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Spirulina platensis contains abundant nitrogen-containing organics, which might react with derivatives of cellulose/lignin during hydrothermal carbonization (HTC), probably affecting yield, property of hydrochar, and pore development in activation of hydrochar. This was investigated herein by conducting co-HTC of spirulina platensis with cellulose, lignin, and sawdust at 260 °C and subsequent activation of the resulting hydrochars with K 2 C 2 O 4 at 800 °C. The results showed that cross-condensation of spirulina platensis-derived proteins with cellulose/lignin-derived ketones and phenolics did take place in the co-HTC, forming more π-conjugated heavier organics, retaining more nitrogen species in hydrochar, reducing yields of hydrochar, making the hydrochar more aromatic and increasing the thermal stability and resistivity towards activation. This enhanced the yield of activated carbon (AC) by 7 %-20 % and significantly increased specific surface area of the AC from activation of hydrochar of spirulina platensis + lignin to 2074.5 m 2 /g (859.3 m 2 /g from spirulina platensis only and 1170.1 m 2 /g from lignin only). Furthermore, more mesopores from activation of hydrochar of spirulina platensis + cellulose (47 %) and more micropores from activation of hydrochar of spirulina + sawdust (93 %) was generated. The AC from spirulina platensis + lignin with the developed pore structures generated sufficient sites for adsorption of tetracycline from aqueous phase and minimized steric hindrance for mass transfer with the abundant mesopores (43 %)., Competing Interests: Declaration of competing interest Title of the article: Unveiling drastic influence of cross-interactions in hydrothermal carbonization of spirulina with cellulose, lignin or poplar on nature of hydrochar and activated carbon. We declare that the material has not been published in whole or in part elsewhere and the paper is not currently being considered for publication elsewhere. All authors have been personally and actively involved in substantive work leading to the report, and will hold themselves jointly and individually responsible for its content. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He/she is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from xun.hu@outlook.com. Signed by all authors as follows: Stelgen Inkoua, Chao Li, Muhammad Rashid, Muhammad Mahboob Naeem, Shu Zhang, Wenran Gao, Mortaza Gholizadeh, Xun Hua. We testify to the accuracy of the above statement on behalf of all the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Countries are grappling with a rapidly worsening upsurge in the opioid-related overdose deaths, misuse and abuse. There is a dearth of data in Pakistan regarding the practices and competencies of pharmacists in handling opioid-related issues., Study Design: A cross-sectional study, conducted across Punjab, Pakistan., Method: The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists., Results: 504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents 'never' or 'sometimes' made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p<0.05). In competency evaluation, three priority areas emerged that require additional training, that is, 'opioid overdose management', 'opioid use monitoring' and 'therapeutic uses of opioids'., Conclusion: Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Application of intracanal medicaments may affect the physical properties of root dentine. Calcium hydroxide (CH), a gold standard intracanal medicament, has proven to decrease root dentine microhardness. A natural extract, propolis, has been shown to be superior to CH in eradicating endodontic microbes, but its effect on the microhardness of root dentine is still not known. This investigation aims to evaluate the effect of propolis on root dentine microhardness compared to calcium hydroxide. Ninety root discs were randomly divided into three groups and treated with CH, propolis, and a control. A Vickers hardness indentation machine with a load of 200 g and dwell time of 15 s at 24 h, 3, and 7 days was used for microhardness testing. ANOVA and Tukey's post hoc test were used for statistical analysis. A progressive decrease in microhardness values was observed in CH ( p < 0.01), whereas a progressive increase was observed in the propolis group ( p < 0.01). At 7 days, propolis demonstrated the highest microhardness value (64.43 ± 1.69), whereas CH demonstrated the lowest value (48.46 ± 1.60). The root dentine microhardness increased over time when propolis was applied, while it decreased over time after application of CH on root dentine sections.

