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Objective: Multidrug-resistant bacteria, including carbapenem-resistant Acinetobacter baumannii (CRAB), are considered a major public health threat, particularly those which are responsible for nosocomial infections. This study aimed to investigate the molecular mechanism of carbapenem resistance and the clonal relationship of CRAB isolates of a probable outbreak in the intensive care unit (ICU) of Saydet Zgharta University Medical Center, in north Lebanon. Methods: Thirty-two non-duplicate CRAB isolates were collected from patients hospitalised in the ICU. Antibiotic susceptibility testing was carried out using the disk diffusion method and carbapenemase-encoding genes were searched for using standard polymerase chain reaction. Epidemiological relatedness was studied using multilocus sequence typing. Results: Polymerase chain reaction and multilocus sequence typing results suggested the presence of two different periods: period 1 (November 2018 to February 2019), where 15 CRAB isolates were collected harbouring the blaOXA-23 and blaOXA-24 genes mainly and belonging to several clones; and period 2 (March to May 2019), considered an outbreak period where 17 carbapenem-resistant isolates were isolated, harbouring mostly the blaNDM-2 gene, never previously described in Lebanon and belonging to ST103. Infection control measures implemented in Saydet Zgharta University Medical Center successfully eradicated the NDM-2-producing CRAB ST103 clone, thus putting an end to this outbreak in the ICU department. Conclusions: This study showed that infection control measures and adequate identification of NDM-producing A. baumannii remain a powerful tool to limit the spread of such resistant micro-organisms.

Abstract Single-cell DNA sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel. Our approach builds on a modification of the 10X Genomics platform for scATAC and multiome profiling. In applications to human cell models and primary tissue, we demonstrate the feasibility to detect rare clones and we combine the assay with combinatorial indexing to profile over 17,000 cells.

Objective: The Enterobacter cloacae complex belongs to a group in which colistin resistance is not well documented due to their frequent heteroresistance. Methods: We investigated the molecular basis of colistin heteroresistance using genome analysis and random mutagenesis in a strain of E. cloacae. Results: The arnA gene was truncated in the six colistin susceptible mutants we obtained. However, the mcr-9 gene was present in these mutants suggesting this gene is not responsible for colistin resistance. Conclusions: Previous studies have highlighted the role of the two-component system PhoPQ and its negative regulator mgrB or the arnBCADTEF operon. Our results confirm the crucial role of this operon.

Abstract Dendritic cells (DCs) are crucial for initiating protective immune responses and have also been implicated in the generation and regulation of Foxp3+ regulatory T cells (Treg cells). Here, we show that in the lamina propria of the small intestine, the alternative NF-κB family member RelB is necessary for the differentiation of cryptopatch and isolated lymphoid follicle-associated DCs (CIA-DCs). Moreover, single-cell RNA sequencing reveals a RelB-dependent signature in migratory DCs in mesenteric lymph nodes favoring DC-Treg cell interaction including elevated expression and release of the chemokine CCL22 from RelB-deficient conventional DCs (cDCs). In line with the key role of CCL22 to facilitate DC-Treg cell interaction, RelB-deficient DCs have a selective advantage to interact with Treg cells in an antigen-specific manner. In addition, DC-specific RelB knockout animals show increased total Foxp3+ Treg cell numbers irrespective of inflammatory status. Consequently, DC-specific RelB knockout animals fail to mount protective Th2-dominated immune responses in the intestine after infection with Heligmosomoides polygyrus bakeri. Thus, RelB expression in cDCs acts as a rheostat to establish a tolerogenic set point that is maintained even during strong type 2 immune conditions and thereby is a key regulator of intestinal homeostasis.

Abstract The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-β-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Cassava is an important root crop that is produced by smallholder farmers across Sub-Saharan Africa. Cassava mosaic disease (CMD), which is caused by a group of cassava mosaic begomoviruses (CMBs), is one of the most devastating diseases of cassava. A previous study showed that SEGS-1 (sequences enhancing geminivirus symptoms), which occur both in the cassava genome and as episomes during CMD, can increase CMD disease severity and overcome host resistance. In this report, we examined the effects of exogenously applied SEGS-1 on the incidence of CMB infection, symptom severity, and viral DNA copy number in five cassava cultivars that ranged from highly susceptible to highly resistant to CMD. These studies revealed that the effect of SEGS-1 is cultivar dependent. Susceptible cultivars developed severe CMD with or without exogenous SEGS-1, while exogenous SEGS-1 increased disease severity in cultivars carrying CMD2 resistance, which is conferred by a single locus, but not CMD1 resistance, which is polygenic. Analysis of infected plants in the absence of exogenous SEGS-1 revealed that some, but not all, cultivars form SEGS-1 episomes during CMD. The presence of endogenous SEGS-1 episomes in TME14, a CMD2 resistant cultivar, correlated with CMD severity. In contrast, TME3, a closely related CMD2 cultivar, did not produce endogenous SEGS-1 episomes and was more resistance than TME14. The different capacities of TME3 and TME14 to form SEGS-1 episomes is unlikely due to sequence differences in and around their genomic SEGS-1 loci. The functional regions of SEGS-1 were mapped using TME3 to sequences flanking the episome junction, but the junction itself was not required for activity. All cassava cultivars have SEGS-1 sequences in their genomes that have the potential to negatively impact the development of stable CMD resistance by cassava breeding programs.

Abstract The 5-2-1 criteria was developed to facilitate the identification and referral of patients with Parkinson’s Disease (PD) inadequately controlled by oral medications. The criterion was not developed to screen patients with PD for device-aided therapy eligibility. The robust design and validation of the 5-2-1 criteria minimizes over or inappropriate referrals, and supports physicians in the timely identification of patients with PD who may warrant further evaluation for treatment optimization. This response letter clarifies concerns raised by Moes et al.

Burkholderia cepacia complex (Bcc) is an important group of opportunistic pathogens most frequently affecting patients with cystic fibrosis and responsible for life-threatening infections. Therapeutic options are limited owing to high levels of resistance of the organism, either intrinsic or acquired, to many antimicrobial agents. We describe here the successful treatment of a patient with cystic fibrosis who developed post-transplant lung abscesses and sternal osteitis caused by pan-resistant Burkholderia cenocepacia. He was treated with a combination of ceftazidime-avibactam, ciprofloxacin, meropenem, minocycline, sulfadiazine, and tobramycin. Repurposing multitarget drugs including old and new antibiotics, and their combinations with synergistic effects is a promising strategy to overcome clinical therapeutic impasses with difficult-to-treat-resistance (DTR) bacteria.

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells’ susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with – or caused by – ferroptosis.

In stand-alone photovoltaic (PV) systems, the main goal is to control the current that the inverter feeds to the load. In this paper, the performance of predictive current control (MPCC) is tested and evaluated for a stand-alone photovoltaic (PV) system. Our evaluation spans various current amplitudes and frequencies, aiming to demonstrate its robust performance and practical applicability. The MPCC method employs a discrete-time model of the system, enabling the prediction of future values of the load current for all potential volt-age vectors generated by the inverter. Implementing the MPCC strategy on RL (resistor-inductor) load alimented by a PV inverter offers the advantage of simplified implementation and significantly reduced computing time. Simulation and experimental results are presented to prove the efficiency and practical applicability of the proposed control. Both results conclusively demonstrate the high efficacy of MPCC in managing a stand-alone photovoltaic (PV) inverter across various current amplitudes and frequencies, ensuring reliable and robust performance

Abstract Background DNA methylation is one of the most stable and well-characterized epigenetic alterations in humans. Accordingly, it has already found clinical utility as a molecular biomarker in a variety of disease contexts. Existing methods for clinical diagnosis of methylation-related disorders focus on outlier detection in a small number of CpG sites using standardized cutoffs which differentiate healthy from abnormal methylation levels. The standardized cutoff values used in these methods do not take into account methylation patterns which are known to differ between the sexes and with age. Results Here we profile genome-wide DNA methylation from blood samples drawn from within a cohort composed of healthy controls of different age and sex alongside patients with Prader–Willi syndrome (PWS), Beckwith–Wiedemann syndrome, Fragile-X syndrome, Angelman syndrome, and Silver–Russell syndrome. We propose a Generalized Additive Model to perform age and sex adjusted outlier analysis of around 700,000 CpG sites throughout the human genome. Utilizing z-scores among the cohort for each site, we deployed an ensemble based machine learning pipeline and achieved a combined prediction accuracy of 0.96 (Binomial 95% Confidence Interval 0.868 $$-$$ - 0.995). Conclusion We demonstrate a method for age and sex adjusted outlier detection of differentially methylated loci based on a large cohort of healthy individuals. We present a custom machine learning pipeline utilizing this outlier analysis to classify samples for potential methylation associated congenital disorders. These methods are able to achieve high accuracy when used with machine learning methods to classify abnormal methylation patterns.

The extreme persistence and environmental mobility of per- and polyfluoroalkyl substances (PFAS) make their presence ubiquitous in the marine environment. Target analysis of 20 most common PFAS revealed the presence of nine perfluoroalkyl acids at low levels in surface sediments from five Norwegian marine areas covering the vast region from the eastern North Sea in the south to the Arctic Ocean north of Svalbard in the north. After correcting for sediment characteristics, no substantial difference in the sum of the nine PFAS (Σ9PFAS) between the five areas was found. Among separate compounds, PFOS, PFOA and PFNA dominate sample composition. Only two compounds, PFOS and PFUnDA, showed a statistically significant difference for one of the areas, the levels of these compounds being somewhat higher in the southernmost area than in the other areas. This may be due to local inputs in the fjords in this area. Open-sea and coastal sediments of the North-east Atlantic outside of locations with significant local sources seem to share a common, anthropogenic “PFAS background”, which may be part of a larger, global pattern.

IntroductionSpinal muscular atrophy (SMA) is caused by homozygous loss of the SMN1 gene with SMN2 gene copy number correlating with disease severity. Rarely SMA is caused by a deletion on one allele and a pathogenic variant on the other. The pathogenic missense variant c.5C>G (p.Ala2Gly) correlates with a mild disease phenotype that does not correlate with SMN2 copy number. In a mouse model the c.5C>G transgene produces SMN that is thought to form partially functional SMN complexes, but levels in humans have not yet been investigated.MethodsWe identified two patients with mild SMA caused by a heterozygous deletion of SMN1 and the heterozygous variant, c.5C>G. Molecular findings were confirmed with deletion/duplication analysis and Sanger sequencing. Skin fibroblasts were collected and cultured, and SMN expression was analyzed using immunofluorescence.ResultsTwo patients with slowly progressing mild weakness were confirmed to have heterozygous pathogenic missense variant c.5C>G and a heterozygous deletion of SMN1. Their clinical presentation revealed much milder disease progression than patients with matched SMN2 copy number. Analysis of the patients’ fibroblasts revealed much higher numbers of SMN nuclear complexes than a patient with a homozygous SMN1 deletion and matched SMN2 copy number.ConclusionsThese case reports reinforce that the rare c.5C>G variant causes mild disease. Furthermore, the analysis of SMA nuclear gems in patient samples supports the theory that the p.Ala2Gly SMN can form partially functional SMN complexes that may carry out essential cellular functions and result in mild disease.

BackgroundImmune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%–46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed. This study aims to generate knowledge on pathogenesis and assess outcomes in cancer centers with intensified patient management.MethodsPatients with cardiac irAEs from the SERIO registry (www.serio-registry.org) were analyzed for demographics, ICI-related information (type of ICI, therapy line, combination with other drugs, onset of irAE, and tumor response), examination results, irAE treatment and outcome, as well as oncological endpoints. Cardiac biopsies of irMyocarditis cases (n = 12) were analyzed by Nanostring and compared to healthy heart muscle (n = 5) and longitudinal blood sampling was performed for immunophenotyping of irMyocarditis-patients (n = 4 baseline and n = 8 during irAE) in comparison to patients without toxicity under ICI-therapy (n = 4 baseline and n = 7 during ICI-therapy) using flow cytometry.ResultsA total of 51 patients with 53 cardiac irAEs induced by 4 different ICIs (anti-PD1, anti-PD-L1, anti-CTLA4) were included from 12 centers in 3 countries. Altogether, 83.0% of cardiac irAEs were graded as severe or life-threatening, and 11.3% were fatal (6/53). Thus, in centers with established consequent troponin monitoring, work-up upon the rise in troponin and consequent treatment of irMyocarditis with corticosteroids and –if required–second-line therapy mortality rate is much lower than previously reported. The median time to irMyocarditis was 36 days (range 4–1,074 days) after ICI initiation, whereas other cardiotoxicities, e.g. asystolia or myocardiopathy, occurred much later. The cytokine-mediated signaling pathway was differentially regulated in myocardial biopsies as compared to healthy heart based on enrichment Gene Ontology analysis. Additionally, longitudinal peripheral blood mononuclear cell (PBMC) samples from irMyocarditis-patients indicated ICI-driven enhanced CD4+ Treg cells and reduced CD4+ T cells. Immunophenotypes, particularly effector memory T cells of irMyocarditis-patients differed from those of ICI-treated patients without side effects. LAG3 expression on T cells and PD-L1 expression on dendritic cells could serve as predictive indicators for the development of irMyocarditis.ConclusionInterestingly, our cohort shows a very low mortality rate of irMyocarditis-patients. Our data indicate so far unknown local and systemic immunological patterns in cardiotoxicity.

