Since the start of the SARS-CoV-2 pandemic, it has been difficult to differentiate between SARS-CoV-2 re-infection and prolonged RNA shedding. In this report, we identified patients with positive rtPCR results for SARS-CoV-2 ≥70 days apart. Clinical and laboratory data were collected and criteria were applied to discern whether the presentation was consistent with SARS-CoV-2 re-infection or prolonged viral RNA shedding. Eleven individuals met the initial testing criteria, of which, seven met at least one criteria for re-infection and four were consistent with prolonged RNA shedding. These data demonstrate the need for criteria to differentiate SARS-CoV-2 re-infection from prolonged RNA shedding.

Objective To assess the effects body mass index (BMI) on live birth rates in patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy and preimplantation genetic testing for aneuploidies (PGT-A) when transferring a single euploid blastocyst. Design Retrospective cohort study. Setting Public fertility center in China. Population 821 women who underwent first cycle of frozen-thawed single euploid blastocyst transfer between 2012 and 2020. Methods Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n=80), normal weight (18.5-24.9, n=602), overweight (25-30, n=112), and obese (≥30, n=27). A logistic regression model was used to assess the association between BMI and live birth while adjusting for potential confounders. Main outcome measures Live-birth rate was primary outcome. Results There was no difference in the birth weight, miscarriage, preterm birth, pregnancy complication, type of delivery and fetal gender by BMI category. The clinical pregnancy rate was higher in the overweight and obese groups. In multivariate logistic regression analysis, we fail to demonstrate a statistically significant relationship between BMI and live birth in underweight (adjusted odds ratio [AOR] 0.80; 95% confidence interval [CI], 0.47-1.35, p=0.402), overweight (AOR 0.85; 95% CI, 0.54-1.35, p=0.491) or obese (AOR 1.07; 95% CI, 0.48-2.38, p=0.864) patients compared with the normal weight reference group. Conclusion No statistically significant relationship was identified between BMI and live birth in patients undergoing IVF with PGT-A, suggesting that the negative impact of obesity on IVF and clinical outcomes may be related to aneuploidy.

Although the regulation in Pi homeostasis of miR399 have been studied in various plants, its molecular mechanisms in response to freezing stress are still elusive. In this work, we found that the expression of tae-miR399 and its target gene TaUBC24 in tillering nodes of strong cold resistance winter wheat cultivar Dongnongdongmai1 (Dn1) was significantly altered subjected to severe winter. tae-miR399 and its target gene TaUBC24 were also responsive to short-term freezing stress in tillering nodes of Dn1 seedlings. TaUBC24 physically interacted with TaICE1. Ehanced freezing tolerance was observed in overexpressing tae-miR399 Arabidopsis lines. Under freezing stress, overexpressing tae-miR399 decreased the expression of AtUBC24 to increase the expression of genes in CBF signaling pathway, Pi translocation pathway and starch metablism, including AtCBFs, AtCOR47, AtCOR413IM, AtPHT1;4, AtAPLs and AtBAMs, inhibit the degradation of AtICE1 and AtPHO1, and promote the activities of SOD, POD and CAT. These findings indicated that the increased freezing tolerance was dependent upon elevating CBF signaling pathway, phosphorus utilization efficiency, starch degradation, accumulation of soluble sugar and ability of ROS scavenge. These results will aid our understanding of molecular mechanism of how miR399-UBC24 module plays a cardinal role in regulating plant freezing stress tolerance through mediating the downstream pathways.

Illicit drugs are marketed both via dark web platforms and social media, but there are also research reports buying these drugs online. This study is intended to analyse the risk factors for the purchase of online illicit drugs. We assumed that social interactions, low levels of self-control, and impaired mental health would be correlated with online opioid sales following criminological and addiction analysis research. Moreover, online drug sales are expected to be related to low self-control and daily drug consumption. Participants in this nationwide study were aged 15 to 25 years and lived in Germany (N=1,732) and France (N=1,732). Measures of impulsivity, ability sensitivity, social association, psychological tension, and repetitive activity (drinking, gambling, and Internet use) predicted online drug use. 4% of German and French respondents reported buying drugs online of which, 63% did so via social media services. Online opioid purchases were associated with lower self-control, elevated social anxiety, heavy gambling, and Internet use, as shown by multinomial logistic regression and binary intervention regression models. It was not a risk factor to have online friends, but close social links with offline friends served as a security factor. The results indicate that more attention should be paid to mainstream social media services as a source for buying drugs as there are many psychological and self-control issues among online drug consumers.

