Volatilization of selenium from agricultural evaporation pond sediments.
Microbial volatilization of Se was evaluated as a means of detoxifying Se-contaminated sediments. Sediment samples containing 60.7 (Kesterson Reservoir) and 9.0 mg Se kg-1 (Peck ponds) were incubated for 273 days in closed systems located in the greenhouse. Volatile Se was collected from a continuous air-exchange stream using activated carbon. Various economical and readily available organic and inorganic amendments were tested for their capacity to enhance the microbial process, including Citrus (orange) peel, Vitis (grape) pomace, feedlot manure, barley straw, chitin, pectin, ZnSO4, (NH4)2SO4, and an inoculum of Acremonium falciforme (an active Se methylating fungus). With the Kesterson sediment, the highest Se removal (44.0%) resulted from the combined application of citrus peel and ZnSO4, followed by citrus peal alone (39.6%), and citrus peel combined with ZnSO4, (NH4)2SO4 and A. falciforme (30.1%). Manure (19.5%), pectin (16.4%), chitin (9.8%) and straw plus N (8.8%) had less pronounced effects. Without the amendments, cumulative Se volatilization was 6.1% of the initial inventory. Grape pomace (3.0%) inhibited the process. With the Peck sediment, the highest amount of Se removed was observed with chitin (28.6%), manure (28.5%), and citrus peel alone (27.3%). Without amendments, 14.0% of the native Se was volatilized in 273 days. Cumulative Se volatilization was 24.7% with citrus plus Zn and N, 17.2% with citrus plus Zn, and 18.8% with citrus plus Zn, N and A. falciforme. Pectin (15.2%), straw plus N (16.4%), and grape pomace (7.3%) were among the less effective amendments for the Peck sediment. The differences in the effectiveness of each treatment between the two seleniferous soils may be a result of the residual N content of the sediments. With the Kesterson sediment, which was high in organic C and N, added N inhibited volatilization of Se, while with Peck sediments (low in organic C and N) N-rich materials tended to accelerate Se volatilization. Inoculation with A. falciforme did not enhance Se evolution from either sediment, indicating that there was a sufficient population of microflora capable of producing gaseous Se.


[Acute respiratory distress syndrome].
Acute respiratory distress syndrome (ARDS) is the clinical manifestation of an acute lung injury caused by a variety of direct and indirect injuries to the lung. The cardinal clinical feature of ARDS, refractory arterial hypoxemia, is the result of protein-rich alveolar edema with impaired surfactant function, due to vascular leakage and dysfunction with consequently impaired matching of ventilation to perfusion. Better understanding of the pathophysiology of ARDS has led to the development of novel therapies, pharmacological strategies, and advances in mechanical ventilation. However, protective ventilation is the only confirmed option in ARDS management improving survival, and few other therapies have translated into improved oxygenation or reduced ventilation time. The development of innovative therapy options, such as extracorporeal membrane oxygenation, have the potential to further improve survival of this devastating disease.


Archaeal communities of low and high microbial abundance sponges inhabiting the remote western Indian Ocean island of Mayotte.
Marine sponges are abundant and ecologically important components of coral reefs and have been shown to harbour exceptionally high microbial densities, which can differ substantially among sponge species. However, this dichotomy between high and low microbial abundance (HMA, LMA) sponges is still not fully understood, particularly as concerns the archaeal community. This study aims to fill this gap by analysing (using 454-pyrosequencing of the 16S rRNA gene) how the archaeal community varies among known LMA (Stylissa carteri, and Stylissa massa), known HMA (Hyrtios erectus and Xestospongia testudinaria) and unknown HMA/LMA status sponge species (Ectyoplasia coccinea, Paratetilla bacca and Petrosia aff. spheroida) collected in a remote location in which very few sponge microbial composition studies have been previously performed (Mayotte, Comores archipelago, France) and comparing the results with those reported in four other geographical areas. Based on archaeal community composition, the known LMA sponges formed a distinct cluster together with Paratetilla bacca, Ectyoplasia coccinea and seawater while the known HMA sponge X. testudinaria formed a cluster with Petrosia aff. spheroida. The known HMA sponge H. erectus, in turn, had an intermediate archaeal community between HMA sponges and sediment samples. In addition to the above, we also showed significant compositional congruence between archaeal and bacterial communities sampled from the same sponge individuals. HMA sponges were mainly dominated by members assigned to the genus Nitrosopumilus while LMA sponges were mainly dominated by members assigned to the genus Cenarchaeum. In general, there was no clear difference in richness between HMA and LMA sponges. Evenness, however, was higher in HMA than LMA sponges. Whilst the present study corroborates some of the traits commonly associated with the HMA-LMA dichotomy (higher evenness in Mayotte HMA sponges), this was not consistent across geographical areas showing that more research is needed to fully understand the HMA/LMA dichotomy as concerns Archaea.


Current characteristics and outcome of cytomegalovirus infections after kidney transplantation.
The clinical course of cytomegalovirus (CMV) infections in the current era is poorly described. We characterized the symptoms and outcome of all CMV infections in a large cohort of kidney transplant recipients. Among 1129 kidney transplant recipients transplanted between 2004 and 2011 in Charité Universitätsmedizin Berlin and Helsinki University Hospital, 297 patients with CMV infection were characterized. CMV disease occurred in 217/1129 patients (19.2%), and CMV infection in 297/1129 (26.3%). Gastrointestinal symptoms were recorded in 58% and fever in 47% patients with primary CMV disease, compared to 46% and 27% patients with symptomatic CMV reactivation, whereas leukopenia or thrombocytopenia were seen in only 17-28% patients, and malaise in 9-10%. Tissue-invasive CMV gastroenteritis was confirmed in 11% and CMV pneumonia in only 1% of patients with CMV disease. Only 1 patient died because of CMV infection (mortality 0.3%). Virus-related factors or the use of secondary prophylaxis did not predict the risk of recurrence, which occurred in 33% patients. In conclusion, CMV disease remains a common problem after kidney transplantation. Gastrointestinal symptoms were common, especially in patients with primary CMV infection, whereas bone marrow suppression, hepatopathy, or malaise were seen less frequently.


Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification.
Coronavirus disease 2019 is a kind of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism whereby SARS-CoV-2 invades host cells remains poorly understood. Here we used SARS-CoV-2 pseudoviruses to infect human angiotensin-converting enzyme 2 (ACE2) expressing HEK293T cells and evaluated virus infection. We confirmed that SARS-CoV-2 entry was dependent on ACE2 and sensitive to pH of endosome/lysosome in HEK293T cells. The infection of SARS-CoV-2 pseudoviruses is independent of dynamin, clathrin, caveolin and endophilin A2, as well as macropinocytosis. Instead, we found that the infection of SARS-CoV-2 pseudoviruses was cholesterol-rich lipid raft dependent. Cholesterol depletion of cell membranes with methyl-β-cyclodextrin resulted in reduction of pseudovirus infection. The infection of SARS-CoV-2 pseudoviruses resumed with cholesterol supplementation. Together, cholesterol-rich lipid rafts, and endosomal acidification, are key steps of SARS-CoV-2 required for infection of host cells. Therefore, our finding expands the understanding of SARS-CoV-2 entry mechanism and provides a new anti-SARS-CoV-2 strategy.


Differentiated Cells Derived from Hematopoietic Stem Cells and Their Applications in Translational Medicine.
Hematopoietic stem cells (HSCs) and their development are one of the most widely studied model systems in mammals. In adults, HSCs are predominantly found in the bone marrow, from where they maintain homeostasis. Besides bone marrow and mobilized peripheral blood, cord blood is also being used as an alternate allogenic source of transplantable HSCs. HSCs from both autologous and allogenic sources are being applied for the treatment of various conditions like blood cancers, anemia, etc. HSCs can further differentiate to mature blood cells. Differentiation process of HSCs is being extensively studied so as to obtain a large number of pure populations of various differentiated cells in vitro so that they can be taken up for clinical trials. The ability to generate sufficient quantity of clinical-grade specialized blood cells in vitro would take the field of hematology a step ahead in translational medicine.


The tonoplast-localized transporter OsNRAMP2 is involved in iron homeostasis and affects seed germination in rice.
Vacuolar storage of iron (Fe) is important for Fe homeostasis in plants. When sufficient, excess Fe could be stored in vacuoles for remobilization in the case of Fe deficiency. Although the mechanism of Fe remobilization from vacuoles is critical for crop development under low Fe stress, the transporters that mediate vacuolar Fe translocation into the cytosol in rice remains unknown. Here, we showed that under high Fe2+ concentrations, the Δccc1 yeast mutant transformed with the rice natural resistance-associated macrophage protein 2 gene (OsNRAMP2) became more sensitive to Fe toxicity. In rice protoplasts and transgenic plants expressing Pro35S:OsNRAMP2-GFP, OsNRAMP2 was localized to the tonoplast. Vacuolar Fe content in osnramp2 knockdown lines was higher than in the wild type, while the growth of osnramp2 knockdown plants was significantly influenced by Fe deficiency. Furthermore, the germination of osnramp2 knockdown plants was arrested. Conversely, the vacuolar Fe content of Pro35S:OsNRAMP2-GFP lines was significantly lower than in the wild type, and overexpression of OsNRAMP2 increased shoot biomass under Fe deficiency. Taken together, we propose that OsNRAMP2 transports Fe from the vacuole to the cytosol and plays a pivotal role in seed germination.


Primary laryngeal T/NK-cell lymphoma, nasal-type: an unusual location for an aggressive subtype of extranodal lymphoma.
Primary haematopoietic neoplasms of the larynx constitute less than 1% of all laryngeal tumours. Most of them are extramedullary plasmocytomas, diffuse large B-cell lymphomas, or MALT-type marginal zone B-cell lymphomas. T- or NK-cell lymphomas have rarely been reported in this location. The diagnosis of laryngeal lymphomas is a challenge, due to the absence of clinical and gross differential criteria. A pathological study is required in all cases. We present hereby a primary laryngeal T/NK-cell lymphoma, nasal-type. The patient, of Mexican origin, presented with involvement of the epiglottis, both aryepiglottic folds, and cervical lymphadenopathies. Polychemotherapy was administrated with initial partial response, but rapid local progression and exitus followed six months after the diagnosis. The extranodal T/NK-cell lymphoma, nasal-type is a very aggressive subtype of extranodal lymphoma, usually located in the nasal cavity or in nearby sites. Primary involvement of the larynx is extremely unusual. The prognosis of extranasal cases of this type of lymphoma is poor, even when they are diagnosed in localized stages.