Background: Root debridement procedures for the treatment of periodontal diseases, produces root surface irregularities and smear layer on the root surface that can adversely affect the healing of periodontal tissues. The objective of the present study was to evaluate the surface texture of root after hand instrumentation with Gracey curette, After Five curette, and Mini Five curette., Methods: A randomised, controlled clinical trial was conducted with 120 participants clinically diagnosed with chronic periodontitis. Participants were equally randomised into four groups, with parallel treatment assignment of scaling and root planning using Gracey Curettes, After five and Mini five curette, and a control group with no instrumentation. Mobile teeth of these patients were then extracted atraumatically and analysed under a Scanning Electron Microscope and graded for "Roughness and Loss of Tooth substance index" and "Smear layer index." Cross Tabulation was made between the test groups (Control, Gracey Curette, After five, and Mini Five) versus "Roughness and Loss of Tooth substance Index" and "Smear Layer Index." A Chi-square test with Bonferroni correction was used to determine the graded distribution among the groups., Results: In the control group, 73.3% of the teeth showed grade 1 roughness. In the Gracey group, 56.7% showed grade 2 roughness; in the After 5 group, 70% showed grade 3 roughness; in the Mini 5 group, 76.7% showed grade 3 roughness. A significant association was found between roughness scores and the use of individual instruments. Regarding smear layer formation, 46.7% of teeth showed a grade 4 smear layer in the control group. 50% of teeth showed grade 2 smear layer thickness in the Gracey group. In the After 5 group, 73.3% of teeth showed a grade 1 smear layer, while in the Mini 5 group, 80.0% showed a grade 1 smear layer. The use of individual instruments was significantly associated with the smear layer scores., Conclusion: Gracey curettes produced relatively smoother root surfaces with less smear layer formation than After Five and Mini Five curettes, which produced relatively more roughened root surfaces with thicker smear layer formation., Trial Registration: ID: ClinicalTrials.gov Identifier: NCT04216966 Date of Registration: January 3, 2020., (© 2022. The Author(s).)

There is a paucity of research conducted on microbial prevalence in pheasants. The microbiota of captive birds has zoonotic significance and must be characterize. Present study is therefore planned to assess the microbiota from oral, fecal and gut content of captive avian species. It will be helpful in characterization of harmful microbes. Different samples taken from oral, gut and feces of ring-necked pheasants (Phasianus colchicus), green pheasants (Phasianus versicolor), golden pheasant (Chrysolophus pictus) and silver pheasant (Lophura nycthemera). Samples were collected, diluted, and inoculated onto different agar plates (MacConkey, SS agar, MSA and nutrient agar) for cultivation of bacterial species. Colonies of E.coli, Staphylococcus spp. Brachyspira spp. and Campylobacter spp were observed based on colony morphology. Colony forming unit showed E. coli as frequently found bacteria in fecal, oral and gut contents of all the above pheasants. The overall significance difference was found among bacterial species of golden pheasants, green pheasant, ring-necked pheasant, and silver pheasants. It was concluded that E.coli is predominant isolated from heathy pheasants followed by Campylobacter, Staphylococcus and Brachyspira.

Objectives:  The main aim of this study was to determine the undergraduate dental students' self-reported effectiveness of online classes offered by various dental institutes of Pakistan., Materials and Methods:  A cross-sectional study was conducted using an online survey. A pretested and validated questionnaire comprising of 31 questions was circulated among dental students. The study participants were inquired about the perceived level of accessibility of resources and the effectiveness of online teaching. The data was analyzed using SPSS version 24. Mann-Whitney U test and Kruskal-Wallis test were used for statistical analysis at p ≤0.05., Results:  A total of 1,207 students from all over Pakistan responded. The majority of students was dissatisfied with the institutional learning management system and quality of learning resources available. Students were also dissatisfied with the level of training of teachers for online lectures. The worst rating was reported for questions related to the effectiveness of online classes (average rating: 3.83 and 3.781/5). First-year students reported poor interaction with teachers ( p < 0.001) and strongly disagreed with the effectiveness of online classes (mean rating: 4.14 ± 0.935)., Conclusions:  The results from the present survey showed that dental students of Pakistan unanimously voiced dissatisfaction toward various elements of online teaching sessions. Findings from this survey will aid the academic institutes to establish proficient learning platforms focused on improving students` learning experience., Competing Interests: None declared., (European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The higher order organization of eukaryotic and prokaryotic genomes is pivotal in the regulation of gene expression. Specifically, chromatin accessibility in eukaryotes and nucleoid accessibility in bacteria are regulated by a cohort of proteins to alter gene expression in response to diverse physiological conditions. By contrast, prior studies have suggested that the mitochondrial genome (mtDNA) is coated solely by mitochondrial transcription factor A (TFAM), whose increased cellular concentration was proposed to be the major determinant of mtDNA packaging in the mitochondrial nucleoid. Nevertheless, recent analysis of DNase-seq and ATAC-seq experiments from multiple human and mouse samples suggest gradual increase in mtDNA occupancy during the course of embryonic development to generate a conserved footprinting pattern which correlate with sites that have low TFAM occupancy in vivo (ChIP-seq) and tend to adopt G-quadruplex structures. These findings, along with recent identification of mtDNA binding by known modulators of chromatin accessibility such as MOF, suggest that mtDNA higher order organization is generated by cross talk with the nuclear regulatory system, may have a role in mtDNA regulation, and is more complex than once thought., (Copyright © 2019 Mishmar, Levin, Naeem and Sondheimer.)

