Selective late steroid withdrawal after renal transplantation.
Steroid withdrawal (SW) after paediatric renal transplantation (RTPL) is controversial. Selective late SW has been performed in our unit since 1995. The safety and effects of SW were analysed retrospectively in 47 patients undergoing RTPL between 1995 and 2004. Initial immunosuppression consisted of cyclosporine A, azathioprine or mycophenolate mofetil and steroids. Criteria for SW were: (1) stable renal function, (2) time interval after RTPL > or = 1 year, (3) no rejection or time interval after last rejection > or = 1 year and (4) good compliance. SW was performed in 30 patients at an age of 13.5 years (range 4.5-18.5) and 2.2 years (range 1-6.6) after RTPL. After SW, one patient experienced a steroid-sensitive rejection. Follow-up after SW (1.3 year; range 0.25-7.5) showed maintained renal function: glomerular filtration rate at SW and currently was 82 (65-128) and 82 (42-115) ml/min per 1.73 m(2), respectively. The number of patients on antihypertensive treatment did not significantly change (at SW: n = 15; currently: n = 11). Height and body mass index (BMI) remained stable: Median standard deviation score (SDS) for height/BMI at SW and currently was -1.1/0.2 and -0.8/0.1, respectively. Selective late SW was safe regarding renal function and had no significant effect on blood pressure and growth.


Can phase response curves of various treatments of circadian rhythms be explained by effects on protein synthesis and degradation?
The phase response curves of circadian rhythms toward pulses of various chemical and physical perturbations are standardized and compared in Gonyaulax, Phaseolus, Kalanchoe, Trifolium, and Aplysia. The time of maximal phase shift, in many of these curves clustered around a given time of day, especially in Gonyaulax and Aplysia. This could be interpreted as being due to a converging effect of these modalities on a single function that is decisive for the mechanism of the circadian clock. Since many of the treatments that results in significant phase response curves (e.g., light pulses, hormones, temperature pulses, changes of ion concentration, etc) have also been shown in independent studies to be capable of affecting protein synthesis, it is possible that these treatments may all affect circadian rhythmicity by virtue of their direct or indirect effect on protein synthesis. There is also a number of treatments which give phase response curves that are not clustered, especially in Phaseolus. This means either that our original assumption is incorrect or that these treatments impinge on sensitive compounds of the clock other than protein synthesis. It is emphasized, however, that the phasing of the phase response curve on one hand is subject to variability of the boundary conditions of the different laboratories and on the other hand seems to depend on the strength, direction, and modality of the perturbing pulse.


Unlocking cardiomyocyte renewal potential for myocardial regeneration therapy.
Cardiovascular disease remains the leading cause of mortality worldwide. Cardiomyocytes are irreversibly lost due to cardiac ischemia secondary to disease. This leads to increased cardiac fibrosis, poor contractility, cardiac hypertrophy, and subsequent life-threatening heart failure. Adult mammalian hearts exhibit notoriously low regenerative potential, further compounding the calamities described above. Neonatal mammalian hearts, on the other hand, display robust regenerative capacities. Lower vertebrates such as zebrafish and salamanders retain the ability to replenish lost cardiomyocytes throughout life. It is critical to understand the varying mechanisms that are responsible for these differences in cardiac regeneration across phylogeny and ontogeny. Adult mammalian cardiomyocyte cell cycle arrest and polyploidization have been proposed as major barriers to heart regeneration. Here we review current models about why adult mammalian cardiac regenerative potential is lost including changes in environmental oxygen levels, acquisition of endothermy, complex immune system development, and possible cancer risk tradeoffs. We also discuss recent progress and highlight conflicting reports pertaining to extrinsic and intrinsic signaling pathways that control cardiomyocyte proliferation and polyploidization in growth and regeneration. Uncovering the physiological brakes of cardiac regeneration could illuminate novel molecular targets and offer promising therapeutic strategies to treat heart failure.


Low loss and high performance interconnection between standard single-mode fiber and antiresonant hollow-core fiber.
We demonstrate halving the record-low loss of interconnection between a nested antiresonant nodeless type hollow-core fiber (NANF) and standard single-mode fiber (SMF). The achieved interconnection loss of 0.15 dB is only 0.07 dB above the theoretically-expected minimum loss. We also optimized the interconnection in terms of unwanted cross-coupling into the higher-order modes of the NANF. We achieved cross-coupling as low as -35 dB into the LP[Formula: see text] mode (the lowest-loss higher-order mode and thus the most important to eliminate). With the help of simulations, we show that the measured LP[Formula: see text] mode coupling is most likely limited by the slightly imperfect symmetry of the manufactured NANF. The coupling cross-talk into the highly-lossy LP[Formula: see text] mode ([Formula: see text] dB/km in our fiber) was measured to be below -22 dB. Furthermore, we show experimentally that the anti-reflective coating applied to the interconnect interface reduces the insertion loss by 0.15 dB while simultaneously reducing the back-reflection below -40 dB over a 60 nm bandwidth. Finally, we also demonstrated an alternative mode-field adapter to adapt the mode-field size between SMF and NANF, based on thermally-expanded core fibers. This approach enabled us to achieve an interconnection loss of 0.21 dB and cross-coupling of -35 dB into the LP[Formula: see text] mode.


Quantitative reactions for the chain elongation of aliphatic compounds.
Procedures are described for the reaction of methanesulfonates with potassium cyanide and for the conversion of the resulting nitriles to methyl esters. Both reactions in this method of chain elongation are quantitative and do not lead to alterations of olefinic double bonds.


The Phospha-Michael addition product {(t-BuNH)P(μ-N-t-Bu)(2)P(=N-t-Bu)-C(=CH(2))CH(p-CH(3)O-C(6)H(4))-P(O)[(OCH(2)C(CH(3))(2)CH(2)O)]}.
The title compound, 2-{2-[1,3-di-tert-butyl-4-(tert-butyl-amino)-2-(tert-butyl-imino)-1,3,2λ(5),4-diaza-diphosphetidin-2-yl]-1-(4-meth-oxy-phen-yl)prop-2-en-1-yl}-5,5-dimethyl-1,3,2λ(5)-dioxaphosphinan-2-one, C(31)H(57)N(4)O(4)P(3), was synthesized from the Phospha-Michael addition reaction of cyclo-diphos-pha-zane [(t-BuNH)P(μ-Nt-Bu)](2) and allenyl-phospho-nate [(OCH(2)C(CH(3))(2)CH(2)O)P(O)C(p-CH(3)O-C(6)H(4))=C=CH(2)]. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules. The structure exhibits pseudosymmetry but attempts to solve it in a higher (monoclinic) space group were unsuccessful.


GREM1 overexpression inhibits proliferation, migration and angiogenesis of osteosarcoma.
Osteosarcoma is the most common malignancy of bone that occurs in young adults and children, with a five-year survival rate of 60-70%. Metastasis of osteosarcoma maintains an even poorer prognosis. GREM1 plays an important role in regulating organogenesis, body patterning, and tissue differentiation. However, there are limited studies on GREM1 in osteosarcomas. This study was carried out to characterize the expression and function of GREM1 in osteosarcoma cells, thus extending our understanding of osteosarcoma metastasis. GREM1 expression was detected in hBMSC, hFOB1.19, Saos-2, MG63 and U2OS cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Gain- and loss-of-function approaches were used to assess the biological function of GREM1 in U2OS cells. The effects of GREM1 on U2OS cell proliferation were examined using the CCK-8 and colony formation assay. Migration and invasion ability were confirmed by the wound healing and Transwell assay, respectively. Flow cytometry was used to analyse the effect of GREM1 on the cell cycle and apoptosis. The expression of GREM1 targets was evaluated by qRT-PCR and western blotting. The expression of GREM1 was significantly downregulated in osteosarcoma. GREM1 overexpression inhibited the proliferation, migration and invasion of U2OS cells. GREM1 overexpression suppressed tumour cell-induced endothelial cell migration and invasion ability. The effect of GREM1 may be transduced through regulation of the BMP target transcription factor inhibitor of MMP-2 and -9 as well as Id1. GREM1 overexpression and knockdown regulates the tumorigenesis of osteosarcoma in vivo. In conclusion, GREM1 is downregulated in osteosarcoma cells, and overexpression of GREM1 inhibits the proliferation, migration, invasion and angiogenesis abilities of osteosarcoma cells in vitro and in vivo.


Rapid liquid chromatography-mass spectrometry quantitation of glucose-regulating hormones from human islets of Langerhans.
Glucose homeostasis is maintained through the secretion of peptide hormones, such as insulin, somatostatin, and glucagon, from islets of Langerhans, clusters of endocrine cells found in the pancreas. This report describes an LC-MS method using multiple reaction monitoring for quantitation of insulin, C-peptide, glucagon, and somatostatin secretion from human islet populations. For rapid analysis, a 5 min separation was achieved using a 2.1 × 30 mm (i.d. x length) C18 column with 2.7 µm diameter core shell particles. A sacrificial protein hydrolysate was used with the sample and found to improve signal magnitude, repeatability, and to reduce carryover between runs. At optimized gradient conditions, the gradient run time was 4.55 min producing an average peak width of 0.3 min, a minimum resolution of 1.2, and a peak capacity of 20. As a proof of concept, the method was used to measure secretions from static incubations of human islets from 2 donors. Insulin and C-peptide were quantified and matched well with literature values of these hormones. We expect that this antibody-free quantitation of multiple hormones secreted from islets will provide insights into the temporal relationships of these peptides in the future.


A review of the interfacial stability mechanism of aging oily sludge: Heavy components, inorganic particles, and their synergism.
Oily sludge is widely produced in the processes of petroleum exploitation, storage, transportation, and refining, and becomes more stable during aging. The interfacial stability of aging oily sludge hinders the recovery and disposal of oil resources. This review summarizes the interfacial film stability of aging oily sludge, which occurs through the formation of viscoelastic and rigid bilayer interfacial films between heavy components (asphaltenes and resins) and inorganic particles. The bilayer interfacial films enhance interfacial film strength and hinder the aggregation of droplets, contributing to the formation of a stable and high-viscosity oil-water-solid three-phase mixture. Recent demulsification technologies for reducing the stability of interfacial films have been classified as follows: removing heavy components, changing asphaltene aggregate structure, and reducing inorganic particle content. More efficient demulsification technologies are expected to be developed by deeply analyzing the microstructure and interfacial properties of asphaltenes and resins, as well as comprehensively studying the complex interactions among various components. This review constructs a bridge between the stability mechanism and the corresponding destabilization methods, which would promote future studies in aging oily sludge treatment.