Bi/tri-specific antibodies (HN-Fc-CD16 and HN-Fc-IL-15-CD16) cross-linking natural killer (NK)-CD16 and Newcastle Disease Virus (NDV)-HN, enhanced NK activation for cancer immunotherapy.
Cancer/tumor cells infected with the "avian paramyxovirus Newcastle Disease Virus (TC-NDV)" express the viral hemagglutinin-neuraminidase (HN) on the cell surface that is used as both the danger signal and anchor for bi/tri-specific antibodies (bs/tsAbs).We constructed a bs-Ab (HN-Fc-CD16) that bindsto HN and natural killer (NK)-CD16 receptor (FcgRIII)and a ts-Ab (HN-Fc-IL15-CD16) harbouring NK-activating cytokine "IL-15" within the bs-Ab.In silicoand computational predictions indicated proper exposure of both Abs in bs/tsAbs.Properbinding of thebi/tsAbstoHN on surface of TC-NDVandCD16+-cells was demonstrated by flow cytometry.The bi/tsAbstriggeredspecificcytotoxicity of NK cells againstTC-NDVand elicited substantial IFN-γproduction by activated NK cells(higher for ts-Ab) that sound promising for cancer immunotherapy purposes.


Characteristics of the binding of Ca2+ and other divalent metal ions to bovine alpha-lactalbumin.
Removal of the tightly bound Ca2+ ion from bovine alpha-lactalbumin (Hiraoka et al. (1980) Biochem. Biophys. Res. Commun. 95, 1098-1104) produces a pronounced conformational change, as indicated by fluorescence and absorbance changes. These changes closely resemble the changes that occur on acid denaturation of the native protein. The binding of ions to apo-alpha-lactalbumin at pH 7.4 has been examined by monitoring fluorescence changes and by direct binding measurements with 45CaCl2. The results indicate the presence of two Ca2+ binding sites on apo-bovine alpha-lactalbumin, a stronger binding site (Ka of 2.7 X 10(6) M-1) and a weaker site (Ka of 3.1 X 10(4) M-1); the fluorescence changes on Ca2+ rebinding correlate with saturation of the stronger site. Mn2+ can also bind to restore a "native" structure but with a lower affinity(Ka of 3.5 X 10(5) M-1). Zn2+ and Co2+ do not produce this change, but Zn2+ (1 mM) greatly inhibits the binding of 45Ca2+ in the direct binding assay and produces a time-dependent displacement of Ca2+ from the native protein to an apo-protein-like conformation. Co2+ does not produce these effects. Studies with metal-depleted galactosyltransferase activated with Zn2+ or Co2+ and apo-alpha-lactalbumin or Ca2+-saturated alpha-lactalbumin show that the Ca2+, Zn2+, and apo-alpha-lactalbumin are all able to bind with galactosyltransferase to produce an active lactose synthase complex.


Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer's disease.
In Alzheimer's disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels-which differ substantially between white matter tracts in the brain-are a key modulating factor of region-specific susceptibility to tau deposition. Here, we investigated whether myelination differences between fiber tracts of the human connectome are predictive of the interregional spreading of tau pathology in AD. We included two independently recruited samples consisting of amyloid-PET-positive asymptomatic and symptomatic elderly individuals, in whom tau-PET was obtained at baseline (ADNI: n = 275; BioFINDER-1: n = 102) and longitudinally in a subset (ADNI: n = 123, mean FU = 1.53 [0.69-3.95] years; BioFINDER-1: n = 39, mean FU = 1.87 [1.21-2.78] years). We constructed MRI templates of the myelin water fraction (MWF) in 200 gray matter ROIs and connecting fiber tracts obtained from adult cognitively normal participants. Using the same 200 ROI brain-parcellation atlas, we obtained tau-PET ROI values from each individual in ADNI and BioFINDER-1. In a spatial regression analysis, we first tested the association between cortical myelin and group-average tau-PET signal in the amyloid-positive and control groups. Secondly, employing a previously established approach of modeling tau-PET spreading based on functional connectivity between ROIs, we estimated in a linear regression analysis, whether the level of fiber-tract myelin modulates the association between functional connectivity and longitudinal tau-PET spreading (i.e., covariance) between ROIs. We found that higher myelinated cortical regions show lower tau-PET uptake (ADNI: rho = - 0.267, p < 0.001; BioFINDER-1: rho = - 0.175, p = 0.013). Fiber-tract myelin levels modulated the association between functional connectivity and tau-PET spreading, such that at higher levels of fiber-tract myelin, the association between stronger connectivity and higher covariance of tau-PET between the connected ROIs was attenuated (interaction fiber-tract myelin × functional connectivity: ADNI: β = - 0.185, p < 0.001; BioFINDER-1: β = - 0.166, p < 0.001). Higher levels of myelin are associated with lower susceptibility of the connected regions to accumulate fibrillar tau. These results enhance our understanding of brain substrates that explain regional variation in tau accumulation and encourage future studies to investigate potential underlying mechanisms.


Decision-making in adult thalassemia patients undergoing unrelated bone marrow transplantation: quality of life, communication and ethical issues.
Bone marrow transplantation (BMT) represents a potentially curative treatment of thalassemia. For patients without an HLA-identical sibling donor, recourse to an unrelated donor is a practicable option but the candidates and their families are faced with a difficult decision. They can either choose to continue the supportive therapy, with no chance of definitive cure, or they accept the mortality risk of BMT in the hope of obtaining a definitive resolution of the disease. We investigated the communication strategies and the post transplantation quality of life (QoL) in 19 adult thalassemia patients surviving after an unrelated donor BMT. The patients were given two questionnaires: a questionnaire to evaluate pre-transplantation communication factors and the EORTC QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the communication modalities employed by the physicians. The global post transplantation QoL in our patient cohort was found to be good. The approach used in this study may offer a contribution to understanding the decision-making process leading to the choice of a treatment with a high mortality risk for a chronic, non-malignant disease. Finally, some ethical issues of this therapeutic approach are briefly addressed.


Fabrication of ordered nanostructures of sulfide nanocrystal assemblies over self-assembled genetically engineered P22 coat protein.
Ordered ZnS and CdS nanocrystal assemblies have been synthesized by a facile bioinspired approach consisting of an initial self-assembly of engineered proteins into spherical biotemplates and a subsequent protein-directed nucleation and growth of ZnS and CdS nanocrystals symmetrically distributed over the self-assembled biotemplates.


In vitro evaluation of sustained ciprofloxacin release from κ-carrageenan-crosslinked chitosan/hydroxyapatite hydrogel nanocomposites.
Although the traditional hydrogels have shown great potential applications in designing drug delivery systems, the burst release of drugs remains an issue. In this work, we develop and evaluate a sustained release of ciprofloxacin using chitosan/hydroxyapatite/κ-carrageenan complexes. The size and structure of HA nanoparticles were characterized by X-ray diffraction, transmittance electron microscopy, and Fourier-transform infrared spectroscopy. The ciprofloxacin-loaded hydrogel nanocomposites exhibited antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. Due to the introduced HA, the release of ciprofloxacin occurred in a sustained release manner. While the pristine chitosan/κ-carrageenan complex released about 98% of ciprofloxacin during 120 h, only 52 and 66% of the loaded drug was released from hydrogel nanocomposites containing high and low content of HA, respectively. The sustained release of ciprofloxacin from the hydrogel nanocomposites identifies them as a potential candidate for designing drug delivery systems with prolonged release ability.


The immobilization, plant uptake and translocation of cadmium in a soil-pakchoi (Brassica chinensis L.) system amended with various sugarcane bagasse-based materials.
Many organic materials have been used to decrease heavy-metal bioavailability in soil via in-situ remediation due to its high efficiency and easy operation; meanwhile, cheap materials have also been pursued to decrease the cost of remediation. Agricultural wastes exhibit their potential in remediation materials due to their low cost; however, raw agricultural wastes have a low ability to immobilize heavy metals in soil. Attempts have been made to modify agricultural wastes to improve the efficiency of heavy-metal passivation. In this study, novel agricultural waste-based materials, raw sugarcane bagasse (SB), citric acid modified (SSB) and citric-acid/Fe3O4 modified (MSB) sugarcane bagasse at 0.5% and 1% addition rates, were compared for their effectiveness in soil Cd passivation and Cd accumulations in pakchoi plants in a 30-day pot experiment. The addition of SB did not decrease soil bioavailable Cd effectively and slightly decreased Cd accumulation in plant roots and leaves. In comparison, SSB and MSB exhibited a great potential to decrease the transformation, translocation and accumulation of Cd with the decrease being greater at 1% than 0.5% rate in the soil-pakchoi system. For example, the addition of SSB and MSB at 0.5% decreased the concentration of Cd in leaves by 10%, and 16%, and at 1% decreased the concentration by 25% and 30%, respectively. High pH and abundant functional groups of three amendments played important roles in Cd immobilization. The enhanced microbial activities might also contribute to Cd passivation. However, plant growth was decreased in the amended treatments except SSB at 0.5% rate. The results suggest that citric-acid-modified sugarcane bagasse at addition rate of 0.5% has a potential to immobilize Cd in soil and decrease Cd accumulation in edible part of pakchoi effectively without decreasing vegetable growth.


Impact of shift work on blood pressure among emergency medical services clinicians and related shift workers: A systematic review and meta-analysis.
Compared to day workers, shift workers face an elevated risk of cardiovascular disease. We reviewed the evidence to address the research question: Does acute exposure to shift work impact (blunt) the natural drop (dip) in Blood Pressure (BP) occurring during sleep and/or nighttime hours? (PROSPERO CRD42018110847). We performed a systematic review of five databases. We compared pooled estimates of mean BP stratified by periods of shift work, rest/leisure, and sleep, and evaluated the quality of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Our search covered 1/1/1980-10/24/2018 and yielded 1,636 records. Inter-rater agreement during screening was high (Kappa=0.87). We retained 44 studies described in 50 publications. We identified wide variation in shift worker type, shift schedules, and regularity of BP measurements. Most studies examined BP during one shift workday and one rest/leisure day. No study examined the impact of repeated exposure to shift work on the sleep-related dip in BP. Eighteen studies examined night shifts and one reported on BP during sleep post night shift. Compared to BP measured during shift work, BP measured during any sleep period separate from shift work was lower by 17.5 mmHg Systolic BP (95%CI 15.75, 19.27) and 15.4 mmHg lower for Diastolic BP (95%CI 14.38, 16.42) (p < 0.05). There is limited research exploring the acute and long-term impact of shift work on BP during sleep. The available evidence is heterogenous, low quality, and suggests that the mean dip in BP during sleep separate from shift work is not blunted.


