Training time frame, a possible key to literature discrepancy on fasting athletes

There is a discrepancy in the literature as to whether fasting during Ramadan affects athletic performance. We suggest in this letter that the time frame for training is a confounding variable that has been missed in the literature. © 2016 The Author(s)

Sars coronavirus 2, severe acute respiratory syndrome, and middle east respiratory syndrome in children: A review on epidemiology, clinical presentation, and diagnosis

Context: Coronavirus Disease 2019 (COVID-19) pandemic has caused irreparable damage to society. The pediatric population may be asymptomatic but has positive viral nucleic acid test results and plays an important role in spreading the infection in populations. However, there is a substantial information gap on the epidemiology, pathology, and clinical presentations of COVID-19 in pediatric patients. Evidence Acquisition: English research articles published before April 18, 2020, were reviewed to understand the clinical characteristics of SARS coronavirus 2, Severe Acute Respiratory Syndrome, and Middle East Respiratory Syndrome in children. The WHO (https://www.who. int/) and CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/) websites were also reviewed to find eligible studies, besides articles extracted from PubMed, Scopus, and Google Scholar. Results: In comparison with SARS and MERS, COVID-19 seems to have wider clinical symptoms and routes of transmission. Multisystem inflammatory syndrome is a unique clinical feature of this novel virus. The low prevalence of COVID-19 in children may be due to lower contacts or incomplete identification rather than resistance to the virus. Conclusions: As this virus is novel, we believe that lessons learned from SARS and MERS outbreaks are very valuable in handling the current pandemic. The aim of this paper was to provide the updated summary of clinical manifestation, diagnostic, molecular, and genetic aspects of the novel coronavirus in comparison with SARS and MERS coronaviruses in children. © 2020, Author(s)

A demonstration of cone function plasticity after gene therapy in achromatopsia

Recent advances in regenerative therapy have placed the treatment of previously incurable eye diseases within arms’ reach. Achromatopsia is a severe monogenic heritable retinal disease that disrupts cone function from birth, leaving patients with complete colour blindness, low acuity, photosensitivity and nystagmus. While successful gene-replacement therapy in non-primate models of achromatopsia has raised widespread hopes for clinical treatment, it was yet to be determined if and how these therapies can induce new cone function in the human brain. Using a novel multimodal approach, we demonstrate for the first time that gene therapy can successfully activate dormant cone-mediated pathways in children with achromatopsia (CNGA3- and CNGB3-associated, 10–15 years). To test this, we combined functional MRI population receptive field mapping and psychophysics with stimuli that selectively measure cone photoreceptor signalling. We measured cortical and visual cone function before and after gene therapy in four paediatric patients, evaluating treatment-related change against benchmark data from untreated patients (n = 9) and normal-sighted participants (n = 28). After treatment, two of the four children displayed strong evidence for novel cone-mediated signals in visual cortex, with a retinotopic pattern that was not present in untreated achromatopsia and which is highly unlikely to emerge by chance. Importantly, this change was paired with a significant improvement in psychophysical measures of cone-mediated visual function. These improvements were specific to the treated eye, and provide strong evidence for successful read-out and use of new cone-mediated information. These data show for the first time that gene replacement therapy in achromatopsia within the plastic period of development can awaken dormant cone-signalling pathways after years of deprivation. This reveals unprecedented neural plasticity in the developing human nervous system and offers great promise for emerging regenerative therapies

Evidence That Two ATP-Dependent (Lon) Proteases in Borrelia burgdorferi Serve Different Functions

The canonical ATP-dependent protease Lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. Borrelia spirochetes are unusual in that they code for two putative ATP-dependent Lon homologs, Lon-1 and Lon-2. Borrelia burgdorferi, the etiologic agent of Lyme disease, is transmitted through the blood feeding of Ixodes ticks. Previous work in our laboratory reported that B. burgdorferi lon-1 is upregulated transcriptionally by exposure to blood in vitro, while lon-2 is not. Because blood induction of Lon-1 may be of importance in the regulation of virulence factors critical for spirochete transmission, the clarification of functional roles for these two proteases in B. burgdorferi was the object of this study. On the chromosome, lon-2 is immediately downstream of ATP-dependent proteases clpP and clpX, an arrangement identical to that of lon of Escherichia coli. Phylogenetic analysis revealed that Lon-1 and Lon-2 cluster separately due to differences in the NH2-terminal substrate binding domains that may reflect differences in substrate specificity. Recombinant Lon-1 manifested properties of an ATP-dependent chaperone-protease in vitro but did not complement an E. coli Lon mutant, while Lon-2 corrected two characteristic Lon-mutant phenotypes. We conclude that B. burgdorferi Lons -1 and -2 have distinct functional roles. Lon-2 functions in a manner consistent with canonical Lon, engaged in cellular homeostasis. Lon-1, by virtue of its blood induction, and as a unique feature of the Borreliae, may be important in host adaptation from the arthropod to a warm-blooded host

Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties

From computational simulations of a serotonin 2A receptor (5-HT2AR) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD) simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011), we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i)-the involvement of cholesterol in the activation of the 5-HT2AR, and (ii)-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

Modeling Maize Production under Different Management Scenarios in Kerman Province

Introduction Agriculture is a cornerstone of many developing economies, providing food, income, and employment for millions of people. It is also projected to play a vital role in feeding a global population of 9.1 billion people by 2050. However, there are growing concerns about the environmental impact of agriculture, particularly in arid and semi-arid regions like Iran. Managing water and fertilizer usage in agriculture is crucial to ensuring food security and sustainability. However, conducting field experiments to assess the interaction of all factors involved is expensive and time-consuming. This research focuses on optimizing maize production in Kerman province, a region where maize is a major crop. The research is motivated by the need to improve resource management in Iran, where water and fertilizer resources are limited. The APSIM model is used to determine the best management scenario for maize production in Kerman province. APSIM is a crop growth simulation model that can be used to predict the impact of different management practices on crop yield, water use efficiency, and nutrient use efficiency. The use of APSIM in this research provides a cost-effective and time-efficient alternative to conducting extensive field experiments. The results of this research will contribute to the development of sustainable and efficient agricultural practices in Kerman province and similar regions. These regions are characterized by resource constraints, such as limited water and fertilizer availability. The research aimed to simulate the effect of management parameters (planting date and irrigation) on Crop yield and subsequently achieve the optimal management scenario.Materials and MethodsThe APSIM model was used for simulation in three regions of Bardsir (temperate to cold climate), Jiroft (hot and humid climate), and Orzuye (hot and dry climate). The model requires four series of data: climate, soil, management, and crop data. The required climate data (from 1998 to 2018) including daily maximum and minimum temperatures, length of sunny hours, and daily precipitation were collected and prepared from the synoptic weather stations of the three mentioned regions.The management data set for each of the study regions was prepared in the form of questionnaires and field research from experts of the Agricultural Jihad Organization, the Agricultural Research Center Organization, and prominent farmers in those regions. The crop data includes the plant genetic coefficients of the maize single cross hybrid 704, which were obtained from the calibration of the APSIM model. To optimize planting date and irrigation management in the studied areas, different planting and irrigation date treatments were investigated. In this research, planting date treatments included the conventional planting date of the region, 20 days before the conventional planting date (as early planting date), and 20 days after the conventional planting date (as late planting date). Irrigation treatments included the usual number of irrigations in the region (13 irrigations), less irrigation (11 irrigations), and more irrigation (15 irrigations).Results and DiscussionOur results showed that the model successfully simulated maize phenology, especially maturity date, with high accuracy for all fertilizer amounts tested. The model performance in predicting biomass under different nitrogen treatments was also satisfactory, with a minimal difference between observed data and model results. The nRMSE of grain yield in the calibration stage was 11.2% and in the validation stage was 9%. The nRMSE for calibration of the biological yield of SC 704 was 14.8% and for validation was 13.9%. Also, the model was able to simulate phenology with very high accuracy (especially the days to maturity). Overall, the nRMSE of days to flowering was less than 10% and for the days to maturity was less than 5%. Late planting dates consistently showed better performance across regions and irrigation treatments, resulting in significantly increased grain yield compared to conventional and early planting dates. The highest seed yield was obtained with 15 times of irrigation, among the various irrigation treatments. Late planting combined with 15 times of irrigation yielded the best results in Kerman province, particularly in Bardsir, with a yield of 9300 kg ha-1. Optimal moisture and air conditions, along with the cultivation of a late-maturing variety, contributed to the higher seed yield. These findings are consistent with previous research that has confirmed the positive impact of late planting and extended ripening periods on maize yield.ConclusionOur results showed that the model simulates the growth and yield of single cross 704 corn in Kerman province well, even after 20 days of late planting. Long-term simulation experiments showed that maize grain yield varied depending on the region, with the highest yield in Bardsir (8317 kg ha-1) and the lowest yield in Jiroft (4735 kg ha-1). The optimum maize grain yield (8872.8 kg ha-1) was obtained by the interaction effect of late planting date and 15 times of irrigation