Most recommendations were related to 'training and education' (466, 61%), 'additional study/review' (104, 14%) and 'review/enhancement of policy/guideline' (39, 5%). Conclusions This study provided insights about the effectiveness of RCA recommendations across all public hospitals in Hong Kong. The results showed a high proportion of root causes were attributed to staff behavioural factors and most of the recommendations were weak. The reasons include the lack of training, tools and expertise, appropriateness of panel composition, and complicated processes in carrying out large scale improvements. The Review Team suggested conducting regular RCA training, adopting easy-to-use tools, enhancing panel composition with human factors expertise, promoting an organization-wide safety culture to staff and aggregating analysis of incidents as possible improvement actions.Background The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages. Methods MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund's Adjuvant (CFA). The viability of then LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages. Conclusion MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.Background This study assessed the direct, indirect and total effect of distal - political - risk indicators (affecting populations), and proximal risk indicators (affecting women) on the global prevalence of early childhood caries (ECC) in 3-5 year old children. Methods Data on global ECC prevalence were obtained from a prior study. Data for distal risk indicators (voice and accountability; political stability/absence of terrorism; control of corruption) were obtained from the World Bank Governance indicators, 2016. Data for proximal risk indicators (women's opportunity for leadership; percentage of female legislators, top officials and managers; basic employability status of women; ability of women to afford time off work to care for newborns; gross national income (GNI) per capita for females) were derived from the Human Development Index, 2016. Associations between variables were assessed with path analysis. Results Voice and accountability (β = - 0.60) and GNI per capita for females (β = - 0.33) were directly associated with a lower ECC prevalence. Political stability/absence of terrorism (β =0.40) and higher percentage of female legislators, senior officials and managers (β = 0.18) were directly associated with a higher ECC prevalence. Control of corruption (β = - 0.23) was indirectly associated with a lower ECC prevalence. Voice and accountability (β = 0.12) was indirectly associated with a higher ECC prevalence. Overall, voice and accountability (β = - 0.49), political stability/absence of terrorism (β = 0.34) and higher female GNI (β = - 0.33) had the greatest effects on ECC prevalence. Conclusion Distal risk indicators may have a stronger impact on ECC prevalence than do proximal risk indicators.. https://www.selleckchem.com/products/AC-220.html Approaches to control ECC may need to include political reforms.Background Pulmonary Cryptococcosis is a common fungal infection mainly caused by Cryptococcus neoformans/C.gattii species in immunocompromised patients. Cases of pulmonary cryptococcosis in patients with normal immune function are increasingly common in China. Clinical and radiographic features of pulmonary cryptococcosis are various and without obvious characteristics, so it is often misdiagnosed as pulmonary metastatic tumor or tuberculosis. When coexisting with malignant lung tumors, it was more difficult to differentiate from metastatic lung cancer, although the coexistence of pulmonary cryptococcosis and central type lung cancer is rare. Reviewing the imaging manifestations and diagnosis of the case and the relevant literature will contribute to recognition of the disease and a decrease in misdiagnoses. Case presentation A 72-year-old immunocompetent Han Chinese man had repeated dry cough for more than half a year. CT examination of chest showed an irregular mass at the left hilum of the lung, and two sod for identification.Background Weight loss outcomes after bariatric surgery are less favorable in super morbidly obese patients (BMI ≥50 kg/m2). Non-response, either defined as insufficient weight loss or weight regain after initial successful weight loss, is a matter of serious concern in these patients. The primary banded Roux-en-Y gastric bypass has shown promising results regarding weight loss in the bariatric population. However, up to now, long-term comparative data about the banded and non-banded bypass in superobese patients is lacking. The aim of this study is to assess the added value of the banded Roux-en-Y gastric bypass in superobese patients on long-term weight loss outcomes. Methods This single center study will evaluate superobese patients who receive a non-banded Roux-en-Y gastric bypass (NB-RYGB) and a banded Roux-en-Y gastric bypass (B-RYGB). Data from the NB-RYGB group will be collected in retrospect, while data from the B-RYGB group will be collected prospectively. When performing a B-RYGB, a 7.0-8.0 cm silastic ring (MiniMizer®) will be placed proximal to the gastrojejunostomy.

The recent demonstration of the significant reduction in mortality in patients with septic shock treated with adjunctive glucocorticoids combined with fludrocortisone and the effectiveness of angiotensin II in treating vasodilatory shock have renewed interest in the role of the mineralocorticoid axis in critical illness. Glucocorticoids have variable interactions at the mineralocorticoid receptor. Similarly, mineralocorticoid receptor-aldosterone interactions differ from mineralocorticoid receptor-glucocorticoid interactions and predicate receptor-ligand interactions that differ with respect to cellular effects. Hyperreninemic hypoaldosteronism or selective hypoaldosteronism, an impaired adrenal response to increasing renin levels, occurs in a subgroup of hemodynamically unstable critically ill patients. The suggestion is that there is a defect at the level of the adrenal zona glomerulosa associated with a high mortality rate that may represent an adaptive response aimed at increasing cortisol levels. Furthermore, cross-talk exists between angiotensin II and aldosterone, which needs to be considered when employing therapeutic strategies.Supplemental Digital Content is available in the text.Purpose Subcortical arteriosclerotic encephalopathy (SAE) is characterized by extensive white matter lesions in the MRI. https://www.selleckchem.com/products/gw-4064.html Clinical symptoms are cognitive impairment, ranging from mild deficits to vascular dementia, impaired executive functioning, and gait disorders. In the EEG of SAE patients with vascular dementia, the lower frequencies are increased. However, it is unclear whether EEG changes also exist in SAE patients with gait disorders but without vascular dementia. Methods The authors analyzed the EEGs of 50 nondemented patients with SAE and gait disorders and 50 healthy controls applying pointwise transinformation as a measure of synchronization. Results Hundred seconds of waking EEG that appeared unaltered in visual analysis were sufficient to prove changes in synchronization. The authors found a decrease in the mean level of