Data-driven subtyping of Parkinson's disease: comparison of current methodologies and application to the Bochum PNS cohort.
Considerable efforts have been made to better describe and identify Parkinson's disease (PD) subtypes. Cluster analyses have been proposed as an unbiased development approach for PD subtypes that could facilitate their identification, tracking of progression, and evaluation of therapeutic responses. A data-driven clustering analysis was applied to a PD cohort of 114 subjects enrolled at St. Josef-Hospital of the Ruhr University in Bochum (Germany). A wide spectrum of motor and non-motor scores including polyneuropathy-related measures was included into the analysis. K-means and hierarchical agglomerative clustering were performed to identify PD subtypes. Silhouette and Calinski-Harabasz Score Elbow were then employed as supporting evaluation metrics for determining the optimal number of clusters. Principal Component Analysis (PCA), analysis of variance (ANOVA), and analysis of covariance (ANCOVA) were conducted to determine the relevance of each score for the clusters' definition. Three PD cluster subtypes were identified: early onset mild type, intermediate type, and late-onset severe type. The between-cluster analysis consistently showed highly significant differences (P < 0.01), except for one of the scores measuring polyneuropathy (Neuropathy Disability Score; P = 0.609) and Levodopa dosage (P = 0.226). Parkinson's Disease Questionnaire (PDQ-39), Non-motor Symptom Questionnaire (NMSQuest), and the MDS-UPDRS Part II were found to be crucial factors for PD subtype differentiation. The present analysis identifies a specific set of criteria for PD subtyping based on an extensive panel of clinical and paraclinical scores. This analysis provides a foundation for further development of PD subtyping, including k-means and hierarchical agglomerative clustering.Trial registration: DRKS00020752, February 7, 2020, retrospectively registered.


Real-Time Distal, Multifocal, Repeated Lenticulostriate Bleeding Points during Thrombectomy in a Patient with Acute Variable M1 Occlusion: A Case Report and a Literature Review.
Intracerebral hemorrhage can be classified as either primary or secondary to various conditions such as vascular anomalies or stroke. We present a case of real-time incident detected on digital subtraction angiography (DSA) during thrombectomy in a patient with acute variable M1 occlusion. A comprehensive literature search of the PubMed and Scopus databases was conducted: this is the first real-time visualization using DSA of a basal ganglia hematoma formation secondary to distal multifocal bleeding points just before a thrombectomy in a patient with acute variable M1 occlusion. We suggest that the positions of the clot before and during the procedure be compared always.


Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and Ga-67 scintigraphy in evaluation of lymphoma.
The accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET; dual-head camera with attenuation correction) and Ga-67 scintigraphy was compared to identify disease sites in patients with Hodgkin disease (HD) and intermediate and high-grade non-Hodgkin lymphoma (NHL) at initial diagnosis or clinical recurrence. Fifty-one contemporaneous FDG-PET and Ga-67 scintigraphies were performed on patients with NHL (35 intermediate grade, 3 high grade) or HD (13 patients). Sites of disease were correlated on a site-by-site basis on FDG-PET and Ga-67 images. Tumor-to-background (T/B) ratios were obtained for both techniques. Discordant FDG-PET and Ga-67 findings were correlated with computed tomography findings or clinical evaluation including repeat FDG-PET scans obtained after therapy. Fluorodeoxyglucose positron emission tomography was positive at all 158 sites in 51 patients compared with 113 sites in 41 positive studies with Ga-67 scintigraphy (single positron emission computed tomography [SPECT] and/or planar images). In 44 patients who had complete Ga-67 SPECT data on all tumor sites, FDG-PET was positive at 126 sites and Ga-67 SPECT was positive at 81 sites. Ga-67 SPECT failed to demonstrate disease at 45 sites (35.7%). In 10 of 44 patients, Ga-67 SPECT completely failed to detect any disease at 22 of 45 sites (17.5%) and partially identified disease sites at 23 of 45 sites (18.2%) in 11 patients regardless of the tumor site and histology. In these patients, the lesions measured between 0.6 and 14.0 cm by CT. Fluorodeoxyglucose positron emission tomography revealed higher stage disease in 13 patients compared with Ga-67 imaging. Tumor-to-background ratios were statistically different between the two techniques with higher ratios obtained with FDG-PET (P < 0.0001). In imaging aggressive lymphoma and HD before therapy, FDG-PET has significantly higher site and patient sensitivity than Ga-67 scintigraphy (100% vs. 71.5% and 100% vs. 80.3%, respectively). The change in disease stage by FDG-PET may result in a change in therapy strategy.


Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity.
Neural stem cells (NSCs) persist in the subventricular zone (SVZ) of the adult brain. Location within this germinal region determines the type of neuronal progeny NSCs generate, but the mechanism of adult NSC positional specification remains unknown. We show that sonic hedgehog (Shh) signaling, resulting in high gli1 levels, occurs in the ventral SVZ and is associated with the genesis of specific neuronal progeny. Shh is selectively produced by a small group of ventral forebrain neurons. Ablation of Shh decreases production of ventrally derived neuron types, while ectopic activation of this pathway in dorsal NSCs respecifies their progeny to deep granule interneurons and calbindin-positive periglomerular cells. These results show that Shh is necessary and sufficient for the specification of adult ventral NSCs.


Splicing factor PRPF6 upregulates oncogenic androgen receptor signaling pathway in hepatocellular carcinoma.
Androgen receptor (AR) signaling is considered to be crucial for the pathogenesis of hepatocellular carcinoma (HCC) with obvious sexual dimorphism. Pre-mRNA processing factor 6 (PRPF6) was identified as a coactivator of AR. However, the molecular mechanism underlying the modulation function of PRPF6 on AR-mediated transcriptional activity in HCC needs to be further clarified. In this study, we analyzed data from The Cancer Genome Atlas to show that PRPF6 is highly expressed in HCC. . Our data indicated that PRPF6 interacts with AR/AR splice variants (AR-Vs) and upregulates AR/AR splice variant 7-mediated transcriptional activity even without dihydrotestosterone treatment. We observed that AR is obviously induced by androgen treatment and is mainly expressed in the nucleus in HCC-derived cell lines. Moreover, overexpression of PRPF6 enhances AR expression accompanied with the increase of AR-Vs expression. We provided evidence that PRPF6 participates in upregulating AR self-transcription. PRPF6 facilitates the recruitment of AR to the androgen responsive element region of the AR gene. Finally, PRPF6 depletion inhibits cell proliferation in HCC cells and mouse xenografts. Taken together, our results suggest that PRPF6 as a splicing factor enhances AR self-transcription, thereby coactivating oncogenic AR/AR-Vs actions in HCC.


Comparison of adaptive versions of the Hong Kong-specific criteria and 2015 Beers criteria for assessing potentially inappropriate medication use in Hong Kong older patients.
The Hong Kong-specific criteria have been established in 2019 to assess potentially inappropriate medication (PIM) use in older adults and improve the local prescribing quality. The aim of this study was to compare the adaptive versions of the Hong Kong-specific criteria and 2015 Beers criteria for assessing the prevalence and correlates of PIM use in Hong Kong older patients. A cross-sectional study was performed from January 1, 2014 to December 31, 2014 using the Hospital Authority (HA) database. A total of 489,301 older patients aged 65 years and older visiting general outpatient clinics (GOPCs) during the study period were included in the study. Two categories of PIM use included in the Hong Kong-specific criteria and 2015 Beers criteria, i.e. PIMs independent of diagnoses and PIMs considering specific medical conditions, were adapted to assess the prevalence of PIM use among the study sample. Characteristics of PIM users and the most frequently prescribed PIMs were investigated for each set of the criteria. Factors associated with PIM use were identified using the stepwise multivariable logistic regression analysis. The adaptive Hong Kong-specific criteria could detect a higher prevalence of patients exposed to at least one PIM than that assessed by the adaptive Beers criteria (49.5% vs 47.5%). Meanwhile, the adaptive Hong Kong-specific criteria could identify a higher rate of patients exposed to PIMs independent of diagnoses (48.1% vs 46.8%) and PIMs considering specific medical conditions (7.3% vs 4.9%) compared with that of the adaptive Beers criteria. The most frequently prescribed PIMs detected by the adaptive Beers criteria were all included in the adaptive Hong Kong-specific criteria. The strongest factor associated with PIM use was number of different medications prescribed. Patients with female gender, aged 65 ~ 74 years, a larger number of GOPC visits, and more than six diagnoses were associated with greater risk of PIM use, whereas advancing age was associated with lower risk of PIM use. The adaptive Hong Kong-specific criteria could detect a higher prevalence of PIM use than the adaptive Beers criteria in older adults visiting GOPCs in Hong Kong. It is necessary to update the prevalence and correlates of PIM use regularly in older adults to monitor the burden of PIM use and identify vulnerable patients who need further interventions.


[Modern visualization of the liver with MRT. Current trends and future perspectives].
This contribution provides an overview and imparts basic knowledge on pertinent technical developments in magnetic resonance imaging (MRI) of the liver: 3D sequences, respiratory triggering, parallel imaging, and 3 Tesla (3T). 3D sequences can be used as T1-weighted (T1w) sequences for analyzing dynamics of contrast enhancement or as T2w sequences for MR cholangiography. Consistent improvements in respiratory triggering make it possible to obtain good image quality on T2w scans even in patients unable to hold their breath. Parallel imaging as a universal technique to accelerate image acquisition is particularly appropriate for MRI of the liver, and it has been shown that the reduced acquisition time is not achieved at the expense of image quality. Further progress in MRI of the liver can be expected with use of the 3T systems, but hitherto irrelevant problems must still be solved. Overall the innovations presented here, applied alone or in combination, facilitate rapid, robust, and high-quality MRI diagnostic assessment of the liver.