Drug-coated balloon angioplasty versus balloon angioplasty for treating patients with in-stent restenosis in the femoropopliteal artery: A meta-analysis.
The introduction of endovascular surgery has led to frequent stent use, although in-stent restenosis (ISR) remains a challenging issue. Drug-coated balloon (DCB) and conventional balloon angioplasty (BA) are common endovascular procedures for addressing ISR in the femoropopliteal artery. However, there is controversy regarding which procedure provides the greatest benefit to patients. The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for prospective controlled trials that compared DCB and BA for patients with ISR in the femoropopliteal artery. The study has been approved by Ethics Committee of Wuhan Central Hospital. The meta-analysis included 6 prospective trials with 541 patients. We found that DCB use was associated with significant reductions in binary restenosis at 6 months (relative risk [RR]: 0.45, 95% confidence interval [CI]: 0.33-0.63; P < .00001), binary restenosis at 1 year (RR: 0.44, 95% CI: 0.34-0.57; P < .00001), target lesion revascularization (TLR) at 6 months (RR: 0.36, 95% CI: 0.20-0.65; P = .0006), and TLR at 1 year (RR: 0.38, 95% CI: 0.27-0.54; P < .00001). The DCB group also had significantly better clinical improvement (RR: 1.39, 95% CI: 1.13-1.71; P = .002), although we did not detect inter-group differences in terms of death, target vessel thrombosis, or ipsilateral amputation. The brand of DCB may a cause of heterogeneity. Relative to BA, DCB use increases the durability of treatment for ISR in the femoropopliteal artery, based on significant reductions in binary restenosis and TLR at 6-12 months after the procedure. Furthermore, DCB use was associated with better clinical improvement. However, additional randomized controlled trials are needed to validate these findings.


Effects of phenytoin on the cyclic nucleotide system in the motor nerve terminal.
The effects of phenytoin on the motor nerve terminal were evaluated on the in vivo cat soleus nerve muscle preparation. Phenytoin, 10 mg/kg, reduced the repetitive aftercharges in motor nerve endings due to tetanic conditioning. It also reduced the repetitive activity due to adenylate cyclase activation with NaF, or to exogeneous dibutyryl cyclic AMP. These effects of phenytoin could be reversed by administering theophylline, a phosphodiesterase inhibitor, or by increasing the extracellular concentration of calcium. The effects of phenytoin could also be reversed by 3-aminopyridine, but not by tetraethylammonium chloride. Verapamil, a calcium current antagonist, produced effects that were identical to phenytoin. It is concluded that phenytoin blocks a cyclic nucleotide-mediated calcium influx that is associated with transmitter release. This calcium flux also appears to control a slow potassium current that is responsible for post-tetanic hyperpolarization.


Chronic hyperglycaemia increases the vulnerability of the hippocampus to oxidative damage induced during post-hypoglycaemic hyperglycaemia in a mouse model of chemically induced type 1 diabetes.
Chronic hyperglycaemia and recurrent hypoglycaemia are independently associated with accelerated cognitive decline in type 1 diabetes. Recurrent hypoglycaemia in rodent models of chemically induced (streptozotocin [STZ]) diabetes leads to cognitive impairment in memory-related tasks associated with hippocampal oxidative damage. This study examined the hypothesis that post-hypoglycaemic hyperglycaemia in STZ-diabetes exacerbates hippocampal oxidative stress and explored potential contributory mechanisms. The hyperinsulinaemic glucose clamp technique was used to induce equivalent hypoglycaemia and to control post-hypoglycaemic glucose levels in mice with and without STZ-diabetes and Nrf2-/- mice (lacking Nrf2 [also known as Nfe2l2]). Subsequently, quantitative proteomics based on stable isotope labelling by amino acids in cell culture and biochemical approaches were used to assess oxidative damage and explore contributory pathways. Evidence of hippocampal oxidative damage was most marked in mice with STZ-diabetes exposed to post-hypoglycaemic hyperglycaemia; these mice also showed induction of Nrf2 and the Nrf2 transcriptional targets Sod2 and Hmox-1. In this group, hypoglycaemia induced a significant upregulation of proteins involved in alternative fuel provision, reductive biosynthesis and degradation of damaged proteins, and a significant downregulation of proteins mediating the stress response. Key differences emerged between mice with and without STZ-diabetes following recovery from hypoglycaemia in proteins mediating the stress response and reductive biosynthesis. There is a disruption of the cellular response to a hypoglycaemic challenge in mice with STZ-induced diabetes that is not seen in wild-type non-diabetic animals. The chronic hyperglycaemia of diabetes and post-hypoglycaemic hyperglycaemia act synergistically to induce oxidative stress and damage in the hippocampus, possibly leading to irreversible damage/modification to proteins or synapses between cells. In conclusion, recurrent hypoglycaemia in sub-optimally controlled diabetes may contribute, at least in part, to accelerated cognitive decline through amplifying oxidative damage in key brain regions, such as the hippocampus. The datasets generated during and/or analysed during the current study are available in ProteomeXchange, accession no. 1-20220824-173727 ( www.proteomexchange.org ). Additional datasets generated during and/or analysed during the present study are available from the corresponding author upon reasonable request.


Is eculizumab indicated in patients with atypical hemolytic uremic syndrome already on prolonged dialysis? A case report and review of the literature.
Eculizumab has caused a revolution in the treatment and prognosis of atypical hemolytic uremic syndrome. Early initiation of treatment is recommended to increase chances of renal recovery. We describe a boy with atypical hemolytic uremic syndrome who started eculizumab therapy after being on dialysis for 4.5 months, with complete anuria. With treatment, he was weaned off dialysis. We review the evidence in the literature and discuss the possible mechanism by which eculizumab induces renal recovery even in patients already on prolonged dialysis. This case report highlights the importance of a treatment trial with eculizumab, even in patients already on prolonged dialysis.


Orem's nursing self-care deficit theory: A theoretical analysis focusing on its philosophical and sociological foundation.
The self-care deficit nursing theory (SCDNT) advocated by Dorothea E. Orem is widely known and used in nursing practice worldwide. However, its broader philosophical and sociological context is often ignored. The theoretical analysis of Orem's SCDNT reported in this article focuses on four aspects of the theory: its essential structure/core values, affirmation of nursing as a practical science, philosophical foundations, and the sociological context surrounding its development. By interpreting the SCDNT from a philosophical and sociological viewpoint, it can be concluded that Orem established human-to-human nursing as a science premised on the existence of human beings as the central value of the theory. Moreover, Orem emphasized that the human-to-human relationship necessarily precedes the nurse-patient interface. The new interpretation and evaluation perspectives presented in this report may further the understanding of Orem's SCDNT. Moreover, they highlight the multifaceted aspects of nursing practice and role of person-to-person relationships as the basis of the SCDNT.


Trimethylsilyl trifluoromethanesulfonate-accelerated addition of catalytically generated zinc acetylides to aldehydes.
In the presence of TMSOTf, a wide variety of terminal acetylenes add rapidly and efficiently to aldehydes via a catalytically generated zinc acetylide. In the absence of TMSOTf, no reaction is observed under otherwise identical conditions.


Correction: Healthy lifestyle behaviors are major predictors of mental wellbeing during COVID-19 pandemic confinement: A study on adult Arabs in higher educational institutions.
[This corrects the article DOI: 10.1371/journal.pone.0243524.].


A role for translational regulation by S6 kinase and a downstream target in inflammatory pain.
Translational controls pervade neurobiology. Nociceptors play an integral role in the detection and propagation of pain signals. Nociceptors can undergo persistent changes in their intrinsic excitability. Pharmacological disruption of nascent protein synthesis diminishes acute and chronic forms of pain-associated behaviours. However, the targets of translational controls that facilitate plasticity in nociceptors are unclear. We used ribosome profiling to probe the translational landscape in dorsal root ganglion (DRG) neurons from male Swiss-Webster mice, after treatment with nerve growth factor and IL-6. Expression dynamics of c-Fos were followed with immunoblotting and immunohistochemistry. The involvement of ribosomal protein S6 kinase 1 (S6K1), a downstream component of mTOR signalling, in the control of c-Fos levels was assessed with low MW inhibitors of S6K1 (DG2) or c-Fos (T-5224), studying their effects on nociceptor activity in vitro using multielectrode arrays (MEAs) and pain behaviour in vivo in Swiss-Webster mice using the hyperalgesic priming model. c-Fos was expressed in sensory neurons. Inflammatory mediators that promote pain in both humans and rodents promote c-Fos translation. The mTOR effector S6K1 is essential for c-Fos biosynthesis. Inhibition of S6K1 or c-Fos with low MW compounds diminished mechanical and thermal hypersensitivity in response to inflammatory cues. Additionally, both inhibitors reduced evoked nociceptor activity. Our data show a novel role of S6K1 in modulating the rapid response to inflammatory mediators, with c-Fos being one key downstream target. Targeting the S6 kinase pathway or c-Fos is an exciting new avenue for pain-modulating compounds.


Leadership and management training of pediatric intensivists: how do we gain our skills?
Intensivists manage a diverse team of health care professionals. For decades, business literature has recognized the value of leadership and management skills, yet this is relatively unexplored in critical care. Investigate the status of intensivists' preparation for the clinical leadership and management roles that they will assume after medical training. Authoritative business leadership literature was reviewed to identify attributes of successful leadership and management relevant to critical care. A survey was designed to assess the process by which intensivists learn these attributes and to assess their perceived level of preparedness (20 items). Each survey item received a preparedness score structured as a Likert scale (1=not prepared, 5=very prepared), representing the averaged response to each item. In addition, an inadequate preparedness percentage was created representing the percentage of respondents answering "not at all prepared" and "hardly prepared" on the Likert-scaled items. Pediatric Critical Care Medicine Board Review Course, Washington, DC, 2004. Physician course participants (n=259). Survey administration. The response rate was 61% (n = 159). The majority of respondents (69%) had completed fellowship training (median, 1 yr posttraining). Modeling the behavior of other physicians was the dominant technique for leadership and management skill acquisition (86%). The respondents were taught these skills by a variety of sources (attendings, 92%; other fellows, 42%; nurses, 37%; teachers, 20%; residents, 14%). Most (82%) thought that leadership and management training was important or very important, yet only 47% had received any formal training (40% fellowship, 36% residency, 21% medical school, 16% masters, 30% other). Overall, respondents felt only "somewhat prepared" for the 20 leadership and management items surveyed (mean+/- sd of preparedness score, 2.8+/- 0.2). Respondents were least prepared to manage conflict within a team, manage conflict with other groups, and manage stress effectively (preparedness scores of 2.5, 2.4, and 2.6 and inadequate preparedness percentages of 19.5%, 15.7%, and 18.9%, respectively). Respondents were most prepared to "set high standards" (preparedness score=3.3). Of the respondents feeling at least somewhat prepared, only 33% credited medical training as preparing them. Although leadership and management training was perceived as important to this sample of pediatric generally young intensivists, most feel inadequately prepared for critical aspects of these responsibilities, most notably, stress and conflict management. These findings provide an opportunity for specific curriculum development in leadership and management for those believing these skills should be further refined.