A document by Dr. Daniel Cebo, written on Authorea.

Management of acute bronchiolitis remains controversial due to lack of strong evidence-based data. Nebulized epinephrine and hypertonic saline have been studied in infants with bronchiolitis, with conflicting results. This systematic review and meta-analysis aimed to evaluate the efficacy on length of stay (LOS), clinical severity scores (CSS), oxygen saturation (SaO2) and safety profile of nebulized epinephrine plus hypertonic saline (HS) in infants with acute bronchiolitis. Outcomes were represented by mean differences (MD) or standard mean differences (SMD) and 95% confidence intervals (CIs) were utilized. 18 trials were systematically selected and 16 of them contributed for the meta-analysis (1,756 patients). Overall, a modest but significant positive impact was observed of the combination therapy on LOS (MD of – 0.35 days, 95% CI -0.62 to -0.08, p = 0.01, I2 = 91%). Stratification by time of CSS assessment unveiled positive results in favor of the combination therapy in CSS assessed 48 hours and 72 hours after the admission (SMD of -0.35, 95% CI -0.62 to -0.09, p = 0.008, I2 = 41% and SMD of -0.27, 95% CI -0.50 to -0.04, p = 0.02, I2 = 0%, respectively). No difference in SaO2 was observed. Additional data showed a consistent safety profile, with a low rate of adverse events (1%), most of them mild and transient. In conclusion, nebulized epinephrine plus HS may be considered as a safe, cheap and efficient alternative for decreasing LOS and CSS in infants with acute bronchiolitis, especially on those who require more than 48 hours of hospitalization.

A 62-year-old man with rare blood type exhibited severe respiratory failure due to novel coronavirus. Extracorporeal membrane oxygenation was inapplicable, which requires numerous blood products with the same blood type. We thoroughly restricted fluid volumes by sacrificing renal function. He was discharged with complete recovery of respiratory and renal functions.

The aim of this study was to investigate plant growth, fruit yields, IWUE and fruit quality in response to a micro/nano-bubble aeration (MNBA) system and a subsurface artificial air layer aeration system (SAALA) under different treatments. The results indicated that both MNBA and SAALA can positively influence plant dry weight, fruit yield, IWUE and, to some degree, fruit quality indices. In comparison with the no-aeration treatment, the MNBA treatment increased the dry matter accumulation, fruit yield, IWUE, lycopene content and soluble protein content by 7.1%, 9.0%, 7.1%, 6.2% and 16.2%, respectively, during the spring, while those during autumn increased by 4.0%, 14.4%, 4.0%, 3.8% and 1.7%, respectively. During the spring, the SAALA increased the dry matter accumulation, fruit yield, IWUE, lycopene content and soluble protein content by 13.0%, 25.1%, 13.0%, 2.9% and 15.1%, respectively, while those during autumn increased by 12.8%, 19.5%, 12.8%, 5.2% and 4.1%, respectively. PFM significantly improved the total dry weight, fruit yield and IWUE during both the spring and autumn seasons. Nevertheless, the soluble protein content decreased in response to the mulch treatment. The increased yield in response to soil aeration during autumn was significantly greater than that during the spring, and the yield increase in response to PFM was significantly greater in the spring than in autumn. Moreover, the nutrition indices in response to both soil aeration and PFM were more significant during spring than during autumn. Taking into account costs, efficiency and benefits, the optimal treatment was the MNBA and full PFM combination