Design in biology and rational design in vaccinology: A conceptual analysis.
This review discusses the philosophical foundations of what used to be called "the scientific method" and is nowadays often known as the scientific attitude. It used to be believed that scientific theories and methods aimed at the truth especially in the case of physics, chemistry and astronomy because these sciences were able to develop numerous scientific laws that made it possible to understand and predict many physical phenomena. The situation is different in the case of the biological sciences which deal with highly complex living organisms made up of huge numbers of constituents that undergo continuous dynamic processes; this leads to novel emergent properties in organisms that cannot be predicted because they are not present in the constituents before they have interacted with each other. This is one of the reasons why there are no universal scientific laws in biology. Furthermore, all scientific theories can only achieve a restricted level of predictive success because they remain valid only under the limited range of conditions that were used for establishing the theory' in the first place. Many theories that used to be accepted were subsequently shown to be false, demonstrating that scientific theories always remain tentative and can never be proven beyond and doubt. It is ironical that as scientists have finally accepted that approximate truths are perfectly adequate and that absolute truth is an illusion, a new irrational sociological phenomenon called Post-Truth conveyed by social media, the Internet and fake news has developed in the Western world that is convincing millions of people that truth simply does not exist. Misleading information is circulated with the intention to deceive and science denialism is promoted by denying the remarkable achievements of science and technology during the last centuries. Although the concept of intentional design is widely used to describe the methods that biologists use to make discoveries and inventions, it will be argued that the term is not appropriate for explaining the appearance of life on our planet nor for describing the scientific creativity of scientific investigators. The term rational for describing the development of new vaccines is also unjustified. Because the analysis of the COVID-19 pandemic requires contributions from biomedical and psycho-socioeconomic sciences, one scientific method alone would be insufficient for combatting the pandemic.


Glaucoma medications and mortality: a retrospective cohort study.
This study presents a retrospective, cohort analysis to estimate the 4-year rate of all-cause risk-adjusted mortality for veterans who were dispensed glaucoma medications. The main outcome measures was hazard of death according to glaucoma medication exposure. Beneficiaries 40 years and older enrolled in Veterans Health Administration (VHA) with International Disease Classification diagnoses of glaucoma. VHA clinical and pharmacy data sets were linked with a national VHA mortality registry. Patients were identified with a primary diagnosis of glaucoma were then put into one of two groups, glaucoma medication exposure or nonexposure medication group. Four-year survival analysis using the Cox proportional hazard method was adjusted for comorbidities using pertinent demographic characteristics and hierarchical condition categories from the Centers for Medicare and Medicaid Services. Of 214,971 beneficiaries with glaucoma or suspected glaucoma, 25,148 (11.7%) died during the study period. Compared to unexposed patients with glaucoma, the use of any class of glaucoma medication was associated with a statistically significant 7% reduced hazard of death (adjusted hazard ratio, 0.93; 95% confidence interval: 0.90-0.95). Reduced risk of death was found for multiple topical medication use, but not individual glaucoma agents. The seemingly inexplicable protective effect of glaucoma agents on all-cause mortality may best be explained by unmeasured confounding variables involved in the clinical decision of whether or not to treat patients with limited life expectancy for glaucoma.


Pyridine-4-carbaldehyde 4-phenylsemicarbazone.
In the title compound, C(13)H(12)N(4)O, the semicarbazone fragment links a benzene and a pyridine ring in the structure. The crystal packing is stabilized by strong inter-molecular N-H⋯O hydrogen bonds, which connect two mol-ecules to form a synthon unit, and by N-H⋯N hydrogen bonds and weak C-H⋯π inter-actions. The mol-ecular conformation is stabil-ized by intra-molecular N-H⋯N and C-H⋯O inter-actions.


Zwitterionic vesicles with AuCl₄⁻ counterions as soft templates for the synthesis of gold nanoplates and nanospheres.
Zwitterionic vesicles with AuCl4(-) counterions were fabricated for the first time as the soft templates for colloidal synthesis of gold nanostructures; gold nanoplates spontaneously generated at the vesicle bilayers were observed and gold nanospheres were achieved via a stepwise reduction approach.


Evaluation of a new Strongyloides ELISA IgG Test Kit.
Strongyloides stercoralis poses a significant clinical and public health challenge not only in endemic regions but also in non-endemic regions associated with travel. Ruling out this infection is essential in immuno-compromised hosts given the high probability of reactivation and mortality. In this study we compared an ELISA based on two recombinant antigens in the United States with a highly sensitive and specific reference serological test. There was 100% agreement between the two methods. ELISA assays based on Strongyloides stercoralis recombinant antigens has the potential to improve specificity. Further studies are warranted.


Sustainability of integrated anaemia prevention activities implemented through non-government organizations and schools, and its effect on haemoglobin status of adolescent girls in urban slums of Pune, in Maharashtra, India.
Programmes for the prevention of iron deficiency anaemia among adolescent girls need sustainable inputs for maximum benefits. To assess the interventions sustained for anaemia prevention implemented through NGOs and schools. An intervention study followed longitudinally in three phases. Phase I comprised (a) needs assessment of the community and (b) capacity assessment of service providers through a cross-sectional survey in nine slums, through six NGOs and three schools. Based on needs assessment, an integrated intervention for anaemia prevention was provided for adolescent girls (n = 384) in the community. To ensure sustainability the capacity of stakeholders (n = 67) was built by providing training in the components of the integrated intervention and establishing linkages with the public health system. Refresher training was conducted during phase II (n = 69) for reinforcing and strengthening of activities introduced in phase I. In phase II and III continuations of activities by the NGOs and schools that were initiated in phase I were monitored. Sustainability of activities was measured using an index that comprised technical, programmatic, social, and financial indicators. The impact of sustained interventions was assessed by comparing the mean rank haemoglobin concentrations of centres with varying levels of coverage. Scores of sustainability indicators decreased from phase II to phase III. Organizations that showed > 50% coverage showed significantly higher mean rank haemoglobin (p = < 0.05) during phases II and III. There is a need to identify and address barriers that prevent sustainable interventions for anaemia control.


A Full-Scale Agent-Based Model to Hypothetically Explore the Impact of Lockdown, Social Distancing, and Vaccination During the COVID-19 Pandemic in Lombardy, Italy: Model Development.
The COVID-19 outbreak, an event of global concern, has provided scientists the opportunity to use mathematical modeling to run simulations and test theories about the pandemic. The aim of this study was to propose a full-scale individual-based model of the COVID-19 outbreak in Lombardy, Italy, to test various scenarios pertaining to the pandemic and achieve novel performance metrics. The model was designed to simulate all 10 million inhabitants of Lombardy person by person via a simple agent-based approach using a commercial computer. In order to obtain performance data, a collision detection model was developed to enable cluster nodes in small cells that can be processed fully in parallel. Within this collision detection model, an epidemic model based mostly on experimental findings about COVID-19 was developed. The model was used to explain the behavior of the COVID-19 outbreak in Lombardy. Different parameters were used to simulate various scenarios relating to social distancing and lockdown. According to the model, these simple actions were enough to control the virus. The model also explained the decline in cases in the spring and simulated a hypothetical vaccination scenario, confirming, for example, the herd immunity threshold computed in previous works. The model made it possible to test the impact of people's daily actions (eg, maintaining social distance) on the epidemic and to investigate interactions among agents within a social network. It also provided insight on the impact of a hypothetical vaccine.


A bilayer triangular lattice with crown-like Co(7) spin cluster SBUs exhibiting high spin frustration.
A novel bilayer metal-organic framework is assembled with a perfect intralayer triangular subnet and ideal interlayer Td arrangement between unprecedented crown-like Co7 cluster units, exhibiting high spin frustration.


Granular cell tumors of the sellar region: what should be done after subtotal resection? A systematic review.
Granular cell tumors (GCT) are highly vascularized and adherent to adjacent structures, and so, complete resection represents a challenge. Adjuvant therapy decisions for residual GCTs currently relies on individual clinician decisions due to a paucity of systematic literature data. We present a comprehensive analysis about the impact of adjuvant therapy in reported cases of patients with incomplete GCT resection. One database (PubMed) and crossed references were queried for GCT with incomplete resection or biopsy from 1962 to 2020. Literature review was performed according to the PRISMA guidelines. Also, two patients with residual GCT from our institutions are added to the analysis. Data regarding clinical presentation, surgical approach, use of adjuvant therapy, Ki-67 labeling, and follow up assessments were extracted and analyzed from selected publications. Thirty-three studies met the predetermined inclusion criteria and 53 patients were selected (including our two reported cases). The median of age was 49 [IQR, 39-60 years], with a slight male predominance (1.2:1). Among the surgical procedures, seven (13%) were biopsies alone. Adjuvant therapy was used in 18 patients (radiotherapy, 94.5%; chemotherapy, 5.5%) but there is no statistical correlation with adjuvant therapy and the progression of the remnant tumor (p = 0.33). Our institutions' patients did not receive adjuvant therapy and did not show tumor progression on MRI. Our systematic literature review suggests there is a limited role for chemo and/or radiotherapy in the management of incomplete GCT resection. It may be reasonable recommending close clinical follow up in patients with incomplete resection.


[Opportunities of the enterosorption and evolution of the enterosorbent for surgical treatment of endotoxicosis].
In this article was shown the efficiency of enterosorbtion in various departments of medicine. You can find a comparative assessment of different enterosorbents. Were presented results of own using of pectin containing sorbents for enterosorbtion and nutritional support in surgical treatment of endotoxemia on the background of intestinal insufficiency syndrome in 161 patients. Application of the PCD had reduced bed-day in 1,4 times and mortality--a 2.05-times in compare with conventional treatment in the control group of 171 patients of the paired samples.


How Chromatin Stiffens Fibroblasts.
Fibroblasts are central to the acute and chronic response of tissues to stress: they are necessary for wound healing, involved in inflammatory responses and critical for long term remodeling of tissue. These diverse roles of fibroblasts arise from the cells' ability to respond to internal and extracellular cues regarding the physical state of the host tissue. In this article, we review recent evidence for the role of chromatin as a sensor of cellular stress and chromatin-dependent gene regulatory events that may be essential for fibroblast activation in the setting of injury. This emerging evidence highlights chromatin structure and accessibility as features necessary for our understanding of how cell type-specific epigenomes sense and respond to stress.