Disease-associated variants in mitochondrial DNA (mtDNA) are frequently heteroplasmic, a state of co-existence with the wild-type genome. Because heteroplasmy correlates with the severity and penetrance of disease, improvement in the ratio between these genomes in favor of the wild-type, known as heteroplasmy shifting, is potentially therapeutic. We evaluated known pathogenic mtDNA variants and identified those with the potential for allele-specific differences in the formation of non-Watson-Crick G-quadruplex (GQ) structures. We found that the Leigh syndrome (LS)-associated m.10191C variant promotes GQ formation within local sequence in vitro. Interaction of this sequence with a small molecule GQ-binding agent, berberine hydrochloride, further increased GQ stability. The GQ formed at m.10191C differentially impeded the processivity of the mitochondrial DNA polymerase gamma (Pol γ) in vitro, providing a potential means to favor replication of the wild-type allele. We tested the potential for shifting heteroplasmy through the cyclical application of two different mitochondria-targeted GQ binding compounds in primary fibroblasts from patients with m.10191T>C heteroplasmy. Treatment induced alternating mtDNA depletion and repopulation and was effective in shifting heteroplasmy towards the non-pathogenic allele. Similar treatment of pathogenic heteroplasmies that do not affect GQ formation did not induce heteroplasmy shift. Following treatment, heteroplasmic m.10191T>C cells had persistent improvements and heteroplasmy and a corresponding increase in maximal mitochondrial oxygen consumption. This study demonstrates the potential for using small-molecule GQ-binding agents to induce genetic and functional improvements in m.10191T>C heteroplasmy., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Mitochondrial disease can arise due to pathogenic sequence variants in the mitochondrial DNA (mtDNA) that prevent cells from meeting their energy demands. Mitochondrial diseases are often fatal and currently there are no treatments directed towards the underlying cause of disease. Pathogenic variants in mtDNA often exist in a state of heteroplasmy, with coexistence of pathogenic and wild type mtDNA. The load of heteroplasmy, defined as the relative amount of pathogenic mtDNA to wild type mtDNA, corresponds to timing and symptom severity. Thus, changing the heteroplasmy load may lead to a shift in disease onset and symptom severity. Here we review techniques aimed at preventing inheritance of pathogenic mtDNA via mitochondrial replacement therapy (MRT) and strategies geared toward shifting of heteroplasmy in individuals with active mitochondrial disease. MRT strategies seek to create embryos with the nuclear genetic makeup of the intended parents and wild type mtDNA from a donor in order to avoid known maternal pathogenic variants. Heteroplasmy shift approaches in patients are of two categories: nuclease dependent and nuclease independent strategies. Despite initial success in mouse models and patient cells, these techniques have not reached clinical use. Translational attempts in this area are urgently needed to improve therapies for a currently untreatable set of disorders.

Proteolytic truncation of microtubule associated human (h) Tau protein by caspase-3 at the carboxy (C) terminus has been linked to the pathogenesis of Alzheimer's Disease (AD). This cleavage likely occurs between Asp 421 ↓Ser 422 leading to the formation of 421-mer truncated Tau protein which has been found to be present as aggregate in high level after phosphorylation in mortal AD brain tissue compared to normal. At least 50 phosphorylation sites involving Ser, Thr and Tyr residues have been identified or proposed in hTau and a selected number of them have been implicated in hTau aggregation following latter's proteolytic truncation. Interestingly, it is further noted that Ser 422 residue present in the P1' position of hTau caspase-3 cleavage region is a potential phosphorylation site. So we became interested to examine in vitro the effect of phospho-Ser 422 residue on hTau cleavage by caspase-3 which is a crucial upstream event associated with hTau self-assembly leading to AD pathogenesis. The goal of this project is to study in vitro the caspase-3 cleavage site of hTau protein and to examine the kinetics of this cleavage following Ser 422 phosphorylation and treatment with caspase-3 inhibitors. This is achieved by designing peptides from the sequence of hTau protein containing the proposed caspase-3 cleavage region. Peptides were designed from 441-mer major human Tau protein sequence that encompasses the proposed caspase-3 cleavage site [Asp 421 ↓Ser 422 ]. Corresponding phospho-, dextro-Ser 422 and dextro-Asp 421 analogs were also designed. Peptides were synthesized by solid phase chemistry, purified and fully characterized by mass spectrometry. These were then incubated with recombinant caspase-3 enzyme under identical condition for digestion and analyzed for cleavage by mass spectrometry and RP-HPLC chromatograms. Our results indicated that while the control peptide is efficiently cleaved by caspase-3 at Asp 421 ↓Ser 422 site producing the expected N- and C-terminal fragment peptides, the corresponding phospho-Ser 422 peptide remained completely resistant to the cleavage. Substitution of Asp 421 by its dextro isoform also blocks peptide cleavage by caspase-3. However substitution of Ser 422 by its dextro isoform in the peptide did not affect the cleavage significantly. The above results were further confirmed by caspase-3 digestion experiment in the presence of varying amounts of caspase-3 inhibitor (Ac-DQVD-aldehyde) which was found to block this cleavage in a highly effective manner. Our results highlighted the crucial significance of Ser 422 phosphorylation and suggest that the kinase associated with this Ser-phosphorylation may protect Tau from aggregation. Thus specific promoters/activators of this kinase may find useful therapeutic benefits in arresting Tau truncation by caspase-3 and the progression of AD. In addition our data demonstrated that Tau-peptides where Ser 422 or Asp 421 are substituted by their respective dextro isomers, exhibit different cleavage kinetics by caspase-3 and this may have important implications in therapeutic intervention of Tau aggregation and associated AD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging modality that measures the concentration changes of oxy-hemoglobin (HbO) and de-oxy hemoglobin (HbR) at the same time. It is an emerging cortical imaging modality with a good temporal resolution that is acceptable for brain-computer interface applications. Researchers have developed several methods in last two decades to extract the neuronal activation related waveform from the observed fNIRS time series. But still there is no standard method for analysis of fNIRS data. This article presents a brief review of existing methodologies to model and analyze the activation signal. The purpose of this review article is to give a general overview of variety of existing methodologies to extract useful information from measured fNIRS data including pre-processing steps, effects of differential path length factor (DPF), variations and attributes of hemodynamic response function (HRF), extraction of evoked response, removal of physiological noises, instrumentation, and environmental noises and resting/activation state functional connectivity. Finally, the challenges in the analysis of fNIRS signal are summarized.

Electroencephalography (EEG) is a portable brain-imaging technique with the advantage of high-temporal resolution that can be used to record electrical activity of the brain. However, it is difficult to analyze EEG signals due to the contamination of ocular artifacts, and which potentially results in misleading conclusions. Also, it is a proven fact that the contamination of ocular artifacts cause to reduce the classification accuracy of a brain-computer interface (BCI). It is therefore very important to remove/reduce these artifacts before the analysis of EEG signals for applications like BCI. In this paper, a hybrid framework that combines independent component analysis (ICA), regression and high-order statistics has been proposed to identify and eliminate artifactual activities from EEG data. We used simulated, experimental and standard EEG signals to evaluate and analyze the effectiveness of the proposed method. Results demonstrate that the proposed method can effectively remove ocular artifacts as well as it can preserve the neuronal signals present in EEG data. A comparison with four methods from literature namely ICA, regression analysis, wavelet-ICA (wICA), and regression-ICA (REGICA) confirms the significantly enhanced performance and effectiveness of the proposed method for removal of ocular activities from EEG, in terms of lower mean square error and mean absolute error values and higher mutual information between reconstructed and original EEG.

Contamination of eye movement and blink artifacts in Electroencephalogram (EEG) recording makes the analysis of EEG data more difficult and could result in mislead findings. Efficient removal of these artifacts from EEG data is an essential step in improving classification accuracy to develop the brain-computer interface (BCI). In this paper, we proposed an automatic framework based on independent component analysis (ICA) and system identification to identify and remove ocular artifacts from EEG data by using hybrid EEG and eye tracker system. The performance of the proposed algorithm is illustrated using experimental and standard EEG datasets. The proposed algorithm not only removes the ocular artifacts from artifactual zone but also preserves the neuronal activity related EEG signals in non-artifactual zone. The comparison with the two state-of-the-art techniques namely ADJUST based ICA and REGICA reveals the significant improved performance of the proposed algorithm for removing eye movement and blink artifacts from EEG data. Additionally, results demonstrate that the proposed algorithm can achieve lower relative error and higher mutual information values between corrected EEG and artifact-free EEG data.

Objective: To determine a change in the mortality of admitted children (neonates and children above 28 days of age to less than 17 years) and to document a change in the causes of neonatal admissions along with their mortality during a four year period., Methods: Conducted in Pediatric Unit-I, Bahawal Victoria Hospital, Bahawalpur. The data of all the children admitted from 1st January 2005 to 31st December 2008 was analyzed., Results: The mortality among admitted neonates was significantly higher than that of children of postneonatal age group. There was decrease in mortality among not only total admitted children but also among admitted children with postneonatal age group, i.e., 1 month to less than 17 years of age over a four year period (2005-2008) while no such decrease was seen in children of neonatal age group. The three common causes of neonatal admission and deaths were sepsis, birth asphyxia and prematurity., Conclusion: There was no improvement in neonatal mortality over a 4 year period. However, a decrease in postneonatal mortality was seen.