Three months of COVID‐19: A systematic review and meta‐analysis

The pandemic of 2019 novel coronavirus (SARS‐CoV‐2019), reminiscent of the 2002‐SARS‐CoV outbreak, has completely isolated countries, disrupted health systems and partially paralyzed international trade and travel. In order to be better equipped to anticipate transmission of this virus to new regions, it is imperative to track the progress of the virus over time. This review analyses information on progression of the pandemic in the past 3 months and systematically discusses the characteristics of SARS‐CoV‐2019 virus including its epidemiologic, pathophysiologic, and clinical manifestations. Furthermore, the review also encompasses some recently proposed conceptual models that estimate the spread of this disease based on the basic reproductive number for better prevention and control procedures. Finally, we shed light on how the virus has endangered the global economy, impacting it both from the supply and demand side.     

Proposed model for in vitro interaction between fenitrothion and DNA,by using competitive fluorescence, 31P NMR, 1H NMR,FT-IR,CD and molecular modeling

In this work we proposed a model for in vitro interaction of fenitrothion (FEN) with calf thymus-DNA by combination of multispectroscopic and two dimensional molecular modeling (ONIOM) methods. The circular dichroism results showed that FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The FT-IR results confirmed a partial intercalation between FEN and edges of all base pairs. The competitive fluorescence, using methylene blue as fluorescence probe, in the presence of increasing amounts of FEN, revealed that FEN is able to release the non-intercalated methylene blue from the DNA. The weak chemical shift and peak broadening of ¹H NMR spectrum of FEN in the presence of DNA confirmed a non-intercalation mode. The ³¹P NMR showed that FEN interacts more with DNA via its –NO₂ moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G (d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results revealed that the interaction is base sequence dependent, and FEN interacts more with AT base sequences.     

Meaning of Self-Care: Lived Experiences of Iranian Diabetic Patients

Background

Diabetes continuously disrupts a patient''s well-being and quality of life. Successful self-care could potentially decrease overall costs and rates of mortality and morbidity. Patients'' experiences could be used to elucidate what they believe about illness and its management. The overall aim of this study was to illuminate the meaning of self-care among diabetic patients in Southeast of Iran.

Methods

Sixteen diabetic patients with a mean age of 34 and 10 years'' experience in self-care for their disease were interviewed. The interviews were recorded, transcribed verbatim, and analyzed with a Ricoeur''s phenomenological hermeneutic method.

Results

The meaning of self- care was comprehensively understood as being empowered. This can be divided into four themes: seeking information, being independent, being optimistic or pessimistic and trust in God.

Conclusion

The results in this study suggest that cultural and religious components could affect diabetic patients'' self-care. Nurses might use patients'' religious beliefs to relieve their stress, help them to retain a sense of control, maintain hope and sense of meaning and purpose in their life.     

Evaluation of the FASTPlaqueTB assay for direct detection of Mycobacterium tuberculosis in sputum specimens.

SETTING: Sputum samples were collected from suspected tuberculosis patients attending out-patient clinics at the Ojha Institute of Chest Diseases, Karachi, Pakistan. OBJECTIVE: To evaluate the performance of the FASTPlaqueTB assay for rapid diagnosis of pulmonary tuberculosis. DESIGN: A comparative study of 584 sputum samples using acid-fast smear microscopy, Lowenstein-Jensen culture and FASTPlaqueTB. RESULTS: A total of 514 samples yielded complete results. Seventy specimens were lost to analysis due to the overgrowth of contaminants. The addition of antimicrobials inhibited growth of gram-positive contaminants, and reduced the overall contamination rate from 18.2% to 7.2%. Mycobacterium tuberculosis was isolated from 175 smear-positive and 70 smear-negative specimens. FASTPlaqueTB detected M. tuberculosis in 81.6% of specimens, with a specificity of 97.7%. The sensitivity and specificity of the assay for smear-positive specimens were respectively 87.4% and 88.2%. For smear-negative specimens, the sensitivity of the assay was 67.1% and the specificity was 98.4%. The combined sensitivity of smear and FASTPlaqueTB for M. tuberculosis was 90%. Test results were available in 48 hours. CONCLUSION: FASTPlaqueTB is a sensitive and specific test for rapid diagnosis of pulmonary tuberculosis in high prevalence areas. The test is sensitive enough to confirm a large number of clinically suspected smear-negative cases and improve case finding.     

What works? Interventions for maternal and child undernutrition and survival

We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.     

Serum adenosine deaminase may predict disease activity in rheumatoid arthritis

To determine the relationship between serum adenosine deaminase (ADA) and disease activity, and to develop a new disease activity index based on serum ADA in rheumatoid arthritis (RA). Seventy RA patients were included. Disease activity based on Disease Activity Score 28-ESR (DAS28-ESR) and Disease Activity Score 28-CRP (DAS28-CRP) and serum ADA were measured. There were correlations when serum ADA compared with DAS28-ESR and DAS28-CRP. (R ²?=?0.014, 0.175, respectively, P values?<?0.00). New disease activity index was developed by replacing ADA with ESR and CRP in DAS28-ESR and DAS28-CRP. There were strong correlations when new model compared with DAS28-ESR and DAS28-CRP. (R ²?=?0.94 and 0.95, respectively, P values?<?0.00) The best new model values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 2.79, 3.4, and 4.82, respectively; and new model values corresponding to DAS28-CRP values of 2.3, 2.7, and 4.1 were 2.1, 2.9, and 4, respectively. There were agreements when the new model compared with DAS28-ESR and DAS28-CRP for determination of patients in different disease activity categories. (Kappa?=?0.81 and 0.71, respectively, P values?<?0.00). The new disease activity index that applies serum ADA may help in predicting disease activity in RA.     

Structure modeling and docking study of HCV NS5B-3a RNA polymerase for the identification of potent inhibitors

Homology modeling in combination with molecular docking studies has been applied to predict the binding modes of the Hepatitis C virus (HCV) NS5B-3a inhibitors within the pocket of NS5B polymerase of HCV genotype 3a. Structure modeling and docking using Genetic Optimization for Ligand Docking (GOLD) were carried out to understand the ligand binding properties of NS5B-3a and to identify a potent inhibitor against it. The three-dimensional homology model of Pakistani strain is not available and was built based on the HCV-J4 NS5B polymerase structure. Compound 1 possessing high GOLD fitness score of 62.17 with IC50 value of 0.04 μM was selected as the potent inhibitor. The docking analysis depicted that hydrogen bonding, ionic and hydrophobic interactions contributed significantly for its ligand binding and the amino acid residues Arg442 and His403 seemed to be the anchor residues for receptor recognition. For developing a connection between the experimental bioactivities and GOLD fitness scores, a squared correlation coefficient was calculated and found as acceptable with the value of r ² = 0.67. These findings may act as potent lead in designing effective NS5B-3a inhibitors.     

HNH proteins are a widespread component of phage DNA packaging machines

The genome packaging reactions of tailed bacteriophages and herpes viruses require the activity of a terminase enzyme, which is comprised of large and small subunits. Phage genomes are replicated as linear concatemers composed of multiple copies of the genome joined end to end. As the terminase enzyme packages the genome into the phage capsid, it cleaves the DNA into single genome-length units. In this work, we show that the phage HK97 HNH protein, gp74, is required for the specific endonuclease activity of HK97 terminase and is essential for phage head morphogenesis. HNH proteins are a very common family of proteins generally associated with nuclease activity that are found in all kingdoms of life. We show that the activity of gp74 in terminase-mediated cleavage of the phage cos site relies on the presence of an HNH motif active-site residue, and that the large subunit of HK97 terminase physically interacts with gp74. Bioinformatic analysis reveals that the role of HNH proteins in terminase function is widespread among long-tailed phages and is uniquely required for the activity of the Terminase_1 family of large terminase proteins.Tailed bacteriophages and herpes viruses package their large double-stranded DNA genomes into a preformed protein shell, known as the “prohead,” using terminase enzymes. In both types of viruses, the genome is synthesized as concatemers composed of multiple copies of the genome joined end to end. This concatemeric DNA is packaged into the prohead and cleaved into genome-length units by terminase in an ATP-dependent reaction. Phage terminases are composed of two proteins: the large subunit harbors an endonuclease domain and an ATPase that powers the DNA packaging reaction, and the small subunit mediates specific DNA-binding required for recognition of packaging sites in the phage genome. A variety of elegant structural and biophysical studies have recently provided insight into the molecular mechanisms of terminase function (1, 2). However, the factors that affect the action of terminase enzymes in vivo have been less well characterized.Terminase enzymes perform several functions. They specifically recognize and bind the viral genome, interact with the prohead, then drive the DNA into the head through the narrow entry channel formed by the portal protein that is positioned at a single vertex of the head. During this process terminases also cleave the viral DNA, either nonspecifically upon head filling or at a specific site known as “cos.” The efficient packaging of a phage genome in vivo may require phage-encoded cofactors in addition to the terminase enzyme. For example, Escherichia coli phage λ gpFI facilitates interaction of the terminase–DNA complex with proheads (3–6). A wide variety of phages appear to encode proteins with a function similar to λ gpFI (7). Additionally, the activity of Bacillus subtilis phage phi29 terminase requires a phage-encoded RNA molecule bound to its portal protein (8), and in vivo packaging of the E. coli phage T4 genome can only be completed with the participation of the phage-encoded endonuclease, gp49 (9). The general prevalence and importance of terminase cofactors is difficult to evaluate because few studies have addressed this issue.We recently reported that phage genomes often encode proteins possessing an HNH motif near their terminase genes (10). The HNH motif is ∼35 aa long, and is characterized by the presence of two highly conserved His residues and one Asn residue. These HNH motifs, as defined by the large (∼7,400-member) HNH Pfam (11) protein sequence family (PF01844), are often found in proteins that possess endonuclease activity, such as site-specific homing endonucleases (12, 13), colicins (14, 15), S pyocins (16), and restriction enzymes (17–19). HNH motif-containing proteins comprised of primarily an HNH motif as found in E. coli colicins, usually possess nonspecific endonuclease activity. Conversely, HNH motif-containing proteins may contain DNA-recognition domains in addition to the HNH motif and thus possess high sequence specificity, as found in the homing endonucleases.The frequent juxtaposition of HNH and phage terminase genes (10, 20) suggests a unique role for HNH proteins in the endonuclease and/or packaging activities of the terminases. To address this issue, we investigated the function of E. coli phage HK97 gp74, a 119-residue protein containing an HNH motif. The gene encoding gp74 is located at the extreme 3′ end of the mature linear HK97 genome, adjacent to the cos site. In both the lysogen and replicative form of the HK97 genome gene 74 is immediately adjacent to genes 1 and 2, which encode the small and large subunits of terminase (TerS and TerL), respectively. Whereas gp74 was previously found to possess endonuclease activity (10), its role in the HK97 replication cycle remained uncharacterized. In this study we used functional and bioinformatic analyses to investigate its function.