IntroductionThe CC chemokine ligand 18 (CCL18) is a chemokine highly expressed in chronic inflammation in humans. Recent observations of elevated CCL18 plasma levels in patients with acute cardiovascular syndromes prompted an investigation into the role of CCL18 in the pathogenesis of human and mouse atherosclerosis.Methods and resultsCCL18 was profoundly upregulated in ruptured human atherosclerotic plaque, particularly within macrophages. Repeated administration of CCL18 in Western-type diet–fed ApoE−/− mice or PCSK9mut-overexpressing wild type (WT) mice led to increased plaque burden, enriched in CD3+ T cells. In subsequent experimental and molecular modeling studies, we identified CCR6 as a functional receptor mediating CCL18 chemotaxis, intracellular Ca2+ flux, and downstream signaling in human Jurkat and mouse T cells. CCL18 failed to induce these effects in vitro in murine spleen T cells with CCR6 deficiency. The ability of CCR6 to act as CCL18 receptor was confirmed in vivo in an inflammation model, where subcutaneous CCL18 injection induced profound focal skin inflammation in WT but not in CCR6−/− mice. This inflammation featured edema and marked infiltration of various leukocyte subsets, including T cells with a Th17 signature, supporting CCR6’s role as a Th17 chemotactic receptor. Notably, focal overexpression of CCL18 in plaques was associated with an increased presence of CCR6+ (T) cells.DiscussionOur studies are the first to identify the CCL18/CCR6 axis as a regulator of immune responses in advanced murine and human atherosclerosis.

Indonesia adalah negara dengan penduduk terbesar keempat di dunia yang akibat pada tingginya produksi sampah baik sampah anorganik atapun organik. Adanya upaya yang dilakukan masyarakat dalam mengurangi sampah organik yaitu daur ulang sampah organik dengan metode biokonversi. Beberapa penelitian terdahulu sudah melakukan daur ulang sampah organik menjadi media untuk budidaya maggot atau dikenal Larva Black Soldier Fly yang bisa dijadikan bahan pakan unggas ataupun ikan. Larva Black Soldier Fly mampu menguraikan sampah organik, baik tumbuhan maupun hewan. Penelitian ini menggunakan metode tinjauan sistematis (Systematic Review). Penelitian ini bertujuan untuk melakukan kajian literature review terkait potensi budidaya Larva Black Soldier Fly untuk pakan unggas dan ikan. Pengumpulan data dilakukan dengan menemukan, mengevaluasi, dan menginterpretasikan artikel yang memiliki penelitian serupa. Berdasarkan penelitian ini didapatkan bahwa budidaya maggot untuk pakan ikan dan unggas merupakan inovasi baru dalam pengurangan sampah organik masih belum maksimal. Berdasarkan kajian literature pengembangan budidaya maggot yang dilakukan secara partisipatif diantara masyarakat dengan suatu komunitas atau lingkup sosial harus dilakukan lebih luas lagi agar terjadi tindakan transformatif dengan memanfaatkan media-media yang terbaru.

This work offers a description of the main lexical characteristics found in the Mexican Spanish variety by focusing on the language use of official exclusively male text producers in multiethnic and multilingual Oaxaca de Juárez from 1890 to 1911. Relevant works of Spanish linguistic historiography still postulate the beginning of an “español modern” from the 18th/19th century onwards. But the present qualitative study shows, based on a corpus, that diverse lexical variation was still realized in official documents in the 19th/20th century, as rubio and claro to characterize exclusively foreign sex-workers or as a limited lexeme repertoire to describe nose(shape), whereas a broad repertoire to characterize skin color is conspicuous. Furthermore, the data helps us to consider a variety that is still conspicuously absent in Spanish language history.

Background Non-communicable diseases (NCDs) kill 41 million people a year. The products and services of unhealthy commodity industries (UCIs) such as tobacco, alcohol, ultra-processed foods and beverages and gambling are responsible for much of this health burden. While effective public health policies are available to address this, UCIs have consistently sought to stop governments and global organisations adopting such policies through what is known as corporate political activity (CPA). We aimed to contribute to the study of CPA and development of effective countermeasures by formulating a model and evidence-informed taxonomies of UCI political activity.Methods We used five complementary methods: critical interpretive synthesis of the conceptual CPA literature; brief interviews; expert co-author knowledge; stakeholder workshops; testing against the literature.Results We found 11 original conceptualisations of CPA; four had been used by other researchers and reported in 24 additional review papers. Combining an interpretive synthesis of all these papers and feedback from users, we developed two taxonomies – one on framing strategies and one on action strategies. The former identified three frames (policy actors, problem, and solutions) and the latter six strategies (access and influence policy-making, use the law, manufacture support for industry, shape evidence to manufacture doubt, displace, and usurp public health, manage reputations to industry’s advantage). We also offer an analysis of the strengths and weaknesses of UCI strategies and a model that situates industry CPA in the wider social, political, and economic context.Conclusion Our work confirms the similarity of CPA across UCIs and demonstrates its extensive and multi-faceted nature, the disproportionate power of corporations in policy spaces and the unacceptable conflicts of interest that characterise their engagement with policy-making. We suggest that industry CPA is recognised as a corruption of democracy, not an element of participatory democracy. Our taxonomies and model provide a starting point for developing effective solutions.