Achieving Baby Friendly through a quality management approach.
In 1994, The Royal Women's Hospital became the first public hospital in Australia to achieve Accreditation to the UNICEF Baby Friendly Hospital Initiative. The 10 Steps to Successful Breastfeeding, effectively created standards against which an organisation can be assessed on their ability to provide women with consistent advice, access to education and support. The application of the Continuous Quality Improvement cycle of Plan, Do, Check, Act, was successful in assisting maternity staff to assess their practice, implement improvements and evaluate against the 10 Steps. Ongoing monitoring ensures that the high standard is maintained by the hospital.


In-vitro and in-vivo comparison of mezlocillin and cefoxitin.
The efficacy, toxicity, microbiology and pharmacology of cefoxitin and mezlocillin were compared in a clinical and laboratory study. In 81 patients treated with cefoxitin and 83 treated with mezlocillin, clinical and bacteriological cures were achieved in 79.2% and 85.5% respectively. Both antibiotics were effective in the treatment of septicaemia, pulmonary infections, urinary tract infections, intra-abdominal and pelvic infections and skin and soft-tissue infections. Both were also effective in the treatment of anaerobic infections. No major haematological, hepatic, or renal toxicity was encountered in patients treated with either drug.


In-hospital recurrence in a Chinese large cohort with acute ischemic stroke.
Acute ischemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. The purpose of this study was to assess the frequency and risk factors of in-hospital recurrence in patients with AIS in China. A retrospective analysis was performed of all of the patients with new-onset AIS who were hospitalized in the past three years. Recurrence was defined as a new stroke event, with an interval between the primary and recurrent events greater than 24 hours; other potential causes of neurological deterioration were excluded. The risk factors for recurrence were analyzed using univariate and logistic regression analyses. A total of 1,021 patients were included in this study with a median length of stay of 14 days (interquartile range,11-18). In-hospital recurrence occurred in 58 cases (5.68%), primarily during the first five days of hospitalization. In-hospital recurrence significantly prolonged the hospital stay (P < 0.001), and the in-hospital mortality was also significantly increased (P = 0.006). The independent risk factors for in-hospital recurrence included large artery atherosclerosis, urinary or respiratory infection and abnormal blood glucose, whereas recurrence was less likely to occur in the patients with aphasia. Our study showed that the patients with AIS had a high rate of in-hospital recurrence, and the recurrence mainly occurred in the first five days of the hospital stay. In-hospital recurrence resulted in a prolonged hospital stay and a higher in-hospital mortality rate.


Effects of exogenous melatonin and tryptophan on fecal shedding of E. coli O157:H7 in cattle.
Fecal prevalence of Escherichia coli O157 in ruminants is highest in the summer decreasing to very low levels in the winter. We hypothesize that this seasonal variation is a result of physiological responses within the host animal to changing day-length. To determine the effects of melatonin (MEL) on fecal shedding of E. coli O157:H7 in cattle, eight crossbred beef steers identified as shedding E. coli O157:H7, were allotted to treatment: control or MEL (0.5 mg/kg body weight (BW); 1x) administered orally daily for 7 days. After a 5-day period of no treatment, a second MEL dose (5.0 mg/kg BW; 10x) was administered daily for 4 days. Fecal samples were collected daily for qualification of E. coli O157:H7. No differences (P > 0.10) were observed in the percentage of E. coli O157:H7 positive fecal samples in steers receiving the 1x MEL dose, however the 10x dose decreased (P = 0.05) the percentage of fecal samples E. coli O157:H7 positive. Serum MEL concentrations were higher in the 1x, but not 10x, treated animals compared to control animals. Although it is difficult to explain, this may be a result of decreasing day-length increasing serum melatonin concentrations that may have masked any treatment effect on serum melatonin. In a second similar experiment, a second group of cattle (heifers and steers) were administered tryptophan (TRP) over a 17-day experimental period (5 g/head/day for 10 days followed by 10 g/head/day for 7 days). Tryptophan had no effect (P > 0.20) on the percentage of fecal samples positive for E. coli O157. Serum TRP (P < 0.05), but not MEL (P > 0.20), concentrations were elevated in TRP-treated animals. The decrease in the number of positive fecal samples observed in the first experiment, may be related to gastrointestinal MEL, affected by the 10x, but not 1x MEL dose.


Knowledge, attitude and factors associated with induced abortion among female students 'of Private Colleges in Ambo town, Oromia regional state, Ethiopia: a cross-sectional study.
Around 73 million induced abortions take place worldwide each year. Six out of 10 (61%) of all unintended pregnancies, and 3 out of 10 (29%) of all pregnancies, end in induced abortion. In Africa, nearly half of all abortions occur under the least safe circumstances. In Ethiopia 35% of women obtaining induced abortions service. Therefore, thisstudy aims to assess knowledge, attitude, and associated factors towards induced abortion serviceamong female students of private Colleges in Ambo town, Ethiopia, 2022. An Institution-based cross-sectional study was conducted from January 15, 2022, to February 15, 2022, among college students in Ambo, Ethiopia. Data were collected from 631 female students using semi-structured self-administered questionnaires by a systematic sampling method. We collected data on demographics, Institutional factors: facility policy and regulation, sexual experience, knowledge, and attitude. Bivariable and multivariable logistic regression analyses were done to identify the association of dependent and independent variables using SPSS, version 26, at 95% of confidence interval by adjusting for confounding factors. Finally, variables with p-value ≤ 0.05 were taken as factors associated. All the participants gave their responses.Among the participants 279 (44.2) have good knowledge while the majority 352 (55.8%) of the students had poor knowledge about induced abortion. Age [AOR = 4.64, 95% CI (2.95,7.30)], Marital status [AOR = 5.24, 95% CI (3.16, 8.69)], religion [AOR = 0.48, 95% CI (0.26,0.81)], Year of study [AOR = 4.51, 95% CI (2.88,7.08)], Monthly earn/income [AOR = 2.07, 95% (CI 1.40,3.07)], Ever had sex [AOR = 1.92, 95% CI (1.26,2.92)] and urban residence [AOR = 1.87, 95% CI (1.26, 4.35)] were factors associated with knowledge of students towards induced abortion. Regarding attitude, 377 (59.7%) of students had good attitude towards induced abortion. Marital status [AOR = 2.30, 95% CI (1.30, 4.0)], and Religion [AOR = 0.47, 95% CI (0.10, 2.23)] were factors significantly associated with attitude towards induced abortion. More than half of the participants have poor knowledge while majority of the students have a good attitude toward induced abortion. Since majority of the students (55.8%) have poor knowledge about induced abortion: health education, short course training, panel discussions and communication programs for youth on induction of abortion services is crucial.


[Systemic lupus erythematosus in men: difficulties of diagnosis and specific features of clinical picture].
To characterize specific clinical features of systemic lupus erythematosus (SLE) in male patients. A total of 146 male patients with verified SLE diagnosis were examined in the Research Institute of Rheumatology. Literature and original data on SLE clinical characteristics in men were analysed. Diagnostic search and variants of SLE in male patients are described. To upgrade knowledge on SLE clinical characteristics, further prospective trials should be made.


Rotational Stability of Intraocular Lenses: A Standardized Method for More Accurate Measurements in Future Studies.
To assess the reliability and reproducibility of a new semiautomated evaluation method, "Rotix," for intraocular lens (IOL) rotation and to define a standardized evaluation method for future toric IOL studies. Reliability and reproducibility study. Setting: Department of Ophthalmology, Medical University of Vienna. A dataset of 25 patients with 2 consecutive follow-up visits was created to test the intra- and interrater reliability. A data test set of 10 patients including 30 pictures taken 5 minutes apart was created to test the short-term reproducibility. Evaluation of IOL rotational stability using nontoric implants in 25 × 2 consecutive follow-up visits. Two experienced graders performed axis evaluation 3 times in a randomized order. One experienced grader performed axis evaluation for the short-term reproducibility study. Reference landmarks at the end of operation were used to assess the IOL axis. Intra- and interrater reliability and short-term reproducibility of axis measurements. Mean standard deviation for intrarater reliability was 0.16 degrees. The intraclass correlation coefficients were 0.97 for grader 1 and 0.96 for grader 2. A very high interrater correlation of 0.95 was found. The mean individual difference between grader 1 and grader 2 was 0.061 ± 0.28 degrees. Short-term reproducibility showed a mean standard deviation of 0.22 ± 0.14 degrees. The novel semiautomated evaluation method showed an accurate inter- and intrarater reliability. Short-term reproducibility was below 0.25 degrees. The method of using nonmovable reference landmarks showed reliable results and should be used as a standard in future toric IOL studies.


Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer.
Patients with epithelial ovarian cancer (EOC) typically present with late-stage disease, posing a significant challenge to treatment. Although taxane and platinum-based chemotherapy plus surgical debulking are initially effective, EOC is marked by frequent recurrence with resistant disease. Immunotherapy represents an appealing treatment paradigm given the ability of immune cells to engage metastatic sites and impede recurrence; however, response rates to checkpoint blockade in ovarian cancer have been disappointing. Here, we tested whether class I HDAC inhibition can promote anti-tumor T cell responses in a spontaneous and nonspontaneous murine model of EOC. We used the spontaneous Tg-MISIIR-Tag and nonspontaneous ID8 models of murine ovarian cancer to test this hypothesis. Whole tumor transcriptional changes were assessed using the nCounter PanCancer Mouse Immune Profiling Panel. Changes in select protein expression of regulatory and effector T cells were measured by flow cytometry. We found that treatment with the class I HDAC inhibitor entinostat upregulated pathways and genes associated with CD8 T cell cytotoxic function, while downregulating myeloid derived suppressor cell chemoattractants. Suppressive capacity of regulatory T cells within tumors and associated ascites was significantly reduced, reversing the CD8-Treg ratio. Our findings suggest class I HDAC inhibition can promote activation of intratumoral CD8 T cells, potentially by compromising suppressive networks within the EOC tumor microenvironment. In this manner, class I HDAC inhibition might render advanced-stage EOC susceptible to immunotherapeutic treatment modalities.