synchronization, combined with an elongation of synchronization time in all examined brain areas. These effects correlated slightly with the extent of subcortical lesions. Conclusions Changes in EEG synchronization in patients with SAE and gait disorders seem to occur independently of cognitive function. The causal relationship of the changes in EEG synchronization and gait disorders remains to be clarified. The results of this study might point to a decrease in coupling efficiency in these patients, with the increase in synchronization duration as a possible compensatory mechanism. Because a time-efficient signal transmission particularly during gait execution is crucial, reduced efficiency might contribute to an impairment of postural stabilization. The study results might indicate a neuronal network for planning and execution of motor activity and particularly gait, extending from the frontal over the central to the parietal cortex.Purpose Cyclic alternating pattern (CAP) is known to increase in many conditions of sleep disruption and sleep disorders, including obstructive sleep apnea syndrome and periodic limb movements in sleep (PLMS). Periodic limb movements in sleep associated with obstructive sleep apnea syndrome may vanish after positive airway pressure treatment, may persist, or emerge at treatment night. Here, the authors aimed to investigate the underlying pathophysiology of nonvanishing, vanishing, or newly emergent PLMS. Methods The authors designed a prospective study and included 10 patients with nonvanishing PLMS during positive airway pressure therapy, 10 patients with vanishing PLMS, 10 patients with newly emergent PLMS, and 10 patients without PLMS at both nights. The CAP analysis was performed in detail at diagnostic polysomnography recording and at positive airway pressure titration. The changes in CAP parameters were evaluated in regard to nonvanishing, vanishing, or newly emergent PLMS. Results Periodic limb movements in sleep related to A1 subtype of CAP were observed to decrease under positive airway pressure titration more than PLMS related to A3 subtype of CAP. The A3 subtype of CAP was higher in patients with vanishing PLMS than those with newly emergent PLMS. The newly emergent PLMS were mostly related to A1 subtype of CAP compared with A3 subtype of CAP. Conclusions This study showed that vanishing, nonvanishing, or newly emerging PLMS may indeed represent different underlying pathophysiology. The authors suggest that organization of sleep and preservation of ultradian rhythms during titration may determine whether PLMS will be vanished or persist. Newly emergent PLMS may probably arise from a separate central generator by the activation of higher cortical areas.Purpose Abnormal activity within the corticospinal system is believed to contribute to the motor dysfunction associated with Parkinson disease. However, the effect of treatment for parkinsonian motor symptoms on dysfunctional descending input to the motor neuron pool remains unclear. Methods We recruited nine patients with PD treated with deep brain stimulation and examined the time course of interaction between a conditioning pulse from transcranial magnetic stimulation and the soleus H-reflex. Patients with Parkinson disease were examined under four treatment conditions and compared with 10 age-matched control subjects. Results In healthy controls, transcranial magnetic stimulation conditioning led to early inhibition of the H-reflex (76.2% ± 6.3%) at a condition-test interval of -2 ms. This early inhibition was absent when patients were OFF medication/OFF stimulation (132.5% ± 20.4%; P > 0.05) but was maximally restored toward control levels ON medication/ON stimulation (80.3% ± 7.0%). Of note, early inhibition ON medication/ON stimulation tended to be stronger than when medication (85.4% ± 5.9%) or deep brain stimulation (95.7% ± 9.4%) were applied separately. Late facilitation was observed in controls at condition-test intervals ≥5 ms but was significantly reduced (by 50% to 80% of controls) in Parkinson disease OFF stimulation at condition-test intervals ≥15 ms. The late facilitation was akin to control subjects when patients were ON stimulation. Conclusions The present pilot study demonstrates that the recruitment of early inhibition and late facilitation is disrupted in untreated Parkinson disease and that medication and deep brain stimulation may act together to normalize supraspinal drive to the motor neuron pool.

The LAH-causing variants were associated with decreased C3ORF52 expression and resulted in markedly reduced lipase H-mediated LPA biosynthesis. CONCLUSION LAH can be caused by abnormal function of at least three proteins which are necessary for proper LPA biosynthesis.Rhizobia-legume symbiosis is an important type of plant-microbe mutualism; however, the establishment of this association is complicated and can be affected by many factors. The soybean rhizosphere has a specific microbial community, yet whether these organisms affect rhizobial nodulation has not been well investigated. Here, we analyzed the compositions and relationships of soybean rhizocompartment microbiota in three types of soil. First, we found that the rhizosphere community composition of soybean varied significantly in different soils, and the association network between rhizobia and other rhizosphere bacteria was examined. Second, we found that some rhizosphere microbes were correlated with the composition of bradyrhizobia and sinorhizobia in nodules. We cultivated 278 candidate Bacillus isolates from alkaline soil. Finally, interaction and nodulation assays showed that the Bacillus cereus group specifically promotes and suppresses the growth of sinorhizobia and bradyrhizobia, respectively, and alleviates the effects of saline-alkali conditions on the nodulation of sinorhizobia as well as affecting its colonization in nodules. https://www.selleckchem.com/products/sto-609.html Our findings demonstrate a crucial role of the bacterial microbiota in shaping rhizobia-host interactions in soybean, and provide a framework for improving the symbiotic efficiency of this system of mutualism through the use of synthetic bacterial communities.BACKGROUND In developed countries, colon cancer is a leading cause of cancer-associated mortality. Dietary changes have resulted in an increased incidence of colon cancer in Asia. This study aimed to investigate the effects of the structural analog of endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH₂) on human colon cancer cells in vitro. MATERIAL AND METHODS Human DLD-1 and RKO colon cancer cells and CCD-18Co normal human colonic fibroblasts were treated with increasing doses of the structural analog of endomorphin-2. Cells underwent the MTT assay, fluorescence confocal flow cytometry, and Hoechst 33258 staining to investigate cell proliferation, the cell cycle, and apoptosis. Western blot was used to measure the expression levels of poly(ADP-ribose) polymerase-1 (PARP-1), cytochrome c, caspase-3, and caspase-9. The 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescence method measured reactive oxygen species (ROS). RESULTS Cell proliferation of DLD-1 and RKO cells was inhibited by the endomorphin-2 analog in a dose-dependent