This research focuses on the noise level at Sultan Thaha Jambi Airport due to aircraft activity which took place from 06.05 to 22.40 WIB. This research started from observation, collecting noise level data and measuring data. The method used is the Weighted Equivalent Continuous Perceived Noise Level (WECPNL) method to measure noise points at each measurement point. Measurement points were taken at 6 points for 24 hours/14 days. This research also uses a Geographic Information System (GIS) to map the distribution of noise levels. The research results showed that the highest noise values ​​occurred in the air side area and occurred during holidays. WECPNL results from April 27 to May 10 showed that the average noise index reached 58 to 59 (dB), close to the noise quality standard of 55 (dB). In the Liverpool airport and residential area, the purple color has an index

Introduction: Mucinous ovarian carcinoma is often diagnosed early and can affect young patients. The preservation of the female reproductive organ is one of the critical issues, especially for nulliparous women. This case report aims to reconsider the safe outcome of fertility-sparing surgery for infiltrative type mucinous ovarian carcinoma. Case Presentation: A 28-year-old woman with a right mucinous ovarian carcinoma, infiltrative subtype stage IA was treated by right salpingo-oophorectomy, omentectomy, and lymph nodes staging. A 5-year follow-up showed no signs of relapse, and she completed two full-term natural pregnancies. Conclusion: Conservative surgery is a crucial matter for this patient category. The infiltrative type has a poorer prognosis, but few papers have reported the outcome and the safety of fertility-sparing surgery in this context.

p53 is a crucial tumor suppressor in vertebrates that is frequently mutated in human cancers. Most mutations are missense mutations that render p53 inactive in suppressing tumor initiation and progression. Developing small-molecule drugs to convert mutant p53 into an active, wild-type-like conformation is a significant focus for personalized cancer therapy. Prior research indicates that reactivating p53 suppresses cancer cell proliferation and tumor growth in animal models. Early clinical evidence with a compound selectively targeting p53 mutants with substitutions of tyrosine 220 suggests potential therapeutic benefits of reactivating p53 in patients. This study identifies and examines the UCI-1001 compound series as a potential corrector for several p53 mutations. The findings indicate that UCI-1001 treatment in p53 mutant cancer cell lines inhibits growth and reinstates wild-type p53 activities, including DNA binding, target gene activation, and induction of cell death. Cellular thermal shift assays, conformation-specific immunofluorescence staining, and differential scanning fluorometry suggest that UCI-1001 interacts with and alters the conformation of mutant p53 in cancer cells. These initial results identify pyrimidine trione derivatives of the UCI-1001 series as candidates for p53 corrector drug development.

IntroductionEfforts to improve medication access in low-and middle-income countries, particularly in Sub-Saharan Africa, have made progress, especially in the fight against infectious diseases such as tuberculosis. However, challenges exist in establishing effective pharmacovigilance systems. The PhArmacoVIgilance Africa (PAVIA) project was committed to enhancing pharmacovigilance in Tanzania, Eswatini, Nigeria, and Ethiopia, with an emphasis on anti-tuberculosis drugs, utilizing various methods, including training. This study evaluates the PAVIA training program’s effectiveness and its adaptation during the COVID-19 pandemic.MethodsA blended e-learning program, incorporating two courses and a platform for educational materials, was developed. This program, designed to train healthcare professionals in pharmacovigilance, was incorporated into a Training of Trainers model. To evaluate the program effectiveness, we used multiple measures such as assessing knowledge gain through pre-and post-test scores, assessing learners’ satisfaction and attitudes via questionnaires, and analyzing Individual Case Safety Reports (ICSRs) in VigiBase to determine the impact on spontaneous reporting systems in the PAVIA countries.Results121 learners enrolled in the pilot trainings, including 36 from Tanzania, 34 from Eswatini, 25 from Nigeria, and 26 from Ethiopia. Notably, post-test scores were significantly higher than pre-test scores in all four countries. Following the pilot trainings, multiple step-down training sessions were held in Tanzania, Eswatini, and Nigeria, with a total of 827 learners registering and 421 successfully completing the program. Learners’ scores on the post-tests were significantly higher than on the pre-tests for both courses in all three countries. Learners’ feedback on the training was overwhelmingly positive. Additionally, a qualitative analysis of ICSRs revealed a substantial increase in reports after the training in Tanzania, Eswatini, and Nigeria.DiscussionAn innovative e-learning program trained healthcare professionals in pharmacovigilance and anti-tuberculosis drug safety over 3 years in four PAVIA countries. The program effectively improved participants’ knowledge, received positive feedback, and likely had an impact on reporting rates in Tanzania, Eswatini, and Nigeria, although a direct causal link could not be definitively established due to data limitations and other factors, such as the heightened reporting rates associated with COVID-19 vaccines, that could have contributed to the notable increase in ICSRs.

تتناول هذه الدراسة تعرض الدعوة الإسلامية إلى المعارضة من قبل القبائل العربية وغيرها، وفي المقابل تمسك الرسول الكريم(ﷺ) بالصبر والسلام والحوار كأساس لدعوته، إلا أنه كان لزاماً أن يلتقي الطرفان بعد أن أذن للمسلمين بحمل السلاح، لذا أهتم الرسول الكريم (ﷺ) بجمع المعلومات عن المشركين بالداخل والخارج وأستخدم العيون في معظم غزواته، الأمر الذي كان له الدور الفعال في تحقيق النصر، ومن هنا تأتي هذه الدراسة للكشف عن تاريخ الجاسوسية في أهم فترات التاريخ الإسلامي ولذلك أشارت الدراسة إلى تعريف الجاسوسية ومترادفاتها لغةً واصطلاحا والشروط التي يجب توفرها بالجاسوس، إضافةً إلى أهمية الجاسوسية وموقف الرسول صلى الله عليه وسلم، من ناصب العداء للدولة ومجتمعه، اعتمدت الدراسة على مجموعة من المصادر والمراجع بالرصد والتحليل والتوثيق الأكاديمي، بينت أهمية هذا الجهاز في الحفاظ على مصلحة الأمة والدولة مراعية في ذلك دقة اختيار الأشخاص والمهام التي يكلفون بها، مع الحرص الشديد على سلامتهم وسلامة المعلومات السرية التي يرسلونها.

