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Clinical presentation and outcome of tuberculosis in chronic kidney disease stage 4 & 5 from a high TB burden country
Background Diagnosis and management of Tuberculosis (TB) in chronic kidney disease (CKD) is challenging. Our aim is to study clinical presentation and outcome in patients with stage 4 & 5 CKD from a high TB burden country. Methods All patients registered in Provincial TB Centre in tertiary care hospital in Pakistan from May 2016 to June 2020 were included. TB cases tested rifampicin resistant (RR) in GeneXpert were excluded from the study. Patients with CKD stage 4 & 5 were studied for demographics, TB history, clinical feature, diagnoses, treatment success and mortality. CKD stage 4 & 5 were compared with other patients registered at the TB treatment center. Results Out of 828, 259 (31%) had CKD stage 4 & 5. Out of 259, 156 (60%) had extra-pulmonary TB (EPTB). Microbiological diagnosis done in 118 (45.51%), 25% in EPTB and 72.9% in pulmonary TB (PTB). TB culture was positive in 46 (17.8%), Isoniazid resistance 21.7%. Treatment success was 80.7%. PTB was significantly associated with mortality (p = 0.031). In CKD stage 4 & 5 treatment success was significantly lower with high mortality (p = 0.033). Conclusion In CKD stage 4 & 5, EPTB is the most common presentation. Microbiological diagnosis could be achieved in one fourth of EPTB. There is high INH resistance. The treatment success is low with high mortality and PTB is a significant risk factor for mortality.
Tracing the evolution of key traits in dorid nudibranchs
Reconstructing trait evolution is critically important for elucidating the processes generating biodiversity. However, this work is in its infancy in non-model clades for which we lack a basic understanding of their ecology and biology. Here, we compile information about prey preference, chemical acquisition and colour pattern in dorid nudibranchs (Nudibranchia: Doridoidei) and reconstruct their ancestral states using a multi-gene phylogeny to investigate the evolution of these key traits. Our analyses show that the most recent common ancestor (MRCA) of Doridoidei preferred sponge prey from which they sequestered metabolites, and subsequent shifts to different prey types and de novo synthesis of defensive compounds occurred multiple times independently across the phylogeny. Additionally, the MRCA likely exhibited complex colour patterns, including spots or stripes, with uniform morphotypes evolving in most families. Despite the fact that many dorid nudibranchs derive both metabolites and pigments from their prey, we found no evidence of correlated evolution amongst these traits. As part of this work, we present a multi-gene phylogeny for Doridoidei with representatives from 88 genera and 18 families, but there remain issues with poor support across the tree. Nonetheless, for the first time, we explore the evolution of key traits that contributed to the diversification of dorid nudibranchs, highlighting the need for more refined trait data and greater phylogenetic resolution for future work.
Intact sensorimotor rhythm abilities but altered audiovisual integration in cochlear implant users
Perception of rhythm significantly impacts various aspects of daily life, including engaging with music, discerning speech prosody nuances, and coordinating physical activities like walking and sports. Numerous studies in cognitive sciences have highlighted that human rhythmic synchronization is more precise when responding to auditory rhythmic stimuli than to visual ones when the timing cues are identical. However, deaf individuals were shown to display a heightened proficiency in synchronizing their movements with visual timing cues, outperforming hearing controls (HC). Furthermore, it was demonstrated that cochlear implant (CI) users can synchronize their movements with the rhythm of unpitched drum tones. These findings raise an important question: do CI users possess a visual synchronization advantage from their pre-implant deafness, while maintaining auditory synchronization skills comparable to those of HC? Alternatively, does the neural reorganization post-implantation negate the visual synchronization advantage acquired before the implant? This study aims to answer these questions by using a sensorimotor synchronization task to probe multisensory processing abilities in CI users. Specifically, we assessed unimodal and multimodal auditory and visual abilities in CI users compared to HC using a finger tapping synchrony task with four isochronous stimulus conditions: an auditory metronome, a visual metronome, a synchronous presentation of both the auditory and visual metronomes at the same tempo, and an asynchronous presentation of the auditory and visual stimuli at differing tempos. Synchronization to auditory stimuli surpassed synchronization to visual stimuli in both groups. CI users and HC demonstrated similar unisensory synchronization consistency within the visual and auditory conditions. While HC enhanced their consistency in the audio-visual synchronous condition compared to the unisensory visual condition, CI users did not display the same improvement. Furthermore, the interference from incongruent auditory information in the asynchronous condition was comparable in HC and CI users. This study highlights that, although pitch processing is known to be impaired in CI users, our findings suggest that rhythm processing remains relatively spared. As anticipated, CI users demonstrate similar auditory rhythmic synchronization skills to those of HC, in line with existing research. Moreover, we find that, unlike deaf individuals, CI users do not exhibit an advantage in visual rhythmic synchronization, which may be due to the relatively few CI users in the study who had early prolonged pre-implantation deafness. The observed shift in audio-visual integration among CI users suggests that post-deafness or post-implantation reorganization of their auditory cortex may impede the effective integration of temporal auditory stimulation from the implant and visual information.
Correction: Layout optimization of irregular storage areas under class storage strategy based on clustering and multi-bin size packing problem
Selective toxicity of ascorbic acid and hydrogen peroxide on human tenon cells without harming scleral cells in vitro: A possible alternative to non-selective mitomycin C?
Background Glaucoma, a leading cause of blindness, is often driven by elevated intraocular pressure (IOP), which damages the optic nerve. Transscleral filtration surgery reduces IOP but is frequently complicated by excessive wound healing from Tenon fibroblasts (TFs), impeding aqueous humor absorption. Mitomycin C (MMC), used for over 30 years in ophthalmic surgeries, inhibits TF proliferation but carries significant side effects, including hypotony, blebitis, and endophthalmitis, due to its non-selective cytotoxicity. MMC’s inability to entirely prevent fibrosis increases surgical failure risk, often necessitating further interventions like bleb needling. This study investigates whether ascorbic acid (AA) and hydrogen peroxide (H2O2) can selectively target TFs without damaging scleral fibroblasts (SFs) in vitro, using MMC as a benchmark. Methods Primary human TFs and SFs were cultured from patient trabeculectomy tissues. Cells were treated with various concentrations of MMC, AA, or H2O2. Cytotoxic effects were analyzed via live-cell imaging. Immunocytochemistry and Western Blot assessed catalase expression in both cell types and recombinant catalase was used to validate its protective effect against AA- and H2O2-induced cell death. Results Short-term exposure (5 min) to 0.02%–0.04% MMC or long-term exposure to 0.00025%–0.001% MMC caused cytotoxicity in TFs and SFs, with SFs dying significantly earlier. In contrast, AA (6–8 mM) selectively induced cell death in TFs without harming SFs. H2O2 also showed selective cytotoxicity towards TFs. Lower catalase expression in TFs compared to SFs was determined via Western blot and immunocytochemistry, highlighting a mechanism for this selective effect. Recombinant catalase neutralized the cytotoxic effects of AA and H2O2 on TFs. Conclusions Unlike MMC, Ascorbic acid and hydrogen peroxide exhibit selective cytotoxicity towards Tenon fibroblasts, which may provide a safer, more targeted approach for preventing fibrosis in glaucoma surgery. Additional in vivo studies are needed to explore the clinical applicability of these findings.
Trait preferences and lentil varietal adoption in central Ethiopia: A multistakeholder approach
Agricultural technologies, including modern/improved crop varieties, are a critical measure for improving productivity, meeting food security needs, and bridging inequalities. This notwithstanding, adoption of some improved crop varieties in sub-Saharan Africa (SSA) tends to be low, with factors such as limited information, poor access to inputs, and risk averseness cited as reasons for low adoption. Few studies in SSA, and Ethiopia particularly, examine the influence of lentil trait preferences on adoption, and the ones that do only look at farmers’ perspectives who are often treated as a homogenous group. This is despite the importance of lentils as a subsistence and growing market crop, and the fact that diverse factors may determine adoption among farmers. To address these knowledge gaps, this study used a mixed methods approach involving multiple stakeholders (n = 808) to understand gendered patterns in lentil varietal adoption and trait preferences, using an intersectional lens. The findings revealed low adoption rates for improved varieties for women and men alike due to poor disease resistance, and insufficient attention from the breeding programs to preferred processing and consumer traits, as well as the differentiated needs of farmers. Paying attention to these trait needs serves to inform gender-intentional breeding and improve the income generation potential of lentil varieties for diverse farmer groups. As such, we recommend sex-disaggregated data collection from socially differentiated groups and market representatives in order to inform breeding priorities along with the development of multiple varieties that suit different needs.
