Role of autoantibodies targeting interferon type 1 in COVID-19 severity: A systematic review and meta-analysis.

Introduction: Impairment of the type I interferon (IFN-I) signaling pathway is associated with increased severity of COVID-19 disease. Here we have undertaken a systematic review and meta = analysis on the association between the severity of COVID-19 and IFN-1 autoantibodies (AAbs; aIFN-1, aIFN-α, aIFN-ω, and aIFN-ß). Methods: Four databases, including Medline [PubMed], Embase, Web of Science, and Scopus, were systematically searched to find papers on the role of aIFN-1 and its subtype AAbs in the severity of COVID-19 infection. Data on the prevalence of aIFN-1, aIFN-α, aIFN-ω, and aIFN-ß were pooled using random- or fixed-effects models. Subgroup analysis was performed based on disease severity. Odds ratios (OR) for COVID-19 disease outcome, including length of hospital stay, ICU admission and death, were calculated in relation to positive or negative plasma IFN-1 AAbs. Results: A total of 33 studies with 13023 patients were included. The overall prevalence of circulating aIFN-1, aIFN-α, and aIFN-ω AAbs was 17.8 % [13.8, 22.8], 7.2 % [4.7, 10.9], and 4.4 % [2.1, 8.6], respectively, and the overall prevalence of neutralizing aIFN-1, aIFN-α, aIFN-ω, and aIFN-ß AAbs was 7.1 % [4.9, 10.1], 7.5 % [5.9, 9.5], 8.0 % [5.7, 11.1] and 1.2 % [0.4, 3.5], respectively. Circulating aIFN-α (OR = 4.537 [2.247, 9.158]), neutralizing aIFN-α (O = 17.482 [8.899, 34.342]), and neutralizing aIFN-ω (OR = 12.529 [7.397, 21.222]) were significantly more frequent in critical/severe patients than in moderate/mild patients (p < 0.001 for all). Anti-IFN-1 was more common in male subjects (OR = 2.248 [1.366, 3.699], p = 0.001) and two COVID-19 outcomes including ICU admission (OR = 2.485 [1.409, 4.385], p = 0.002) and death (OR = 2.593 [1.199, 5.604], p = 0.015) occurred more frequently in patients with positive anti-IFN-1.Conclusion: aIFN-1 and its subtypes AAbs are associated with severe and critical COVID-19 disease and may be a predictive marker for a poor prognosis, particularly in men.

Ordinal Poincaré sections: Reconstructing the first return map from an ordinal segmentation of time series.

We propose a robust algorithm for constructing first return maps of dynamical systems from time series without the need for embedding. A first return map is typically constructed using a convenient heuristic (maxima or zero-crossings of the time series, for example) or a computationally nuanced geometric approach (explicitly constructing a Poincaré section from a hyper-surface normal to the flow and then interpolating to determine intersections with trajectories). Our method is based on ordinal partitions of the time series, and the first return map is constructed from successive intersections with specific ordinal sequences. We can obtain distinct first return maps for each ordinal sequence in general. We define entropy-based measures to guide our selection of the ordinal sequence for a "good" first return map and show that this method can robustly be applied to time series from classical chaotic systems to extract the underlying first return map dynamics. The results are shown for several well-known dynamical systems (Lorenz, Rössler, and Mackey-Glass in chaotic regimes).

Household food insecurity during pregnancy as a predictor of anthropometric indices failures in infants aged less than 6 months: a retrospective longitudinal study.

OBJECTIVE: To investigate the impact of household food insecurity during the third trimester of pregnancy on the growth indicators of infants aged less than 6 months. DESIGN: Retrospective longitudinal study. SETTING: 137 healthcare centres (15 cities) in Khorasan Razavi province, Iran. Data were extracted from the Sina Electronic Health Record System (SinaEHR®). PARTICIPANTS: This study was conducted on 2481 mother and infant dyads during November 2016-March 2019. The Household Food Insecurity Access Scale (nine-item version) was used to measure food insecurity in the third trimester of pregnancy. Women who delivered singleton infants were included in the study, and anthropometric indices of infants were measured throughout the first 6 months of life. RESULTS: Approximately 67 % of the participants were food secure, while 33 % had varying degrees of food insecurity. The children born to the mothers in the food-insecure households were, respectively, 2·01, 3·03, and 3·83 times more likely to be stunted at birth (95 % CI 1·17, 3·46), 4 months (95 % CI 1·21, 7·61) and 6 months of age (95 % CI 1·37, 10·68) compared to their counterparts in the food-secure households. However, there were no significant differences in mean birth weight, birth height and head circumference at birth between the two groups. CONCLUSIONS: Household food insecurity during pregnancy is a risk factor for stunting in infants aged less than 6 months. Therefore, national nutrition programs could considerably support women in food-insecure households during and before pregnancy.