Tanah gambut memiliki karakterisitik kandungan air dan kompresebilitasnya tinggi menyebabkan gambut rentan terjadi penurunan permukaan tanah ketika ada pembebanan. Penelitian ini bertujuan untuk menganalisis ketebalan lapisan tanah gambut di Desa Pandan Jaya Kecamatan Geragai Kabupaten Tanjung Jabung. Metode yang digunakan adalah metode geolistrik resistivitas konfigurasi Wenner-Schlumberger dengan sebanyak 4 lintasan pengukuran masing-masing 110 meter dengan jarak antar elektroda 10 meter. Dari hasil pengukuran resistivitas diperoleh bahwa lapisan gambut di Desa Pandan Jaya Kecamatan Geragai Kabupaten Tanjung Timur memiliki nilai resistivitas mulai dari 5,03 Ωm hingga 130 Ωm. Dapat disimpulkan lapisan gambut pada lokasi penelitian memiliki ketebalan antara 5 m hingga 7 m. Informasi ini sangat penting untuk pertimbangan kedalaman pondasi saat akan mendirikan bangunan di daerah tersebut.

Abstract Cassava mosaic disease is caused by a complex of whitefly-transmitted begomoviruses, which often occur in co-infections. These viruses have bipartite genomes consisting of DNA-A and DNA-B that are encapsidated into separate virions. Individual viruses exist in plants and whitefly vectors as populations comprising both genome segments, which can occur at different frequencies. Both segments are required for infection, and must be transmitted for virus spread to occur. Cassava plants infected with African cassava mosaic virus (ACMV) and/or East African cassava mosaic Cameroon virus (EACMCV), in which the ratios of DNA-A:DNA-B titers differed between plants, were used to examine how titers of the segments in a plant relate to their respective probabilities of acquisition by whiteflies and to the titers of each segment acquired and subsequently transmitted by whiteflies. The probabilities of acquiring each segment of ACMV did not reflect their relative titers in the source plant but they did for EACMCV. However, for both viruses, DNA-A:DNA-B ratios acquired by whiteflies differed from those in the source plant and the ratios transmitted by the whitefly did not differ from one – the ratio at which the highest probability of transmitting both segments is expected.

Abstract Background Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis. Methods We have designed a phase 3 randomized trial with a 2 × 2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10–12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients’ intervention assignment. Discussion By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem. Trial registration ClinicalTrials.gov Identifier: NCT03581123.

ABSTRAK Kabupaten Muaro Jambi merupakan kabupaten di Provinsi Jambi dengan luas karhutla terbesar dengan luas 4.054 hektar (34,55%). Hal ini dikarenakan sebagian besar jenis tanah di Kabupaten Muaro Jambi merupakan jenis tanah gambut. Pada penelitian bertujuan untuk melihat hubungan antara parameter cuaca dan distribusi titik panas di Kabupaten Muaro Jambi. Parameter cuaca yang akan dianalisis yaitu curah hujan pada tahun 2019 dan 2020 dimana tahun 2019 mewakili tahun terjadinya El Nino dan tahun 2020 merupakan tahun tanpa El Nino. Data yang digunakan adalah antara lain data curah hujan tahun 2019 dan tahun 2020, data ENSO (El Nino-Shouthern Oscillation) dan IOD (lndian Ocean Dipole), dan data titik panas. Pada tahun 2019, curah hujan terendah terjadi pada bulan september sebesar 39,3 mm/bulan dan pada tahun 2020, terendah pada bulan Juli sebesar 154,5 mm/bulan. Jumlah titik panas pada bulan September tahun 2019 sebanyak 3000 titik atau sekitar 77,88% dari total titik panas pada tahun 2019. Sedangkan pada tahun 2020, jumlah titik panas terbanyak hanya sebanyak 13 titik panas di bulan April. Hal ini menunjukkan bahwa peristiwa El Nino yang menyebabkan rendahnya curah hujan sangat berpengaruh terhadap pertambahan jumlah titik panas sebagai potensi terjadinya kebakaran hutan dan lahan. Kata kunci: kebakaran hutan dan lahan; el nino; curah hujan; titik panas. ABSTRACT Muaro Jambi Regency is a district in Jambi Province with the largest area of forest and land fires with an area of 4,054 hectares (34.55%). Most of the soil types in Muaro Jambi Regency are peat soil types. This study aims to look at the relationship between weather parameters and the distribution of hotspots in Muaro Jambi Regency. The weather parameters to be analyzed are rainfall in 2019 and 2020 where 2019 represents the year El Nino occurs and 2020 is the year without El Nino. The data used includes rainfall data for 2019 and 2020, ENSO (El Nino-Southern Oscillation) and IOD (Indian Ocean Dipole) data, and hotspot data. In 2019, the lowest rainfall occurred in September of 39.3 mm/month and in 2020, the lowest was in July of 154.5 mm/month. The number of hotspots in September 2019 was 3,000 points or around 77.88% of the total hotspots in 2019. Meanwhile, in 2020, the highest number of hotspots was only 13 hotspots in April. This shows that the El Nino event which causes low rainfall greatly influences the increase in the number of hotspots as a potential for forest and land fires. Keywords: forest and land fires; el nino; rainfall; hotspots.

Abstract Human activities have facilitated the invasion of freshwater ecosystems by various organisms. Especially, invasive bivalves such as the quagga mussels, Dreissena bugensis, have the potential to alter ecosystem function as they heavily affect the food web. Quagga mussels occur in high abundance, have a high filtration rate, quickly spread within and between waterbodies via pelagic larvae, and colonize various substrates. They have invaded various waterbodies across the Northern Hemisphere. In Central Europe, they have invaded multiple large and deep perialpine lakes with first recordings in Lake Geneva in 2015 and 2016 in Lake Constance. In the deep perialpine lakes, quagga mussels quickly colonized the littoral zone but are also abundant deeper (>80 m), where they are often thinner and brighter shelled. We analysed 675 quagga mussels using ddRAD sequencing to gain in‐depth insights into the genetic population structure of quagga mussels across Central European lakes and across various sites and depth habitats in Lake Constance. We revealed substantial genetic differentiation amongst quagga mussel populations from three unconnected lakes, and all populations showed high genetic diversity and effective population size. In Lake Constance, we detected no genetic differentiation amongst quagga mussels sampled across different sites and depth habitats. We also did not identify any convincing candidate loci evidential for adaptation along a depth gradient and a transplant experiment showed no indications of local adaptation to living in the deep based on investigating growth and survival. Hence, the shallow‐water and the deep‐water morphotypes seem to be a result of phenotypic plasticity rather than local adaptation to depth. In conclusion, our ddRAD approach revealed insight into the establishment of genetically distinct quagga mussel populations in three perialpine lakes and suggests that phenotypic plasticity and life history traits (broadcast spawner with high fecundity and dispersing pelagic larvae) facilitate the fast spread and colonization of various depth habitats by the quagga mussel.

