Potentials of microcrystalline cellulose prepared from wood dusts wastes of Ficus Platyphyla, Planatus Occidentalis and Gmelina Aborea

This research aims to prepare microcrystalline cellulose (MCCs) from native cellulosic wastes in order to find potential applications for each of the tree species. The physico-chemical characteristics of the MCCs were studied using physical and spectroscopic techniques. Acid hydrolysis in 2M HCl was used for the preparation of microcrystalline cellulose (MCC) obtained from agricultural waste sample, Gmelina aborea (GA) Ficus platyphyla (FP) and Planatus occidentalis (PO) wood dust. The MCCs obtained were off-white and powdery in appearance. The yield of MCCs were 67.55% for Ficus platyphyla, 77.00% Planatus occidentalis and 80% for Gmelina Aborea (GA). The functional groups in the MCC samples were confirmed by the Fourier transform infrared (FTIR) spectroscopic method with characteristic absorption bands of ;OH stretching at 3416 cm-1; C-H stretching at 2918 cm-1; -OH bending at1377 cm-1;, 1159 cm-1; and C-O-C pyranose ring skeletal vibrations at 1026-1033 cm-1, with crystallinity absorption bands showing up at 1432 and 850 cm-1 respectively. The thermal stabilities were determined from Thermogravimetric Analysis (TGA) and showed that the MCC samples are thermally stable (50% weight loss at 450OC or PO, 50% weight loss 470OC for FP and 50% weight loss at 590OC for GA). The characteristic morphological features were established by scanning electron micrograph (SEM) and the crystallinity of the microcrystalline cellulose were further confirmed using the X-Ray Diffraction (X-RD) technique which showed three main reflections at 2?=14.70, 22.09 and 34.24, this therefore indicates microcrystalline cellulose were cellulose I type and that acid pretreatment did not affect the structure of the MCC. The crystallinity index values were 69.4, 68.7 and 79.6 for FP, PO and GM MCCs and respectively. The Samples were tested for pH, Moisture content, Hydration and swelling capacities as well. These results showed that the wood dusts form the tree species are good potential sources of high-grade cellulose which can serve as useful starting materials for further processing and applications

Children’s comprehension of informational text: Reading, engaging, and learning

The Reading, Engaging, and Learning project (REAL) investigated whether a classroom intervention that enhanced young children's experience with informational books would increase reading achievement and engagement. Participants attended schools serving low income neighborhoods with 86% African American enrollment. The longitudinal study spanned second through fourth grades. Treatment conditions were: (1) Text Infusion/Reading for Learning Instruction -- students were given greater access to informational books in their classroom libraries and in reading instruction; (2) Text Infusion Alone -- the same books were provided but teachers were not asked to alter their instruction; (3) Traditional Instruction -- students experienced business as usual in the classroom. Children were assessed each year on measures of reading and reading engagement, and classroom instructional practices were observed. On most measures, the informational text infusion intervention did not yield differential growth over time. However, the results inform efforts to increase children’s facility with informational text in the early years in order to improve reading comprehension

The impact of COVID-19 pandemic on the preventive services in Qatar

Background: In March 2020, Qatar started reporting increased numbers of COVID-19 cases. At that stage, containment measures were put in place. The health authority in Qatar developed an emergency action plan to respond to the outbreak with the Primary Health Care as the main component of that response and suspended all non-urgent services including preventive health services. The aim of the retrospective analysis to measure the Impact of COVID-19 on the preventive services provided in Qatar.Methods: A retrospective data analysis was conducted for all the preventive services utilization volume across the 27 PHCC health centres from the 1st of January 2017 to the 31st of July 2020.Results: With 17,012 no-show appointments, well-baby and Immunization services utilization demonstrated a reduction of 40% in May and started to come back to volumes higher than expected in June. The breast cancer and colorectal cancer screening programmes expected volumes demand has dropped by 100% in comparison to 2017 demand due to their respective appointments’ cancelation. Wellness services only met 20% of its projected utilization in April, however, the services picked up in June.Conclusion: These findings will guide the public health policymakers to understand the effects COVID-19 on preventive services and the risk of having an increased number of outbreaks for childhood communicable disease, cancer cases with delayed diagnosis due to the screening services suspension. In addition, the plan will address the increased number of sedately behaviour due to the service's reduced utilization of wellness services

Pre-Existing Isoniazid Resistance, but Not the Genotype of Mycobacterium Tuberculosis Drives Rifampicin Resistance Codon Preference in Vitro

Both the probability of a mutation occurring and the ability of the mutant to persist will influence the distribution of mutants that arise in a population. We studied the interaction of these factors for the in vitro selection of rifampicin (RIF)-resistant mutants of Mycobacterium tuberculosis. We characterised two series of spontaneous RIF-resistant in vitro mutants from isoniazid (INH)-sensitive and -resistant laboratory strains and clinical isolates, representing various M. tuberculosis genotypes. The first series were selected from multiple parallel 1 ml cultures and the second from single 10 ml cultures. RIF-resistant mutants were screened by Multiplex Ligation-dependent Probe Amplification (MLPA) or by sequencing the rpoB gene. For all strains the mutation rate for RIF resistance was determined with a fluctuation assay. The most striking observation was a shift towards rpoB-S531L (TCG→TTG) mutations in a panel of laboratory-generated INH-resistant mutants selected from the 10-ml cultures (p<0.001). All tested strains showed similar mutation rates (1.33×10−8 to 2.49×10−7) except one of the laboratory-generated INH mutants with a mutation rate measured at 5.71×10−7, more than 10 times higher than that of the INH susceptible parental strain (5.46–7.44×10−8). No significant, systematic difference in the spectrum of rpoB-mutations between strains of different genotypes was observed. The dramatic shift towards rpoB-S531L in our INH-resistant laboratory mutants suggests that the relative fitness of resistant mutants can dramatically impact the distribution of (subsequent) mutations that accumulate in a M. tuberculosis population, at least in vitro. We conclude that, against specific genetic backgrounds, certain resistance mutations are particularly likely to spread. Molecular screening for these (combinations of) mutations in clinical isolates could rapidly identify these particular pathogenic strains. We therefore recommend that isolates are screened for the distribution of resistance mutations, especially in regions that are highly endemic for (multi)drug resistant tuberculosis

Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability.

Febrile seizures are the most common type of developmental seizures, affecting up to 5% of children. Experimental complex febrile seizures involving the immature rat hippocampus led to a persistent lowering of seizure threshold despite an upregulation of inhibition. Here we provide a mechanistic resolution to this paradox by showing that, in the hippocampus of rats that had febrile seizures, the long-lasting enhancement of the widely expressed intrinsic membrane conductance Ih converts the potentiated synaptic inhibition to hyperexcitability in a frequency-dependent manner. The altered gain of this molecular inhibition-excitation converter reveals a new mechanism for controlling the balance of excitation-inhibition in the limbic system. In addition, here we show for the first time that h-channels are modified in a human neurological disease paradigm

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB