Moreover, two shared sequences and accounted for the highest proportion in GM -CSF group have been detected in animal model of chronic lymphocytic leukemia. These results revealed that GM -CSF can partially restore changes in the BCR heavy chain CDR3 repertoire while promoting lymphocyte regeneration, but it may also lead to rearrangement, proliferation and activation of abnormal B cells, which can provide a basis for further study on the adverse immunological effects and mechanism of GM -CSF treatment.


[Primary health care during the COVID-19 pandemic in Mexico].
Primary health care is the provision of comprehensive and accessible medical services provided by clinical health professionals. It plays an indispensable role in the health emergency, as it represents the first contact for many Mexicans with and without social security. Its work during the COVID-19 pandemic is crucial as it forms the gateway to health systems. The contingency due to the SARS-CoV-2 virus in Mexico has only increased this inequality between those who have access to quality services and those who do not. Certain weaknesses are evident in the country, such as the saturation of hospitals, care times and the shortage of medicines. However, they have also highlighted strengths such as the vaccination strategy (being one of the first Latin American countries to implement the vaccine against COVID-19). On the other hand, the hospital reconversion that has made it possible to care for a greater number of patients, avoiding the saturation of hospitals. A resource that became relevant in pandemic times was technology. Doctors adapted to the needs of patients and through wireless communication, telemedicine was a resource used to provide health care remotely and thus prevent the risk of contagion. This manuscript represents an overview of the panorama in Mexico from the social perspective and the first level of care.


Design of polyelectrolyte core-shells with DNA to control TMPyP binding.
The interaction of DNA with 5,10,15,20-tetrakis(4-N-methylpyridiniumyl)porphyrin (TMPyP) in polyelectrolyte core-shells obtained via layer by layer adsorption of poly(sodium 4-styrenesulfonate), PSS, and poly(allylamine hydrochloride), PAH, polyelectrolytes was followed by steady state, time resolved fluorescence and by Fluorescence Lifetime Imaging Microscopy (FLIM). Our results show that DNA adsorption onto polyelectrolyte core-shell changes the TMPyP interaction within PSS/PAH core-shells structure and increase significantly the TMPyP uptake. Specific DNA/TMPyP interactions are also altered by DNA adsorption favouring porphyrin intercalation onto GC pair rich regions. Circular dichroism (CD) spectra reveal that DNA undergoes important conformational changes upon adsorption onto the core-shell surface, which are reverted upon TMPyP encapsulation.


Leucocyte ascorbic acid and the leucocyte count.
1. During the course of a nutritional survey on an Antarctic base, leucocyte ascorbic acid estimations (Denson & Bowers, 1961) were found to be significantly affected (P less than 0.0001) by the leucocyte count measured during analysis. 2. The effect was significantly less (P less than 0.05) when leucocyte levels were at or near saturation than when subsaturated. 3. This suggests that leucocytes share available ascorbic acid, especially in subsaturated subjects, and that assessment of nutritional status from the leucocyte ascorbic acid level should take account of the leucocyte count and the plasma ascorbic acid titre.


Monoclonal antibodies against human DNA polymerase-alpha do not cross-react with glucocorticoid receptors.
None of 16 independent monoclonal antibodies against human (KB cell) DNA polymerase-alpha recognizes epitopes on cytoplasmic glucocorticoid receptors prepared from the same cells. Consistently negative results are obtained with separate assays that measure antibody binding to uncharged receptors or to charged receptor complexes that have been preloaded with a specific steroid ligand. These results must qualify the interpretation of possible immunological relations between polymerase-alpha and glucocorticoid receptors that were inferred from studies with polyclonal antisera of poorly defined specificity.


Feasibility of Cerebellar Measurements with Phased Array Sonography through the Anterior Fontanelle in Comparison to MRI.
Cerebral sonography (CS) through the anterior fontanelle is a neonatal brain imaging method that has become an integral part of modern neonatal bedside care for both screening and diagnostic purposes. Premature infants with cognitive delay have a reduction in cerebellar size at term corrected age on magnetic resonance imaging (MRI). We aimed to determine the level of agreement between postnatal MRI and CS for cerebellar biometry and to determine the level of agreement within one and between different examiners. Cerebellar sonography and MRI measurements of the cerebellum from 30 term infants was assessed by Bland-Altman plots. Measurements between both modalities were compared using Wilcoxon's signed rank test. A p-value < 0.01 was considered statistically significant. Intraclass correlation coefficients (ICC) for intra- and interrater reliabilities of CS measurements were calculated. There was no statistically significant difference between CS and MRI for linear measurements, but the measurements of perimeter and surface area differed significantly between the two techniques. There was a systematic bias between both modalities for most measurements except for anterior-posterior (AP) width and vermis height (VH). For measurements that were not statistically different from MRI, we found excellent intrarater ICC for the AP width, VH, and cerebellar width. The interrater ICC was excellent for the AP width and VH, but poor for the transverse cerebellar width. With a strict imaging protocol, cerebellar measurements of the AP width and the VH can be used as an alternative to MRI for diagnostic-screening purposes in a neonatal department where multiple clinicians perform bedside CS. · Abnormal cerebellar growth and injuries affect neurodevelopmental outcome.. · Cerebral sonography through the anterior fontanelle is used for bedside imaging.. · Postnatal sonographic cerebellar measurements are not validated against MRI.. · Measuring vermis height and anterior-posterior width are reliable.. · Measuring transverse cerebellar width through anterior fontanelle is unreliable..


Dolichol phosphate mannose synthase is differentially expressed in male and female worms of Schistosoma mansoni.
The cDNA encoding the Schistosoma mansoni dolichol phosphate mannose synthase was completely sequenced, displaying the highest homology with Cricetulus griseus and Saccharomyces pombe genes. The Schistosome enzyme had a K(m) of 0.127 microM, a value that is within the range of those reported for several other species. Thin-layer chromatography of the radiolabelled schistosome lipid intermediate showed it was identical to dolichol-phosphate (C80-C105). Expression of dolichol phosphate mannose synthase of S. mansoni (SmDPMS) was analysed by Northern blot and quantified by semi-quantitative RT-PCR with cDNA from mature and immature male and female worms. Northern blot analysis revealed a single 1-kb band. Both approaches confirmed a higher level of expression in mature female worms, as compared to immature and male worms.


A vector-free gene interference system using delaminated Mg-Al-lactate layered double hydroxide nanosheets as molecular carriers to intact plant cells.
The Mg-Al-lactate layered double hydroxide nanosheet (LDH-NS) has shown great potential as an optimal nanocarrier for extensive use in plants. However, previous studies in plant sciences have not provided a clear description of the application for the LDH-NSs-based double-stranded RNA (dsRNA) delivery (LDH-dsRNA) system in different tissues of both model and non-model species. LDH-NSs were synthesized by using the co-precipitation method, while the dsRNAs targeting genes of interest were prepared in vitro using T7 RNA polymerase. The LDH-dsRNA bioconjugates with a neutral charge were produced by incubating with the mass ratio of LDH-NSs to dsRNA at 3:1, which were then introduced into intact plant cells using three different approaches, including injection, spray, and soak. The LDH-dsRNA delivery method was optimized by inhibiting the expression of the Arabidopsis thaliana ACTIN2 gene. As a result, soaking A. thaliana seedlings in a medium containing LDH-dsRNA for 30 min led to the silencing of 80% of the target genes. The stability and effectiveness of the LDH-dsRNA system were further confirmed by the high-efficiency knockdown of plant tissue-specific genes, including that encoding phytoene desaturase (PDS), WUSCHEL (WUS), WUSCHEL-related homeobox 5 (WOX5), and ROOT HAIR DEFECTIVE 6 (RHD6). In addition, the LDH-dsRNA system was employed in cassava, where it was found that the expression of the gene encoding nucleotide-binding site and leucine-rich repeat (NBS-LRR) was significantly reduced. As a result, the resistance of cassava leaves to pathogens was weakened. Noteworthy, the injection of LDH-dsRNA into leaves resulted in a significant downregulation of target genes in both stems and flowers, indicating the successful transport of LDH-dsRNA from leaves to other parts of plants. LDH-NSs have proven to be a highly effective molecular tool for delivering dsRNA into intact plant cells, enabling accurate control of target gene expression.


Antioxidant activity of Pistacia atlantica var mutica kernel oil and it's unsaponifiable matters.
In this research, antioxidant activity of Pistacia atlantica var mutica (a wild type of pistachio in Iran) kernel oil (PAKO) and unsaponifiable matters of kernel oil (UKO) were compared with those of sesame seed oil (SSO) and rice bran oil (RBO) as well as with their unsaponifiable matters (USO and UBO) and α-tocopherol (natural antioxidant) was selected as control. Also, some chemical properties such as (FRAP, DPPH radical-scavenging, rancimat and oven assays (peroxide value and carbonyl value) were assessed. The amount of unsaponifiable matters of studied oils was between 1.4 and 3.5%. The highest total phenolics was observed in SSO (1024 mg/kg), followed by RBO, and PAKO was 174, and 75 mg/kg, respectively. In DPPH radical-scavenging assay, the EC50 values of PAKO, SSO, RBO, UKO, USO, UBO, and α-tocopherol were determined as 38.9, 50, 48.4, 14, 12.7, 15.9 and 61.4 mg/mL, respectively. In FRAP assay, the highest value was nominated for UKO (434 mmol/L); followed by USO, UBO, PAKO, SSO, RBO and α-tocopherol (404, 357, 364, 298, 210 and 58 mmol/L; respectively). Also, considering the results of oven test, the incorporation of UKO into pure sunflower oil resulted in the highest oxidative stability; followed by UBO, USO, PAKO, SSO, RBO and α-tocopherol. According to results of the rancimat test, the incorporation of unsaponifiable matters (UKO, USO, and UBO) resulted in the highest oil/oxidative stability index (OSI) in pure sunflower oil, followed by oils studied (PAKO, SSO, and RBO). According to results, UKO had the highest antioxidant activity, followed by USO, UBO, PAKO, SSO, RBO, and α-tocopherol.


A longitudinal study of dentine lead levels and intelligence, school performance and behaviour: the measurement of dentine lead.
Shed deciduous teeth were obtained from a sample of 996 New Zealand children who were participants in a longitudinal study. For each child, estimates of dentine lead were obtained from two samples of dentine. The information was used to estimate the magnitude of random errors of measurement in dentine lead values and it was estimated that between 15 and 20% of the variance in dentine lead values was attributable to random errors of measurement. In addition, dentine lead levels were influenced by small systematic errors of measurement arising from the age at which the tooth was collected and the type of tooth analysed. These sampling factors, however, accounted for less that 3% of the variance in dentine lead values. The implications of these findings for the interpretation of correlations between dentine lead levels and other variables are discussed.


Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model.
The purpose of this study was to investigate the intraluminal processing of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Amphotericin B (AmB) was formulated in three lipid-based formulations consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various lipid loads (0.25, 0.5, 1 and 2 g) were digested using the lipolysis model to assess AmB distribution among the lipolysis phases. The duration of lipolysis was comparable among the three formulations except for 2 g load of iCo-009 which had a significantly longer lipolysis than iCo-010 and iCo-011. The lipid components of iCo-009 experienced lower extent of lipolysis as compared to other formulations. Amphotericin B concentration in the aqueous phases was the highest with iCo-010 which also had the lowest sediment recovery. Amphotericin B levels in the undigested lipid layers were comparable between iCo-009 and iCo-010 and were higher than with iCo-011. Given the observation that iCo-010 had the highest aqueous micellar solubilization and the lowest sediment recovery of AmB among the tested formulations, these results could potentially be used to interpret and predict the in vivo performance of AmB- SEDDS formulations in future studies.


The relationship between dysfunctional attitudes, maladaptive perfectionism, metacognition and symptoms of mania and depression in bipolar disorder: The role of self-compassion as a mediating factor.
Maladaptive cognitions appear to be associated with the severity of mood symptoms in bipolar disorder (BD), but findings are mixed and generally cross-sectional in design. This study (n = 331) explored the associations between maladaptive cognitions and mood symptoms in BD over time (3 months), and the potential mediating effect of self-compassion cross-sectionally. Dysfunctional attitudes, maladaptive perfectionism and maladaptive metacognitions were explored separately with depressive and manic symptoms, and with current mood state in BD. The results showed maladaptive metacognitions to be the only significant predictor of depression at 3-month follow-up (β = 0.31, p < .001), with no relationship to mania over time. Cross-sectionally, self-compassion partially mediated the relationship between all maladaptive cognitions and depression, with higher dysfunctional cognitions and lower self-compassion predicting increased severity of depressive symptoms. Only the relationship between dysfunctional attitudes and mania was partially mediated by self-compassion, however, the relationship was weak and suggestive that higher self-compassion predicted increased mania. The study duration limited the possible analysis. Future longitudinal research is needed. Also, the study sample was not representative of the clinical population, making results less generalisable. Additionally, limited significant findings regarding manic symptoms supports the need for further research into active cognitions during this phase of BD. Maladaptive metacognitions were predictive of future depression severity, therefore, further exploration of metacognitive therapy for BD should be explored. Furthermore, self-compassion was shown to partially mediate the relationship between negative cognitions and mood, therefore further exploration of compassion-based therapies for BD is needed.


Obstruction of mechanical mitral valves by preserved posterior leaflet remnants.
We report two cases of mechanical prosthetic mitral valve obstruction caused by remnants of the mitral valve posterior leaflet tissue preserved from the previous surgery. Both patients had rheumatic mitral stenosis causing New York Heart Association class III symptoms prior to mitral valve replacement.


Erratum: Regulation of the microvasculature during small muscle mass exercise in chronic obstructive pulmonary disease vs. chronic heart failure.
[This corrects the article DOI: 10.3389/fphys.2022.979359.].


Effects of opioid blockade with nalmefene in older impotent men.
We evaluated the effect of the opioid antagonist nalmefene on the HPG axis and on food consumption in 14 older impotent men. These patients had low to low normal mean serum testosterone values and normal gonadotrophin levels on screening evaluation. Normal response to GnRH was demonstrated in all the men. The protocol called for 24 hours of evaluation before and during administration of nalmefene 2.0 mg IV every 8 hours for 3 doses. During each 24 hour period, the following determinations were made: serum testosterone, FSH, and LH by five separate determinations between 8 AM and noon; 8 AM and 11 PM serum cortisols; 24 hour urine collections for free cortisol; and nocturnal penile tumescence (NPT). Food consumption was measured from 4 PM to 10 AM during the two periods. Nalmefene resulted in significant rises in testosterone, LH, and FSH. Nalmefene significantly elevated morning and evening cortisol measurements in all the patients. Nalmefene decreased total calorie consumption, principally by decreasing fat consumption. There was no effect on NPT. We conclude that in older impotent men, nalmefene acutely increases activity of the HPG axis and decreases calorie intake predominantly by decreasing fat consumption.


Relation between salivary cortisol as stress biomarker and dietary pattern in children.
Psychological stress has been suggested to result in hormonal effects (e.g. changes in cortisol pattern) that may change food selection in unhealthy ways. This study examines whether children's dietary pattern is indeed related to salivary cortisol levels. In 323 children (5-10 years old) participating in the Belgian ChiBS study, salivary cortisol samples, a biomarker for stress, was sampled when waking up, 30 and 60 min after wake up and in the evening on two consecutive weekdays. Data on the children's dietary pattern (frequency of sweet foods, fatty foods, snacks, fruit and vegetables) was collected with a food frequency questionnaire. Multilevel time modelling was used with adjustments for sex, age, body mass index, parental education and wake up time. Higher overall cortisol levels and a large cortisol awakening response (CAR) were associated with more frequent consumption of sweet foods. A steeper diurnal cortisol decline was associated with a higher sweet, fatty and snack food consumption frequency. No associations with fruit and vegetables consumption were found. High cortisol levels were linked to an unhealthier dietary pattern (more fatty food, snacks and especially sweet food). This supports the theory of cortisol-induced comfort food preference and strengthens the stress-diet relation.


Role of HIF1α and HIF2α in Cre Recombinase-Induced Retinal Pigment Epithelium Pathology and Its Secondary Effect on Choroidal Neovascularization.
CreTrp1 mice are widely used for conditional retinal pigment epithelium (RPE) gene function studies. Like other Cre/LoxP models, phenotypes in CreTrp1 mice can be affected by Cre-mediated cellular toxicity, leading to RPE dysfunction, altered morphology and atrophy, activation of innate immunity, and consequent impairment of photoreceptor function. These effects are common among the age-related alterations of RPE that feature in early/intermediate forms of age-related macular degeneration. This article characterizes Cre-mediated pathology in the CreTrp1 line to elucidate the impact of RPE degeneration on both developmental and pathologic choroidal neovascularization. Nonredundant roles of the two major components of the hypoxia-inducible factor (HIF) family of transcription regulators, HIF1α and HIF2α, were identified. Genetic ablation of Hif1a protected against Cre-induced degeneration of RPE and choroid, whereas ablation of Hif2a exacerbated this degeneration. Furthermore, HIF1α deficiency protected CreTrp1 mice against laser-induced choroidal neovascularization, whereas HIF2α deficiency exacerbated the phenotype. Cre-mediated degeneration of the RPE in CreTrp1 mice offers an opportunity to investigate the impact of hypoxia signaling in the context of RPE degeneration. These findings indicate that HIF1α promotes Cre recombinase-mediated RPE degeneration and laser-induced choroidal neovascularization, whereas HIF2α is protective.


[Disease-related knowledge acquisition through structured patient information in rheumatoid arthritis (StruPI-RA) : First results of the StruPI-RA study in Germany].
The structured patient information for rheumatoid arthritis (StruPi-RA) program was the first standardized outpatient education program in rheumatoid arthritis (RA) in Germany. The main objective of the study was to determine the efficacy of the StruPi-RA program concerning disease-specific knowledge acquisition in patients with early stage RA or after changing the treatment regimen. A total of 61 patients were included in a control group design, 32 in the intervention group (IG) and 29 in the control group (CG). Patients of the IG attended 3 modules of 90 min in a structured patient information program (StruPI-RA) including the topics of diagnostics, treatment and living with RA. Patients in the CG only received information material from the German Rheumatism League. The primary target criterion was the disease-related acquisition of knowledge, measured with the patient knowledge questionnaire (PKQ). Data were collected before and after participation in StruPI-RA. The improvement in knowledge in the IG attending the StruPI-RA compared to the CG was significant in time and group comparisons. No influence of disease duration or educational level was observed. The subscale treatment alone showed a significant difference in the group and time comparison. Participation in the StruPI-RA program in early RA was associated with a significant increase in disease-specific knowledge compared to the control group of patients. This leads to better decision-making in terms of treatment, a more beneficial doctor-patient communication and better self-management. In the long term an improvement in treatment adherence and quality of life is expected.


A motor neuron-specific epitope and the low-affinity nerve growth factor receptor display reciprocal patterns of expression during development, axotomy, and regeneration.
Somatic motor neurons begin to express the transmitter synthesizing enzyme, choline acetyltransferase (ChAT) and the low-affinity nerve growth factor receptor (NGFR) during embryonic development. However, as motor neurons mature in postnatal life, they lose immunoreactivity for NGFR and acquire a motor neuron-specific epitope that is recognized by the monoclonal antibody, MO-1. The present study was undertaken to examine the effect of nerve injury in adult rats on these three developmentally regulated markers in two populations of somatic motor neurons. Unilateral transection, ligation, or crushing of the sciatic nerve resulted in a loss of MO-1 binding and a concomitant rise in immunoreactivity for NGFR within axotomized motor neurons in lumbar levels of the spinal cord. These changes, detectable within 5 days following nerve injury, are reversed with reinnervation, but persist if reinnervation is prevented by chronic axotomy. Thus, regulation of the expression of NGFR and the MO-1 epitope appears to be critically dependent upon interactions between motor neurons and target muscles. These observations are also consistent with the idea that during regeneration, neurons may revert to a developmentally immature state; in motor neurons, this state is characterized by the presence of NGFRs and the absence of the MO-1 epitope. Transection of the hypoglossal nerve, a purely motor nerve, resulted in a similar loss of MO-1 binding and a selective rise in NGFR immunoreactivity in neurons within the ipsilateral hypoglossal motor nucleus. In addition, immunoreactivity for ChAT was also lost in axotomized hypoglossal motor neurons. In contrast, injury to the sciatic nerve, which bears both sensory and motor axons, did not result in any detectable change in ChAT immunoreactivity in spinal motor neurons.


Profiling The Compendium Of Changes In Saccharomyces cerevisiae Due To Mutations That Alter Availability Of The Main Methyl Donor S-Adenosylmethionine.
The SAM1 and SAM2 genes encode for S-AdenosylMethionine (AdoMet) synthetase enzymes, with AdoMet serving as the main methyl donor. We have previously shown that independent deletion of these genes alters chromosome stability and AdoMet concentrations in opposite ways in S. cerevisiae. To characterize other changes occurring in these mutants, we grew wildtype, sam1∆/sam1∆, and sam2∆/sam2∆ strains in 15 different Phenotypic Microarray plates with different components, equal to 1440 wells, and measured for growth variations. RNA-Sequencing was also carried out on these strains and differential gene expression determined for each mutant. In this study, we explore how the phenotypic growth differences are linked to the altered gene expression, and thereby predict the mechanisms by which loss of the SAM genes and subsequent AdoMet level changes, impact S. cerevisiae pathways and processes. We present six stories, discussing changes in sensitivity or resistance to azoles, cisplatin, oxidative stress, arginine biosynthesis perturbations, DNA synthesis inhibitors, and tamoxifen, to demonstrate the power of this novel methodology to broadly profile changes due to gene mutations. The large number of conditions that result in altered growth, as well as the large number of differentially expressed genes with wide-ranging functionality, speaks to the broad array of impacts that altering methyl donor abundance can impart, even when the conditions tested were not specifically selected as targeting known methyl involving pathways. Our findings demonstrate that some cellular changes are directly related to AdoMet-dependent methyltransferases and AdoMet availability, some are directly linked to the methyl cycle and its role is production of several important cellular components, and others reveal impacts of SAM gene mutations on previously unconnected pathways.


Apolipoprotein AIMilano. Partial lecithin:cholesterol acyltransferase deficiency due to low levels of a functional enzyme.
The cholesterol esterification process was analyzed in 19 carriers of the apolipoprotein AIMilano (AIM) variant and in 19 age-sex matched controls by measuring lecithin:cholesterol acyltransferase (LCAT) mass, activity (i.e., cholesterol esterification with a standard proteoliposome substrate) and cholesterol esterification rate (i.e., cholesterol esterification in the presence of the endogenous substrate). The AIM subjects had lower LCAT mass (3.30 +/- 0.85 micrograms/ml), activity (71.1 +/- 36.4 nmol/ml per h) and cholesterol esterification rate (23.6 +/- 12.5 nmol/ml per h) compared to controls (5.22 +/- 0.74 micrograms/ml, 121.6 +/- 54.6 nmol/ml per h and 53.6 +/- 29.9 nmol/ml per h, respectively). The specific LCAT activity, i.e., LCAT activity per microgram of LCAT, was similar in the two groups, indicating that the LCAT protein in the AIM carriers is structurally and functionally normal. However, the specific cholesterol esterification rate was 23% lower in the AIM subjects (8.03 +/- 6.01 nmol/h per microgram) compared to controls (10.49 +/- 5.86 nmol/h per microgram; P less than 0.05). The capacity of HDL3, purified from both AIM and control plasma, to act as substrates for cholesterol esterification was similar, thus suggesting that other mechanism(s) may be in play. Carriers with a relative abundance of abnormal, small HDL3b particles had the most altered cholesterol esterification pattern. Upon evaluating all AIM subjects, a complex relationship between HDL structure, plasma lipid-lipoprotein levels and cholesterol esterification emerged, making the AIMilano condition a unique model for the study of the mechanisms regulating the cholesterol esterification-transfer process in man.


Financial conflicts of interest of physicians followed by oncology journals on Twitter.
Physicians have increasingly adopted Twitter as a discussion and distribution platform for oncology research. While the influence of financial conflicts of interests (FCOI) on medical research is well documented, their role in the dissemination of research on social media platforms is not well known. In this study, we sought to evaluate the FCOIs of physicians followed by the top three oncology journals on Twitter. We used the Open Payments Search Tool ( https://openpaymentsdata.cms.gov ) to assess FCOIs between 2016 and 2021 of United States (US) physicians followed by three oncology journals (Journal of Clinical Oncology, The Lancet Oncology, and Annals of Oncology) on Twitter. Of 1914 Twitter accounts followed by the top three oncology journals on Twitter, 547 (28.6%) belonged to US physicians. Of these, 463 (84.6%) received general payments between 2016 and 2021. After excluding 30 US physicians currently in residency or fellowship, this percentage increased to 88.2% (n = 456/517). Combined, the median (interquartile range) general payment amount was $8100 ($200-90,000). Additionally, over $42 million in general payments were made between 2016 and 2021. Our findings offer insight on FCOIs between oncology journals and US physicians on Twitter. These findings may serve as the foundation for future research regarding optimal medical journal conduct on social media platforms.


Synovial sarcoma in children: imaging features and common benign mimics.
Synovial sarcoma is the most common malignant nonrhabdomyosarcoma soft-tissue sarcoma in children. This article shows examples of synovial sarcoma in children and corresponding examples of benign mimics. It is important for radiologists to recognize the often nonaggressive appearance of synovial sarcoma in the pediatric population to guide surgical resection and expedite diagnosis before the development of locoregional spread or metastatic disease.


Population studies of fruit flies (Diptera: Tephritidae) in south-east Queensland.
Weekly fruit fly captures for a 12-month period on Mt Glorious (south-east Queensland) suggested that at higher altitudes very few flies survived the winter and that there was an annual colonisation of the higher altitudes by flies from the lower altitudes. The peak trap captures of Dacus tryoni (Froggatt) and Dacus neohumeralis Hardy corresponded with the fruiting times of their major hosts. The fly populations increased with the onset of higher temperatures and the beginning of the summer rain period and decreased with the decline in temperature and rainfall in autumn. Studies on Dacus cacuminatus (Hering) showed that when environmental conditions are suitable this species efficiently exploits its host resulting in rapid population increases.


Immunoglobulin class switch of anti-ganglioside monoclonal antibody from IgM to IgG.
Ganglioside GM2, which is one of the major gangliosides expressed on cell surface of neuroectodermal-origin human tumors, has been focused on as a target molecule for passive immunotherapy. One of the problems in this area was that monoclonal antibodies (mAbs) raised against GM2 were of IgM class even if donors of B cells were varied in mouse, rat or human. We stimulated two kinds of mice hybridomas having membrane-bound anti-GM2 IgM on their surface with GM2 incorporated in synthetic liposomes in the presence of the mouse thymocytes to accelerate the class switch of immunoglobulins (Igs). After the stimulation, protein A-reactive clones were sorted out using a cell sorter. We finally isolated two class switch variants generating mouse IgG3, designated KM796 and KM750, from original hybridomas producing mouse IgM anti-GM2 mAbs, KM696 and KM697, respectively after over 20-time repetitions of the sorting. ELISA with 11 common gangliosides revealed that one of the variant, KM750, retained the same binding specificity to N-acetyl GM2 as that of the parental IgM, KM697. By ELISA using panel of anti-idiotype (Id) mAbs to anti-GM2 mAbs, KM750 was shown to retain the parental KM697 Id. Another variant KM796 almost lost its activity in purification process in acidic condition and changes in Id were suggested. In immunofluorescence assay, KM750 was confirmed to bind to GM2-expressing tumor cell lines. The class switch hybridoma has been stably cultured with the production of the IgG3-class mAb for more than 22 months.


Immunization with DNA vaccines encoding different mycobacterial antigens elicits a Th1 type immune response in lambs and protects against Mycobacterium avium subspecies paratuberculosis infection.
Paratuberculosis, or Johne's disease, is a disease of domestic and wild ruminants that culminate with a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis. The aim of this work was to evaluate the type of immune response, Th1 or Th2, induced by DNA vaccinations in lambs of Sarda breed. Twenty-five lambs, serum negative for M. paratuberculosis, were selected at birth from equally serum negative mothers. The lambs were inoculated at 5 months of age with three different mycobacterial antigens cloned into a mammalian expression vector as fusion protein with the enhanced green fluorescent protein (pEGFP-N1). The animals were divided in five groups containing each five lambs. Each group was vaccinated as following (A: physiological solution; B: Gudair; C: p-85A-Mav; D: p-85A-BCG; E: p-Hsp65). Immune response was evaluated by measuring the expression of INF-gamma (Th1 type response) and IL-10 (Th2 type response) by real-time PCR. Gene expression was estimated by comparing the results with that of beta-actin. INF-gamma expression level was increased in lambs vaccinated with plasmids codifying mycobacterial antigens, in particular with p-Hsp65, in comparison with the controls suggesting stimulation of a Th1 immune response similar to that supported by natural infection of M. paratuberculosis. Moreover, animals were infected orally with live M. paratuberculosis. Three months after vaccination and again INF-gamma and IL-10 expression was evaluated in order to verify in vivo the protection level of the vaccines. Plasmids p-85A-BCG and p-Hsp65 seem to elicit a stronger protective immune response against M. paratuberculosis by evaluating the expression level of INF-gamma and evaluating the presence of M. paratuberculosis and animal cell organ damage post-mortem.


Multiple transduction as a means of preserving ganciclovir chemosensitivity in sarcoma cells carrying retrovirally transduced herpes thymidine kinase genes.
The potential value of retroviral gene transfer as a means of targeting therapeutic genes to neoplastic cells is threatened by the tendency of occasional cells to lose transduced genes or their expression. To determine whether this threat could be reduced by transducing multiple copies of a therapeutic gene, we compared 8 murine sarcoma sublines carrying from 1 to 6 copies of a retrovirally transduced herpes simplex virus thymidine kinase gene, which sensitizes cells to ganciclovir (GCV). When variability consequent to differences in vector integration site was excluded, increased copy number was associated with an increase in GCV sensitivity and a major reduction in the frequency of GCV-resistant mutants. The results suggest a potential means of preserving the efficacy of future antineoplastic gene therapy strategies.


A patient with cystic duct remnant calculus treated by laparoscopic surgery combined with near-infrared fluorescence cholangiography.
The recurrence of symptoms present before cholecystectomy may be caused by a cystic duct remnant. The resolution of cystic duct remnant syndrome may require surgical resection, but identification of the duct remnant during laparoscopic surgery may be difficult because of adhesions following the previous procedure. Open surgery, which is more invasive than laparoscopic surgery, is frequently chosen to avoid bile duct injury. The patient was a 24-year-old woman with previous laparoscopic cholecystectomy for chronic cholecystitis and repeated attacks of biliary colic. The postoperative course was uneventful, but computed tomography revealed a remnant cystic duct calculus. Ten months after surgery, the patient returned to our department for right hypochondriac pain. Laparoscopic remnant cystic duct resection was performed with intraoperative near-infrared (NIR) fluorescence cholangiography to visualize the common bile duct and remnant cystic duct. The postoperative course was uneventful and the patient was discharged on day 3 after surgery. At the 6-month follow-up, she had no recurrence of pain. Laparoscopic surgery with NIR cholangiography is a safe and effective alternative for the removal of a cystic duct remnant calculus after cholecystectomy.


The neuronal population of the marginal zone (lamina I) of the rat spinal cord. A study based on reconstructions of serially sectioned cells.
Complete series of silver-stained semithin transverse sections were used to reconstruct 177 nerve cells of rat lamina I. According to the three-dimensional shape of the perikarya and the number and orientation of primary dendritic trunks, lamina I cells formed four distinct groups: (1) Fusiform cells with long rostrocaudal axis and having 1-4 primary dendrites oriented rostrocaudally or ventrally, which were the most numerous (50%) and predominated in the lateral third of lamina I. (2) Flattened cells (12%) which were thin discs of angular contour, spread out parallel to the lamina dorsal border; they emitted thick lateral and medial, but no dorsal or ventral, primary dendrites, and were mainly located in the middle third. (3) Multipolar cells (20%) with polyhedric somata emitting 4-12 primary dendritic trunks in several directions, which were practically confined to the medial third of the lamina. (4) Prismatic, wedge-shaped cells (18%), partly situated or encased, in the white matter, emitting one dorsal interstitial dendrite and several transversely oriented dendrites, which were distributed throughout the whole dorsal border of lamina I, though more abundant in its lateral portion. A subpopulation of large cells was identified in all groups, except in the multipolar one. These four cell types may help establish a basic morphologic classification of the neuronal population of lamina I, and may explain the different appearances under which local cells have previously been described in preparations using different planes of section and varied staining methods.


Control of post-stroke movement disorders using chronic motor cortex stimulation.
The effects of motor cortex (MC) stimulation on post-stroke movement disorders were analyzed in 50 patients. These individuals either underwent MC stimulation primarily for the purpose of controlling their post-stroke involuntary movements (n = 8) or underwent MC stimulation for the purpose of controlling their post-stroke central pain (n = 42). In the latter patients, the effects of MC stimulation on co-existent involuntary or voluntary movement disorders were analyzed retrospectively. Good control of involuntary movements was observed in 2 of 3 patients with hemichoreo-athetosis, 2 of 2 patients with distal resting or action tremor, and 1 of 3 patients with proximal postural tremor. Subjective improvements in motor performance were reported by 8 patients who had mild motor weakness, and the effects appeared to be attributable to attenuation of rigidity. We consider that these findings justify further clinical studies on MC stimulation for the control of post-stroke movement disorders.


Dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit Junin virus replication in vitro.
In the present paper the in vitro antiviral activity of dehydroepiandrosterone (DHEA), epiandrosterone (EA) and 16 synthetic derivatives against Junin virus (JUNV) replication in Vero cells was studied. DHEA and EA caused a selective inhibition of the replication of JUNV and other members of the Arenaviridae family such as Pichinde virus and Tacaribe virus. The compounds were not virucidal to cell-free JUNV. The impairment of viral replication was not due to an inhibitory effect of the steroids on virus adsorption or internalization. An inhibitory effect of the compounds on JUNV protein synthesis and both intracellular and extracellular virus production was demonstrated. A partial inhibitory action on cell surface expression of JUNV glycoprotein G1 was also detected on DHEA- and EA-treated cultures. Like DHEA and EA, three compounds obtained from EA by chemical synthesis showed selectivity indexes higher than ribavirin, the only antiviral compound that has shown partial efficacy against arenavirus infections.


The lactoperoxidase-thiocyanate-hydrogen peroxide antibacterium system.
Lactoperoxidase present in various secretions oxidizes thiocyanate (SCN-) in the presence of H2O2 to an unstable oxidation product--hypothiocyanite (OSCN-), which is bactericidal for enteric pathogens including multiple antibiotic resistant strains of E. coli. The system damages the inner membrane causing leakage and cessation of uptake of nutrient, leading eventually to death of the organisms and lysis. The possible involvement of O2- and 1O2 is discussed.


International evaluation of circumferential resection margins after rectal cancer resection: insights from the Swedish and Dutch audits.
This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I-III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011-2015). Separate analyses were performed for cT1-3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1-3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1-3 Dutch population. Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer.


Recombinant factor VIIa partially reverses the inhibitory effect of fondaparinux on thrombin generation after tissue factor activation in platelet rich plasma and whole blood.
Fondaparinux (Arixtra), a specific AT-dependent FXa inhibitor, is effective and safe in the prevention and treatment of venous thromboembolism, but some major hemorrhagic events may occur. No specific antidote to fondaparinux has been proposed. Recombinant FVIIa (Novoseven) could be used as an haemostatic treatment, but this option has not been well documented. We studied the effect of rFVIIa (1 micro g/ml) on the inhibition of thrombin generation induced by fondaparinux (0.1 micro g/ml to 1 micro g/ml). Coagulation was triggered in platelet rich plasma (PRP) or in whole blood by recalcification in the presence of diluted thromboplastin. In PRP thrombin generation was assessed using the thrombinoscope assay. In whole blood, prothrombin activation was assessed by measuring the kinetics of F(1+2) formation using an ELISA assay. Fondaparinux at concentrations equal or greater than 0.5 micro g/ml prolonged the initiation phase of thrombin generation, and reduced the velocity of prothrombin activation. It also decreased by 60% the endogenous thrombin potential. In the presence of fondaparinux (0.5 micro g/ml to 1 micro g/ml) rFVIIa accelerated the initiation phase of thrombin generation, but it did not significantly increase the endogenous thrombin potential. However, rFVIIa did not completely reverse the inhibitory effect of fondaparinux on the parameters of thrombin generation and prothrombin activation. This study shows that rFVIIa accelerates thrombin generation, but does not completely reverse the inhibitory effect of fondaparinux on thrombin generation. The potential clinical use of rFVIIa as haemostatic treatment of major bleedings related to fondaparinux has to be evaluated.


Decline in the prevalence of HIV and sexually transmitted diseases among female sex workers in Cotonou, Benin, 1993-1999.
Within an ongoing HIV/STD prevention project aimed at female sex workers (FSW) in Cotonou, Benin, we evaluated time trends in HIV and STD prevalences from 1993 to 1999. Three serial cross-sectional surveys were conducted in 1993 (n = 374), 1995-1996 (n = 365), and 1998-1999 (n = 591). A questionnaire was administered to the FSW and they were screened for HIV, syphilis, Neisseria gonorrhoeae, and Chlamydia trachomatis. The mean percentage of condom use with clients in the week preceding the interview increased from 62.2% in 1993 to 80.7% in 1998-1999 (P = 0.0001). The prevalence of all infections decreased significantly (all P < 0.02; chi-square for trend) over time: HIV from 53.3% in 1993 to 40.6% in 1998-1999; syphilis from 8.9 to 1.5%; gonorrhoea from 43.2 to 20.5%; and chlamydia from 9.4 to 5.1%. However, the mean age of FSW decreased from 31.0 to 28.4 years between 1993 and 1998-1999. Moreover, the country of origin of these women changed dramatically over time: the proportion of Ghanaian women decreased from 66.3% in 1993 to 21.6% in 1998-1999 when the predominant group became Nigerian (38.0%). When controlling for age and country of origin, HIV prevalence was stable over time (P = 0.71), whereas the downward trend remained significant for syphilis and gonorrhoea (both P < 0.001), and was present but not significant for chlamydia (P = 0.13). These data suggest that the time trends in HIV and STD prevalences are partly due to the changing sex work milieu, but that the intervention also had an impact. Prevention programmes aimed at FSW should be highly prioritized.


Renal magnesium wasting, incomplete tubular acidosis, hypercalciuria and nephrocalcinosis in siblings.
Polyuria, hyposthenuria, hypomagnesemia, hypercalciuria, advanced nephrocalcinosis, low citrate excretion and low glomerular filtration rates were observed in two female siblings who were followed over 10 years. Acid loading revealed incomplete distal tubular acidosis. Hypomagnesemia was due to renal magnesium wasting. It is suggested that the defect in tubular transport of magnesium is an important factor in the pathogenesis of this syndrome.


Gastric sarcomatoid carcinoma.
Sarcomatoid carcinoma is an uncommon biphasic malignant tumor of the stomach. The histogenesis remains unknown, and a definitive diagnosis is obtained with immunohistochemical staining. Since prognosis is poor after surgery, more effective diagnostic tools are needed in order to select the optimal therapeutic approach. We report the case of an old female patient presenting with an endophytic tumor in the gastric fundus who underwent partial resection of the stomach. Histology revealed a poorly differentiated adenocarcinoma component mixed with sarcomatoid component. Immunohistochemically, the carcinoma components exhibited a positive reaction to pan-cytokeratin, whereas fusiform cells showed positive reactions to vimentin.


Selective and fast magnetic dispersive solid phase micro-extraction of copper and lead in water and vegetables after synthesis of magnetic mesoporous carbon.
Magnetic mesoporous carbon (Fe3O4@C, MMC) was synthesized and characterized. It was used for the first time as a sorbent for the magnetic dispersive solid phase microextraction (M-dSPμE) of copper and lead in water and vegetables. FAAS was used to determine the analyte concentrations after elution. The MMC was found to be have surface area of 145.9 m2 g-1 and average pore diameter of 15 nm. The analytical parameters affecting M-dSPμE of copper and lead were optimized. They were pH of sample, 6; eluent, 2 mol L-1 HCl (3 mL); and sample volume, 250 mL. The MMC reaches equilibrium very fast without vortexing for adsorption and only 5 s for elution. The LOD and PF of the M-dSPμE method for copper and lead were found to be 0.87 μg L-1 and 83 for Cu(II) and 2.8 μg L-1 and 167 for Pb(II), respectively. The precision of the M-dSPμE method was found to be ≤ 3.2%. The M-dSPμE method was verified by certificate reference materials (TMDA-53.3 Fortified Lake water and NIST SRM 1573a Tomato Leaves). It was successfully applied to the determination of copper and lead in lake water, wastewaters, sea water, radish, spinach, lettuce, and celery samples.


Membrane-bound delta-4 notch ligand reduces the proliferative activity of primitive human hematopoietic CD34+CD38low cells while maintaining their LTC-IC potential.
To examine the role of the Notch ligand Delta-4 on hematopoietic stem cells, human CD34+CD38low cord blood cells were cocultured on S17 cells transduced with transmembrane Delta-4 (mbD4/S17) or an empty vector (C/S17). By the end of a 3-week culture, mbD4/S17 induced a 25-fold reduction in nucleated cell production, as compared to C/S17, by maintaining a higher proportion of cells in G0/G1 phase. A specific retention of a high proportion of CD34+ cells throughout the culture was observed with mbD4/S17, contrary to C/S17. Although mbD4/S17 promoted expansion of cells with the phenotype of committed lymphoid precursors (CD34+CD7+CD45RA+), these cells still retained their myeloid differentiation potential. mbD4/S17 maintained a higher LTC-IC frequency in output CD34+ cells, compared to C/S17, as in the subsets of cells having completed the same number of divisions on mbD4/S17. A Delta4-Fc protein (extracellular part of human Delta4 fused to Fc human IgG1 portion), immobilized on plastic, also reduced cell production and retained the LTC-IC potential. Transplantation of cells grown on mbD4/S17 into NOD/SCID mice showed no significant enhancement of the long-term repopulating ability. Thus, Delta4 appears to inhibit hematopoietic stem cell proliferation, in association with the maintenance of short-term lymphoid and myeloid repopulation capacity.


Beta-radiation therapy for long lesions in native coronary vessels: a matched comparison between de novo and in-stent restenotic lesions.
The purpose of this study was to evaluate effectiveness and to compare clinical outcome of intracoronary beta-radiation to treat long lesions (>20 mm) in patients with de novo stenosis vs. patients with in-stent restenosis (ISR). A matched comparison of 44 patients with 63 de novo lesions and 48 patients with 63 ISR lesions (>20 mm) treated with intracoronary beta-radiation was performed. Stents were implanted in 65.1% of de novo and 19% of ISR lesions (P=.001). Radiation doses delivered were 17.2+/-3.0 vs. 20.3+/-3.0 Gy at 2 mm from the source center for de novo and ISR lesions. There was no difference in the incidence of in-hospital events. Clinical follow-up at 16.4+/-6.7 months showed no difference in major adverse cardiac events (MACE) between de novo and ISR patients (27.3% vs. 25%, P=.8). Late total occlusions (LTOs) occurred in eight patients (four in each group) treated with stents at the time of radiation and after discontinuation of ticlopidine. By multivariate analysis, stent implantation was the only predictor of late occlusions (OR 8.25, 95% CI 1.73-38.46, P<.008). Restenosis rates were similar for de novo and ISR lesions (29.3% vs. 23.2%, P=.46), as well as target lesion revascularization (TLR) and target vessel revascularization (TVR) rates (22.7% vs. 22.9% and 29.5% vs. 29.2%, respectively). Intracoronary beta-radiation gives comparable results when used to treat de novo or ISR lesions provided new stent implantation can be avoided. Long-term combined antiplatelet therapy is mandatory for patients who receive new stents at the time of radiation treatment.


Pectus bar removal - why, when, where and how.
Despite its less invasive nature, the widespread use of the minimally invasive repair of pectus excavatum (MIRPE) procedure has been associated with a significant number of serious complications. On the other hand, Pectus bar removal (PBR) is often considered a simple procedure and often scheduled in an outpatient setting. However, several studies report near-fatal complications not only during bar placement, but also during bar removal. The aim of our study was to clarify why a pectus bar should be removed, timing for removal, where PBR should be performed, and overall setup for safe removal. A comprehensive review was performed in accordance with PRISMA guidelines, searching for articles published since 1998 in English. "Pectus bar removal AND (near-fatal) complications" were the applied terms. Inclusion criteria were articles reporting on the focus of PBR after MIRPE. Eligible study designs included (retrospective) case study series, case report and reviews. Full-text articles in which the technique in general was described were omitted. Recently published results of an online survey raised awareness about type and number of possible complications during PBR. Furthermore, our comprehensive literature review identified only a few, but serious complications during PBR. PBR has a high safety profile but in rare cases may be associated with major complications such as life-threatening hemorrhage from various thoracic sources. This risk is higher in patients with a history of complex MIPRE. In an effort to decrease these complications we recommend bilateral opening of surgical incisions, unbending the bar and meticulous mobilization of the bar. To manage these complications if they occur, we recommend removal in a hospital setting with adequate resources and personal including cardiac surgeons. If the postoperative course is uneventful discharge on the same day is reasonable.


Cytokine-mediated regulation of antimicrobial proteins.
Antimicrobial proteins constitute a phylogenetically ancient form of innate immunity that provides host defence at skin and mucosal surfaces. Although some components of this system are constitutively expressed, new evidence reviewed in this Progress article shows that the production of certain antimicrobial proteins by epithelial cells can also be regulated by cytokines of the innate and adaptive immune systems. In particular, the effector cytokines interleukin-17 and interleukin-22, which are produced by the T-helper-17-cell subset, are emerging as crucial regulators of antimicrobial-peptide production in the gut and the lungs. This suggests that this T-cell lineage and its cytokines have important roles in skin and mucosal immunity.


Clinical subtypes of depression are associated with specific metabolic parameters and circadian endocrine profiles in women: the power study.
Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences. ClinicalTrials.gov NCT00006180.


Childhood height, adult height, and the risk of prostate cancer.
We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect on the risk of prostate cancer apart from adult height. We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk. When adjusted for adult height, height at age 7 years was no longer significantly associated with the risk of prostate cancer. Height at 13 years was significantly and positively associated with prostate cancer risk even when adult height was adjusted for; per height z-score the hazard ratio was 1.15 [95% confidence interval (CI) 1.01-1.32]. The effect of height at 13 years on the risk of prostate cancer was not entirely mediated through adult height, suggesting that child height and adult height may be associated with prostate cancer through different pathways.


Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer.
Accumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this bacterium in locally advanced rectal cancer (LARC). In this study, we quantified Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients and investigated its association with therapy response and survival. A total of 254 samples from 143 patients with rectal adenocarcinomas were analyzed for the presence and abundance of F. nucleatum using RNA in situ hybridization and digital image analysis. Assay accuracy was determined using infected cell lines and tumor samples with available quantitative PCR data. We studied the impact of F. nucleatum load on pathologic complete response and relapse-free survival. Treatment-induced changes were evaluated in paired pre- and post-nCRT samples (n = 71). Finally, tumor microenvironment changes during nCRT were assessed in paired samples (n = 45) by immune contexture analysis. F. nucleatum tissue levels by RNA in situ hybridization strongly correlated with quantitative PCR (r = 0.804, P < 0.001). F. nucleatum abundance was higher in untreated [median, 7.4; 95% confidence interval (3.7-16.2)] compared with treated [median, 1.6; 95% confidence interval (1.3-2.4)] tumors (P <0.001) with 58% (73/126) and 26% (22/85) positive tumors, respectively (P < 0.001). Baseline F. nucleatum levels were not associated with pathologic complete response. F. nucleatum positivity after nCRT, but not baseline status, significantly increased risk of relapse [hazard ratio = 7.5, 95% confidence interval (3.0-19.0); P < 0.001]. Tumors that turned F. nucleatum-negative after nCRT had a strong increase in CD8+ T cells post-nCRT (P < 0.001), while those that persisted F. nucleatum-positive after nCRT lacked CD8+ T cells induction in post-nCRT samples compared with baseline (P = 0.69). F. nucleatum persistence post-nCRT is associated with high relapse rates in LARC, potentially linked to suppression of immune cytotoxicity.


Wearable activity trackers for nurses' health: A qualitative acceptability study.
To assess the practical, social and ethical acceptability of the use of a POLAR® H7 chest-strap wearable device to influence health behaviours among pre-registered nurses. Qualitative acceptability study including a simulated test of use reported using COREQ guidelines. Pre-registered nurses simulated nine nursing tasks while wearing the chest strap in a clinical simulation facility in a Scottish university in 2016. Focus groups and semi-structured interviews were conducted to assess technology acceptance with participants who did and did not participate in the simulated nursing tasks. Focus groups and interviews were transcribed and analysed thematically guided by a theoretical model of technology acceptance. Pre-registered nurses thought the use of chest-strap devices to monitor their own health in real-time was acceptable. However, participants shared that it was important that the use of technology was inclusive and supportive of nurses' health and cautioned against misuse of data from wearable devices for individual performance management or stigmatisation.


Acoustic cues for the perception of place of articulation in aphasia.
Two experiments assessed the abilities of aphasic patients and nonaphasic controls to perceive place of articulation in stop consonants. Experiment I explored labeling and discrimination of [ba, da, ga] continua varying in formant transitions with or without an appropriate burst onset appended to the transitions. Results showed general difficulty in perceiving place of articulation for the aphasic patients. Regardless of diagnostic category or auditory language comprehension score, discrimination ability was independent of labeling ability, and discrimination functions were similar to normals even in the context of failure to reliably label the stimuli. Further there was less variability in performance for stimuli with bursts than without bursts. Experiment II measured the effects of lengthening the formant transitions on perception of place of articulation in stop consonants and on the perception of auditory analogs to the speech stimuli. Lengthening the transitions failed to improve performance for either the speech or nonspeech stimuli, and in some cases, reduced performance level. No correlation was observed between the patient's ability to perceive the speech and nonspeech stimuli.


Comparison of a screening test and screening checklist for auditory processing disorders.
This study was carried out to determine the relationship between two screening tools to detect auditory processing disorders (APDs). The two screening tools were the screening checklist for auditory processing (SCAP) and screening test for auditory processing (STAP). Four hundred school-going children (218 males, 182 females) studying in grades III-VIII in three schools were randomly selected for the study. These children, aged 8-13 years, were screened using the SCAP and the STAP. The SCAP was administered by teachers while the STAP was administered by an audiologist. The children were categorised as at-risk for APD by comparing their scores with the cut-off criteria recommended for SCAP and STAP. The relationship between the two screening tools was determined. Among the 400 children, 49 (12.3%) children were found to be at-risk for APD on the SCAP and 64 (16%) were found to be at-risk on the STAP. A Chi square test of association was carried out using the data of children who were passed or referred on each of the screening tools (SCAP and STAP). A significant association (χ(2)=2.93, df=1, p<0.001) was found between the two screening tools. This was confirmed using Spearman's rank correlation coefficient, which revealed a significant correlation (r=0.86, p<0.001) between SCAP and STAP. Using the scores of 31 children referred on both the screening tools, a relationship was derived between the SCAP and subsections of the STAP (speech-in-noise, dichotic consonant vowel (CV) combinations, gap detection and auditory memory). Pearson's product moment correlation coefficient indicated the presence of a significant correlation (r=-0.46, p<0.01) between the SCAP and the auditory memory subsection of the STAP. However, no significant correlation was seen for other three subsections. The study indicates an overall high correlation between the SCAP and the STAP. However, both the screening tools examine different aspects of auditory processing and thus, should be administered together to identify more children at-risk for APD.


Low-temperature thermal desorption and secure landfill for oil-based drill cuttings management: Pollution control, human health risk, and probabilistic cost assessment.
Oil-based drill cuttings (OBDCs) were managed in two scenarios including low-temperature thermal desorption (LTTD) and secure landfill through a case study. The removal of polycyclic aromatic hydrocarbons (PAHs) and heavy metals in OBDCs by LTTD under different conditions was investigated. Probabilistic human health risk assessment was performed to quantify the health risk posed to waste management workers under the two scenarios, while the associated costs were also analyzed. The results show that LTTD at 300 °C for >20 min could remove 96.27% of PAHs in OBDCs but its removal effect on heavy metals was not significant. It was found that cancer risks posed by PAHs in both securely landfilled and LTTD-treated OBDCs were not significant (<1e-06); however, significant cancer risks (7.95e-05-9.45e-05) were identified for exposure to toxic heavy metals. Increased health risk was observed as a result of exposure to LTTD treatment residues compared to securely landfilled OBDCs. Inhalation of chromium(VI) and oral ingestion of arsenic in OBDCs were critical exposure routes. Both cancer and non-cancer risks in the secure landfill scenario were negligible. The cost analysis results suggest that LTTD combined with stabilization/solidification could be more economically attractive than secure landfill for the handling of OBDCs.


Multiplanar computed tomography: a multidimensional tool for evaluation and treatment of acetabular fractures.
Fractures of the acetabulum present a formidable diagnostic and therapeutic challenge. Improved management has decreased the mortality associated with these injuries. Prolonged survival of the severely injured has raised the associated morbidity. To improve diagnosis and treatment in these patients, computed tomography with multiplanar reconstructions has been utilized in the pre- and post-operative period in 30 patients. This refinement provides a precise, accurate, and reproducible method of establishing the diagnostic data base. Consequently it is possible to better define the pathoanatomy, make decisions as to the best technique for intervention, and facilitate execution of these techniques by improved preoperative planning and postintervention assessment. It is concluded that computed tomography with multiplanar reconstructions optimizes the ability to manage these injuries.


Placental growth factor measurements in the assessment of women with suspected Preeclampsia: A stratified analysis of the PARROT trial.
Placental growth factor testing decreases time to recognition of preeclampsia and may reduce severe maternal adverse outcomes. This analysis aims to describe the clinical phenotype of women by PlGF concentration, and to determine the mechanism(s) underpinning the reduction in severe maternal adverse outcomes in the PARROT trial, in order to inform how PlGF testing may be optimally used within clinical management algorithms. This was a planned secondary analysis from the PARROT trial that compared revealed PlGF testing and management guidance with usual care in the assessment of women with suspected preterm preeclampsia. Maternal and perinatal outcomes following stratification of women by trial group, and measured PlGF concentration. 1006 women were included. PlGF < 100 pg/ml identified women with more marked hypertension, increased adverse maternal outcomes and preterm delivery rates, and higher rates of small for gestational age infants. There was a reduction in adverse maternal outcomes in women whose results were revealed when PlGF levels were 12-100 pg/ml compared to usual care (3.8% vs 6.9%; aOR 0.15(95% CI 0.03-0.92). There was no significant difference in gestation at delivery between concealed or revealed groups in any PlGF categories. Low PlGF concentrations are associated with severe preeclampsia. The reduction in severe adverse maternal outcomes may be mediated through quicker diagnosis and intensive surveillance, as recommended by the management algorithm for those at increased risk. PlGF is particularly beneficial in those who test 12-100 pg/ml, as these may be women with silent multi-organ disease who otherwise may go undetected.


Plant growth promotion and enhanced uptake of Cd by combinatorial application of Bacillus pumilus and EDTA on Zea mays L.
In developing countries, Cd contamination is ubiquitous which limits agriculture productivity. The current study was designed to investigate the efficacy of plant-Bacillus pumilus-ethylene diamine tetraacetic acid (EDTA) and plant-microbe-chelator (PMC) synergy for enhanced plant growth and Cd-uptake potential of Zea mays in industrially contaminated and cadmium (Cd) spiked soil. A pot experiment was conducted by growing Z. mays seedlings either inoculated with B. pumilus or un-inoculated along with the application of 5 mM EDTA. Plants were exposed to two levels of Cd contamination for 45 days. An increase in Cd uptake was observed in Z. mays inoculated with B. pumilus followed by EDTA treatment as compared to non-inoculated and un-treated ones. Zea mays showed improved values with PMC approach for different growth parameters including root length (41%), shoot length (40%), fresh weight (59%), dry weight (49%), chlorophyll contents (49%), and relative water contents (30%). Higher tolerance index (117%) was observed for plants grown in soil spiked with 300 mg kg-1 Cd (S2). PMC application markedly enhanced Cd uptake potential of Z. mays up to 12% and 68.8%, respectively, in S1 and S2 soil. While the PMC application increased Cd accumulation capacity of Z. mays by 71.2% and 52.5% in S1 and S2 soil. The calculated bioaccumulation and translocation factor revealed that Z. mays possess Cd uptake potential, and this ability can be significantly enhanced with PMC application.


Fumonisins B1 and B2 in the corn-milling process and corn-based products, and evaluation of estimated daily intake.
The distribution of fumonisins (FBs: FB1 and FB2) in the corn-milling process and in corn-based products, as well as daily intake estimates for the Brazilian population were evaluated. Among corn fractions samples, corn meal had the highest mean concentration of FB1 (1305 µg kg(-1)) and FB2 (651 µg kg(-1)) and a distribution factors of 452% and 256% in relation to corn grain, respectively. On the other hand, the distribution factor of FB1 and FB2 in corn flour was found to be 144% and 88% respectively, which demonstrates that fumonisins in this fraction were reduced compared with corn grain. As a result, almost half the corn meal samples (47%) would be non-compliant with future Brazilian regulation (2017) for fumonisins. However, corn-based products, such as corn flakes and popcorn, were in compliance with the regulation. The average probable daily intake and maximum probable daily intake of fumonisins estimated for the Santa Catarina state (Brazil) population were below the provisional maximum tolerable daily intake of 2 µg kg(-1) body weight day(-1) for all corn samples. Despite this, the adoption of practices to control the occurrence of fumonisins should be applied to the corn-milling fractions that may contain a higher concentration of this toxin, such as corn meal, often used for animal feed in Brazil.


Pressurized Intraperitoneal Aerosol Chemotherapy Enhanced by Electrostatic Precipitation (ePIPAC) for Patients with Peritoneal Metastases.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new mode of intraperitoneal chemotherapy administration that can potentially be improved by the addition of electrostatic precipitation (ePIPAC). This study aimed to describe the procedural details of ePIPAC and to analyze its safety for patients with nonresectable peritoneal metastasis as well as their tolerance and response to this treatment. This retrospective cohort study included consecutive patients treated with ePIPAC in three centers from April 2019 to April 2020. The toxicities of each patient were assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Complications were documented according to the Clavien classification. Quality of life (QoL) was assessed using EORTC-QLQ-C30, and the peritoneal regression grading score (PRGS) was used to grade histologic responses. Further surrogates for responses were the Peritoneal Cancer Index (PCI), ascites, and symptoms. Overall, 69 patients received 147 ePIPACs with oxaliplatin (n = 34) or cisplatin/doxorubicin (n = 35) mainly for colorectal (n = 25), ovarian (n = 14), and gastric (n = 13) primary cancers. Systemic chemotherapy was used in the treatment of 54 patients (76%). The median electrostatic therapy time was 12 min (range 6-30 min). The overall and major CTCAE toxicity rates were respectively 24.6% and 15.9%. The postoperative complications rate according to Clavien classification was 4.7%. The responses of 22 patients who had three or more ePIPAC treatments were evaluated as follows: PCI (16 vs 14; p = 0.4), ascites (320 vs 98 ml; p = 0.1), and PRGS (2.23 vs 1.73; p = 0.15). The complete (PRGS1) and major (PRGS2) histologic responses at the third ePIPAC were respectively 38.5% and 53.8%. Overall QoL was stable during the first ePIPACs. Repetitive ePIPACs were safe and well tolerated for patients with unresectable peritoneal metastasis.


Unsuccessful postoperative extraction of retained common duct stones: an analysis.
An analysis of unsuccessful extractions of retained biliary calculi using basket catheters reveals more than half the failures are related to the selection, placement, and size of the T tube. A new T tube has been developed which will improve postoperative access to the common duct and facilitate removal of retained calculi.


Self-recruited feedback: a cost-effective procedure for maintaining behavior.
The maintenance of learned behavior is a problem faced frequently by teachers of persons with severe disabilities. The present study examines the use of a self-management procedure to improve and maintain work performance of young adults with severe disabilities in integrated job settings. Students were taught to self-monitor work rate on job tasks, evaluate daily performance against a criterion, and recruit contingent feedback from supervisors. A multiple baseline design across subjects, and two within series reversals, indicate a functional relationship between self-recruited feedback and maintenance of improved work rate. Self-monitoring of work rate alone was not a consistently effective maintenance strategy. Results are discussed in terms of the need for a comprehensive technology of maintenance that requires a low response cost to apply over long periods of time.


Non-invasive electrochemistry-driven metals tracing in human biofluids.
Wearable analytical devices represent the future for fast, de-centralized, and human-centered health monitoring. Electrochemistry-based platforms have been highlighted as the role model for future developments amid diverse strategies and transduction technologies. Among the various relevant analytes to be real-time and non-invasively monitored in bodily fluids, we review the latest wearable achievements towards determining essential and toxic metals. On-skin measurements represent an excellent possibility for humankind: real-time monitoring, digital/fast communication with specialists, quick interventions, removing barriers in developing countries. In this review, we discuss the achievements over the last 5 years in non-invasive electrochemical platforms, providing a comprehensive table for quick visualizing the diverse sensing/technological advances. In the final section, challenges and future perspectives about wearables are deeply discussed.


Pentazocine increases bispectral index without surgical stimulation during nitrous oxide-sevoflurane anesthesia.
Although there have been a large number of reports on the effects of opioids on the bispectral index (BIS) during anesthesia, the effects of pentazocine on the BIS have not been reported. In this study, 60 patients scheduled for elective oral surgery [30 females, 30 males; all American Society of Anesthesiologists Physical Status (ASA PS) category 1] were enrolled in the trials. Maintaining gender parity, we randomly assigned the patients to one of three groups: pentazocine group (0.3 mg/kg; n = 20), fentanyl group (1 μg/kg; n = 20), or saline group (n = 20); these opioids were administered intravenously 15 min after the intubation. Anesthesia was induced with thiopental and vecuronium bromide and maintained with nitrous oxide (4 l/min)-oxygen (2 l/min)-sevoflurane (1%). At 15 min after the intubation, mean arterial blood pressure (MAP), heart rate (HR), and BIS index were recorded as baseline values. MAP, HR, and BIS values were measured at 2.5-min after the intubation up to 30 min. All data were expressed as the mean ± standard deviation. Differences in BIS values, MAP, and HR among the three groups throughout the experiment were analyzed using two-way repeated-measures analysis of variance (ANOVA), and demographic data among the three groups were analyzed using one-way ANOVA. Post hoc comparisons were performed using Fisher's protected least significant difference test. A P value of <0.05 was considered to indicate statistically significance. MAP and HR showed no significant differences among the three groups during the study. BIS values significantly increased between 5 and 15 min after the intubation relative to the baseline value in the pentazocine group (P < 0.001), and BIS values in this group were significantly during this time period than those in the fentanyl and saline group (P < 0.001). BIS values were not significantly different between the fentanyl group and saline group. These results indicated that pentazocine, but not fentanyl, under nitrous oxide-sevoflurane anesthesia caused a statistically significant increase in BIS in our patients.