A review of Cremastra appendiculata (D.Don) Makino as a traditional herbal medicine and its main components.
Cremastra appendiculata (D.Don) Makino is a herbal medicine with a medicinal history of more than a thousand years in China. It is traditionally used to treat carbuncle, swelling, abscess, fistula, scrofula and scleroma (related to modern lymph node enlargement and various tumors.). This paper comprehensively reviewed the botany, traditional application, phytochemistry, pharmacological activities, and quality control of C. appendiculata, discussesed the application of ethnic medicine, modern scientific research and the relationship between them, and put forward some suggestions to promote the further development and utilization of C. appendiculata. We hope to provide a valuable reference for all researchers who are interested in obtaining relevant information about C. appendiculata. The relevant information on C. appendiculata was collected through published materials and electronic databases, including ancient and modern books, Chinese Pharmacopoeia, Ph.D. and M. Sc. dissertations, PubMed, ScienceDirect, Wiley, ACS, CNKI, Springer, Taylor & Francis, Web of Science, Google Scholar, and Baidu Scholar. At present, 190 compounds have been isolated from C. appendiculata, including phenanthrene, dihydrophenanthrene, bibenzyl, flavonoids, terpenoids, glycosides, aromatics, and other compounds. These compounds have been reported to have a variety of pharmacological activities, such as anti-tumor, anti-bacterial, anti-angiogenesis, anti-oxidation, etc. Modern pharmacological studies have proved that C. appendiculata has significant anti-tumor activity and has a good therapeutic effect on liver cancer, gastric cancer, colon cancer, breast cancer, thyroid cancer and other malignant tumors. C. appendiculata is not only an excellent traditional Chinese medicine for the treatment of tumors, but also a source of bioactive molecules with good application prospects. At present, the close relationship between the chemical components and pharmacological activities of C. appendiculata has not been established, and there is a lack of systematic and in-depth research on its anti-tumor components and its mechanism. In addition, it is necessary to establish systematic and effective index components and determination standards of C. appendiculata to better explore its therapeutic potential. Therefore, it is necessary to carry out further research on C. appendiculata.


Ownership reasoning in children across cultures.
To what extent do early intuitions about ownership depend on cultural and socio-economic circumstances? We investigated the question by testing reasoning about third party ownership conflicts in various groups of three- and five-year-old children (N=176), growing up in seven highly contrasted social, economic, and cultural circumstances (urban rich, poor, very poor, rural poor, and traditional) spanning three continents. Each child was presented with a series of scripts involving two identical dolls fighting over an object of possession. The child had to decide who of the two dolls should own the object. Each script enacted various potential reasons for attributing ownership: creation, familiarity, first contact, equity, plus a control/neutral condition with no suggested reasons. Results show that across cultures, children are significantly more consistent and decisive in attributing ownership when one of the protagonists created the object. Development between three and five years is more or less pronounced depending on culture. The propensity to split the object in equal halves whenever possible was generally higher at certain locations (i.e., China) and quasi-inexistent in others (i.e., Vanuatu and street children of Recife). Overall, creation reasons appear to be more primordial and stable across cultures than familiarity, relative wealth or first contact. This trend does not correlate with the passing of false belief theory of mind.


Diversity of Gut Microbiota and Bifidobacterial Community of Chinese Subjects of Different Ages and from Different Regions.
Gut microbiota composition and functionality are closely linked to host health. In this study, the fecal microbiota and bifidobacterial communities of 111 healthy volunteers from four regions of China of varying age profiles (Child, 1-5 years; Young, 18-50 years; Elder, 60-80 years; Longevity, ≥90 years) were investigated via high-throughput sequencing. Canonical analysis revealed that the gut microbiota, as well as bifidobacteria profiles of the subjects, clustered according to their regions and age. Eight genera were shared among all subjects, however, certain genera distributed differently in subjects grouped by region and age. Faecalibacterium was enriched in samples from Zhongxiang, unclassified Ruminococcaceae and Christensenellaceae were enriched in the Longevity group, and Bifidobacterium was enriched in Child. Within Bifidobacterium, B. longum was the most abundant species in almost all samples except for Child, in which B. pseudocatenulatum was the most abundant. Additionally, the abundances of B. adolescentis and B. dentium were lower in Child. In conclusion, our results suggest that geography and age affect the structure of the gut microbiota, as well as Bifidobacterium composition, and this variation may greatly associate with the metabolic and immune changes that occur during the process of aging.


The complete chloroplast genome of Craigia yunnanensis, an endangered plant species with extremely small populations (PSESP) from South China.
Craigia yunnanensis is an Endangered tree species, enlisted in the national plant species with extremely small population (PSESP) of China for urgent protection. The chloroplast genome is characterized using Illumina pair-end sequencing data. The whole chloroplast genome is 163,166 bp in length and consists of a pair of inverted repeat (IR) regions of 25,573 bp each, which are separated by the large single copy (LSC: 91,580 bp) region and small single copy (SSC: 20,440 bp) regions. The chloroplast genome encodes 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNA, and 4 rRNA genes. The overall GC content of the whole chloroplast genome is 36.4%. The phylogenetic tree revealed a close relationship between C. yunnanensis and Tilia species of Malvaceae family.


Lead removal from water using organic acrylic amine fiber (AAF) and inorganic-organic P-AAF, fixed bed filtration and surface-induced precipitation.
Granular porous sorbents were normally used for heavy metals removal from water. To search for the new commercial sorbent and treatment strategy, an organic acrylic amine fiber (AAF) and phosphorus loading inorganic-organic AAF (P-AAF) were prepared and used for lead (Pb) removal from water. A new strategy of inorganic-organic coupling technology was proposed for Pb removal, based on the hypothesis of surface-induced precipitation mechanism. The AAF showed a Pb adsorption capacity of 417 mg/g from the Langmuir fitting, while the column filtration technology was further applied to measure the adsorption edge and applications. Effects of different initial Pb concentrations, hydraulic retention time, and co-existing P were considered in the filtration experiments. The presence of 0.8 mg/L P in water significantly improved the Pb breakthrough point from 15,000 to 41,000 bed volumes of water spiked with 85 µg/L Pb, while the P-AAF fixed bed showed better removal of Pb than AAF SEM/EDX and XRD spectra were employed for determining the surface functional groups and the formation of surface-induced precipitation of pyromorphite (Pb5(PO4)3OH) on AAF. This study verified the application of AAF sorbent for Pb removal and the enhanced effect of coating P on AAF, thus improved our fundamental understanding and application of the surface chemistry process of Pb with P.


Case report of Osteopoikilosis in patient with psoriatic arthritis.
Osteopoikilosis (OPK) is one of the rare genetic musculoskeletal, non-inflammatory disorders that we should increase awareness toward. We report a case of a patient diagnosed with psoriatic arthritis with incidental imaging findings of lesions suggestive of osteopoikilosis.


Minced Cartilage Procedure for One-Stage Arthroscopic Repair of Chondral Defects at the Glenohumeral Joint.
Chondral defects of the glenohumeral joint are common but still remain a diagnostic and management challenge. Whereas arthroplasty is a reasonable treatment option in the elderly and low-demand population, joint preservation should be aimed for the remaining patients. For larger defects the current gold standard of treatment is autologous chondrocyte implantation. However, disadvantages such as high cost, the restriction in availability of specialized laboratories, and the 2-stage surgical design need to be accounted for if choosing this option. Showing first good clinical results for the knee joint, minced cartilage implantation is moreover a cost-effective procedure bringing autologous cartilage chips harvested from the defect walls and bringing them into the area of damage in a single-step open or arthroscopic approach. We describe an arthroscopic strategy of this technique to treat chondral defects at the glenohumeral joint.


Comparing digital serial cephalogram images for growth or treatment changes.
Superimposing serial radiographs is an easy method for assessing growth changes or treatment progress. Conventional films could be superimposed manually over a light box. The layering and variable-opacity features of digital imaging software can be used to superimpose digital images on your computer screen. Digital imaging software can be used to compare digital radiographs to identify growth patterns or treatment progress.


Influence of post-cam design on stresses on posterior-stabilized tibial posts.
Polyethylene wear and fracture at the tibial post of posterior- stabilized knee prostheses are common complications. Analyzing the stresses on various designs of tibial posts should predict the risk of damage. The post-cam of knee prostheses generally are designed either as flat-on-flat or curve-on- curve contact surfaces. We investigated stress on such tibial posts using a finite element method. We applied a 500-N anteroposterior shear force to the knee at neutral contact and 10 degrees tibial internal rotation when the knee was flexed at 60 degrees , 90 degrees , 120 degrees , and 150 degrees . There was more stress during tibial rotation compared with during neutral contact. The greatest increments of maximum von Mises stress and contact stress in the flat-on-flat model were from 20.4 to 46.1 MPa (126.3%) and from 22.2 to 55.7 MPa (151%), respectively, whereas in the curve-on-curve design they were from 20.5 to 22.7 MPa (10.7%) and from 33.0 to 35.4 MPa (7.2%), respectively. Increased stress concentration at the tibial post occurred at increased flexion angles along with axial tibial rotation. The curve-on-curve design reduced stress concentration when the knee sustained an anteroposterior shear force with tibial rotation.


Insight into population structure of Mycobacterium tuberculosis isolates in the multiethnic province of Alborz, Iran.
Genetic diversity of Mycobacterium tuberculosis clinical isolates from tuberculosis patients in the multiethnic province of Alborz, Iran was assessed. A total of 17 isolates in the period of 2012-2013 were collected and subjected to a Multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) consisted of 6 variable numbers of tandem repeats (VNTRs) including ETR-A, ETR-B, ETR-C, ElTR-D, ETR-E, ETR-F, 5 Mycobacterial Interspersed Repetitive Units including MIRU10, MIRU16, MIRU26, MIRU39, MIRU40, and 1 Queen University of Belfast locus, QUB11. This classified all isolates into 17 distinct MIRU-VNTR types, a reflection of a highly heterogenic population. Within the 12 used VNTR loci, ten proved highly or moderately discriminant according to the calculated HGDI scores. No cluster of isolates was identified in the study panel, giving a clustering rate of 0%, several events of SVL (N=5) and DVL (N=4) and TVL (N=3) were detected. The greater heterogeneity observed here by MLVA-VNTR analysis is most likely due to limited background data in the study region rather than a genuine more heterogeneous population compared to other provinces of the country.


