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Novel coronavirus (SARS-CoV-2), which causes COVID-19, has thus far affected more than 15 million individuals, resulting in more than 600000 deaths worldwide, and the number continues to rise. In a large systematic review and meta-analysis of the literature including 2567 pregnant women, 7% required intensive care admission, with a maternal mortality ~1% and perinatal mortality below 1%. There has been a rapid increase in publications on COVID-19-associated coagulopathy, including disseminated intravascular coagulopathy and venous thromboembolism, in the non-pregnant population, but very few reports of COVID-19 coagulopathy during pregnancy; leaving us with no guidance for care of this specific population.
This is a collaborative effort conducted by a group of experts that was reviewed, critiqued, and approved by the International Society on Thrombosis and Haemostasis Subcommittee for Women's Health Issues in Thrombosis and Hemostasis. A structured literature search was conducted, and the quality of curreata to support the management of COVID-19 and associated coagulopathy in pregnancy was established.Humans and other mammalian species possess an endogenous circadian clock system that has evolved in adaptation to periodically reoccurring environmental changes and drives rhythmic biological functions, as well as behavioural outputs with an approximately 24-hour period. In mammals, body clocks are hierarchically organized, encompassing a so-called pacemaker clock in the hypothalamic suprachiasmatic nucleus (SCN), non-SCN brain and peripheral clocks, as well as cell-autonomous oscillators within virtually every cell type. A functional clock machinery on the molecular level, alignment among body clocks, as well as synchronization between endogenous circadian and exogenous environmental cycles has been shown to be crucial for our health and well-being. Yet, modern life constantly poses widespread challenges to our internal clocks, for example artificial lighting, shift work and trans-meridian travel, potentially leading to circadian disruption or misalignment and the emergence of associated diseases. For instance many of us experience a mismatch between sleep timing on work and free days (social jetlag) in our everyday lives without being aware of health consequences that may arise from such chronic circadian misalignment, Hence, this review provides an overview of the organization and molecular built-up of the mammalian circadian system, its interactions with the outside world, as well as pathologies arising from circadian disruption and misalignment.Alcohol dehydrogenases (ADH) are widely used to enantioselectively reduce ketones to chiral alcohols, but their application in industrial scale oxidations is rare. Reasons are the need for an NAD(P)+ cofactor regeneration system, often low performance in oxidative reactions and the limited substrate scope of ADHs. ADHA from Candida magnoliae DSMZ 70638 is identified to efficiently catalyze the regio-selective hydroxy-lactone oxidations to hydroxy-lactones. Hydroxy-lactones are common intermediates in industrial processes to cholesterol lowering (va)statin drugs. A biocatalytic aliphatic hydroxy-lactone oxidation process is developed using pure oxygen as oxidant reaching volumetric productivities of up to 12 g L-1 h-1 , product concentrations of almost 50 g L-1 and 95% reaction yield. For co-factor recycling a previously engineered, water-forming NAD(P)H-oxidase from Streptococcus mutans is used. The process is scaled up to industrial pilot plant scale and it could be demonstrated that ADH catalyzed oxidations can be developed to efficient and safe processes. However, the ADHA wild-type enzyme is not productive enough in chlorolactol oxidation. Therefore, enzyme engineering and multi-parameter screening is successfully applied to optimize the enzyme for the target reaction. The optimized ADHA variant shows a 17-fold higher oxidative activity, a 26°C increased stability and is applied to develop an efficient chlorolactol oxidation process.
NG2 cells in the brain are comprised of pericytes and NG2 glia and play an important role in the execution of cerebral hypoxia responses, including the induction of erythropoietin (EPO) in pericytes. Oxygen-dependent angiogenic responses are regulated by hypoxia-inducible factor (HIF), the activity of which is controlled by prolyl 4-hydroxylase domain (PHD) dioxygenases and the von Hippel-Lindau (VHL) tumour suppressor. However, the role of NG2 cells in HIF-regulated cerebral vascular homeostasis is incompletely understood.
To examine the HIF/PHD/VHL axis in neurovascular homeostasis, we used a Cre-loxP-based genetic approach in mice and targeted Vhl, Epo, Phd1, Phd2, Phd3 and Hif2a in NG2 cells. Cerebral vasculature was assessed by immunofluorescence, RNA in situ hybridization, gene and protein expression analysis, gel zymography and in situ zymography.
Vhl inactivation led to a significant increase in angiogenic gene and Epo expression. This was associated with EPO-independent expansion of capillary networks in cortex, striatum and hypothalamus, as well as pericyte proliferation. A comparable phenotype resulted from the combined inactivation of Phd2 and Phd3, but not from Phd2 inactivation alone. Concomitant PHD1 function loss led to further expansion of the neurovasculature. Genetic inactivation of Hif2a in Phd1/Phd2/Phd3 triple mutant mice resulted in normal cerebral vasculature.
Our studies establish (a) that HIF2 activation in NG2 cells promotes neurovascular expansion and remodelling independently of EPO, (b) that HIF2 activity in NG2 cells is co-controlled by PHD2 and PHD3 and (c) that PHD1 modulates HIF2 transcriptional responses when PHD2 and PHD3 are inactive.