Human sentiments monitoring during COVID-19 using AI-based modeling.
The whole world is facing health challenges due to wide spread of COVID-19 pandemic. To control the spread of COVID-19, the development of its vaccine is the need of hour. Considering the importance of the vaccines, many industries have put their efforts in vaccine development. The higher immunity against the COVID can be achieved by high intake of the vaccines. Therefore, it is important to analysis the people's behaviour and sentiments towards vaccines. Today is the era of social media, where people mostly share their emotions, experience, or opinions about any trending topic in the form of tweets, comments or posts. In this study, we have used the freely available COVID-19 vaccines dataset and analysed the people reactions on the vaccine campaign using artificial intelligence methods. We used TextBlob() function of python and found out the polarity of the tweets. We applied the BERT model and classify the tweets into negative and positive classes based on their polarity values. The classification results show that BERT has achieved maximum values of precision, recall and F score for both positive and negative sentiment classification.


Synthesis, in vitro biological investigation, and molecular dynamics simulations of thiazolopyrimidine based compounds as corticotrophin releasing factor receptor-1 antagonists.
Corticotrophin releasing factor receptor-1 (CRFR1) is a potential target for treatment of depression and anxiety through modifying stress response. A series of new thiazolo[4,5-d]pyrimidine derivatives were designed, prepared and biologically evaluated as potential CRFR1 antagonists. Four compounds produced more than fifty percent inhibition in the [125I]-Tyr0-sauvagine specific binding assay. Assessment of binding affinities revealed that compound (3-(2,4-dimethoxyphenyl)-7-(dipropylamino)-5-methylthiazolo[4,5-d]pyrimidin-2(3H)-one) 8c was the best candidate with highest binding affinity (Ki = 32.1 nM). Further evaluation showed the ability of compound 8c to inhibit CRF induced cAMP accumulation in a dose response manner. Docking and molecular dynamics simulations were used to investigate potential binding modes of synthesized compounds as well as the stability of 8c-CRFR1 complex. These studies suggest similar allosteric binding of 8c compared to that of the co-crystalized ligand CP-376395 in 4K5Y pdb file.


The evaluation of autonomic nervous function in a patient with hereditary sensory and autonomic neuropathy type IV with novel mutations of the TRKA gene.
We report on a 10-year-old girl with anhidrosis and insensibility to pain, but no severe mental retardation or self-mutilation, diagnosed as hereditary sensory and autonomic neuropathy type IV (HSAN IV). Genetic analysis of her TRKA gene, which is responsible for HSAN IV, revealed two novel missense mutations in the tyrosine kinase domain. Cardiovascular autonomic nervous system function tests showed normal muscle sympathetic nerve activity associated with arterial baroreflex, reduced skin sympathetic nerve activity in the second and fifth fingers and palms, and abnormal circadian rhythm of cardiovascular autonomic nervous system. These findings have never before been reported in HSAN IV and may provide a clue to the neurological pathophysiology of this disease.


Microfluidic measurement of individual cell membrane water permeability.
This paper reports a microfluidic lab-on-chip for dynamic particle sizing and real time individual cell membrane permeability measurements. To achieve this, the device measures the impedance change of individual cells or particles at up to ten time points after mixing with different media, e.g. dimethyl sulfoxide or DI water, from separate inlets. These measurements are enabled by ten gold electrode pairs spread across a 20 mm long microchannel. The device measures impedance values within 0.26 s after mixing with other media, has a detection throughput of 150 samples/second, measures impedance values at all ten electrodes at this rate, and allows tracking of individual cell volume changes caused by cell osmosis in anisosmotic fluids over a 1.3 s postmixing timespan, facilitating accurate individual cell estimates of water permeability. The design and testing were performed using yeast cells (Saccharomyces cerevisiae). The relationship between volume and impedance in both polystyrene calibration beads as well as the volume-osmolality relationship in yeast were demonstrated. Moreover, we present the first noninvasive and non-optically-based water permeability measurements in individual cells.


Response to treatment in panic disorder with associated depression.
Thirty outpatients with panic disorder (PD) were treated at an anxiety clinic using a symptom-focused approach. Thirteen (43%) had no history of major depressive disorder (MDD), 12 (40%) had a history of secondary MDD, and 5 (17%) had history of primary MDD. The outcome was equally good in patients with no history of MDD (77% had good or excellent outcomes) and patients with a history of secondary MDD (83% had good or excellent outcomes). Patients with a history of primary MDD had the worst outcomes. These findings agree with earlier studies showing that secondary MDD does not adversely affect prognosis of patients presenting for treatment of PD.


Design, Synthesis and Pharmacological Activity of New Pyrrolo[1,2-A] Pyrazine Translocator Protein (TSPO) Ligands.
Translocator protein 18 kDa (TSPO) is a promising target for the creation of effective and safe neuropsychotropic drugs. The ligands of TSPO exhibit anxiolytic, antidepressant, neuroprotective and other activities without the side effects of benzodiazepines. New TSPO ligands in the series of N,1-diphenylpyrrolo[1,2-a]pyrazine-3-carboxamides derivatives were designed using calculated pharmacophore model and molecular docking analysis. The synthesis of new compounds was carried out by two schemes using [3+3]-cycloaddition reaction of 2-azidoacrylic acid derivatives with pyrrolphenylketone as a key stage. The anxiolytic activity of new substances has been established using open field test with flash. Several synthesized N,1-diphenylpyrrolo[1,2-a]pyrazine-3-carboxamides derivatives significantly increased the total motor activity of Balb/c mice compared to the control. The structureactivity relationship was investigated. The most effective compound was found to be GML-11 (Nbenzyl- N,1-diphenylpyrrolo[1,2-a]pyrazine-3-carboxamide), which had anxiolytic action in the dose range from 0.001 to 0.100 mg/kg (Balb/c, i.p.). This compound is two orders of magnitude higher in dose activity than all other pyrrolo[1,2-a]pyrazine TSPO ligands. Molecular modelling methods allowed us to create new TSPO ligands in the series of N,1-diphenylpyrrolo[1,2-a]pyrazine-3-carboxamides with high anxiolytic activity.


CHD1L prevents lipopolysaccharide-induced hepatocellular carcinomar cell death by activating hnRNP A2/B1-nmMYLK axis.
Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L) has been characterized to be a driver gene in hepatocellular carcinoma (HCC). However, the intrinsic connections between CHD1L and intestinal dysbacteriosis-related inflammation reaction in HCC progression remain incompletely understood. In this study, a specific correlation between CHD1L and nonmuscle isoform of myosin light chain kinase (nmMLCK/nmMYLK), a newly identified molecule associated NF-κB signaling transduction, was disclosed in HCC. CHD1L promotes nmMYLK expression and prevents lipopolysaccharide (LPS) induced tumor cell death. In vitro experiment demonstrated that overexpressed nmMYLK is essential for CHD1L to maintain HCC cell alive, while knocking down nmMYLK significantly attenuate the oncogenic roles of CHD1L. Mechanism analysis revealed that nmMYLK can prevent Caspase-8 from combining with MyD88, an important linker of TLRs signaling pathway, while, knocking down nmMYLK facilitate the MyD88 combines with Caspase-8 and lead to the proteolytic cascade of Caspase as well as the consequent cell apoptosis. Mechanism analysis showed that CHD1L promotes the nmMYLK expression potentially through upregulating the heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) expression, which can bind to myosin light chain kinase (MYLK) pre-mRNA and lead to the regnant translation of nmMYLK. In summary, this work characterizes a previously unknown role of CHD1L in preventing LPS-induced tumor cell death through activating hnRNP A2/B1-nmMYLK axis. Further inhibition of CHD1L and its downstream signaling could be a novel promising strategy in HCC treatment.


The diagnostic impact of implementing a molecular-based algorithm to standard mycobacterial screening at a reference laboratory with an intermediate prevalence for non-respiratory samples.
Rapid, reliable results can be given by molecular, direct detection and identification of the Mycobacterium tuberculosis (MTB/Mtb) complex from clinical samples. The Xpert MTB/RIF assay is an assay that has been availablefor more than a decade for identification of Mycobacterium tuberculosis and resistance to rifampicin. However, there is minimal evidence on its clinical usefulness in paucibacillary, non-respiratory samples. The Xpert MTB/RIF assay clinical utility index, its diagnostic characteristics and the number required to diagnose 2935 non-respiratory specimens submitted for routine mycobacterial work-up in a reference laboratory in an intermediate prevalence setting per specimen form were evaluated. The Xpert MTB/RIF assay showed a variable clinical utility index and number required to diagnose (NND) depending on the type of specimen, which was moderate in tissue biopsies (NND = 1.8) and excellent in pus and urine samples, compared to acid-fast microscopy and culture as a gold standard technique (NND = 1.1 and 1.2). Microscopy, on the other hand, consistently showed a weak to fair index of clinical usefulness in all specimen forms, with in NND of 2.3-12.5. The NND for detecting tuberculous infection in the cerebrospinal fluid by the Xpert MTB/RIF assay was noted to be 1.2, with a moderate clinical utility index of 0.8. The evidence presented indicates that the overall appropriate diagnostic utility of the Xpert MTB/RIF assay is clinically successful in most non-respiratory samples. To check the cost-effectiveness and prognostic effect of integrating this completely automated molecular-based assay into the routine testing algorithm for non-respiratory mycobacterial specimens, further data must be collected.


Short-term changes in meteorological conditions and suicide: A systematic review and meta-analysis.
Suicide is a leading cause of death, particularly for young adults. Suicidal behaviours are influenced by a wide-range of personal, social, and cultural factors. Emerging evidence suggests that daily changes in meteorological conditions, including temperature, increases the risk of suicide. We conducted a systematic review and meta-analysis of studies that examined associations between either daily, or weekly, variations for eight meteorological variables and suicide outcomes (attempts, or deaths). Meta-analytic methods were applied to derive summary measures of association using random effect models. We assessed the heterogeneity in these associations by region and biological sex. We identified 29 studies of suicide. Of these, 26 reported associations between temperature, while fewer studies reported on rain (n = 4), solar radiation (n = 4), humidity (n = 3), sunshine (n = 3), atmospheric pressure (n = 2), wind (n = 2) and cloud cover (n = 2). The overall relative risk for suicide deaths/attempts per 1 °C increase in ambient temperature was 1.016 (95% CI: 1.013-1.019). Subgroup analysis of temperature found stronger associations with suicide when using the maximum rather than the mean daily temperature, among men, and for completed suicides relative to attempts. Regionally, the strongest associations were found in the East Asia and Pacific region. While associations were found for solar radiation and cloud coverage and suicide, we did not undertake a meta-analysis for these exposures as it was not possible to standardize measures of association across studies. Statistically significant associations were not observed for other identified meteorological variables. Our findings suggest that daily increases in temperature increase the risk of suicide, particularly, among men and in the East Asia and Pacific region.