An updated analysis of shoulder and elbow questions on the Orthopedic In-Training Examination.
The Orthopedic In-Training Examination (OITE) is an annual examination for orthopedic surgery residents used to assess orthopedic knowledge across a national standard. Having an updated understanding of currently tested topics and resources is useful to help residents guide their education. The purpose of this study is to analyze the shoulder and elbow domain of the OITE in an effort to provide current trends and commonly tested topics. All OITE questions related to shoulder and elbow topics over the years 2009-2013 and 2017-2020 were analyzed. Subcategories, the number and types of references used, publication lag time, imaging modalities, taxonomic classification, and resident performance were recorded. Shoulder and elbow topics comprised 8.61% of all OITE questions from 2009-2013 and 2017-2020. The most commonly tested shoulder topics were rotator cuff arthropathy and reverse total shoulder arthroplasty (13.6%), followed by hemiarthroplasty and total shoulder arthroplasty (12.9%), rotator cuff-related pathology (12.9%), anterior shoulder instability and/or dislocation (10.2%), and general anatomy (10.2%). The most commonly tested elbow topics were trauma (21%), ulnar collateral ligament injuries (12.12%), general anatomy (10%), and arthroplasty (10%). Decisions regarding management or appropriate next steps (taxonomy T3) comprised 39% of all question types. The incorporation of imaging modalities continues to be an important component of the OITE questions. The Journal of Shoulder and Elbow Surgery (JSES), the Journal of the American Academy of Orthopedic Surgeons (JAAOS), the Journal of Bone and Joint Surgery (JBJS), and the American Journal of Sports Medicine (AJSM) comprised 65% of articles referenced in all questions over our analysis period. This study provides an updated analysis of trends within the shoulder and elbow domain of the OITE. Application of these data can aid residents in their preparation for the examination.


Cor Triatriatum and Intracardiac Anomalous Pulmonary Venous Return: An Inborn Atrial Flow Inversion.
A neonate with a diagnosis of nonobstructive intracardiac type total anomalous pulmonary venous connection presented with profound cyanosis in the first days of life. The preoperative specialist echocardiographic examination also identified the presence of partial cor triatriatum dexter. The anatomic pattern of this exceedingly rare disease's association, its peculiar clinical presentation, and surgical management are discussed.


Age-Specific Characteristics of Lumbopelvic Alignment in Patients with Spondylolysis: How Bilateral L5 Spondylolysis Influences Lumbopelvic Alignment During the Aging Process.
To elucidate the influence of spondylolysis on age-related lumbar degenerative changes, age-specific lumbopelvic alignment in patients with or without spondylolysis was examined. Sagittal reconstructed computed tomography images of the lumbar spine in consecutive patients (n = 581) undergoing computed tomography scans of abdominal or lumbar regions for reasons other than low back disorders were obtained. Lumbar lordosis (LL), L5-S1 angle, and sacral slope (SS) were measured. Lumbopelvic parameters in patients with or without spondylolysis were evaluated in 3 age groups (<50, 50-69, and ≥70). The influence of bilateral L5 spondylolysis (L5-lysis) and L5 vertebral slip on each lumbopelvic parameter, as well as correlation between cross-sectional area (CSA) of paraspinal muscles and the degree of vertebral slip, were examined by multiple regression analysis. Patients with bilateral spondylolysis showed greater LL and SS than patients without spondylolysis. When analyzing the influence of L5-lysis, only elderly patients (≥70) with L5-lysis showed significantly greater LL and SS than nonspondylolysis (nonlysis) patients. L5-lysis patients more frequently showed L5 vertebral slip than nonlysis patients, and a smaller L5-S1 angle was observed when L5 vertebral slip accompanied L5-lysis. The degree of vertebral slip was significantly correlated with CSA of psoas muscles, but not with CSA of paraspinal extensor muscles. When patients have L5-lysis, lumbar lordosis and pelvic anteversion occurred age dependently. In elderly patients with L5-lysis, L5 vertebral slip with decrease of the L5-S1 angle occurs frequently. The progression of vertebral slip was correlated with atrophy of psoas muscles, but not that of paraspinal extensor muscles.


Functional control of oscillator networks.
Oscillatory activity is ubiquitous in natural and engineered network systems. The interaction scheme underlying interdependent oscillatory components governs the emergence of network-wide patterns of synchrony that regulate and enable complex functions. Yet, understanding, and ultimately harnessing, the structure-function relationship in oscillator networks remains an outstanding challenge of modern science. Here, we address this challenge by presenting a principled method to prescribe exact and robust functional configurations from local network interactions through optimal tuning of the oscillators' parameters. To quantify the behavioral synchrony between coupled oscillators, we introduce the notion of functional pattern, which encodes the pairwise relationships between the oscillators' phases. Our procedure is computationally efficient and provably correct, accounts for constrained interaction types, and allows to concurrently assign multiple desired functional patterns. Further, we derive algebraic and graph-theoretic conditions to guarantee the feasibility and stability of target functional patterns. These conditions provide an interpretable mapping between the structural constraints and their functional implications in oscillator networks. As a proof of concept, we apply the proposed method to replicate empirically recorded functional relationships from cortical oscillations in a human brain, and to redistribute the active power flow in different models of electrical grids.


Do effects of methylphenidate on cognitive performance last beyond treatment? A randomized placebo-controlled trial in boys and men with ADHD.
Methylphenidate (MPH) is the first-choice pharmacological treatment for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) across the lifespan. However, it is unclear whether MPH affects cognitive development, while recent (pre-) clinical studies suggest effects on the developing brain. The present randomized, placebo-controlled trial aims to determine whether MPH has short-term, age-dependent effects on cognitive performance in ADHD after a 1-week washout. Effects of 16 weeks MPH treatment were assessed after a one-week washout on cognitive functioning. Boys (age=10-12) and men (age=23-40) with ADHD were assigned to MPH treatment (boys n=25, men n=24) or placebo (boys n=25, men n=24). Outcome measures were working memory, response inhibition, response speed, episodic memory, and delay aversion. Differences in task performances over time (pre-, mid-, and post-treatment, following a 1-week wash-out) were compared between age and treatment conditions with mixed ANOVAs. MPH improved working memory and response speed, but only during treatment. No lasting age*treatment effects were observed post intervention. Overall, the results from the present randomized, placebo-controlled trial show that the effects of MPH on cognition do not extend past treatment in children or adults. While treatment with MPH improves cognition during treatment, these effects appear transient after 16-weeks of treatment. (Title trial: "Effects of methylphenidate on the developing brain"; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3103).


Acute meningitis with a negative Gram's stain: clinical and management outcomes in 171 episodes.
To characterize the diagnostic spectrum and physician management decisions of patients presenting to an emergency department with an acute, community-acquired illness, cerebrospinal fluid (CSF) white blood cell count > 5/mm3, and a negative Gram's stain for bacteria. In this retrospective cohort study over a 2-year period, symptoms, examination findings, paraclinical data, physician management, and clinical outcomes were assessed for each patient. One hundred sixty-eight patients (171 patient episodes) were evaluated. Almost half of the cohort presented in nonsummer months (48%); 20% of concurrent comorbid disease, and 15% had identified immunocompromising conditions. The reported examination findings were diverse, with diverse, with fever [49%] and neck stiffness [39%] being the most frequent findings. The majority were hospitalized (70%), with a median stay of 4 days. Approximately one half underwent computed tomography or magnetic resonance imaging (49%), and received empiric treatment with antibiotics (52%). A diagnostic cause was established in 23%, with the majority being inherently treatable diseases (including syphilis, bacteremia, Lyme disease). Variables significantly associated with a subsequent proven diagnostic cause included: age > 60 years; presence of comorbid disease (especially immunodeficiency); and presentation in winter months. A large proportion of patients presenting with acute meningitis and a negative CSF Gram's stain undergo hospitalization, noninvasive cranial imaging, and receive empiric antibiotic therapy. Better clinical guidelines are needed to identify the diagnostic and management decisions that benefit patient outcome.


Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management.
Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients' outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome. Retrospective analysis of prospectively collected data. adult cardiac arrest survivors treated by targeted temperature management (TTM). trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3-5 assessed 3 months after CA defined unfavorable neurological outcome (UO). We included 50 patients (Jan 2015-Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10-35] min. HT (core body temperature 33.7 [33.2-34] °C) lasted for 24 [23-28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6-37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11-0.58] vs. 0.58 [0.30-0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43-0.83] vs. 0.31 [- 0.01-0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO. CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.


Sonocatalytic rapid degradation of Congo red dye from aqueous solution using magnetic Fe0/polyaniline nanofibers.
Nano-sized magnetic Fe0/polyaniline (Fe0/PANI) nanofibers were used as an effective material for sonocatalytic degradation of organic anionic Congo red (CR) dye. Fe0/PANI, was synthesized via reductive deposition of nano-Fe0 onto the PANI nanofibers at room temperature. Prepared catalyst was characterized using HR-TEM, FE-SEM, XRD, FTIR instruments. The efficacy of catalyst in removing CR was assessed colorimetrically using UV-visible spectroscopy under different experimental conditions such as % of Fe0 loading into the composite material, solution pH, initial concentration of dye, catalyst dosage, temperature and ultrasonic power. The optimum conditions for sonocatalytic degradation of CR were obtained at catalyst concentrations=500mg.L-1, concentration of CR=200ppm, solution pH=neutral (7.0), temperature=30°C, % of Fe0 loading=30% and 500W ultrasonic power. The experimental results showed that ultrasonic process could remove 98% of Congo red within 30min with higher Qmax value (Qmax=446.4 at 25°C). The rate of degradation of CR dye was much faster in this ultrasonic technique rather than conventional adsorption process. The degradation efficiency declined with the addition of common inorganic salts (NaCl, Na2CO3, Na2SO4 and Na3PO4). The rate of degradation suppressed more with increasing salt concentration. Kinetic and isotherm studies indicated that the degradation of CR provides pseudo-second order rate kinetic and Langmuir isotherm model compared to all other models tested. The excellent high degradation capacity of Fe0/PANI under ultrasonic irradiation can be explained on the basis of the formation of active hydroxyl radicals (OH) and subsequently a series of free radical reactions.