manner, and a 100 µM dose reduced DLD-1 and RKO cell proliferation by 28% and 23%, respectively, at 72 h. Endomorphin-2 analog induced cell apoptosis and the generation of ROS, activated caspase-3 and caspase-9, and increased the levels of p53 and cytochrome c release, and down-regulated of Akt activation in DLD-1 and RKO cells in a dose-dependent manner. Treatment of the DLD-1 and RKO cells with the endomorphin-2 analog increased the expression of Bax and reduced the expression of Bcl-2. CONCLUSIONS Endomorphin-2 analog inhibited colon cancer cell proliferation, activated apoptosis, and down-regulated Akt phosphorylation of human DLD-1 and RKO colon cancer cells in vitro in a dose-dependent manner.BACKGROUND Calcific uremic arteriolopathy (CUA) is a rare and incredibly painful cutaneous disorder secondary to microvascular involvement in which calcium dysregulation leads to stenosis of medium sized arterial blood vessels along with endothelial dysregulation and thrombosis. Ultimately, these patients are at high risk for non-healing wounds with risk of death from sepsis and multi-organ failure. It is a poorly understood condition with limited therapies that do not offer mortality benefit. Prevalence is about 4% in hemodialysis patients. Sodium thiosulfate (STS) can be used in hemodialysis patients but therapy is often limited by the development of high anion gap metabolic acidosis. CASE REPORT A 53-year-old male who had end stage renal disease and who was on hemodialysis and taking warfarin for bio-prosthetic mitral valve replacement and atrial fibrillation presented with non-healing right lower extremity cellulitis which had failed outpatient treatment. A skin biopsy of the lesion was consistent with CUA. The patient failed to improve on calcitriol and cinacalcet and was started on intravenous STS. Subsequently, he developed life threatening metabolic acidosis requiring a bicarbonate drip. He died 12 weeks after his initial diagnosis of CUA. CONCLUSIONS This article seeks to describe how the treatment of CUA; a rare disease with high mortality, is limited by the development of metabolic acidosis when using STS therapy. There is an 80% mortality rate within 6 months from CUA with major adverse effect of a high anion gap metabolic acidosis. Further research is needed in the field of establishing optimal dosing and frequency.BACKGROUND The primary purpose of this study was to investigate the protective effect of metformin against hydrogen peroxide (H₂O₂)-induced cellular senescence and to explore the underlying molecular mechanism of lens epithelial cell senescence. MATERIAL AND METHODS We used H₂O₂ to establish senescence in human lens epithelial B3 cells. The cells were exposed to H₂O₂ for different numbers of days to mimic aging. Senescence was assessed by senescence-associated ß-galactosidase staining, and the molecular mechanism was assessed by real-time polymerase chain reaction (RT-PCR) and western blot analysis. The cultured cells were exposed to 150 μM H₂O₂ for 7 days with or without metformin to detect the underlying molecular mechanism of lens epithelial cell senescence. RESULTS The lens epithelial cells exposed to 150 µM H₂O₂ for 7 days exhibited senescence. The expression levels of senescence-related markers were increased in H₂O₂-treated cells. Metformin prevented H₂O₂-induced cellular senescence in human lens epithelial B3 cells. CONCLUSIONS These findings suggest that senescence marker expression is increased in the cells exposed to H₂O₂. Metformin protects human lens epithelial B3 cells from H₂O₂-induced senescence.

within soil aggregates, particularly in the labile OC fractions within macroaggregates under high plant inputs with 31 years of grassland conversion. For the cropland and bareland soils without organic inputs, more OC was stabilized within fine aggregates via organo-mineral interactions, tending to be more recalcitrant.All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-IXcc) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-IXcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-IXcc expression platform not only can repress gene expression in response to SAM binding to SAM-IXcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species.Acute lymphoblastic leukaemia (ALL) is the most common form of paediatric cancer and epigenetic aberrations are determinants of leukaemogenesis. The aim of this study was to investigate the methylation degree of a distinct phospholipase A2 receptor 1 (PLA2R1) promoter region in paediatric ALL patients and to evaluate its relevance as new biomarker for monitoring treatment response and burden of residual disease. The impact of PLA2R1 re-expression on proliferative parameters was assessed in vitro in Jurkat cells with PLA2R1 naturally silenced by DNA methylation. Genomic DNA was isolated from bone marrow (BM) and peripheral blood (PB) of 44 paediatric ALL patients. PLA2R1 methylation was analysed using digital PCR and compared to 20 healthy controls. Transfected Jurkat cells were investigated using cell growth curve analysis and flow cytometry. PLA2R1 was found hypermethylated in BM and PB from pre-B and common ALL patients, and in patients with the disease relapse. PLA2R1 methylation decreased along with leukaemic blast cell reduction during ALL induction treatment. In vitro analysis revealed an anti-proliferative phenotype associated with PLA2R1 re-expression, suggesting a tumour-suppressive function of PLA2R1. Collected data indicates that PLA2R1 promoter methylation quantitation can be used as biomarker for ALL induction treatment control, risk stratification, and early detection of ALL relapse.The orbitofrontal cortex (OFC) encodes expected outcomes and plays a critical role in flexible, outcome-guided behavior. The OFC projects to primary visual cortex (V1), yet the function of this top-down projection is unclear. We find that optogenetic activation of OFC projection to V1 reduces the amplitude of V1 visual responses via the recruitment of local somatostatin-expressing (SST) interneurons. Using mice performing a Go/No-Go visual task, we show that the OFC projection to V1 mediates the outcome-expectancy modulation of V1 responses to the reward-irrelevant No-Go stimulus. Furthermore, V1-projecting OFC neurons reduce firing during expectation of reward. In addition, chronic optogenetic inactivation of OFC projection to V1 impairs, whereas chronic activation of SST interneurons in V1 improves the learning of Go/No-Go visual task, without affecting the immediate performance. Thus, OFC top-down projection to V1 is crucial to drive visual associative learning by modulating the response gain of V1 neurons to non-relevant stimulus.Agriculture, forestry and other land uses are currently the second highest source of anthropogenic greenhouse gases (GHGs) emissions. In soil, these gases derive from microbial activity, during carbon (C) and nitrogen (N) cycling. To investigate how Eucalyptus land use and growth period impact the microbial community, GHG fluxes and inorganic N levels, and if there is a link among these variables, we monitored three adjacent areas for 9 months a recently planted Eucalyptus area, fully developed Eucalyptus forest (final of rotation) and native forest. We assessed the microbial community using 16S rRNA gene sequencing and qPCR of key genes involved in C and N cycles. No considerable differences in GHG flux were evident among the areas, but logging considerably increased inorganic N levels. Eucalyptus areas displayed richer and more diverse communities, with selection for specific groups. Land use influenced communities more extensively than the time of sampling or growth phase, although all were significant modulators. Several microbial groups and genes shifted temporally, and inorganic N levels shaped several of these changes. No correlations among microbial groups or genes and GHG were found, suggesting no link among these variables in this short-rotation Eucalyptus study.