Noninvasive skin measurements to monitor chronic renal failure pathogenesis.
Cutaneous manifestations are common in hemodialysis (HD) patients with chronic renal failure (CRF). Associated with uremia, pruritus is a frequently observed symptom in CRF patients and increases with deteriorating renal function. Skin hydrophilic biomarkers (SHB) may be altered in CRF compared to healthy controls. A noninvasive skin wash sampling technique to detect the expression of SHB, by measuring their secretion on skin surface, was used on HD patients and healthy controls. Hydrophilic antioxidants such as total antioxidant scavenging capacity (TSC) and uric acid (UA) content, and cytokine inflammatory biomarkers such as TNFα and IL-10 levels were estimated. Our findings demonstrate significant alterations of the SHB level between HD patients and healthy volunteers. Furthermore, such alterations of secreted SHB correlated markedly with detected changes in blood biochemistry and dermatology severity score. Skin wash sampling of SHB is a noninvasive technique that distinguishes between HD patients and healthy controls. In HD patients, SHB is associated with biochemical markers in blood and dermatologic symptom severity. This technique is also suggested, as a monitoring tool for diagnosis and treatments of various diseases, in which skin dysfunction is involved.


Total vertebrectomy and spine shortening for the treatment of T12-L1 spine dislocation: Management with suboptimal resources.
Total vertebrectomy with spine shortening has been reported for the treatment of difficult cases of traumatic spine dislocation, both in acute and chronic phase. We report an exceptional case of a five-week-old T12-L1 spine dislocation in a 25-year-old female with complete paraplegia as a result of trauma in Ciudad de León (Nicaragua). In view of the time since the dislocation, we performed a complete L1 vertebrectomy in order to reduce the dorsolumbar hinge. For osteosynthesis material we had only eight screws and two Steffee plates. We therefore introduced pedicle screws at levels T11, T12, L2 and L3 on the right side and T11, T12, L3 and L4 on the left, and performed manual reduction of the spine. Steffee plates were placed and we added sublaminar wires to reinforce the osteosynthesis. Fifteen months after surgery, there has been no neurological improvement.


Detubulation effects on the action of zinc on frog skeletal muscle action potential.
Detubulation of the untreated fiber decreases the time constant of the action potential's foot (tauf) and increases the maximal rate of rise of the spike (Vmax). Zinc at all concentrations, and regardless of whether the fiber is intact or detubulated, increases tauf and decreases Vmax, and thus seems to decrease Na activation of the fiber. Detubulation was used principally to elucidate the localization and mechanism of the Zn2+-induced retardation of the falling phase of the frog sartorius fiber action potential, which evidently results from a general depression of delayed rectification. At 50 to 1000 mum, Zn2+ not only prolongs repolarization of intact fibers (measured by increase in t0.5, the half-time of the spike's fall), but also produces a marked hump early in this phase. Detubulation of zinc-free fibers reduces t0.5 to about 80% of its intact value, and under Zn2+ treatment t0.5 is increased but only to about 80% of that produced in the inus, detubulation decreases t0.5 in Zn2+-treated fibers not only to about 80% of that produced in the intact fiber, and the falling-phase hump is completely obliterated. Thus, detubulation decreases t0.5 in Zn2+-treated fibers not only by generally eliminating T-tubular participation in action potential generation, but also by subtracting a Zn2+-induced retardation of tubular delayed rectification. Tubular delayed rectification must therefore be an intrinsic feature of normal excitation. These results are further analyzed by means of (i) Stanfield's findings about retardation of delayed rectification by Zn2+ and (ii) Adrian-Peachey's theory of T-tubule participation in action potential generation, which suggests that the Zn2+-evoked repolarization hump signals onset of Zn2+-altered active participation of T-tubules in determining the spike's shape.


Left Circumflex Artery Injury After Mitral Valve Surgery: An Algorithm Management Proposal.
Left circumflex coronary (LCx) artery injury during mitral valve surgery is a life-threatening complication. This report describes a series of patients with this complication in a high-volume mitral surgery center. Between January 2004 and December 2017, a total of 6501 mitral valve procedures were performed at the San Raffaele Scientific Institute in Milan, Italy. An LCx injury occurred in 10 patients (10 of 6501; 0.15%) after either mitral valve repair (n = 5) or replacement (n = 5). Coronary angiography was performed in 9 patients and showed 5 cases of left coronary artery dominance, 2 cases of right dominance, and 2 cases of codominance. All data were prospectively collected in the hospital database and were retrospectively reviewed. Suspicion of LCx injury was raised in the operating room in 5 patients and in the intensive care unit in the other 5 patients. Postoperative coronary angiography confirmed the LCx lesion. In the presence of total LCx occlusion, coronary artery bypass grafting (n = 3) or partial removal of the annuloplasty ring(n = 1) was performed. In cases of partial kinking (n = 4), percutaneous coronary intervention (PCI) was preferred. In the 2 patients with extrinsic subocclusion of the LCx, rescue PCI was initially attempted, but both procedures were complicated by artery disruption and stent underexpansion. In our series, LCx occlusion occurred more commonly in patients with left-dominant coronary artery circulation. Clinical presentation may be variable. Rescue PCI is a valid option in cases of kinking of the artery, but in other cases emergency coronary bypass grafting should be the first choice. Repositioning of the prosthesis may be an option in specific circumstances.


Clues to calcineurin function in mammalian fast-twitch muscle.
It is believed that brief, high amplitude Ca2+ transients, as found in fast-twitch muscles, are not sufficient to activate the calcineurin (Cn)-dependent signaling pathway involved in regulation of slow myosin and slow sarcoplasmic reticulum Ca2+-ATPase genes (Olson and Williams, Cell 101: 689-692, 2000). The results reported here try to fill the gap between this molecular knowledge, and the still fragmentary pieces of information on a possible different role of calcineurin in the same type of muscles. In the present work calcineurin was determined immunocytochemically by labeling fast- and slow-twitch fibers of representative rabbit muscles with anti-CnB antibodies, and was assessed by western blotting of isolated subcellular fractions. Calcineurin was found to be largely soluble and to be constitutively overexpressed in fast muscle as CnAalpha and CnAbeta isoforms, the latter appearing to be predominant. Particulate calcineurin was not only associated with myofibrils but also with membranes of various origins. Fluorescence microscopy showed that calcineurin was distributed in the same pattern with respect to sarcomeres in both types of fibers, and formed punctate dots spanning the I-Z-I region, rather than being exclusively located at the Z-line, a disposition described for cardiomyocytes (Frey et al., Proc Natl Acad Sci USA 97: 14,632-14,637, 2000). From knowledge that, in mammalian skeletal muscle fibers, junctional triads are located at the A-I band boundary, we explored the distribution of calcineurin between triadic components, after having verified that it was present in very low amounts in dystrophin-enriched sarcolemmal membranes. Our results demonstrate that a small but significant proportion of calcineurin coenriched with transverse tubules (TT), and copurified with the DHPR and with DHPR-associated PKA-AKAP15/18, thus suggesting that it is assembled as a multiprotein complex in the junctional membrane domain of TT. The membrane specificity of this association is further corroborated by the negative evidence for the presence of calcineurin in SR terminal cisternae. Calcineurin was separated from the DHPR and isolated as a AKAP15/18 subcomplex, including beta2 adrenergic receptor, in addition to PKA and calcineurin, following equilibrium centrifugation of detergent extracts on a linear sucrose gradient. We show that the alpha1 subunit skeletal isoform of the DHPR, is a substrate for calcineurin dephosphorylation, after previous phosphorylation by endogenous PKA.


Unfolding mechanics of holo- and apocalmodulin studied by the atomic force microscope.
The structural stability of calmodulin (CaM) has been investigated previously by chemical and thermal methods. The calcium-loaded form of CaM has been found to be exceptionally stable, because it can be exposed to temperatures >90 degrees C or to a 9 M urea solution without a marked change in its tertiary structure, and is therefore not experimentally accessible for unfolding studies using conventional analytical methods. In this study, we have developed a system for measuring the force for mechanically unfolding CaM using an atomic force microscope (AFM) by stretching the protein from its N- and C-terminal residues; we have been successful in obtaining force versus extension (F-E) curves for both apo and holo forms of CaM. In our experiment, distinguishable F-E curves have been obtained upon stretching of apoCaM and holoCaM to their full extensions. A very low force observed upon stretching of apoCaM indicated a relatively high flexibility of the apo form. On the contrary, a relatively high unfolding force and the appearance of a characteristic force peak were noted during full stretching of holoCaM. The F-E curve of the latter form of CaM most likely reflects a more rigid and probably more organized conformation of holoCaM than that of apoCaM. These experiments confirmed that the AFM is able to clearly distinguish two functionally distinct forms of CaM in terms of their mechanical properties.


Evaluation of a monoclonal antibody based ELISA for detection of feline Chlamydia psittaci.
A commercially available ELISA designed for the detection of C trachomatis in human urogenital specimens was compared with cell culture for the detection of Chlamydia psittaci in cat conjunctival swabs and in twofold dilutions of a cell culture pool of a feline strain of C psittaci. Cell culture was more sensitive than the ELISA test for detection of C psittaci.


Concise Synthesis of 1,4-Benzoquinone-Based Natural Products as Mitochondrial Complex I Substrates and Substrate-Based Inhibitors.
A short, efficient one-step synthesis of 2-methyl-5-(3-methyl-2-butenyl)-1,4-benzoquinone, a natural product from Pyrola media is described. The synthesis is based on a direct late C-H functionalization of the quinone scaffold. The formation of the natural product was confirmed by means of 2D-NMR spectroscopy. Additional derivatives were synthesized and tested alongside the natural product as potential substrate and substrate-based inhibitors of mitochondrial complex I (MCI). The structure-activity relationship study led to the discovery of 3-methylbuteneoxide-1,4-anthraquinone (1 i), an inhibitor with an IC50 of 5 μM against MCI. The identified molecule showed high selectivity for MCI when tested against other quinone-converting enzymes, including succinate dehydrogenase, and the Na (+)-translocating NADH:quinone oxidoreductase. Moreover, the identified inhibitor was also active in cell-based proliferation assays. Therefore, 1 i can be considered as a novel chemical probe for MCI.