Hydrogen peroxide is produced by E. coli challenged haemocytes and regulates phagocytosis, in the medfly Ceratitis capitata. The active role of superoxide dismutase.
Hydrogen peroxide (H(2)O(2)) participates as a second messenger in cell signaling. In this paper, the role of H(2)O(2) was investigated, in Escherichia coli phagocytosis by the haemocytes of the medfly Ceratitis capitata. Block of H(2)O(2) synthesis by specific enzymic inhibitors, namely N-ethylmaleimide (NEM) for NADPH oxidase and diethyldithiocarbamate (DDC) for SOD, resulted in the increase of E. coli phagocytosis. Immunoblot analysis, flow cytometry and confocal microscopy, revealed the constitutive expression of SOD, in the medfly haemocytes. Phagocytosis increased by small interfering RNA (siRNA) for SOD, revealing the active involvement of SOD and H(2)O(2). Immunoblot analysis showed an increase of the ERK1/2 phosphorylation, in the presence of the above H(2)O(2) synthesis enzymic inhibitors. In addition, confocal microscopy showed no co-localization of SOD with β integrin subunit. It appears that SOD participates in the regulation of bacterial phagocytosis, due to involvement of the produced H(2)O(2) in the differential phosphorylation of MAP kinases.


The impact of S2 mutations on Omicron SARS-CoV-2 cell surface expression and fusogenicity.
SARS-CoV-2 Omicron subvariants are still emerging and spreading worldwide. These variants contain a high number of polymorphisms in the spike (S) glycoprotein that could potentially impact their pathogenicity and transmission. We have previously shown that the S:655Y and P681H mutations enhance S protein cleavage and syncytia formation. Interestingly, these polymorphisms are present in Omicron S protein. Here, we characterized the cleavage efficiency and fusogenicity of the S protein of different Omicron sublineages. Our results showed that Omicron BA.1 subvariant is efficiently cleaved but it is poorly fusogenic compared to previous SARS-CoV-2 strains. To understand the basis of this phenotype, we generated chimeric S protein using combinations of the S1 and S2 domains from WA1, Delta and Omicron BA.1 variants. We found that the S2 domain of Omicron BA.1 hindered efficient cell-cell fusion. Interestingly, this domain only contains six unique polymorphisms never detected before in ancestral SARS-CoV-2 variants. WA1614G S proteins containing the six individuals S2 Omicron mutations were assessed for their fusogenicity and S surface expression after transfection in cells. Results showed that the S:N856 K and N969 K substitutions decreased syncytia formation and impacted S protein cell surface levels. However, we observed that 'first-generation' Omicron sublineages that emerged subsequently, had convergently evolved to an enhanced fusogenic activity and S expression on the surface of infected cells while 'second-generation' Omicron variants have highly diverged and showed lineage-specific fusogenic properties. Importantly, our findings could have potential implications in the improvement and redesign of COVID-19 vaccines.


Trends in oncological imaging during the COVID-19 pandemic through the vaccination era.
This study examines the impact that the COVID-19 pandemic has had on computed tomography (CT)-based oncologic imaging utilization. We retrospectively analyzed cancer-related CT scans during four time periods: pre-COVID (1/5/20-3/14/20), COVID peak (3/15/20-5/2/20), post-COVID peak (5/3/20-12/19/20), and vaccination period (12/20/20-10/30/21). We analyzed CTs by imaging indication, setting, and hospital type. Using percentage decrease computation and Student's t-test, we calculated the change in mean number of weekly cancer-related CTs for all periods compared to the baseline pre-COVID period. This study was performed at a single academic medical center and three affiliated hospitals. During the COVID peak, mean CTs decreased (-43.0%, p < 0.001), with CTs for (1) cancer screening, (2) initial workup, (3) cancer follow-up, and (4) scheduled surveillance of previously treated cancer dropping by 81.8%, 56.3%, 31.7%, and 45.8%, respectively (p < 0.001). During the post-COVID peak period, cancer screenings and initial workup CTs did not return to prepandemic imaging volumes (-11.4%, p = 0.028; -20.9%, p = 0.024). The ED saw increases in weekly CTs compared to prepandemic levels (+31.9%, p = 0.008), driven by increases in cancer follow-up CTs (+56.3%, p < 0.001). In the vaccination period, cancer screening CTs did not recover to baseline (-13.5%, p = 0.002) and initial cancer workup CTs doubled (+100.0%, p < 0.001). The ED experienced increased cancer-related CTs (+75.9%, p < 0.001), driven by cancer follow-up CTs (+143.2%, p < 0.001) and initial workups (+46.9%, p = 0.007). The pandemic continues to impact cancer care. We observed significant declines in cancer screening CTs through the end of 2021. Concurrently, we observed a 2× increase in initial cancer workup CTs and a 2.4× increase in cancer follow-up CTs in the ED during the vaccination period, suggesting a boom of new cancers and more cancer examinations associated with emergency level acute care.


Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase.
Five positions in the Escherichia coli malate dehydrogenase (eMDH) sequence, which distinguish MDH from lactate dehydrogenase (LDH) activity, were identified through a combination of Venn diagrams constructed from whole genomic data and from unbiased representative sequences from terminal clades. Incorporation of the five changes in eMDH sufficed to convert the enzyme from one with (k(cat)/K(m)(pyruvate))/(k(cat)/K(m)(oxaloacetate)) = 6.1 x 10(-9) to one with that ratio = 28. The substrate specificity was thus changed by a factor of 4.6 x 10(9). The k(cat)/K(m)(pyruvate) value for the pentamutant (eMDH I12V/R81Q/M85E/G210A/V214I) is 3,500 M(-1).s(-1), which is approximately equal 1/1,000 of the values found for typical wild-type LDHs. The procedure isolates an intersection of "strong forcing sets" that should prove to be of general use in switching paralog function.


In vitro activity, safety and in vivo efficacy of the novel bumped kinase inhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected with Neospora caninum tachyzoites and Toxoplasma gondii oocysts.
Bumped kinase inhibitors (BKIs) target the apicomplexan calcium-dependent protein kinase 1 (CDPK1). BKI-1748, a 5-aminopyrazole-4-carboxamide compound when added to fibroblast cells concomitantly to the time of infection, inhibited proliferation of apicomplexan parasites at EC50s of 165 nM (Neospora caninum) and 43 nM (Toxoplasma gondii). Immunofluorescence and electron microscopy showed that addition of 2.5 μM BKI-1748 to infected HFF monolayers transformed parasites into multinucleated schizont-like complexes (MNCs) containing newly formed zoites, which were unable to separate and form infective tachyzoites or undergo egress. In zebrafish (Danio rerio) embryo development assays, no embryonic impairment was detected within 96 h at BKI-1748 concentrations up to 10 μM. In pregnant mice, BKI-1748 applied at days 9-13 of pregnancy at a dose of 20 mg/kg/day was safe and no pregnancy interference was observed. The efficacy of BKI-1748 was assessed in standardized pregnant mouse models infected with N. caninum (NcSpain-7) tachyzoites or T. gondii (TgShSp1) oocysts. In both models, treatments resulted in increased pup survival and profound inhibition of vertical transmission. However, in dams and non-pregnant mice, BKI-1748 treatments resulted in significantly decreased cerebral parasite loads only in T. gondii infected mice. In the T. gondii-model, ocular infection was detected in 10 out of 12 adult mice of the control group, but only in 3 out of 12 mice in the BKI-1748-treated group. Thus, TgShSp1 oocyst infection is a suitable model to study both cerebral and ocular infection by T. gondii. BKI-1748 represents an interesting candidate for follow-up studies on neosporosis and toxoplasmosis in larger animal models.


Sustainable isolation of nanocellulose from cellulose and lignocellulosic feedstocks: Recent progress and perspectives.
As a type of sustainable nanomaterials, nanocellulose has drawn increasing attention over the last two decades due to its great potential in diverse value-added applications such as electronics, sensors, energy storage, packaging, pharmaceuticals, biomedicine, and functional food. Sourcing nanocellulose from lignocellulose is commonly accomplished via the use of mineral acids, oxidizers, enzymes, and/or intensive mechanical energy. Yet, the economic and environmental concerns associated with these conventional isolation techniques pose major obstacles for commercialization. Considerable progress has been achieved in the last few years in developing sustainable nanocellulose isolation technologies involving organic acid/anhydride, Lewis acid, solid acid, ionic liquid, and deep eutectic solvent. This paper provides a comprehensive review of these alternatives with regard to general procedures and key advantages. Important knowledge gaps, including total biomass utilization, complete life cycle analysis, and health/safety, require urgently bridging in order to develop economically competitive and operationally feasible nanocellulose isolation technology for commercialization.


On Correcting Biases in Self-Reports of Age at First Substance Use with Repeated Cross-Section Analysis.
Household survey data on age at first use of alcohol, tobacco, marijuana, and hard drugs can be biased due to sample selection and inaccurate recall. One potential concern is attrition, whereby individuals who get involved with substance use at an early age become increasingly less likely to be surveyed in successive years. A comparison of data from the National Household Survey on Drug Abuse (NHSDA) with data from a longitudinal study suggested that attrition might have caused substantially less bias than did "forward telescoping," the inflating of age at first use over time. The evidence of forward telescoping was particularly pronounced with respect to age at first use of alcohol. This paper presents a procedure for correcting the distribution of age at first use for forward telescoping (but not attrition) by viewing a portion of the NHSDA data collected in successive years as constituting a cohort study. Results are presented from applying this procedure with NHSDA data collected from 1982 to 1995 for respondents born 1968-1973. The findings suggest that prevention programs need to be introduced at an earlier age than would be indicated by "uncorrected" retrospective data. Other implications are also highlighted.


Measuring molecular order and orientation using coherent anti-stokes Raman scattering microscopy.
Coherent anti-Stokes Raman scattering microscopy develops rapidly into a powerful technique to image both the chemical composition and physical state in complex samples from biophysics, biology, and the material sciences. This nonlinear vibrational technique increases the signal relative to spontaneous Raman scattering and does not require labeling of the specimen. A theoretical description of the technique is provided and the two major modes of operation: picosecond- and multiplex coherent anti-Stokes Raman scattering are discussed. The potential of the technique is demonstrated with examples of direct measurement of acyl chain order and orientation in lipid monolayers, bilayers, and lipid vesicles.


Relationship between of working hours, weekend work, and shift work and work-family conflicts among Korean manufacturers.
In the manufacturing industry, work-family conflict (WFC) is related to working hour characteristics. Earlier studies on the relationship between working hour characteristics and WFC in the manufacturing industry have been limited to some regions in Korea. No study has addressed the data on a national scale. Thus, this study investigated the impact of weekly working hours, weekend work, and shift work on WFC using national-scale data. This study was based on the fifth Korean Working Conditions Survey of 5,432 manufacturers. WFC consists of 5 variables; WFC1 "kept worrying about work"; WFC2 "felt too tired after work"; WFC3 "work prevented time for family"; WFC4 "difficult to concentrate on work"; WFC5 "family responsibilities prevented time for work". As WFC refers to the inter-role conflict between the need for paid work and family work, WFC has been measured in two directions, work to family conflict (WTFC: WFC1, 2, 3) and family to work conflict (FTWC: WFC4, 5). With these WFC variables, we conducted multiple logistic analyses to study how working hours, weekend work, and shift work impact WFC. Korean manufacturers' prolonged working hours increased all aspects of WFCs. Odds ratios (ORs) of WFCs based on working hours (reference of under 40 hours) of 41-52, 53-60, over 61 were 1.247, 1.611, 2.279 (WFC1); 1.111, 2.561, 6.442 (WFC2); 1.219, 3.495, 8.327 (WFC3); 1.076, 2.019, 2.656 (WFC4); and 1.166, 1.592, 1.946 (WFC5), respectively. Shift-work in the WFC2 model showed a significantly higher OR of 1.390. Weekend work 'only on Saturday' had significant ORs with WFC2 (1.323) and WFC3 (1.552). An increase in working hours leads to the spending of less time attending to problems between work and family, causing both WTFC and FTWC to increase. As weekends, evenings, and nighttime are considered to be family-friendly to people, working on weekends and shift-work were highly correlated to WTFC.


Assessment of antibiotic storage practices, knowledge, and awareness related to antibiotic uses and antibiotic resistance among household members in post-conflict areas of Pakistan: Bi-central study.
The storage of antimicrobials at home is frequently in-practice in various developing countries, resulting an irrational use, antibiotic resistance, and toxicities. This condition may worsen more in conflict zones where health facilities are limited. This study aimed to determine the storage and use of leftover antibiotics among households (HHs) along with knowledge and awareness about antibiotics and antibiotic resistance (ABR). A descriptive cross-sectional study design was employed. Members of HHs were invited to participate in the survey while using a convenient sampling technique. The data were obtained using a validated questionnaire and analyzed through SPSS. A total of 96 HHs were randomly selected from two districts (n = 50, n = 46), with most of the participants being men between the ages of 18 and 28 (n = 45, 46.9%) years. The majority of HHs (n = 32, 33.3%) had six to eight total family members, with one to two chronic diseases (n = 63, 65.6%), individual families (n = 60, 62.5%), and with (n = 35, 36.5%) LRTIs (lower respiratory tract infections). The HHs were aware of the word "antibiotic" (n = 59, 61.5%) and gave correct replies to amoxicillin as an antibiotic (n = 42, 43.8%); on the other hand, HHs also thought of paracetamol as an antibiotic (n = 45, 47.9%). They identified the most common brands of antibiotics easily, and a majority of them (n = 69, 71.9%) had never heard of ABR before and had lower levels of awareness. The most stored antibiotic at home (n=38, 39.6%) was azithromycin (J01FA10). In addition, they had multiple needless (1-2, n = 62, 64.6%; 3-4, n = 29, 30.2%) and antibiotics in their houses. Age had a strong association (p = 0.017, H = 12) affected the mean knowledge scores related to antibiotic use. Association of education levels (p = 0.001, H = 52.8) and occupation (p = 0.04, H = 10) with proper antibiotics use were found to be significant. However, family members with more than one chronic illness (p = 0.09, H = 0.8) showed a significant relationship with their awareness of antibiotics. Participants generally stored various antibiotics of different classes in their homes. Lack of knowledge related to the appropriate usage of antibiotics, use of leftover antibiotics, and awareness related to ABR were unknown to the participants.


Electrospun nanomaterials for ultrasensitive sensors.
Increasing demands for ever more sensitive sensors for global environmental monitoring, food inspection and medical diagnostics have led to an upsurge of interests in nanostructured materials such as nanofibers and nanowebs. Electrospinning exhibits the unique ability to produce diverse forms of fibrous assemblies. The remarkable specific surface area and high porosity bring electrospun nanomaterials highly attractive to ultrasensitive sensors and increasing importance in other nanotechnological applications. In this review, we summarize recent progress in developments of the electrospun nanomaterials with applications in some predominant sensing approaches such as acoustic wave, resistive, photoelectric, optical, amperometric, and so on, illustrate with examples how they work, and discuss their intrinsic fundamentals and optimization designs. We are expecting the review to pave the way for developing more sensitive and selective nanosensors.


Accurate determination of marker location within whole-brain microscopy images.
High-resolution whole-brain microscopy provides a means for post hoc determination of the location of implanted devices and labelled cell populations that are necessary to interpret in vivo experiments designed to understand brain function. Here we have developed two plugins (brainreg and brainreg-segment) for the Python-based image viewer napari, to accurately map any object in a common coordinate space. We analysed the position of dye-labelled electrode tracks and two-photon imaged cell populations expressing fluorescent proteins. The precise location of probes and cells were physiologically interrogated and revealed accurate segmentation with near-cellular resolution.


Comparison of cumulative incidence analysis and Kaplan-Meier for analysis of shock reversal in patients with septic shock.
Kaplan-Meier (KM) has become the most used method to evaluate time-to-event analysis, although it is unsuitable in competing event situations such as death and shock reversal. Despite that the use of this methodology is not widely disseminated, cumulative incidence analysis (CIA) is more appropriate in these situations. We used CIA and KM (with 2 different techniques of censoring) to compare shock reversal in a cohort of patients with septic shock after steroid therapy. Furthermore, we have analyzed shock reversal in responders and nonresponders to high-dose cortrosyn test (250 μg). Analysis of shock reversal in a cohort of 74 patients with septic shock at a university hospital was done. Shock reversal by the 28th day was estimated to be 88% and 72% by KM methods and 59% by CIA. In nonresponders to cortrosyn test (Δ ≤ 9 μg/dL), shock reversal was estimated in 80% and 56% according to KM and 47% according to CIA. As for responders to cortrosyn test, shock reversal was estimated in 90% and 77% according to KM and 64% according to the CIA method. Kaplan-Meier overestimates shock reversal. Cumulative incidence analysis seems to be a more appropriate method to analyze shock reversal. Future trials intended to analyze shock reversal should apply CIA.


Stroke care in Spain. What do we have? What do we need?
The high level of scientific evidence which supports the recommendations for the care of acute stroke in Stroke Units (SU) with a good health care network, it does not correspond to the level of introduction in Spain. In this regard, the Cerebrovascular Diseases Study Group (GEECV) of the Spanish Society of Neurology has taken the initiative to conduct the "National Survey of Stroke Care" that will help to determine the real situation in acute stroke management in Spain just before the approval of the National Stroke Strategy (NSS) by the Ministry of Health and concludes that in the first semester of 2009 there were 39 SUs, unevenly distributed with higher concentration in Madrid and Barcelona. Although the approval of the NSS was a major achievement, much remains to be done to meet the objectives. We thank the GEECV́s initiative, which gives us an "X-ray" of the, not very satisfactory, state of stroke care in Spain in December 2008, and highlighting some achievements and the many shortcomings. Therefore, we must continue to improve, refine our data collection with records that include all available resources and all the stroke patients attended. We invite GEECV to carry out a second study to evaluate the impact of NSS and to serve as a stimulus to achieve a substantial improvement in stroke care in Spain, closer to the recommendations of the new PASI document.


To collapse or not to collapse blastocysts before vitrification? A matched case-control study on single vitrified-warmed blastocyst transfers.
Does laser-induced artificial blastocoel collapse result in better blastocyst cryopreservation survival and a higher live birth rate (LBR) in comparison with intact counterparts? Half of the supernumerary blastocysts from IVF cycles were randomly selected before vitrification for laser-induced artificial collapsing or vitrification in intact form. A matched case-control study of first transfers of single blastocysts artificially collapsed (case) or intact (control) before vitrification was conducted. Controls were matched to cases on a 1:1 ratio by female age, parity, fresh and vitrified cycle protocol, blastocyst age and quality, resulting in 309 case-control pairs. The two groups were comparable in terms of their characteristics. Survival rates in the case and control groups (97.8% and 95.7%; P = 0.133) were comparable, but the optimal survival rate was higher in the case group (78.2% and 69.3%; P = 0.03). Clinical pregnancy rates (38.2% and 35.3%; P = 0.518), miscarriage rates (15.2% and 22%; P = 0.190), LBR per transfer (32.4% and 27.5%; P = 0.221) and LBR per warmed blastocyst (31.6% and 26.3%; P = 0.137) were not statistically different between the case and control groups. No significant difference in preterm births (11.1% versus 15.7%), birthweights (3333 ± 723 g versus 3304 ± 609 g) or sex ratio (49.3% versus 50.7% boys) was observed between the two groups. No major malformations were detected in the study population. Compared with vitrification of intact blastocysts, collapsed blastocysts resulted in a significantly higher optimal survival rate, and although they resulted in a 5% higher LBR, this was not significant for the chosen sample size. Neonatal outcomes were comparable in the two groups.


A double-loop structure in the adaptive generalized predictive control algorithm for control of robot end-point contact force.
Robot force control is an essential issue in robotic intelligence. There is much high uncertainty when robot end-effector contacts with the environment. Because of the environment stiffness effects on the system of the robot end-effector contact with environment, the adaptive generalized predictive control algorithm based on quantitative feedback theory is designed for robot end-point contact force system. The controller of the internal loop is designed on the foundation of QFT to control the uncertainty of the system. An adaptive GPC algorithm is used to design external loop controller to improve the performance and the robustness of the system. Two closed loops used in the design approach realize the system׳s performance and improve the robustness. The simulation results show that the algorithm of the robot end-effector contacting force control system is effective.