IntroductionThe lymphatic system has a pivotal role in immune homeostasis. To better understand this, we investigated the impact of Primary Lymphatic Anomalies (PLA) on lymphocyte numbers and phenotype.MethodsThe study comprised (i) a retrospective cohort: 177 PLA subjects from the National Primary Lymphatic Anomaly Register with clinical and laboratory data, and (ii) a prospective cohort: 28 patients with PLA and 20 healthy controls. Patients were subdivided using established phenotypic diagnostic categories and grouped into simplex (localised tissue involvement only) and systemic (involvement of central lymphatics). Further grouping variables included genital involvement and the likelihood of co-existent intestinal lymphangiectasia. Haematology laboratory parameters were analysed in both cohorts. In the prospective cohort, prospective blood samples were analysed by flow cytometry for markers of proliferation, differentiation, activation, skin-homing, and for regulatory (CD4+Foxp3+) T cells (Treg).ResultsIn patients with PLA, lymphopaenia was frequent (22% of subjects), affected primarily the CD4+ T cell subset, and was more severe in subjects with systemic versus simplex patterns of disease (36% vs 9% for lymphopaenia; 70% vs 33% for CD4+ cells). B cells, NK cells and monocytes were better conserved (except in GATA2 deficiency characterised by monocytopaenia). Genital oedema and likelihood of concomitant intestinal lymphangiectasia independently predicted CD4+ T cell depletion. Analysing CD4+ and CD8+ T cells by differentiation markers revealed disproportionate depletion of naïve cells, with a skewing towards a more differentiated effector profile. Systemic PLA conditions were associated with: increased expression of Ki67, indicative of recent cell division, in naïve CD4+, but not CD8+ T cells; increased levels of activation in CD4+, but not CD8+ T cells; and an increased proportion of Treg. Skin-homing marker (CCR10, CLA and CCR4) expression was reduced in some patients with simplex phenotypes.DiscussionPatients with PLA who have dysfunctional lymphatics have a selective reduction in circulating lymphocytes which preferentially depletes naïve CD4+ T cells. The presence of systemic disease, genital oedema, and intestinal lymphangiectasia independently predict CD4 lymphopaenia. The association of this depletion with immune activation and increased circulating Tregs suggests lymphatic-lymphocyte interactions and local inflammatory changes are pivotal in driving immunopathology.

Teachers are professional educators with the main task of educating, teaching, guiding, directing, training, assessing, and evaluating students in every teaching and learning process in schools. In the learning process, various skills are needed for the continuity of the learning process, one of which is the skill of making lesson plans. The skill of a teacher in making lesson plans determines the learning outcomes that will be accepted by students. This study aims to analyze the effect of RADEC-based workshop activities in improving the skills of elementary school teachers to make good lesson plans. This study uses the One Group pretest posttest method with a sample of elementary school teachers in Purwakarta Regency. The instrument used is the result of adaptation of the assessment of the learning implementation plan in the PPG program. There are seven indicators used in the instrument used. The results showed that the RADEC model had an impact on teachers in developing learning planning skills. The average n-gain score obtained from this study was 58 which was categorized as quite effective.

Artikel ini membahas hasil pengabdian kepada masyarakat mengenai pemanfaatan copywriting untuk personal branding. Peserta pelatihan ini terdiri atas 67% remaja dan 33% kalangan dewasa awal. Kegiatan pengabdian dilakukan secara daring melalui Zoom meeting sehingga peserta berasal dari berbagai daerah di Indonesia. Copy writing dalam personal branding dapat dilakukan dengan menyampaikan (a) alasan bertahan dalam sebuah konten, (b) cerita menarik, (c) argumentasi, (d) ajakan untuk mengikuti nilai atau value yang dikampanyekan. Materi copy writing untuk personal branding dapat dipraktikkan oleh peserta dalam melakukan personal proof di media sosial Instagram. Pelatihan copy writing untuk personal branding dapat mempermudah peserta dalam mengarahkan kontennya dalam menyampaikan pesan-pesan atau value yang ingin disebarkan kepada masyarakat.

Introduction: Extremely premature (EP) infants (

Nonalcoholic fatty liver disease (NAFLD) is a fast growing, chronic liver disease affecting ∼25% of the global population. Nonalcoholic fatty liver disease severity ranges from the less severe simple hepatic steatosis to the more advanced nonalcoholic steatohepatitis (NASH). The presence of NASH predisposes individuals to liver fibrosis, which can further progress to cirrhosis and hepatocellular carcinoma. This makes hepatic fibrosis an important indicator of clinical outcomes in patients with NASH. Hepatic stellate cell activation dictates fibrosis development during NASH. Here, we discuss recent advances in the analysis of the profibrogenic pathways and mediators of hepatic stellate cell activation and inactivation, which ultimately determine the course of disease in nonalcoholic fatty liver disease/NASH.

Abstract Objective: Restaurants may be important settings for interventions to reduce children’s energy intake. The objective of this study was to test the impact of a parent-focused social marketing campaign to promote healthy children’s meals on calories ordered and consumed by children at quick-service restaurants (QSR). Design: Using a repeated cross-sectional study design, two urban communities were randomised to intervention (IN) v. control (C) condition. A community-wide social marketing campaign was implemented in the IN community to empower Black and Latinx mothers who frequent QSR (priority population) to select healthier options for their child. Setting: Data were collected in 2016 at QSR located within the communities pre- and post-IN and analysed in 2017. Participants: Parents (n 1686; n 819 and n 867 for I and C conditions, respectively) were recruited after placing their QSR order; a survey, receipt and their child’s leftovers were collected. Results: Calories ordered did not differ significantly between the IN and C conditions (changeadj = –146·4 kJ (–35·0 kcal); 95 % CI –428·0 kJ (–102·3 kcal), 134·6 kJ (32·2 kcal)). In a sub-analysis of only the priority audience, children in the IN community ordered significantly fewer calories compared to C children in unadjusted models (changeunadj = –510·4 kJ (–122·0 kcal); 95 % CI –1013·4 kJ (–242·2 kcal), –7·5 kJ (–1·8 kcal)), but the trend did not persist after adjusting for covariates (changeadj = –437·2 kJ (–104·5 kcal); 95 % CI –925·5 kJ (–221·2 kcal), 50·6 kJ (12·1 kcal)). Calories consumed followed similar trends. Conclusion: The campaign did not significantly reduce children’s QSR calories ordered or consumed. However, a quantitatively important mean reduction in calories was suggested among the priority audience, indicating potential for community-wide promotion of healthful children’s meals.

Abstract Background Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described. Methods Sixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment. Results The maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment. Conclusions Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.

Since the outbreak of Covid-19 pandemic, the Special Region of Yogyakarta (henceforth DIY) had experienced a dramatic economic downturn particularly in the tourism industry. The worst effect was faced by those who earned their living, either direct or indirect income, from tourism activities. In response to this issue, this community service program was conducted to contribute to the recovery of tourism by fostering the potency of villages in DIY as tourism villages using Wiwitan ceremony as a tourist attraction. Wiwitan is a rice harvest ritual which is an expression of gratitude because the time to harvest crop finally comes. Gratitude is also everyone’s feeling when the height of global pandemic finally is already over and people are eager to welcome the new normal. Therefore, Wiwitan is worth to be highlighted as the main tourist attraction because of its universal philosophy. To achieve the goal, a training program was carried out and used four approaches, namely lecture, discussion, hands-on practice, and simulation. The results of this activity was to open the eyes that Wiwitan can become an interesting tourist attraction. Keywords: tourism villages, package tour, Wiwitan ceremony Abstrak. Sejak pandemi Covid-19 Daerah Istimewa Yogyakarta (DIY) mengalami penurunan perekonomian yang tajam karena terganggunya sektor pariwisata. Dampak paling signifikan dirasakan oleh para pelaku pariwisata dan masyarakat yang memperoleh pendapatan secara langsung dan tidak langsung dari aktivitas pariwisata. Dengan mempertimbangkan masalah tersebut, kegiatan pengabdian masyarakat ini bertujuan untuk membantu pemulihan kembali sektor pariwisata di propinsi DIY melalui pengembangan potensi kawasan pedesaan di DIY sebagai desa wisata budaya khususnya melalui upacara Wiwitan. Upacara yang dilakukan sebelum panen padi ini melambangkan rasa syukur karena panen tiba. Rasa syukur ini juga dirasakan umat manusia karena puncak pandemi terlewati dan mulai menyongsong fase normalisasi. Maka Wiwitan layak dijadikan atraksi wisata utama karena maknanya yang universal bagi umat manusia. Kegiatan ini menggunakan metode pelatihan dengan pendekatan ceramah, diskusi, praktik langsung, dan simulasi. Hasil dari kegiatan ini adalah terbangunnya kesadaran peserta bahwa upacara Wiwitan dapat menjadi daya tarik wisata.

Abstract This study investigated the role of vector acquisition and transmission on the propagation of single and co-infections of tomato yellow leaf curl virus (TYLCV,) and tomato mottle virus (ToMoV) (Family: Geminiviridae, Genus: Begomovirus) by the whitefly vector Bemisia tabaci MEAM1 (Gennadius) in tomato. The aim of this research was to determine if the manner in which viruses are co-acquired and co-transmitted changes the probability of acquisition, transmission and new host infections. Whiteflies acquired virus by feeding on singly infected plants, co-infected plants, or by sequential feeding on singly infected plants. Viral titers were also quantified by qPCR in vector cohorts, in artificial diet, and plants after exposure to viruliferous vectors. Differences in transmission, infection status of plants, and titers of TYLCV and ToMoV were observed among treatments. All vector cohorts acquired both viruses, but co-acquisition/co-inoculation generally reduced transmission of both viruses as single and mixed infections. Co-inoculation of viruses by the vector also altered virus accumulation in plants regardless of whether one or both viruses were propagated in new hosts. These findings highlight the complex nature of vector-virus-plant interactions that influence the spread and replication of viruses as single and co-infections.

Strategies to advance T cell based immune therapies are mostly focusing on the improvement of CD8 T cell effector functions, such as cytotoxicity or recruitment to the tumor. Here authors show that by combining in situ vaccination with oncolytic Newcastle Disease Virus and Flt3L-driven dendritic cell expansion, the anti-tumor T cell response is amplified via increased antigen cross-presentation.

Abstract Background Dolutegravir (DTG) is an Integrase Strand Transfer Inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV infection. It is available in a number of pharmaceutical preparations including the fixed-dose combination (TLD) containing tenofovir (300 mg) + lamivudine (300 mg) + dolutegravir (50 mg). In 2018, Eswatini adopted TLD as the preferred first-line HIV treatment regimen for adults and adolescents as per WHO recommendations. From March 2019 to March 2020, the National Pharmacovigilance Center (NPC) in Eswatini received 8 reports of hyperglycaemia associated with the use of DTG. This study was conducted to investigate if Eswatini NPC database included cases suggestive of causality between dolutegravir and hyperglycaemia. Method A qualitative synthesis of information from the Eswatini national pharmacovigilance database from March 2019 to March 2020 was conducted to investigate a casual association between hyperglycaemia and dolutegravir. Results All reports with dolutegravir containing regimen and suspected Adverse Event of hyperglycaemia in the period of March 2019 to March 2020 were included in the study. Seven of the reports were serious (resulted in hospitalization and one case concerned optic neuritis, leading to blindness). Two patients had a medical history of diabetes while the rest of the patients had never experienced hyperglycaemia before starting dolutegravir. For all the reports, the time to onset of hyperglycaemia ranges from 2–5 months after the initiation of DTG. None of the patients discontinued the use of DTG. All the patients were treated with oral hypoglycaemic medication. In severe cases, patients were treated with intravenous normal saline and ringer lactate as well as rapid-acting insulins. All patients are currently stable on oral hypoglycaemic drugs. Conclusion Cases that support causality between dolutegravir containing regimen and hyperglycaemia were found. These cases were mainly serious. Based on these findings it is recommended that healthcare professionals (HCPs) actively screen all patients for risk factors of hyperglycaemia before DTG initiation. In addition, it is important that HCPs are aware of the possible association between DTG and hyperglycaemia.