Simple fluorimetric determination of selenium in food and biological materials. A validation study.
A method for the determination of selenium in food and biological materials has been developed. The method involves sample decomposition in a closed system at 150 degrees C with nitric acid, perchloric acid treatment of the digest, reduction of selenium to the tetravalent state with hydrochloric acid followed by Se-2,3-diaminonaphthalene (DAN) complex formation and extraction in a single-step operation. Performance characteristics of the method (accuracy and repeatability) were extensively tested for eleven reference materials and ten practice samples covering both a wide variety of matrices and a wide range of selenium content. Almost all results for reference materials were within the 95% confidence range of the certified value or the best estimate thereof. The coefficient of variation for all samples ranged from 2.3 to 10.1%, average value 4.7%. Average recovery for spiking experiments-levels 0.060, 0.075 and 0.150 micrograms/g was 102%; range 84-114%.


NANOS1 and PUMILIO2 bind microRNA biogenesis factor GEMIN3, within chromatoid body in human germ cells.
Nanos and pumilio bind each other to regulate translation of specific mRNAs in germ cells of model organisms, such as D. melanogaster or C. elegans. Recently described human homologues NANOS1 and PUMILIO2 form a complex similar to their ancestors. This study was aimed to identify the proteins interacting with NANOS1-PUMILIO2 complex in the human spermatogenic cells. Here, using the yeast two-hybrid system we found that NANOS1 and PUMILIO2 proteins interact with RNA DEAD-box helicase GEMIN3, a microRNA biogenesis factor. Moreover, GEMIN3 coimmunoprecipitates with NANOS1 and PUMILIO2 in transfected mammalian cells. By double immunofluorescence staining, we observed that complexes built of NANOS1, PUMILIO2 and GEMIN3 are located within cytoplasmic region of germ cells. These proteins condense to form a compact aggregate in the round spermatids of the human and mouse germ cells. This aggregate was reminiscent of the chromatoid body (CB), a perinuclear structure present in the mammalian male germ line. This structure is considered evolutionary remnant of germ plasm, a hallmark structure of germ cells in lower metazoan. Using a CB marker VASA protein, we demonstrated that CBs are present in the human round spermatids, as they are in the mouse. Moreover, NANOS1, PUMILIO2 and GEMIN3 colocalize with VASA protein. We demonstrated for the first time that a mammalian Nanos-Pumilio complex functions within CB, a center of RNA storing and processing, involving microRNAs. NANOS1-PUMILIO2 complex, together with GEMIN3 and small noncoding RNAs, possibly regulate mRNA translation within CB of the human germ cells.


The relationship of tooth size to body size in a population of rhesus monkeys (Macaca mulatta).
Tooth areas correlate significantly with long bone measurements in a skeletal population of rhesus monkeys from Cayo Santiago. Correlations are relatively large for the troop as a whole, as well as for males and females separately. Femur and humerus length measurements show the higheres correlations with tooth size.


Blood harmane concentrations and dietary protein consumption in essential tremor.
Beta-carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood harmane concentrations were elevated in patients with essential tremor (ET) vs controls. Whether this difference is due to greater animal protein consumption by patients or their failure to metabolize harmane is unknown. The aim of this study was to determine whether patients with ET and controls differ with regard to 1) daily animal protein consumption and 2) the correlation between animal protein consumption and blood harmane concentration. Data on current diet were collected with a semiquantitative food frequency questionnaire and daily calories and consumption of animal protein and other food types was calculated. Blood harmane concentrations were log-transformed (logHA). The mean logHA was higher in 106 patients than 161 controls (0.61 +/- 0.67 vs 0.43 +/- 0.72 g(-10)/mL, p = 0.035). Patients and controls consumed similar amounts of animal protein (50.2 +/- 19.6 vs 49.4 +/- 19.1 g/day, p = 0.74) and other food types (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In controls, logHA was correlated with daily consumption of animal protein (r = 0.24, p = 0.003); in patients, there was no such correlation (r = -0.003, p = 0.98). The similarity between patients and controls in daily animal protein consumption and the absence of the normal correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect) may be increasing blood harmane concentration in patients.


Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging to Early Detect Tissue Injury and Microcirculation Alteration in Hepatic Injury Induced by Intestinal Ischemia-Reperfusion in a Rat Model.
Intravoxel incoherent motion (IVIM) can provide quantitative information about water diffusion and perfusion that can be used to evaluate hepatic injury, but it has not been studied in hepatic injury induced by intestinal ischemia-reperfusion (IIR). Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) can provide perfusion data, but it is unclear whether it can provide useful information for assessing hepatic injury induced by IIR. To examine whether IVIM and DCE-MRI can detect early IIR-induced hepatic changes, and to evaluate the relationship between IVIM and DCE-derived parameters and biochemical indicators and histological scores. Prospective pre-clinical study. Forty-two male Sprague-Dawley rats. IVIM-diffusion-weighted imaging (DWI) using diffusion-weighted echo-planar imaging sequence and DCE-MRI using fast spoiled gradient recalled-based sequence at 3.0 T. All rats were randomly divided into the control group (Sham), the simple ischemia group, the ischemia-reperfusion (IR) group (IR1h, IR2h, IR3h, and IR4h) in a model of secondary hepatic injury caused by IIR, and IIR was induced by clamping the superior mesenteric artery for 60 minutes and then removing the vascular clamp. Advanced Workstation (AW) 4.6 was used to calculate the imaging parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], perfusion-related diffusion [D* ] and volume fraction [f]) of IVIM. OmniKinetics (OK) software was used to calculate the DCE imaging parameters (Ktrans , Kep , and Ve ). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with an automatic biochemical analyzer. Superoxide dismutase (SOD) activity was assessed using the nitro-blue tetrazolium method. Malondialdehyde (MDA) was determined by thiobarbituric acid colorimetry. Histopathology was performed with hematoxylin and eosin staining. One-way analysis of variance (ANOVA) and Bonferroni post-hoc tests were used to analyze the imaging parameters and biochemical indicators among the different groups. Pearson correlation analysis was applied to determine the correlation between imaging parameters and biochemical indicators or histological score. ALT and MDA reached peak levels at IR4h, while SOD reached the minimum level at IR4h (all P < 0.05). ADC, D, D* , and f gradually decreased as reperfusion continued, and Ktrans and Ve gradually increased (all P < 0.05). The degrees of change for f and Ve were greater than those of other imaging parameters at IR1h (all P < 0.05). All groups showed good correlation between imaging parameters and SOD and MDA (r[ADC] = 0.615, -0.666, r[D] = 0.493, -0.612, r[D* ] = 0.607, -0.647, r[f] = 0.637, -0.682, r[Ktrans ] = -0.522, 0.500, r[Ve ] = -0.590, 0.665, respectively; all P < 0.05). However, the IR groups showed poor or no correlation between the imaging parameters and SOD and MDA (P [Ktrans and MDA] = 0.050, P [D and SOD] = 0.125, P [the remaining imaging parameters] < 0.05). All groups showed a positive correlation between histological score and Ktrans and Ve (r = 0.775, 0.874, all P < 0.05), and a negative correlation between histological score and ADC, D, f, and D* (r = -0.739, -0.821, -0.868, -0.841, respectively; all P < 0.05). For the IR groups, there was a positive correlation between histological score and Ktrans and Ve (r = 0.747, 0.802, all P < 0.05), and a negative correlation between histological score and ADC, D, f, and D* (r = -0.567, -0.712, -0.715, -0.779, respectively; all P < 0.05). The combined application of IVIM and DCE-MRI has the potential to be used as an imaging tool for monitoring IIR-induced hepatic histopathology. 1 TECHNICAL EFFICACY STAGE: 2.


Automatic Sleep Staging Based on Contextual Scalograms and Attention Convolution Neural Network Using Single-channel EEG.
Single-channel EEG based sleep staging is of interest to researchers due to its broad application prospect in daily sleep monitoring recently. We proposed using contextual scalograms as input and developed a convolutional neural network with attention modules named Co-ScaleNet for sleep staging. The contextual scalograms were obtained by combining the same color channels of three original RGB scalograms from consecutive epochs, and a simple and efficient data augmentation was designed according to their various forms. The Co-ScaleNet consists of two main parts. Firstly, three parallel convolutional branches with attention modules correspondingly extract and fuse features from contextual scalograms at the top layers. The remaining part is a stack of lightweight blocks. We achieved an overall accuracy of 87.0% for healthy individuals, 84.7% for depressed patients. And we obtained comparable performance on the public Sleep-EDFx (82.8%), ISRUC (84.6%) and SHHS datasets (87.7%), including a high recall of N1. The contextual scalograms of R channel as input achieved the best performance, which conform to the features of interest in visual scoring. The attention modules improved the recall of N1 and N3. Overall, the contextual scalograms provided a novel scheme for both contextual information extraction and data augmentation. Our study successfully expanded its application to depression datasets, as well as patients with sleep apnea, demonstrating its wide applicability.


Anaerobic treatment of poultry mortality in a temperature-phased leachbed-UASB system.
Anaerobic digestion has been proposed as an alternative to the conventional disposal methods of burial, incineration, rendering and aerobic composting. A temperature-phased system consisting of one UASB (at 55 degrees C) and three leach-bed reactors (at ambient temperatures) was tested for its efficiencies in treating poultry mortality. The thermophilic UASB was difficult to start-up. It also showed signs of inhibited methanogenesis. Chemical parameters such as long chain fatty acids, volatile fatty acids and ammonia concentrations were all very high for the thermophilic UASB. Lowering its temperature to 35 degrees C enhanced its stability and improved its performances. Lowering the pH of the 55 degrees C UASB also improved its chemical oxygen demand (COD) reduction efficiency as well as its methane production rate. The results were compared to that of another similar system where the UASB reactor was maintained at 35 degrees C instead of at 55 degrees C.