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Neosporosis primarily affects cattle and dogs and is not currently considered a zoonotic disease. Toxoplasmosis is a zoonosis with a worldwide distribution that is asymptomatic in most cases, but when acquired during pregnancy, it can have serious consequences. The seropositivity rates determined by the indirect fluorescent antibody test for Neospora caninum (N. caninum) and Toxoplasma gondii (T. gondii) were 24.3% (49 samples) and 26.8% (54 samples), respectively. PCR positivity for N. https://www.selleckchem.com/products/tmp269.html caninum was observed in two samples of cord blood (1%) using the Nc5 and ITS1 gene, positivity for T. gondii was observed in 16 samples using the primer for the B1 gene (5.5% positivity in cord blood and 2.5% positivity in placental tissue). None of the samples showed structures characteristic of tissue cysts or inflammatory infiltrate on histopathology. Significant associations were observed only between N. caninum seropositivity and the presence of domestic animals (p = 0.039) and presence of dogs (p = 0.038) and between T. gondii seropositivity and basic sanitation (p = 0.

ful findings.The development of technologically advanced recirculation aquaculture systems (RAS) implies the reuse of water in a high recirculation rate (>90%). One of the most important phases for water management in RAS involves water disinfection in order to avoid proliferation of potential pathogens and related fish diseases. Accordingly, different approaches have been assessed in this study by performing a comparison of photolytic (UV-LEDs) at different wavelengths (λ = 262, 268 and 262 + 268 nm), photochemical (UV-LEDs/H2O2, UV-LEDs/HSO5- and UV-LEDs/S2O82-) and photocatalytic (TiO2/SiO2/UV-LEDs and ZnO/SiO2/UV-LEDs) processes for the disinfection of water in RAS streams. Different laboratory tests were performed in batch scale with real RAS stream water and naturally occurring bacteria (Aeromonas hydrophyla and Citrobacter gillenii) as target microorganisms. Regarding photolytic processes, higher inactivation rates were obtained by combining λ262+268 in front of single wavelengths. Photochemical processes showed higher efficiencies by comparison with a single UV-C process, especially at 10 mg L-1 of initial oxidant dose. The inactivation kinetic rate constant was improved in the range of 15-38%, with major efficiency for UV/H2O2 ∼ UV/HSO5- > UV/S2O82-. According to photocatalytic tests, higher efficiencies were obtained by improving the inactivation kinetic rate constant up to 55% in comparison with a single UV-C process. Preliminary cost estimation was conducted for all tested disinfection methods. Those results suggest the potential application of UV-LEDs as promoter of different photochemical and photocatalytic processes, which are able to enhance disinfection in particular cases, such as the aquaculture industry.To clarify the effect of the hydrophobic/hydrophilic polarity of extracellular polymeric substances (EPS) on sludge filterability improvement during S2O82-/Fe2+ oxidation, waste activated sludge (WAS), glucose-fed hydrophilic sludge (HPI-WAS), and sodium acetate-fed hydrophobic sludge (HPO-WAS) samples were cultivated, and their dewatering behaviors were individually explored. Experimental results showed that S2O82- oxidation effectively disintegrated the polymeric EPS and led to a more significant reduction in the water content for HPO-WAS than for HPI-WAS (12.87-15.23% vs 9.31-12.12%), especially regarding the bound water (Wb) content. After oxidation, as high as 38.88-42.61% of the Wb within HPO-WAS samples were declined, much higher than the HPI-WAS samples (19.27-29.20%). Specifically, carbohydrates within sludge EPS negatively influenced the dewatering process of S2O82-/Fe2+ oxidation. By contrast, abundant existence of humic acids and polymeric proteinaceous components (especially those hydrophilic proteins and transitional humic acids) within the sludge EPS exhibited a converse trend. FT-IR and EEM spectral, as well as particle sizes variation for the sludge samples before and after S2O82-/Fe2+ oxidation was also evaluated. This study provides new insight into the enhancement of S2O82-/Fe2+ oxidation for sludge dewatering based on polarity analysis of EPS.Volatile organic compounds (VOCs) exists ubiquitously in chemical industries and were regarded as major contributors to air pollution, which should be strictly regulated. Vacuum ultraviolet irradiation coupled with photocatalytic oxidation (VUV-PCO) has been considered as an efficient approach to VOCs removal due to high-energy photons which could break down VOCs directly and be absorbed by photocatalysts to generate free radicals for further oxidation. However, the photochemical transformation mechanisms of VOCs have not been fully revealed. Herein, we systematically analyzed the intermediates using proton-transfer-reaction mass spectrometer (PTR-MS) to explore the transformation mechanisms of toluene degradation in VUV and VUV-PCO processes. VUV-PCO process displayed superior toluene degradation efficiency (50 %) and mineralization efficiency (65 %) compared with single VUV photolysis (35 %) and UV photocatalysis (5 %). TiO2 was deeply involved into CO2 generalization by amplifying the advantages of VUV system and further mineralizing the intermediates. In VUV and VUV-PCO processes, O2 participation changed the intermediates distribution by increasing multiple oxygenated products, while the introduction of water contributed to the formation and degradation of most intermediates. https://www.selleckchem.com/products/loxo-195.html A possible degradation mechanism of toluene under VUV irradiation combined with TiO2 was proposed. This study provides a deep mechanistic insight into VOCs degradation by VUV-PCO process.Palladium based catalysts are highly attractive for catalytic reactions. However, the catalytic activity is dependent on the dispersion and size of Pd nanoparticles (NPs). Herein, an efficient strategy is developed to regulate the size and dispersion of Pd NPs in nanoconfined spaces provided by Santa Barbara Amorphous-15 (SBA-15) occluded with template. The Pd precursor is introduced to the confined spaces between the template and silica walls in as-synthesized SBA-15 (AS) by grinding. Subsequent reduction allow template removal and precursor conversion to Pd0 in single step and avoids aggregation that take place in calcined SBA-15 (CS). Our results show that up to 1.0 wt% of Pd can be well