How variations in carbon supply affect wood formation remains poorly understood in particular in mature forest trees. To elucidate how carbon supply affects carbon allocation and wood formation, we attempted to manipulate carbon supply to the cambial region by phloem girdling and compression during the mid- and late-growing season and measured effects on structural development, CO2 efflux, and nonstructural carbon reserves in stems of mature white pines. Wood formation and stem CO2 efflux varied with location relative to treatment (i.e., above or below the restriction). We observed up to twice as many tracheids formed above versus below the treatment after the phloem transport manipulation, whereas cell-wall area decreased only slightly below the treatments, and cell size did not change relative to the control. Nonstructural carbon reserves in the xylem, needles, and roots were largely unaffected by the treatments. Our results suggest that low and high carbon supply affects wood formation, primarily through a strong effect on cell proliferation, and respiration, but local nonstructural carbon concentrations appear to be maintained homeostatically. This contrasts with reports of a decoupling of source activity and wood formation at the whole-tree or ecosystem level, highlighting the need to better understand organ-specific responses, within-tree feedbacks, as well as phenological and ontological effects on sink-source dynamics.

Aim: With the widespread use of SGLT2i, various adverse events (AEs) have been reported. This study aimed to describe the distribution of SGLT2i-related AEs in different systems, quantify the association of important medical events (IMEs) and SGLT2i regimens, and build a signal profile of SGLT2i- induced IMEs. Methods: Data from 2015 Q1 to 2020 Q4 in the FDA Adverse Event Reporting System database (FAERS) were selected to conduct disproportionality analysis. Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to evaluate the correlation between SGLT2i and IMEs. The lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed a signal. For ROR, it was defined a signal if ROR025 over one, with at least 3 cases. Results: A total of 45,771,436 records were involved, including 111,564 records related to SGLT2i, with 38,366 records of SGLT2i-induced IMEs. Overall, SGLT2i was significantly associated with IMEs (IC=0.36, 95% CI: 0.35-0.38; ROR=1.44, 95% CI: 1.42-1.46). Most SGLT2i-related adverse events occurred in monotherapy (92.93%). Diabetic ketoacidosis was the most IMEs. Specifically, acute osteomyelitis has the strongest signal of all SGLT2i (IC025=7.83), and it was unique to canagliflozin. Diabetic ketoacidosis, acute kidney injury, ketoacidosis, Fournier’s gangrene, and euglycemic diabetic ketoacidosis were common to the four FDA-approved SGLT2i. Conclusion: Our study demonstrated that different SGLT2i regimens lead to different important adverse events, but there are overlapping events. Early identification and management of SGLT2i-associated IMEs are essential for clinical practice.

Background: Titration of inspired oxygen is a challenge in preterm infants with hypoxemic respiratory failure (HRF). Monitoring of brain oxygen by near infrared spectroscopy (NIRS) has been proven to minimize the burden of hyperoxia and hypoxemia, with better understanding of cerebral autoregulation (CAR). integrating NIRS and pulse oximetry (SpO2) for titrating inspired oxygen is a novel approach. Methods: We aimed to study the impact of integrated monitoring of oxygen saturation by SpO2 and cerebral regional tissue oxygen (crRTO) by NIRS during oxygen reduction test (ORT) on reducing oxygen requirement in preterm infants with HRF. The correlation between SpO2 with crRTO, and fractional oxygen extraction (FOE) was assessed, concordance levels (r>0.5) were determined during the assessment period, and was considered as a sign of impaired autoregulation. The primary outcome was the achievement of significantly lower FiO2 at 72 hours after start of the integrated monitoring. Results: Total of 38 preterm infants were included, 27 had normal cerebral autoregulation (CAR), (group 1) in whom SpO2 was poorly correlating with cerebral regional tissue oxygen (crRTO) with (r<0.5) and had significantly greater percentage of reduction below baseline in FiO2 (Mean:34%). Eleven infants had impaired CAR (group 2) with SpO2 significantly correlating with crRTO (r>0.5) and had a linear trend of FOE inverse to SpO2 and crRTO; this was considered as an arterial saturation dependent oxygen delivery (SadDO2). Conclusion: Integrated monitoring of preterm infants by SpO2 and crRTO was associated with easier weaning of oxygen with less burden of both hyperoxia and hypoxemia.

This work discusses the results from tests conducted to investigate the uniaxial compression and creep behavior of red sandstone. The original untreated sample and the 800 ℃ treated sample have been selected to carry out the experiments. It has been found that high temperature has obvious influence on the mechanical properties of red sandstone. The relationship between creep strain and instantaneous strain, as well as instantaneous deformation modulus and creep viscosity coefficient have been analyzed. It has been found that high temperature reduces the ability of red sandstone to resist instantaneous deformation and creep deformation. Acoustic emission (AE) technology has been also used in the loading process of uniaxial compression and creep tests, providing a powerful means for damage evolution analysis of red sandstone.

Key points 1. This is the first report of adult primary herpetic oropharyngitis in the view point of the differences between the two types of herpes simplex virus (HSV). 2. 41 (25 type 1 and 16 type 2) HSV specific antigen positive cases among 68 immunoserologically confirmed adult HSV primary infection cases were investigated. 3. Significantly low incidence of oral lesions and high incidence of nausea were seen in HSV type 2 oropharyngitis cases, that might mean particular correlation vagus nerve and HSV type 2. 4. Significantly increased white blood cell count and high C-reacative protein value were seen in oropharyngitis by HSV type 2. 5. HSV type 2 possibly cause more severe symptoms and higher inflammatory reactions than type 1, without oral lesions.

Keypoints: • Implementing a one-stop Transnasal oesophagoscopy (TNO) service will benefit patients, clinicians as well as the NHS Trusts. • TNO is safe, well-tolerated and improves diagnostic and therapeutic precision in the upper aerodigestive tract and oesophagus. • The one-stop TNO service has clear financial benefits. • The one-stop TNO service is a streamlined pathway which improves patient care and experience. • Both the clinical and financial risk of introducing the service is low.

Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their negative genetic load but recent work suggests that the impact of load may be minimized by purging resulting from long term population bottlenecks. Empirical studies that examine this idea using genome-wide estimates of inbreeding and genetic load in threatened species are limited. Here we use genome resequencing data to compare levels of inbreeding, levels of genetic load and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus) which exist in small isolated populations and closely-related yet outbred Western massasauga rattlesnakes (S. tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of ROHs of varying sizes indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome-wide levels of genetic load in the form of greater numbers of derived deleterious mutations compared to S. catenatus presumably due to long-term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped the “drift sieve” and were polymorphic within S. catenatus populations were more abundant and more often found in homozygote genotypes than in S. tergeminus suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present which impacts implementation of conservation actions such as genetic rescue.

A document by Mina Kelleni, written on Authorea.

A document by Mina Kelleni, written on Authorea.

A document by Mina Kelleni, written on Authorea.

A document by Mina Kelleni, written on Authorea.

IntroductionMediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Moreover, a weak, irregular, or inhibited early interferon response to SARS CoV-2 infection was shown to trigger an exaggerated inflammatory response leading to the COVID-19 associated mortality. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach.Areas coveredWe present a concise analysis and interpretations of selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the recent results that suggested a potential survival benefit of low dose aspirin and colchicine when used for COVID-19.Expert opinionNitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that were unfortunately almost globally avoided early in the COVID-19 era and still avoided in many developing ones or at best of second choice in the developed ones, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their ability to prevent, constrain or reverse COVID-19 associated dysregulated immune and hyper-inflammatory responses through mitigating the formation of several inflammatory cytokines and pathways including the interleukin-6 amplifier and its NF-kB component, as well as modulation of a described monocytic immunological dysrhythmia, which is also known to trigger the COVID-19 cytokine storm. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials as COVID-19 potential safe and economic cure might be available and unfortunately repeatedly ignored for one year.

ACE2 polymorphisms have been previously linked to increased susceptibility to multiple diseases and are currently linked to SARS CoV-2 susceptibility and complications. Notably, ACE2 transcribed or regulated proteins include the activity of metaloproteinsase-2 and apelin-13 and 36, might be linked to abnormal immune responses and complications. Potential genetic or serological tests might be developed to detect the higher vulnerable groups to SARS CoV-2 complications and/or mortality. Moreover, we postulate that diabetic and obese patients suffer from exhausted and/or abnormally functioning apelinergic peptides that predispose them to a higher severe COVID-19 risk. Finally, infusion of apelin-13 to treat selected critical cases of COVID-19, especially those complaining of refractory advanced heart failure, might be considered for clinical trials. 

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.

A document by Mina Kelleni, written on Authorea.

A document by Mina Kelleni, written on Authorea.