A rare case of pulmonary hypertension. As a result of arteriovenous fistula after cardiac surgery.
A 19 year-old woman who underwent corrective surgery for an atrial septal defect (ASD) and ventricular septal defect (VSD) 12 years previously presented with pulmonary hypertension. Cardiac catheterization showed a fistula between the right subclavian artery and vena jugularis interna. In this case, a rare example of secondary pulmonary hypertension due to acquired arteriovenous fistula after cardiac surgery is presented.


Molecular characterization of genes coding for wild-type and sulfonylurea-resistant acetolactate synthase in the cyanobacterium Synechococcus PCC7942.
We present here the isolation and molecular characterization of acetolactate synthase (ALS) genes from the cyanobacterium Synechococcus PCC7942 which specify a sulfonylurea-sensitive enzyme and from the sulfonylurea-resistant mutant SM 3/20, which specify resistance to sulfonylurea herbicides. The ALS gene was cloned and mapped by complementation of an Escherichia coli ilv auxotroph that requires branched-chain amino acids for growth and lacks ALS activity. The cyanobacterial gene is efficiently expressed in this heterologous host. The ALS gene codes for 612 amino acids and shows high sequence homology (46%) at the amino acid level with ALS III of E. coli and with the tobacco ALS. The resistant phenotype is a consequence of proline to serine substitution in residue 115 of the deduced amino acid sequence. Functional expression of the mutant gene in wild-type Synechococcus and in E. coli confirmed that this amino-acid substitution is responsible for the resistance. Yet the deduced amino-acid sequence as compared with other ALS proteins supports the notion that the amino-acid context of the substitution is important for the resistance.


Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores.
In metazoans, a ≈1 megadalton (MDa) multiprotein complex comprising the dynein-dynactin adaptor Spindly and the ROD-Zwilch-ZW10 (RZZ) complex is the building block of a fibrous biopolymer, the kinetochore fibrous corona. The corona assembles on mitotic kinetochores to promote microtubule capture and spindle assembly checkpoint (SAC) signaling. We report here a high-resolution cryo-EM structure that captures the essential features of the RZZ complex, including a farnesyl-binding site required for Spindly binding. Using a highly predictive in vitro assay, we demonstrate that the SAC kinase MPS1 is necessary and sufficient for corona assembly at supercritical concentrations of the RZZ-Spindly (RZZS) complex, and describe the molecular mechanism of phosphorylation-dependent filament nucleation. We identify several structural requirements for RZZS polymerization in rings and sheets. Finally, we identify determinants of kinetochore localization and corona assembly of Spindly. Our results describe a framework for the long-sought-for molecular basis of corona assembly on metazoan kinetochores.


Hereditary spastic paraplegia: Novel mutations and expansion of the phenotype variability in SPG56.
We describe a novel sporadic case of SPG56, a rare complicated form of HSP, that expands the clinical and molecular spectrum of the disease, being associated to novel mutations in CYP2U1 and showing as novel feature dorsal hydromyelia at spinal cord MRI. The patient presented an early-onset, slowly progressive paraparesis associated with mild mental retardation. Neurological assessments included the Spastic Paraplegia Rating Scale (SPRS), Mental Deterioration Battery (MDB), and Wechsler Adult Intelligence Scale (WAIS), neurophysiological and neuroimaging studies. Targeted next-generation sequencing panels for the whole set of genes associated with HSP were performed in the probands and her relatives. Neuroimaging studies showed dorsal hydromyelia but no brain MRI abnormalities. Targeted next-generation identified two novel mutations: the c.5C > A/p.S2* on the maternal allele in compound heterozygosity with the paternally-inherited c.1288+5G > C in CYP2U1. Both mutations predict early protein truncation and a loss of function. So far, only few SPG56 cases have been reported. This case, expands and further characterize the clinical and molecular spectrum of SPG56. In this regard, in consideration of the putative gene function in neurodevelopment, we suggest a causal association between CYP2U1 mutations and hydromyelia in our patient.


Kinetic properties of four plasmid-mediated AmpC beta-lactamases.
The heterologous production in Escherichia coli, the purification, and the kinetic characterization of four plasmid-encoded class C beta-lactamases (ACT-1, MIR-1, CMY-2, and CMY-1) were performed. Except for their instability, these enzymes are very similar to the known chromosomally encoded AmpC beta-lactamases. Their kinetic parameters did not show major differences from those obtained for the corresponding chromosomal enzymes. However, the K(m) values of CMY-2 for cefuroxime, cefotaxime, and oxacillin were significantly decreased compared to those of the chromosomal AmpC enzymes. Finally, the susceptibility patterns of different E. coli hosts producing a plasmid- or a chromosome-encoded class C enzyme toward beta-lactam antibiotics are mainly due to the overproduction of the beta-lactamase in the periplasmic space of the bacteria rather than to a specific catalytic profile of the plasmid-encoded beta-lactamases.


Island effect in the shell phenotypic plasticity of an intertidal gastropod.
The pattern of shell shape variation in populations of the top shell, Phorcus sauciatus from Madeira Island (NE Atlantic) was analysed as a function of substrate type and wave exposure, using geometric morphometrics. We hypothesized that P. sauciatus shows morphological variations to inhabit contrasting environments. Highly significant differences in shell shape were found depending on both substrate type and coastal exposure. The most marked differences were found between exposed and sheltered environments. Rounded shells in exposed environments may be explained by physiological reasons, since larger muscles are needed to ensure attachment to substrate in areas subject to harsh conditions. On the other side, conically-shaped shells may accommodate a larger body but with a smaller foot, an adaptation to sheltered environments. Slight shape variations were also observed among substrates, mostly in the degree of differentiation of some whorls. Differences could be related to a particular use of habitat and/or to the degree of exposure to water current. These results suggest that P. sauciatus is locally adapted to varying coastal hydrodynamics and may be considered as a good model in studies on adaptations of fauna to certain climate change effects.


Assessing risks of algal blooms in water transfer based on algal growth potential.
Water transfer is an effective way to solve the unequal distribution of water resources to meet the needs of urban residents and industry. Annual wet weight data indicated that there may be algal blooms during water transfer. We explored the ecological risk of water transfer from Xiashan to the Jihongtan reservoir through algae growth potential (AGP) tests. The results showed that the Jihongtan reservoir had certain self-regulation abilities. When the total dissolved phosphorus (TDP) concentration was not more than 0.04 mg/L, the risk of algal bloom was low. When the N/P ratio (by mass) was less than 40, the ecological imbalance of algal growth may be caused. When the N/P ratio was 20, it was the best environment for algal growth. Under the current nutrient condition of the Jihongtan reservoir, the volume of ecological safety threshold in water transfer was 60% of the Jihongtan reservoir's capacity. If the nutrient level was further increased, the water transfer threshold would rise to 75%. In addition, water transfer may cause the homogenization of water quality and accelerate the eutrophication process of reservoirs. Regarding risk assessment, we believe that controlling nitrogen and phosphorus are more consistent with the natural evolution of reservoirs than controlling phosphorus alone for solving the problem of eutrophication.


Understanding the Role of Magnetic and Magneto-Quasistatic Fields in Human Body Communication.
With the advent of wearables, Human Body Communication (HBC) has emerged as a physically secure and power-efficient alternative to the otherwise ubiquitous Wireless Body Area Network (WBAN). Whereas the most investigated HBC modalities have been Electric and Electro-quasistatic (EQS) Capacitive and Galvanic, recently Magnetic HBC (M-HBC) has been proposed as a viable alternative. Previous works have investigated M-HBC through application points-of-view, without exploring its fundamental working principle. In this paper, a ground up analysis is performed to study the possible effects and contributions of the human body channel in M-HBC over 1kHz to 10 GHz, by electromagnetic simulations and supporting experiments. The results show that while M-HBC can be successfully operated as a body area network, the human body itself plays a minimal or negligible role in its functionality. For Magneto-quasistatic (MQS) HBC (frequencies less than ∼30 MHz), the body is transparent to the quasistatic magnetic field. Conversely for higher frequencies, the conductivity of human tissues attenuates Magnetic HBC fields due to induced Eddy currents, preventing the body to support efficient waveguide modes. With this conceptual understanding developed, different modes of operations of MQS HBC are outlined for both high impedance capacitive and 50Ω termination cases, and their performances are compared with EQS HBC for similar sized devices, over varying distances between TX and RX. The resulting report presents a fundamental understanding towards M-HBC operation and its contrast with EQS HBC, aiding HBC device designers to make educated design decisions, depending on application scenarios.


Effects of chlorhexidine mouthrinse on oral health in patients with acute leukemia.
The effects of chlorhexidine mouthrinses, used as a supplement to mechanical oral hygiene measures, were studied in patients receiving treatment for acute leukemia. Twenty-eight patients were randomly divided into two groups. During two periods, when the patients were taking medication for the leukemia, one group rinsed with a 0.2% chlorhexidine solution twice daily and the other group did not. Chlorhexidine had no effects of any clinical significance on parameters such as number of days with fever, number of oral lesions, plaque score, gingival bleeding score, or occurrence of candidiasis. There was, however, an increased number of patients who had a burning sensation in the mouth, and a tendency toward increased numbers of salivary enterococci, enterobacteria, and/or Pseudomonas in patients who rinsed with chlorhexidine. The results of the present study do not support the use of chlorhexidine mouthrinses in patients who are able to maintain good oral hygiene by mechanical means during their illness.