dispersed in confined spaces of AS (denoted as 1.0PdAS), while sever aggregation take place from CS with the same Pd loading (denoted as1.0PdCS). We also demonstrated that 1.0PdAS is highly efficient for catalytic reduction of p-nitrophenol (P-NP) and Methylene blue (MB) with rate constant of 0.4924 and 0.626 min-1, respectively, which is superior than 1.0PdCS attributed to well dispersed and smaller size (3 nm) Pd NPs. Furthermore, no change in the rate constant of P-NP (0.4924 min-1) and MB (0.626 min-1) after regeneration presents good stability of 1.0PdAS in catalytic reactions.Nanomaterials stabilization in lube oils poses an acute challenge in nanolubricants/nanofluids formulation. This study aims to improve the dispersion stability of copper (Cu) nanomaterials in polyalphaolefin-6 (PAO6) oil to overcome the agglomeration/sedimentation problem. Here, we modified the surface of Cu nanomaterials using ionic liquids (ILs) to enhance the electrostatic repulsion force in Cu nanomaterials. We evaluated the dispersion behavior of Cu nanolubricants by visual observation, ultraviolet-visible spectroscopy, dynamic light scattering, and zeta potential measurements. Furthermore, we determined the rheological and thermo-oxidation behavior of Cu nanolubricants using Brookfield viscometer, thermogravimetric, and Fourier transform infrared. Our experiments showed that dispersion stability depends on Cu concentration and settling time. IL demonstrated effective miscibility when blended with PAO6 oil and displayed non-Newtonian behavior. The results suggest that Cu modified by IL provides superior dispersion in PAO6 oil without sedimentation for 60 days, compared to unmodified Cu.

Cleavage of amyloid precursor protein (APP) by BACE-1 (β-site APP cleaving enzyme 1) is the rate-limiting step in amyloid-β (Aβ) production and a neuropathological hallmark of Alzheimer's disease (AD). Despite decades of research, mechanisms of amyloidogenic APP processing remain highly controversial. Here, we show that in neurons, APP processing and Aβ production are controlled by the protein complex-2 (AP-2), an endocytic adaptor known to be required for APP endocytosis. Now, we find that AP-2 prevents amyloidogenesis by additionally functioning downstream of BACE1 endocytosis, regulating BACE1 endosomal trafficking and its delivery to lysosomes. AP-2 is decreased in iPSC-derived neurons from patients with late-onset AD, while conditional AP-2 knockout (KO) mice exhibit increased Aβ production, resulting from accumulation of BACE1 within late endosomes and autophagosomes. Deletion of BACE1 decreases amyloidogenesis and mitigates synapse loss in neurons lacking AP-2. Taken together, these data suggest a mechanism for BACE1 intracellular trafficking and degradation via an endocytosis-independent function of AP-2 and reveal a novel role for endocytic proteins in AD. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.PURPOSE To identify nonpharmacological clinically effective interventions for constipation in adults. METHODS A systematic review of experimental studies of nonpharmacological interventions addressing participants' management of constipation using samples of adults over 18 years of age was conducted. In evaluating the methodological quality of the eligible studies, we used the assumptions of the Cochrane Collaboration, and for the reporting of items in the systematic review we used the Model of Preferential Reporting Items for Systematic Reviews and Meta-Analyses. The protocol of this review was recorded in the International Prospective Register of Systematic Reviews of the University of York under number 43693. RESULTS This review included 12 randomized controlled trials. Nonpharmacological effective interventions for the resolution of constipation were identified individualized intervention based on the participant's modifiable risk factors of constipation promoting literacy in health; educational measures in dietary modification and lifestyle; and abdominal massage. CONCLUSIONS Specific nonpharmacological interventions are crucial for nurses' clinical practice and of major importance for clients and families. Evidence on these interventions in resolving constipation is still scarce and fails to provide evidence-based data to support nursing clinical practice. CLINICAL RELEVANCE Personal lifestyles, comorbidities, medication, and sedentary habits are likely to be risk factors in constipation. Thus, it is important to invest in nonpharmacological interventions that promote changes in behavior regarding prevention or resolution of constipation. Moreover, nursing researchers worldwide should conduct research for clinical practice regarding the fundamentals of care. © 2020 Sigma Theta Tau International.Extrusion-based 3D bioprinting is hampered by the inability to print materials of low-viscosity. In this study, a single initiating system based on ruthenium (Ru) and sodium persulfate (SPS) is utilized for a sequential dual-step crosslinking approach 1) primary (partial) crosslinking in absence of light to alter the bioink's rheological profile for print fidelity, and 2) subsequent secondary post-printing crosslinking for shape maintenance. Allyl-functionalized gelatin (Gel-AGE) is used as a bioink, allowing thiol-ene click reaction between allyl moieties and thiolated crosslinkers. https://www.selleckchem.com/products/cerdulatinib.html A systematic investigation of primary crosslinking reveals that a thiol-persulfate redox reaction facilitates thiol-ene crosslinking, mediating an increase in bioink viscosity that is controllable by tailoring the Ru/SPS, crosslinker, and/or Gel-AGE concentrations. Thereafter, subsequent photoinitiated secondary crosslinking then facilitates maximum conversion of thiol-ene bonds between AGE and thiol groups. The dual-step crosslinking method is applicable to a wide biofabrication window (3-10 wt% Gel-AGE) and is demonstrated to allow printing of low-density (3 wt%) Gel-AGE, normally exhibiting low viscosity (4 mPa s), with high shape fidelity and high cell viability (>80%) over 7 days of culture. The presented approach can therefore be used as a one-pot system for printing low-viscous bioinks without the need for multiple initiating systems, viscosity enhancers, or complex chemical modifications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This study evaluated the effect of thermosensitive hydroxybutyl chitosan (HBC) hydrogel loaded with human platelet lysate (hPL) on skin wound healing in rats. hPLs were generated by freeze-thaw method of platelet-rich plasma from healthy donors. Successful grafting of hydroxybutyl group to chitosan molecular chain to obtain HBC hydrogel was confirmed by Fourier-transform infrared spectroscopy. HBC/hPL was prepared by combining 10% (vol/vol) hPL with HBC solution. Surface morphologies were determined by Scanning Electron Microscopy, rheological properties were measured by rheometer, and sustained release of factors from HBC/hPL was measured by enzyme-linked immunoassay. We evaluated the in vitro effect of HBC/hPL on human umbilical cord vein endothelial cell (HUVEC) proliferation, migration, and tube formation. The effect of growth factors released from HBC/hPL in promoting skin wound healing was evaluated by gross observation, histology, immunohistochemistry, and immunofluorescence in vivo. Rheological analyses indicated the gelation temperatures of HBC and HBC/hPL were 17 and 14°C, respectively. ELISA showed sustained release of human platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β1 from HBC/hPL hydrogel. In vitro studies revealed HBC/hPL promoted greater levels of HUVECs proliferation, migration, and tube formation than the HBC and control groups. In vivo studies showed better wound healing, greater amounts of newly formed collagen, as well as neovascular and neo-epidermis markers in the wound site of HBC/hPL-treated group compared to the HBC and control groups. HBC/hPL is a promising potential therapeutic agent for promoting skin wound healing via the sustained release of growth factors. © 2020 Wiley Periodicals, Inc.