Orthostatic hypotension due to quinidine and propranolol.
Orthostatic hypotension developed in a 65-year-old man during treatment with quinidine and propranolol. Quinidine reduced standing blood pressure, attenuated the Valsalva response, and increased plasma norepinephrine concentrations, suggesting the presence of nonselective alpha-adrenergic blockade. The addition of propranolol inhibited the compensatory tachycardia and produced symptomatic orthostatic hypotension. Physicians should be alerted to the possibility of orthostatic hypotension when the alpha blocking effects of quinidine are combined with a beta blocking agent such as propranolol.


Protein-coated microplastics corona complex: An underestimated risk of microplastics.
Traditionally, toxicity of microplastics is ascribed to the chemicals adsorbed on them. However, microplastics can also interact with biomolecules, such as secretory proteins from aquatic organisms, and form protein-coated microplastics corona complex with unknown toxic effects. Here, we investigated the toxic effects of polystyrene microplastics (PS) and bovine serum albumin (BSA) coated PS corona complex (PS + BSA) on adult zebrafish (Danio rerio) intestines. The food intake ratio, accumulation and distribution of microplastics, histopathological changes, and molecular effects related to the antioxidant system in the intestine were studied. For the first time, we observed that PS + BSA aggregated on the inner surface of the zebrafish intestine, whereas PS dispersed. The aggregation of PS + BSA resulted in increased microplastics accumulation and longer residence time in the zebrafish intestine, which inhibited food intake and generated reactive oxygen species (ROS) in the intestine. Furthermore, the functions of the Keap1-Nrf2-ARE antioxidant signaling pathway and the activation of antioxidant enzymes were significantly affected by PS + BSA after a 21-day exposure. Ultimately, a higher accumulation of ROS and stronger inhibition of antioxidants led to more severe intestinal injury. These results suggest that the increased toxicity of protein-coated microplastics corona complex may be affected by oxidative damage and can result in the inhibition of digestion due to their aggregation and longer residence time in the intestine. Therefore, the ecological risk of microplastics may be underestimated owing to the interactive mechanisms of microplastics and protein coronas.


Genetics of Anthracycline Cardiomyopathy in Cancer Survivors: JACC: CardioOncology State-of-the-Art Review.
Anthracyclines are an integral part of chemotherapy regimens used to treat a variety of childhood-onset and adult-onset cancers. However, the development of cardiac dysfunction and heart failure often compromises the clinical utility of anthracyclines. The risk of cardiac dysfunction increases with anthracycline dose. This anthracycline-cardiac dysfunction association is modified by several demographic and clinical factors, such as age at anthracycline exposure (<4 years and ≥65 years); female sex; chest radiation; presence of cardiovascular risk factors (diabetes, hypertension); and concurrent use of cyclophosphamide, paclitaxel, and trastuzumab. However, the clinical variables alone yield modest predictive power in detecting cardiac dysfunction. Recently, attention has focused on the molecular basis of anthracycline-related cardiac dysfunction, providing an initial understanding of the mechanism of anthracycline-related cardiomyopathy. This review describes the current state of knowledge with respect to the pathogenesis of anthracycline-related cardiomyopathy and identifies the critical next steps to mitigate this problem.


Nutrition and the community-dwelling older person: a pilot study in general practice.
Nutrition is vital for health, and undernutrition can compromise physical and mental wellbeing. The prevalence of undernutrition among older community-dwelling adults attending general practice in Australia is not readily known. The aims of the study were to determine the prevalence of malnutrition of the elderly in Australian general practice, to assess malnutrition-related factors and to describe the older people's perception about nutrition. The study sample comprised 60 older people aged 75 years and above attending one general practice in South Australia. The combination of qualitative and quantitative data provided a more complete account of nutrition and its meaning for the older person. Three commonly used, validated nutritional screening tools were useful in determining undernutrition between 15 and 20% in a community population. One screening tool determined a 62% incidence of nutritional risk. Health characteristics determined almost 75% of participants identified at oral health risk. Frailty, medications and chronic disease were identified as factors associated with nutritional risk. Examination of older persons' perceptions about nutrition and wellbeing identified two major themes: older people have nutritional awareness but lack details, especially in relation to the benefits of protein intake, and there is limited awareness on the health benefits of good nutrition. This study confirms that nutritional risk is common in general practice. Understanding older person's perceptions of good nutrition is vital to be able to effectively change their nutritional status and plan amenable interventions. Screening practices with valid and reliable screening tools are imperative to ensure appropriate identification and management of older people at risk. WHAT THIS ARTICLE ADDS.


Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early-onset and late-onset preeclampsia.
To analyze the differential genetic expression and protein localization of thrombomodulin (THBD) and tissue factor (F3) in the placentas of pregnancies affected by preeclampsia. We assessed the expression of THBD and F3 by immunohistochemistry and real-time polymerase chain reaction (PCR) in placentas from 20 PE cases: 10 early-onset PE placentas, 10 late-onset PE placentas, and 10 control cases (normal pregnancies). In cases, we found higher THBD and F3 RNA levels in placental tissue. Protein expression in controls differed from that in late-onset PE placentas, which had lower THBD levels in syncytiotrophoblasts and amniotic cells. Likewise, late-onset PE placentas exhibited comparatively lower F3 expression in the perivillous fibrin. In contrast, early-onset PE had high F3 expression in the subdecidual fibrin. We found no significant differences in the F3/THBD ratio between the groups. Our study supports evidence that shows the involvement of F3 and THBD in placental disorders. Furthermore, this finding contributes to a better understanding of the physio-pathological role that these molecules may play in the development of this heterogeneous disease.


Diversity of human T cell receptor sequences of T cell clones with specificity for Bet v 1 peptide/MHC II complexes.
T cell clones (TCC) were raised from the peripheral blood of patients suffering from tree pollen allergy. All TCC were restricted by HLA-DR molecules. In order to investigate possible intervention targets in Type I allergic diseases, we have examined T cell receptor (TCR) alpha- and beta-chain nucleotide sequences of several allergen-reactive human CD4+ TCC specific for four frequently found epitopes of Bet v 1, the major birch pollen allergen. In general, TCC specific for the 4 epitopes investigated, used diverse TCRAV and TCRBV gene segments. Moreover, the junctional regions encoding the third complementarity determining regions (CDR3) of the TCR showed striking heterogeneities in length and amino acid composition. A more restricted use of two J gene segments (TCRBJ1S4 and 2S7) was only observed in the beta-chain of TCR used by TCC specific for epitope 1. In addition, all TCC specific for epitope 4 showed an arginine residue in the N-terminal region of their TCRBV CDR3 loops despite their sequence diversities. In view of the striking heterogeneities found, therapeutical strategies aimed at the clonal deletion of allergen-specific T cell clones, providing help for IgE synthesis, may not be feasible. Moreover, our results cast a doubt on the theory, that the CDR3 exclusively provides the primary contact with the peptide bound in the major histocompatibility (MHC) groove, and suggest additional interaction with MHC class II.


Activation of skin renin-angiotensin system in diabetic rats.
The renin-angiotensin system (RAS) is reportedly involved in chronic diabetic complications such as diabetic nephropathy, but changes of the RAS in diabetic skin remain unknown. The aim of this study was to investigate the expression of angiotensin (Ang) II and its type 1 (AT1) and type 2 (AT2) receptors in diabetic skin tissues, and explore the relationship between the local RAS and pathological changes of diabetic skin. Our results showed that thinning of epidermis, degeneration of collagen, fracture of dermal layer, and atrophy/disappearance of subcutaneous fat were observed in diabetic skin. The expression level of AngII was increased in diabetic skin tissues compared to that in controls. mRNA and protein expression of AT1 receptor were also increased while the level of AT2 receptor decreased; the relative expression of AT1 to AT2 receptors was approximately threefold higher in diabetes than in controls. Furthermore, in the culture medium of primary cultured fibroblasts from diabetic skin, the concentration of AngII was significantly higher than that of normal control. The mRNA and protein expression of AT1 receptor was also increased in fibroblasts of diabetic skin compared to controls, while the protein expression of AT2 receptor was decreased. Taken together, our results suggest that the local RAS system is activated in diabetic skin and AngII receptor is likely to mediate the pathological changes of diabetic skin.


Utility of intracranial pressure monitoring in patients with traumatic brain injuries: a propensity score matching analysis of TQIP data.
Intracranial pressure monitoring (ICPM) is central to traumatic brain injury (TBI) management, but its utility is controversial. The 2016-2017 TQIP database was queried for isolated TBI. Patients with ICPM [(ICPM (+)] were propensity-score matched (PSM) to those without ICPM [ICPM (-)] and divided into three age groups by years (< 18, 18-54, ≥ 55). PSM yielded 2125 patients in each group. Patients aged < 18 years had a higher survival probability (p = 0.013) and decreased mortality (p = 0.016) in the ICPM (+) group. Complications were higher and LOS was longer in ICPM (+) patients aged 18-54 years and ≥ 55 years, but not in patients aged < 18 years. ICPM (+) is associated with a survival benefit without an increase in complications in patents aged < 18 years. In patients aged ≥ 18 years, ICPM (+) is associated with more complications and longer LOS without a survival benefit.


Improving the diversity of captured full-length isoforms using a normalized single-molecule RNA-sequencing method.
Human genes form a large variety of isoforms after transcription, encoding distinct transcripts to exert different functions. Single-molecule RNA sequencing facilitates accurate identification of the isoforms by extending nucleotide read length significantly. However, the gene or isoform diversity is lowly represented by the mRNA molecules captured by single-molecule RNA sequencing. Here, we show that a cDNA normalization procedure before the library preparation for PacBio RS II sequencing captures 3.2-6.0 fold more full-length high-quality isoform species for different human samples, as compared to the non-normalized capture procedure. Many lowly expressed, functionally important isoforms can be detected. In addition, normalized PacBio RNA sequencing also resolves more allele-specific haplotype transcripts. Finally, we apply the cDNA normalization based long-read RNA sequencing method to profile the transcriptome of human gastric signet-ring cell carcinomas, identify new cancer-specific transcriptome signatures, and thus, bring out the utility of the improved protocols in gene expression studies.