Incidence of infectious diseases after earthquakes: a systematic review and meta-analysis.

OBJECTIVES: Evaluation of the incidence of infectious diseases after natural disasters can help develop healthcare policies. This study provides a global review of the most prevalent infectious diseases observed after earthquakes. STUDY DESIGN: A systematic review and meta-analysis were performed. METHODS: A systematic review was performed on electronic databases, including PubMed, Scopus and Web of Science, up to March 2020 (with no time limitations). Studies addressing earthquakes and infectious diseases were collected based on specified inclusion and exclusion criteria. Subsequently, the quality of the studies was assessed by the Newcastle-Ottawa scale (NOS). Data analyses were carried out on six subgroups under five different disease categories using comprehensive meta-analysis software. RESULTS: In total, 24 studies qualified for the systematic review and 18 were included in the meta-analysis. The incidences of gastrointestinal infections, dermal infections, respiratory infections, central nervous system infections and other infectious diseases were as follows: odds ratio (OR) 163.4 (95% confidence interval [CI]: 31.0-858.1), OR 84.5 (95% CI: 27.1-262.8), OR 9.9 (95% CI: 3.5-27.7), OR 0.5 (95% CI: 0.2-1.1) and OR 4.4 (95% CI: 1.9-9.9) cases per 100,000 people, respectively. The association between the incidences of infectious diseases before and after earthquakes was significant, namely, 1.561 (95% CI: 1.244-1.957) with a P-value <0.001. CONCLUSIONS: The results show an increase in the prevalence of infectious diseases after earthquakes. Governments should take essential measures to be better prepared for such unpredictable catastrophes.

Extensive bilateral diffuse infiltrates and deterioration of lung following infection with severe acute respiratory syndrome coronavirus 2 in a pregnant woman: a case report.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 is the third member of the coronavirus family to cause global concern in the twenty-first century. Pregnant women are particularly at higher risk of developing severe viral pneumonia, possibly because of a partial immune suppression during their pregnancy. Under such critical and rapidly evolving circumstances, these poor findings might be helpful for the treatment of infected pregnant women with the 2019 novel coronavirus. CASE PRESENTATION: In this study, we report the case of a 33-year-old Asian pregnant woman at 25 gestational weeks with coronavirus disease 2019 who developed severe complications, including hypoxemia, acute respiratory distress syndrome, pulmonary infiltration, and bilateral pleural effusion. She died 1 month after admission to the hospital. CONCLUSION: Pregnant populations are especially at higher risk of viral pneumonia development caused by severe acute respiratory syndrome coronavirus 2. Further research on the prevention and treatment of the new coronavirus is necessary.

Neonates with coronavirus disease 2019 acquired from infected mothers: the incompatibility of maternal intensity and infant lung involvement: two case reports.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a public health emergency by the World Health Organization on January 30, 2020. The results of recent studies have suggested that neonates may present symptoms of COVID-19. Although the presentation of the disease in neonates is known to vary, only a limited number of studies have investigated newborns infected with COVID-19. CASE PRESENTATION: This study presents two Asian cases of newborns with COVID-19. Maternal-fetal or postnatal transmission was suggested based on the simultaneity of maternal infection. Chest radiography in one of the neonates showed severe lung involvement. Despite support and resuscitation attempts, the poor clinical condition of the neonate led to his death. However, the two mothers and one of the neonates were discharged from the hospital in good general condition. CONCLUSION: The neonates had worse clinical conditions than the mothers, and the intensity of pneumonia and level of lung involvement in the newborns were not associated with the stage and severity of the disease in the mothers with COVID-19.

Therapeutic Potential of Saffron (Crocus sativus L.) in Ischemia Stroke.