Instead, they consist of the isomerization of the μ3-η2-alkyne and μ3-alkylidyne ligands on each side of the Ru₃ plane into μ3-alkylidyne and μ3-η2-alkyne, respectively. This implies the migration of three H atoms within the hydrocarbyl ligands, and it is aided by the cluster's ability to behave as a H reservoir. All in all, this study highlights the plasticity of these structures, whereby Ru-Ru, Ru-C, Ru-H, C-C, and C-H bonds are formed and broken with surprising ease.Upconverting phosphors (UCPs) convert multiple low energy photons into higher energy emission via the process of photon upconversion and offer an attractive alternative to organic fluorophores for use as luminescent probes. Here, UCPs were capped with functionalized silica in order to provide a surface to covalently conjugate proteins with surface-accessible cysteines. Variants of green fluorescent protein (GFP) and the flavoenzyme pentaerythritol tetranitrate reductase (PETNR) were then attached via maleimide-thiol coupling in order to allow energy transfer from the UCP to the GFP or flavin cofactor of PETNR, respectively. PETNR retains its activity when coupled to the UCPs, which allows reversible detection of enzyme substrates via ratiometric sensing of the enzyme redox state.In the last decade, aryldiazonium salts have attracted interest as coupling partners in cross-coupling reactions mediated by gold. Initially, the presence of a photocatalyst and a light source was needed to achieve gold oxidation with these electrophiles. However, recently it has been shown that in some instances just heating, light irradiation or the addition of certain bases and/or nucleophiles is enough. In this review, we summarized the transformations developed so far using aryldiazonium salts as electrophiles with special emphasis on mechanistic studies. The information gained by different authors, points that the specific steps of gold oxidation with aryldiazonium salts depends upon the activation mode of the diazonium salt.This study investigated possible female-related causes for inconsistent success among reproductive pairs in the zoo-based red wolf (Canis rufus) population. Females (n = 13) at seven institutions were assessed for evidence of ovulation and normal reproductive cycles through the measurement of estradiol and progesterone metabolite excretion in feces. Fecal cortisol metabolites (FCM) were also measured. Factors potentially affecting FCM and/or estrous cyclicity were recorded, including exhibit status (on vs. off), reproductive history (proven vs. unproven), copulatory behaviors (ties observed yes or no), pregnancy/parturition (pups or no pups produced), and translocation before the observed breeding season (yes or no). No differences were observed in baseline FCM between females housed on versus off-exhibit (p = .46) or between females producing pups and those who did not (p = .19). Baseline FCM were significantly lower among females observed in copulatory ties compared to females never observed in a tie (p = .04), and tended to be higher in females translocated before the breeding season compared to females in existing reproductive pairs (p = .11), and among historically unproven females compared to proven females (p = .11). All females evaluated had an endocrine profile indicative of ovulation and among the four females translocated to be paired with a new male before the breeding season, two had successful pregnancies, producing litters. Therefore, despite observed differences in baseline FCM among factors, estrous cyclicity and reproductive success are unaffected by translocation for the formation of new reproductive pairs in the zoo-based red wolf population.Voltage-gated Ca2+ (CaV ) channels are crucial for neuronal excitability and synaptic transmission upon depolarization. Their properties in vivo are modulated by their interaction with a variety of scaffolding proteins. Such interactions can influence the function and localization of CaV channels, as well as their coupling to intracellular second messengers and regulatory pathways, thus amplifying their signaling potential. Among these scaffolding proteins, a subset of PDZ (postsynaptic density-95, Drosophila discs-large, and zona occludens)-domain containing proteins play diverse roles in modulating CaV channel properties. At the presynaptic terminal, PDZ proteins enrich CaV channels in the active zone, enabling neurotransmitter release by maintaining a tight and vital link between channels and vesicles. In the postsynaptic density, these interactions are essential in regulating dendritic spine morphology and postsynaptic signaling cascades. In this review, we highlight the studies that demonstrate dynamic regulations of neuronal CaV channels by PDZ proteins. We discuss the role of PDZ proteins in controlling channel activity, regulating channel cell surface density, and influencing channel-mediated downstream signaling events. We highlight the importance of PDZ protein regulations of CaV channels and evaluate the link between this regulatory effect and human disease.Piscine orthoreovirus genotype 1 (PRV-1) is the causative agent of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar L.). The virus has also been found in Pacific salmonids in western North America, raising concerns about the risk to native salmon and trout. Here, we report the results of laboratory challenges using juvenile Chinook salmon, coho salmon and rainbow trout injected with tissue homogenates from Atlantic salmon testing positive for PRV-1 or with control material. Fish were sampled at intervals to assess viral RNA transcript levels, haematocrit, erythrocytic inclusions and histopathology. https://www.selleckchem.com/products/tmp269.html While PRV-1 replicated in all species, there was negligible mortality in any group. We observed a few erythrocytic inclusion bodies in fish from the PRV-1-infected groups. At a few time points, haematocrits were significantly lower in the PRV-1-infected groups relative to controls, but in no case was anaemia noted. The most common histopathological finding was mild, focal myocarditis in both the non-infected controls and PRV-1-infected fish. All cardiac lesions were judged mild, and none were consistent with those of HSMI. Together, these results suggest all three species are susceptible to PRV-1 infection, but in no case did infection cause notable disease in these experiments.