Healthcare utilization and financial impact of acute-graft-versus host disease among children undergoing allogeneic hematopoietic cell transplantation.
The impact of AGVHD on healthcare utilization and cost is not well described. In this retrospective single center cohort study of 240 pediatric patients, we analyzed cost, healthcare utilization and patient outcomes for the first year post-alloHCT. Costs were estimated from charges recorded in the Pediatric Health Information System database and the hospital's accounting system. The overall incidence of grade I-IV aGVHD was 40.4%. The incidence of grade I, grade II, and grade III-IV aGVHD was 6.6%, 16.2%, and 17.5%, respectively. The overall incidence of steroid refractory (SR)-aGVHD was 10.8%. The median number of days of hospitalization in the first year post-alloHCT was significantly higher for patients with aGVHD vs. no aGVHD: 113 days (range: 35-354 days) vs. 63 days (range: 25-298 days), p < 0.001. Patients with SR-aGVHD had increased hospitalization compared with the patients with steroid responsive aGVHD (152.8 ± 66.6days vs. 111.3 ± 59.3 days, p = 0.004), with associated increased alloHCT cost of ~$200,000. On multivariable analysis of risk factor for alloHCT cost, aGVHD, was associated with significantly higher cost ($141,094 [SE = 31247], p < 0.001). In summary, aGVHD and SR-aGVHD is associated with prolonged hospitalization and higher cost and inferior survival among children. Better aGVHD prevention strategies are desperately needed. Despite significant advances, lack of effective salvage regimens for SR-aGVHD remains a major concern.


Analysis of treatment planning parameters in the Gamma Knife® technique for different prescription isodoses and volumes of meningiomas.
The following Indexes: Homogeneity, Gradient, Conformity, Paddick Conformity and New Conformity of the dose distribution were compared. The parameters to assess a high dose to the organs at risk: V10/TV, V90%/TV and the Integral Dose were discussed. The higher the prescription isodose, the more uniform the dose distribution in the target, which is highly beneficial in the case of larger tumor sizes due to the lower risk of complications. For smaller tumors, higher dose heterogeneity is desirable. This can be obtained with a 40% prescription isodose.


Case report and review of nonischemic spontaneous papillary muscle rupture reports between 2000 and 2015.
Spontaneous papillary muscle rupture (PMR) is a rare cardiovascular emergency. We present a 63-year-old male who presents with acute dyspnea who was found to have an anterior PMR, with no evidence of coronary artery disease, infection, or trauma. A review of cases of nonischemic spontaneous PMR published in 2000-2015 identified 11 additional cases of spontaneous PMR. Posterior and anterior papillary muscles involvement was identified in 54.5% and 45.5% of cases, respectively. Rapid identification due to advances in imaging modalities and improved surgical management has led to optimal outcomes in patients with spontaneous PMR.


Use of robust variance components models to analyse triglyceride data in families.
A robust approach for analysis of variance components models is presented which does not rely on the assumption of multivariate normality for its validity. This approach uses the multivariated normal distribution as a 'working model' but obtains standard errors for the final estimators which do not depend on this underlying distribution. By using the observed variance in the first derivatives of the multivariate normal 'working model' to modify the conventional score test, hypotheses regarding specific components can also be tested without relying directly on the assumption of multivariate normality. A special case is presented where both the modified score test and the likelihood ratio test are equally robust, and simulated data are used to illustrate this situation. Measurements of triglyceride levels in 391 individuals in 60 families randomly selected from the membership of a health maintenance organization are used to illustrate this robust approach to variance components.


NAIF1 inhibits gastric cancer cells migration and invasion via the MAPK pathways.
Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood. The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo. The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin-proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2. Our study revealed that NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways. It could be a therapeutic target for gastric cancer.


The cost of cancer care: how far would you go for a trial?
Clinical trials are often considered the gold standard in cancer care. However, patients face barriers in trial participation including distances to cancer centres and personal costs including changing employment status, cost of medications, inpatient admissions, and parking tariffs. Our aim was to compare the distances patients travelled for clinical trials compared to those receiving standard systemic anticancer therapy (SACT). We also investigated the additional costs associated with this. This was a retrospective review of electronic patient medical records. The distance from the patients' home address to Beaumont was calculated as a one-way journey in kilometres. Patients attending for clinical trials were compared to those receiving standard of care SACT. A total of 271 patients receiving standard SACT over a 5-day period and 111 patients enrolled on 24 clinical trials were included. The median one-way distance travelled by patients enrolled in clinical trials was 41.4 km, compared to 14 km in those patients' receiving standard of care SACT. The median estimated cost was €13 vs €4.20 for those enrolled on clinical trials compared to those receiving standard of care treatment, respectively. Patients enrolled on clinical trials often travel more than twice as far to receive their anti-cancer treatment compared to those receiving standard of care SACT and incur an increased cost of travel expenses.


Temporary dialysis treatments for heart failure in chronic kidney disease.
Patients with cardiac disease and chronic kidney disease are admitted to our emergency unit with signs and symptoms of severe heart failure more and more frequently. Resistance to high-dose loop diuretics imposes the use of renal replacement therapy. We treated a group of these patients with personalized bicarbonate dialysis, deciding the number and frequency of treatment sessions according to the patient's clinical conditions. Heart failure can be classified as mainly diastolic or systolic. Results show that bicarbonate dialysis is effective and well tolerated, primarily in the treatment of patients with prevalently diastolic heart failure. Patients with prevalently systolic heart failure have a worse prognosis.


Effects of Women's Weight Changes on Adverse Outcomes in a Second Pregnancy.
To estimate the effects of women's weight changes in four sequential perinatal periods across first and second pregnancies (pregravid, first gestation, interpregnancy, second gestation) on adverse maternal and neonatal outcomes in the second pregnancy while accounting for interdependencies in weight across the four periods (Aim 1) and to test the influence of the sequential path of weight changes through the four perinatal periods of risk on maternal and neonatal outcomes in the second pregnancy (Aim 2). Secondary data analysis. Thirty-one Wisconsin hospitals. Women with 24,795 linked records from first and second births from 2006 through 2013. We used a fully recursive system of linear and logistic regression equations to examine the relationships among weight changes in the four perinatal periods with maternal (gestational diabetes mellitus, gestational hypertension, cesarean birth) and neonatal (macrosomia, small for gestational age, large for gestational age, low birth weight, congenital anomalies, and perinatal death) adverse outcomes in the second pregnancy. Pregravid weight was weakly and inconsistently associated with weight changes in subsequent periods. Each 5-kg incremental weight change in the first pregnancy, interpregnancy, and second pregnancy contributed to a 0.75- to 5-kg weight change in subsequent periods, 9% to 25% change in risk for adverse maternal outcomes, and 8% to 47% change in risk for adverse neonatal outcomes in the second pregnancy. Fluctuations in weight across pregnancies and associations with outcomes were strongest among normal-weight and overweight women. Weight changes across two pregnancies affected maternal and neonatal outcomes in the second pregnancy in all body mass index categories; the larger weight fluctuations observed in normal and overweight women were associated with greater risk of adverse outcomes. Attention to pregnancy weight during and between pregnancies is important for targeted weight counseling to reduce risks in subsequent pregnancies.


Extracellular vesicles-mediated transfer of miR-208a/b exaggerate hypoxia/reoxygenation injury in cardiomyocytes by reducing QKI expression.
In this study, we tested the hypothesis that extracellular vesicles (EVs)-mediated transfer of miR-208a/b can exacerbate apoptosis of cardiomyocytes (CMs) induced by hypoxia/reoxygenation (H/R) injury by reducing the expression of the RNA-binding protein Quaking (QKI). EVs were isolated from culture medium of hypoxic H9c2 cells (EVs-H). In in vitro H9c2 cell model, the EVs-H could be taken up by normoxic CMs and exacerbated cell apoptosis induced by H/R injury. In addition, miR-208a and miR-208b were enriched in EVs-H. Suppression of miR-208a and miR-208b loading significantly suppressed the detrimental effect of EVs-H on H/R injury in H9c2 cells. Inhibition of endogenous miR-208a and miR-208b restored QKI5 and QKI6 after H/R treatment. Dual-luciferase assay confirmed direct bindings between miR-208a/b and QKI 3'UTR. Functionally, QKI5 overexpression significantly suppressed H/R-induced CM apoptosis and suppressed the enhancing effect of EVs-H on CM apoptosis. Therefore, we infer that EVs-mediated transfer of miR-208a/b can exaggerate H/R injury in CMs by reducing QKI expression. This represents a previously unrecognized pathway of H/R injury in CMs.


A new Thy-1 alloantigen as a temporal marker of T lymphocyte differentiation.
A new Thy-1 alloantigenic specificity is defined in the mouse. Antigen expression is restricted to 'mature' and memory T cells, with either helper or killer activity.


Too little but not too late: nowcasting poverty and cash transfers' incidence during COVID-19's crisis.
The economic crisis triggered by COVID-19 has caused a world-wide economic downturn, and the deepest GDP contraction in Latin America since the beginning of the XX th century. One of the most dramatic outcomes of the crisis is the increase in poverty, but its extent will remain unknown until household income data is collected and analyzed. We propose a simple approach to provide early estimates, micro-simulating the short-run effect of the crisis on the poverty rate. It combines household level micro-data, estimates on the feasibility of working from home, information on key public policies (e.g., cash-transfers, unemployment insurance), and forecasts of GDP contraction. This approach, which can be easily adapted and applied to different countries, allows to nowcast the current poverty level and the poverty-reducing effect of public policies, while providing full micro-macro consistency between heterogeneous impacts on households and the shock to aggregate GDP. Moreover, it enables to estimate the effect on informal and self-employed workers, of utmost importance in developing countries. We illustrate the methodology with an application for Uruguay, finding that during the first full trimester of the crisis, the poverty rate grew by more than 38%, reaching 11.8% up from 8.5%. Moreover, cash transfers implemented by the government in the period had a positive but very limited effect in mitigating this poverty spike, which could be neutralized with additional transfers worth under 0.5% of Uruguay's annual GDP.


Cultural and linguistic influence on brain organization for language and possible consequences for dyslexia: a review.
Current neuroimaging and neurophysiologic techniques have substantially increased our possibilities to study processes related to various language functions in the intact human brain. Learning to read and write influences the functional organization of the brain. What is universal and what is specific in the languages of the world are important issues. Most studies on healthy bilinguals indicate that essentially the same neural mechanisms are used for first and second languages, albeit with some linguistic and cultural influences related to speech and writing systems, particularly between alphabetical and nonalphabetical languages. Proficiency, age of acquisition, and amount of exposure can affect the cerebral representations of the languages. Accumulating data support the important role of working memory for acquiring high proficiency in the reading of native and second languages. It is proposed that longitudinal studies on second language acquisition are essential and that the specific problems related to second language learning in dyslexic children should have high priority.