Cassava is a major crop in Sub-Saharan Africa, where it is grown primarily by smallholder farmers. Cassava production is constrained by Cassava mosaic disease (CMD), which is caused by a complex of cassava mosaic begomoviruses (CMBs). A previous study showed that SEGS-1 (sequences enhancing geminivirus symptoms), which occurs in the cassava genome and as episomes during viral infection, enhances CMD symptoms and breaks resistance in cassava. We report here that SEGS-1 also increases viral disease severity in Arabidopsis thaliana plants that are co-inoculated with African cassava mosaic virus (ACMV) and SEGS-1 sequences. Viral disease was also enhanced in Arabidopsis plants carrying a SEGS-1 transgene when inoculated with ACMV alone. Unlike cassava, no SEGS-1 episomal DNA was detected in the transgenic Arabidopsis plants during ACMV infection. Studies using Nicotiana tabacum suspension cells showed that co-transfection of SEGS-1 sequences with an ACMV replicon increases viral DNA accumulation in the absence of viral movement. Together, these results demonstrated that SEGS-1 can function in a heterologous host to increase disease severity. Moreover, SEGS-1 is active in a host genomic context, indicating that SEGS-1 episomes are not required for disease enhancement.

Introduction: Retained intraocular foreign body (IOFB) remains an important cause of acquired visual impairment. The visual prognosis following treatments for eyes with retained IOFB was observed to be distinct from other mechanisms of open globe injury due to the specific nature and associated circumstances. This study evaluated the risk behaviors, visual results, and predictive values of Ocular Trauma Score (OTS) in determining visual outcomes in patients with IOFB that were not related to terrorism. Methods: Medical records of patients who underwent surgical interventions between January 2015 and December 2020 were retrospectively reviewed. Results: A total of one hundred and sixty-one patients (162 eyes) were recruited. The patients had a mean (standard deviation) age of 47.6 (14.0) years with working male predominance (93.2%). The majority of patients were injured by activities related to grass trimming (63.4%) and metallic objects were the main materials causing injuries (75.7%). Following treatments, the proportion of eyes having vision worse than 20/400 decreased from 126 eyes (77.8%) to 55 eyes (33.9%) at final visit. Ocular trauma score (OTS) had a high potential prediction for final vision in eyes in OTS categories 4 and 5. However, the discordance of final visual acuity distribution was observed in some subgroups of eyes in OTS categories 1 to 3. Conclusion: This study highlights the significance of IOFB related eye injuries in a tertiary care setting. Decision making on treatments should be carefully considered, particularly in eyes in lower OTS categories, in light of a rise in the proportion of patients who experience improved vision after IOFB removal.

Outside Finland, gender differences in opinions on defence and security policy have been the subject of analysis in Western states of all sizes. This study investigates whether political opinions on key issues of defence policy in Finland are affected by differences in gender and age, and how such differences can be understood in the context of a small-state where there is conscription for men. Gender differences are suggested in relation to both the Finnish social and political context and the gendered division of labour in a society long characterised by a high willingness to defend the country, male conscription, and military non-alignment. Generational differences are proposed to be related to the directions of potential social change in the population. We analyse survey data from the Finnish Advisory Board for Defence Information collected between 2000 and 2020 on four survey items and test whether opinions on (a) willingness to defend Finland, (b) mandatory male conscription, (c) defence spending, and (d) military alignment vary as a function of sex or age. What emerges as statistically significant is that Finnish men will support the military defence of the country if it is attacked, while older cohorts tend to support mandatory male conscription. Defence spending and military non-alignment in the years 2000 to 2020 were mostly inconclusive on gender and generational differences. With illustrative findings from qualitative interview data from women’s preparedness training in voluntary defence, we suggest a contextual explanation of situated socialisation, where self-perceived proximity to defence issues leads to men being more convinced and women being more ambivalent in their views on defence policy.

Buildings are constructed and operated to satisfy human needs and improve quality of life. Good indoor air quality (IAQ) and thermal comfort are prerequisites for human health and well-being. For their provision, buildings often rely on heating, ventilation, and air conditioning (HVAC) systems, which may lead to higher energy consumption. This directly impacts energy efficiency goals and the linked climate change considerations. The balance between energy use, optimum IAQ and thermal comfort calls for scientifically solid and well-established limit values for exposures experienced by building occupants in indoor spaces, including homes, schools, and offices.The present paper aims to appraise limit values for selected indoor pollutants reported in the scientific literature, and to present how they are handled in international and national guidelines and standards. The pollutants include carbon dioxide (CO2), formaldehyde (CH2O), particulate matter (PM), nitrogen dioxide (NO2), carbon monoxide (CO), and radon (Rn). Furthermore, acknowledging the particularly strong impact on energy use from HVAC, ventilation, indoor temperature (T), and relative humidity (RH) are also included, as they relate to both thermal comfort and the possibilities to avoid moisture related problems, such as mould growth and proliferation of house dust mites.Examples of national regulations for these parameters are presented, both in relation to human requirements in buildings and considering aspects related to energy saving. The work is based on the Indoor Environmental Quality (IEQ) guidelines database, which spans across countries and institutions, and aids in taking steps in the direction towards a more uniform guidance for values of indoor parameters. The database is coordinated by the Scientific and Technical Committee (STC) 34, as part of ISIAQ, the International Society of Indoor Air Quality and Climate.

With working life being in the middle of both a demographic and a digital transition, a key question is whether digitalization may counteract the policy goal of delaying work exit. Here, we use survey data from the Norwegian Senior Policy Barometer to investigate the association between how digital tools are experienced and the preference for timing of work exit. We find that, even after controlling for various potential confounders, experiencing digital difficulties at the workplace is correlated with preferring to leave work early. A relevant follow-up question is then which factors increase the likelihood among older workers of experiencing such difficulties. The analyses show that workplace conditions are more important than individual characteristics, suggesting that efforts taken to reduce experiences of digital difficulties at the workplace could be effective in preventing early exits.