Indoor surfaces can be large reservoirs of acids and bases. This extensive review of the state of knowledge establishes a foundation for future inquiry to better understand how acids and bases influence the suitability of indoor environments for occupants, cultural artifacts, and sensitive equipment. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Staphylokinase (SAK), a 136 amino acid bacterial protein with profibrinolytic properties, has emerged as an important thrombolytic agent because of its fibrin specificity and reduced inhibition by α-2 antiplasmin. In an attempt to enhance the clot dissolution ability of SAK, a 30 amino acid peptide (VEK-30) derived from a plasminogen (Pg) binding protein (PAM), was fused at the C-terminal end of SAK with a RGD (Arg-Gly-Asp) linker. The chimeric protein, SAKVEK, was expressed in E. coli and purified as a soluble protein. Pg-activation by equimolar complexes of SAKVEK and SAK with plasmin revealed that the fusion of VEK-30 peptide has significantly enhanced the catalytic activity of SAK. https://www.selleckchem.com/products/aprotinin.html The kinetic constant, kcat / Km of SAKVEK for the substrate Pg appeared 2.7 times higher than that of SAK and the time required for the fibrin and platelet rich clot-lysis was shortened by 30% and 50%, respectively. The binary activator complex of SAKVEK with plasmin gets inhibited by α2- antiplasmin but remains protected in the presence of fibrin, very similar to SAK. Thus, the present study suggests that SAKVEK is more potent and effective as a thrombolytic agent due to its higher catalytic activity for Pg-activation in a fibrin specific manner and its ability to clear platelet rich plasma clot faster than SAK. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The paper describes how borate-containing background electrolytes (BGEs) modify ζ-potential and so electroosmotic flow (EOF) in bare fused silica capillaries. This surface modification can be used to suppress EOF and improve the separation performance of CZE including capillary sieving electrophoresis (CSE). Boric acid forms complexes with polysaccharides used as sieving matrices in CSE and other compounds containing hydroxyl groups, including polyol bases like TRIS, triethanolamine (TEA) and Bis-Tris Propane (BTP). High concentration of boric acid in BGEs leads to a strong interaction of boric acid with the silica surface of the capillary wall and this suppresses or even completely eliminates ζ-potential and EOF. Using a polyol base with several charge-carrying amino groups, such as BTP, can actually reverse EOF. We demonstrate the use of various borate-containing BGEs in bare fused silica capillaries for size-separation of DNA fragments, size-separation of proteins by SDS CSE and also by CZE in the absence of any sieving matrix. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The ongoing pandemic of SARS-CoV-2 virus and its associated disease COVID-19 has resulted in widespread ventilator shortages and rationing of care. Massive global supply chain disruption and quarantine measures prevent equipment movement and medical device production. This article is protected by copyright. All rights reserved.Interactions between heparin and tetraarginine in an acidic background electrolyte were investigated in capillary electrophoresis. The results showed that tetraarginine and heparin form a stable complex that migrates towards the anode immediately after coming into contact. When a zone of tetraarginine at a mg/mL concentration level passes through a zone of heparin at a μg/mL concentration level, tetraarginine is gradually removed by the formation of the complex that migrates in the opposite direction, thereby decreasing the tetraarginine peak area. The variation of the tetraarginine peak area as a function of the unfractionated heparin concentration was linear within the range from 2 to 20 μg/mL, which enables us to detect and determine heparin concentrations undetectable with a UV detector. The same behavior was confirmed for low-molecular-weight heparin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.In mammals, microRNAs can be actively secreted from cells to blood. miR-29b-3p has been shown to play a pivotal role in muscle atrophy, but its role in intercellular communication is largely unknown. Here, we showed that miR-29b-3p was upregulated in normal and premature aging mouse muscle and plasma. miR-29b-3p was also upregulated in the blood of aging individuals, and circulating levels of miR-29b-3p were negatively correlated with relative appendicular skeletal muscle. Consistently, miR-29b-3p was observed in exosomes isolated from long-term differentiated atrophic C2C12 cells. When C2C12-derived miR-29b-3p-containing exosomes were uptaken by neuronal SH-SY5Y cells, increased miR-29b-3p levels in recipient cells were observed. Moreover, miR-29b-3p overexpression led to downregulation of neuronal-related genes and inhibition of neuronal differentiation. Interestingly, we identified HIF1α-AS2 as a novel c-FOS targeting lncRNA that is induced by miR-29b-3p through down-modulation of c-FOS and is required for miR-29b-3p-mediated neuronal differentiation inhibition. Our results suggest that atrophy-associated circulating miR-29b-3p may mediate distal communication between muscle cells and neurons. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence-associated lysosomal β-galactosidase (SA-β-gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose-encapsulated nanoparticles within these cells. Here, we show that galacto-conjugation of the BCL-2 family inhibitor Navitoclax results in a potent senolytic prodrug (Nav-Gal), that can be preferentially activated by SA-β-gal activity in a wide range of cell types. Nav-Gal selectively induces senescent cell apoptosis and has a higher senolytic index than Navitoclax (through reduced activation in nonsenescent cells).