Stroke is the second leading cause of death and a main cause of disability worldwide. The majority (approximately 80%) of strokes are ischemic. Saffron (Crocus sativus L.) has been considered for medicinal purposes since ancient times. Pharmacological effects of saffron are attributed to the presence of crocin, crocetin, picrocrocin, and safranal. In the present review, we summarized the reported neuroprotective effects of saffron and its active constituents against cerebral ischemia stroke. Saffron and its components exert its beneficial effects as an antioxidant, anti-inflammatory, and antiapoptotic agent though inhibition of biochemical, inflammatory, and oxidative stress markers. Taken together, this review indicates that saffron and its ingredients could be a potent candidate in the process of new drug production for the treatment of ischemia stroke.

Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair complex.

Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5΄-phosphate/3΄-hydroxyl DNA termini that are critical for ligation by the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein, XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail, while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the assembled PNKP-XRCC4-LigIV complex remains uncharacterized. Here, we report purification and characterization of a recombinant PNKP-XRCC4-LigIV complex. We show that the stable binding of PNKP in this complex requires XRCC4 phosphorylation and that only one PNKP protomer binds per XRCC4 dimer. Small angle X-ray scattering (SAXS) reveals a flexible multi-state complex that suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of a surface on the PNKP phosphatase domain that may contact XRCC4-LigIV. A mutation on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ. This mutation impairs PNKP recruitment to damaged DNA in human cells and provides a possible disease mechanism. Together, this work unveils multipoint contacts between PNKP and XRCC4-LigIV that regulate PNKP recruitment and activity within NHEJ.

Characterization of DNA Substrate Binding to the Phosphatase Domain of the DNA Repair Enzyme Polynucleotide Kinase/Phosphatase.

Polynucleotide kinase/phosphatase (PNKP) is a DNA strand break repair enzyme that uses separate 5' kinase and 3' phosphatase active sites to convert damaged 5'-hydroxyl/3'-phosphate strand termini to ligatable 5'-phosphate/3'-hydroxyl ends. The phosphatase active site has received particular attention as a target of inhibition in cancer therapy development. The phosphatase domain dephosphorylates a range of single- and double-stranded substrates; however, structural studies have shown that the phosphatase catalytic cleft can bind only single-stranded substrates. Here we use a catalytically inactive but structurally intact phosphatase mutant to probe interactions between PNKP and a variety of single- and double-stranded DNA substrates using an electrophoretic mobility shift assay. This work indicates that the phosphatase domain binds 3'-phosphorylated single-stranded DNAs in a manner that is highly dependent on the presence of the 3'-phosphate. Double-stranded substrate binding, in contrast, is not as dependent on the 3'-phosphate. Experiments comparing blunt-end, 3'-overhanging, and frayed-end substrates indicate that the predicted loss of energy due to base pair disruption upon binding of the phosphatase active site is likely balanced by favorable interactions between the liberated complementary strand and PNKP. Comparison of the effects on substrate binding of mutations within the phosphatase active site cleft with mutations in surrounding positively charged surfaces suggests that the surrounding surfaces are important for binding to double-stranded substrates. We further show that while fluorescence polarization methods can detect specific binding of single-stranded DNAs with the phosphatase domain, this method does not detect specific interactions between the PNKP phosphatase and double-stranded substrates.

Structural basis for the phosphatase activity of polynucleotide kinase/phosphatase on single- and double-stranded DNA substrates.

Polynucleotide kinase/phosphatase (PNKP) is a critical mammalian DNA repair enzyme that generates 5'-phosphate and 3'-hydroxyl groups at damaged DNA termini that are required for subsequent processing by DNA ligases and polymerases. The PNKP phosphatase domain recognizes 3'-phosphate termini within DNA nicks, gaps, or at double- or single-strand breaks. Here we present a mechanistic rationale for the recognition of damaged DNA termini by the PNKP phosphatase domain. The crystal structures of PNKP bound to single-stranded DNA substrates reveals a narrow active site cleft that accommodates a single-stranded substrate in a sequence-independent manner. Biochemical studies suggest that the terminal base pairs of double-stranded substrates near the 3'-phosphate are destabilized by PNKP to allow substrate access to the active site. A positively charged surface distinct from the active site specifically facilitates interactions with double-stranded substrates, providing a complex DNA binding surface that enables the recognition of diverse substrates.