Our studies establish (a) that HIF2 activation in NG2 cells promotes neurovascular expansion and remodelling independently of EPO, (b) that HIF2 activity in NG2 cells is co-controlled by PHD2 and PHD3 and (c) that PHD1 modulates HIF2 transcriptional responses when PHD2 and PHD3 are inactive.We performed an updated meta-analysis to compare the efficacy of the zipper device and sutures for wound closure after surgery. A computerised literature search was performed for published trials in PubMed, Web of Science, the Cochrane Library, and Google Scholar. Two reviewers independently scrutinised the trials, extracted data, and assessed the quality of trials. The primary outcome was surgical site infections (SSI). The secondary outcomes were wound dehiscence, total wound complications, wound closure time, and scar score. Statistical analysis was performed in the Stata 12.0. Of the 130 citations, eight trials (1207 participants) met eligibility criteria and were included. The zipper device achieved a lower SSI rate (RR 0.63, [95% CI 0.41-0.96, P = 0.032]), a shorter wound closure time (SMD -8.53 [95% CI -11.93 to -5.13, P = 0.000]) and a better scar score (SMD 0.42 [95% CI 0.22-0.62, P = 0.000]) than sutures. No significant difference was shown in the incidence of wound dehiscence and total wound complications. Therefore, the zipper device provides the advantages of anti-infection, time-saving, and cosmesis for wound closure.Highlight Sasaki and colleagues report their experience with double stenting combined with endoscopic ultrasound-guided choledochoduodenostomy using a new anti-reflux metal stent to prevent duodenobiliary reflux in combined biliary and duodenal obstruction. This double stenting method is a new strategy for the management of combined biliary and duodenal obstruction.The Triton X-114-based solubilization and temperature-dependent phase separation of proteins is used for subcellular fractionation where, aqueous, detergent, and pellet fractions represents cytoplasmic, outer membrane (OM), and inner membrane proteins, respectively. Mass spectrometry-based proteomic analysis of Triton X-114 fractions of proteomic analysis of Leptospira interrogans identified 2957 unique proteins distributed across the fractions. The results are compared with bioinformatics predictions on their subcellular localization and pathogenic nature. Analysis of the distribution of proteins across the Triton X-114 fractions with the predicted characteristics is performed based on "number" of unique type of proteins, and "quantity" which represents the amount of unique protein. The highest number of predicted outer membrane proteins (OMPs) and pathogenic proteins are found in aqueous and pellet fractions, whereas detergent fraction representing the OM has the highest quantity of OMPs and pathogenic proteins though lower in number than the aqueous and pellet fractions. This leaves the possibility of an upsurge in pathogenic proteins and OMPs on the OM under pathogenic conditions suggesting their potential use to combat leptospirosis. Further, the Triton X-114 subcellular fractions are more correlated to enrichment of pathogenic proteins predicted by MP3 software than predicted localization.Hollow organic molecular cocrystals comprised of 9-methylanthracene-1,2,4,5-tetracyanobenzene (9MA-TCNB) and naphthalene-1,2,4,5-tetracyanobenzene (NAPH-TCNB) were fabricated using a surfactant-mediated co-reprecipitation method. The crystals exhibit a narrow size distribution that can be easily tuned by varying the concentration of surfactant and incubation temperature. The rectangular crystals possess symmetrical twinned cavities with an estimated storage volume on the order of 10-10 L. An aqueous dye solution can be incorporated into the cavities during crystal growth and stored inside for up to several hours, confirming the sealed nature of the hollow chambers. Our results demonstrate that it is possible to harness non-classical crystal growth to fabricate organic molecular crystals with novel topologies.
Few studies exist that examined the role of radiofrequency microneedling (RFMN) in skin electrocoagulation. This research utilized a porcine model to understand bipolar dermal delivery from an RFMN device.
The objective of this study was to elucidate and compare the dermal thermal effects of a RFMN device producing 1 and 2MHz signal amplitudes, with respective voltage and current gradients, utilizing noninsulated and insulated needles by examining the histologic effects on porcine skin.
Two separate animal studies were conducted to evaluate the electrocoagulation and thermal diffusion effects using the RFMN device. The electrocoagulation effects were assessed histologically using hematoxylin and eosin (H&E) staining, and heating effects were assessed through thermal imaging.
Histology results of the thermal injury induced by insulated needles demonstrated that 2MHz resulted in a narrow and concentrated coagulation zone as compared to 1MHz. Further, the 1MHz insulated needle resulted in ovular shaped tissue coagulation as compared to 2MHz tissue coagulation that was columnar. Finally, full thermal diffusion occurs seconds after the set RF conduction time.
The findings showed that 1MHz insulated needle produces larger coagulations with an increase in power level, the 1MHz noninsulated array was comparable to the 2MHz insulated array with similar histologic features, and heat dissipates seconds after the set conduction time.
The findings showed that 1 MHz insulated needle produces larger coagulations with an increase in power level, the 1 MHz noninsulated array was comparable to the 2 MHz insulated array with similar histologic features, and heat dissipates seconds after the set conduction time.
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