in English, German ZIEL  Testen der Benutzerfreundlichkeit (Usability) und des Anwendungserlebnisses eines neu entwickelten eLearning-Tools zum Unterrichten von Medizinstudenten in PET/CT und CT. METHODEN  Das eLearning-Tool ermöglicht die webbasierte Darstellung von PET- und CT-DICOM-Bildern. Es enthält Bilder eines Normalprobanden mit Annotationen der anatomischen Strukturen und eine klinische Fallstudie. Die Usability und das Anwendungserlebnis des eLearning-Tools wurde an Medizinstudenten der Medizinischen Fakultät der RWTH Aachen evaluiert. Wir haben eine Umfrage durchgeführt, die auf verschiedenen bereits existierenden und validierten Fragebögen wie System-Usability-Scale (SUS) und User-Experience-Questionnaire (UEQ-S) sowie auf spezifischen Fragen zum eLearning-Tool basiert. ERGEBNISSE  38 Freiwillige (9 Männer) nahmen an unserer Studie teil. Die Anwendung des SUS ergab einen Mittelwert von 82,24 und einen Median von 83,75. Diese positive Bewertung wird durch die Ergebnisse der UEQ-S gestützt, die hinsichtlich der pragmatischen Qualität 2,2, hinsichtlich der hedonistischen Qualität 2,3 und hinsichtlich der Gesamtqualität 2,3 betrugen, was auf eine sehr positive Bewertung hindeutet. In den Freitextantworten wurde der einfache und intuitive Umgang mit dem zusätzlich als interessant und spannend bezeichneten eLearning-Tool hervorgehoben. Die Studierenden äußerten sich auch positiv über die Fallstudie und die Möglichkeit des praxisbezogenen Lernens. Negative Aspekte waren hauptsächlich Probleme bei der Synchronisation der PET- und CT-Bilder. SCHLUSSFOLGERUNGEN  Die positive Bewertung ist ermutigend und bildet eine Grundlage für die Weiterentwicklung des eLearning-Moduls. Es kann die Grundlage für die Umsetzung eines nachhaltigen Blended-Learning-Konzepts im nuklearmedizinischen Lehrplan sein.in English, German HINTERGRUND Das Praktische Jahr (PJ) stellt als letzter Abschnitt des Medizinstudiums eine prägende Ausbildungszeit dar, in der medizinisches Wissen konsequent in ärztliche Kompetenzen umgewandelt werden soll. https://www.selleckchem.com/products/lonafarnib-sch66336.html Seit Novellierung der Ärztlichen Approbationsordnung (ÄApprO) vom 17. Juli 2012 sind ab 1. April 2013 die deutschen Universitäten verpflichtet, einen Ausbildungsplan in Form von PJ-Logbüchern für das Praktische Jahr in den Pflichttertialen Chirurgie und Innere Medizin bereitzustellen. In Vorbereitung dieser Neuerung hat der Medizinische Fakultätentag (MFT) im Juni 2012 Basis-Logbücher als Konsensusdokumente vorgelegt. An der Medizinischen Fakultät der Universität Magdeburg wird zur Ausbildung der PJ-Studierenden im Fach Chirurgie ein klinikspezifisches und in Eigeninitiative entwickeltes Portfolio genutzt. Es wurde überarbeitet und zu einem konkretisierten, alltagsbezogenen und stark klinisch orientierten, fakultätsspezifischen PJ-Logbuch nach Vorgabe des MFT umgestaltet. Ziel dieses des MFT und ist gleichzeitig an die Gegebenheiten und die Lehre der Magdeburger Medizinischen Fakultät angepasst. Den Studierenden wird ein alltagsbezogenes, klinisch relevantes Dokument an die Hand gegeben, um gemeinsam mit einem schlüssigen Ausbildungskonzept unverzichtbare praktisch-klinische Kompetenzen zu erwerben.BACKGROUND UW Medicine was one of the first health systems to encounter and treat COVID-19 patients in the United States, starting in late February 2020. OBJECTIVE Here we describe the rapid rollout of capabilities by UW Medicine Information Technology Services (ITS) to support our clinical response to the COVID-19 pandemic and provide recommendations for health systems to urgently consider, as they plan their own response to this and potentially other future pandemics. METHODS Our recommendations include establishing a hospital incident command structure that includes tight integration with IT, creating automated dashboards for incident command, optimizing emergency communication to staff and patients, and preparing human resources, security, other policies, and equipment to support the transition of all nonessential staff to telework.We describe how UW Medicine quickly expanded telemedicine capabilities to include most primary care providers and increasing numbers of specialty providers. We look at how we managed expedited change control processes to quickly update electronic health records (EHR) with new COVID-19 laboratory and clinical workflows. We also examine the integration of new technology such as tele-intensive care (ICU) equipment and improved integration with teleconferencing software into our EHR. To support the rapid preparation for COVID-19 at other health systems, we include samples of the UW Medicine's COVID-19 order set, COVID-19 documentation template, dashboard metric categories, and a list of the top 10 things your health care IT organization can do now to prepare. CONCLUSION The COVID-19 response requires new and expedited ways of approaching ITS support to clinical needs. UW Medicine ITS leadership hope that by quickly sharing our nimble response to clinical and operational requests, we can help other systems prepare to respond to this public health emergency. Georg Thieme Verlag KG Stuttgart · New York.BACKGROUND  With the consequences of inadequate dosing ranging from increased bleeding risk to excessive drug costs and undesirable administration regimens, the antihemophilic factors are uniquely suited to dose individualization. However, existing options for individualization are limited and exist outside the flow of care. We developed clinical decision support (CDS) software that is integrated with our electronic health record (EHR) and designed to streamline the process for our hematology providers. OBJECTIVES  The aim of this study is to develop and examine the usability of a CDS tool for antihemophilic factor dose individualization. METHODS  Our development strategy was based on the features associated with successful CDS tools and driven by a formal requirements analysis. The back-end code was based on algorithms developed for manual individualization and unit tested with 23,000 simulated patient profiles created from the range of patient-derived pharmacokinetic parameter estimates defined in children and adults.