Potential diagnostic markers and therapeutic targets for DM2 and periodontitis based on bioinformatics analysis
Background Diabetes Mellitus type 2 (DM2) is thought to have a bidirectional relationship with Periodontitis (PD). However, the complex molecular interactions between DM2 and PD remain unclear. This study aimed to explore the shared genes and common signatures of DM2 and PD via bioinformatic analysis. Methods Firstly, using bioinformatic methods to investigate common genes. The series matrix files of GSE6751 for DM and GSE15932 for PD were downloaded from the Gene Expression Omnibus (GEO) database. The data was normalized using the R package, and the limma package was utilized to identify the Differentially Expressed Genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs were performed using the “clusterProfiler” package in the R software. The protein-protein network was constructed to analyze the potential relationship among the proteins. CytoHubba, a plugin for the Cytoscape software, was used to identify the hub genes. The validation datasets selected for DM2 and PD were GSE10334 and GSE7014, respectively. Receiver Operating Characteristic (ROC) curve analysis was performed to obtain the area under the ROC curve. Lipopolysaccharide (LPS) + high glucose-induced DM-related PD was simulated to verify the three hub genes through quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot (WB). Results In total, 44 common DEGs were identified. ITGAM, H2BC21, S100A9 was identified as he hub genes of DM2 and PD, with all of them were up-regulated. In addition, the area under the curve of all three hub genes was more than 0.65. In-vitro experiments revealed that the relative expression of S100A9 was increased after the treatment with LPS + high glucose. Besides, TLR4 and p-NF-κB levels were also improved in model group. Conclusion S100A9 was identified as the hub gene of DM2 and PD. S100A9 could trigger TLR4 signaling way to promote disease development, which can be the potential targets for diagnosis and treatment.
Short-term persistence of foliar insecticides and fungicides in pumpkin plants and their pollinators
To minimize the risk to bees and other beneficial insects, plant protection chemicals are typically applied to pollinator-dependent crop plants when flowers are absent or unopened. However, this approach does not entirely remove the risk of pollinator exposure. Much research has focused on negative effects of systemic insecticides (e.g., seed treatments) on pollinators, but less is known about the level of hazard posed by translocation of non-systemic foliar-applied pesticides to pollen and nectar that bees consume. In this study we assess the frequency and persistence of six foliar-applied pesticides in pumpkin ( Cucurbita pepo ) tissues and in their bee visitors. We analyzed residues of three insecticides (carbaryl, lambda-cyhalothrin, permethrin) and three fungicides (chlorothalonil, quinoxyfen, triflumizole) in pumpkin leaves, pollen, and nectar collected from five farms in the north-central USA, one day before a spray event, and one, three, and seven days after. Bees foraging on pumpkin flowers were collected one day before and one day after spray and screened for the same pesticides. Overall, insecticides were present in 56% of leaf samples. Compared to leaves, fewer pollen (insecticide detected in 16%, fungicide in 16%) and nectar samples (14%, 0%) contained pesticides. We detected one insecticide (carbaryl) in two out of 69 samples of foraging bees, and only in male squash bees (not in bumble or honey bees), which have life history traits that bring them into prolonged close contact with the sprayed crop plants. The persistence of some agrochemicals in leaves, pollen, and nectar up to a week following application merits consideration when managing pollinator-dependent crops. Even pesticides that are traditionally considered contact-based and applied when flowers are unopened can reach pollen and nectar and produce measurable risk to bees.
Covalent inhibition of the SARS-CoV-2 NiRAN domain via an active-site cysteine
Protocol for a Randomized Controlled Trial to Enhance Executive Function via Brief Mindfulness Training in Individuals with Internet Gaming Disorder
Background Internet Gaming Disorder (IGD) is characterized by uncontrolled gaming behavior, leading to emotional distress, neglect of academic or life responsibilities, and damage to interpersonal relationships, all of which have serious negative impacts on individuals and society. IGD has been associated with neuropsychological impairments, especially executive function deficits, and emotional difficulties. Mindfulness interventions have been indicated to improve executive functions to varying degrees in individuals with IGD. The purpose of this study is to investigate whether the three subcomponents of executive function (i.e., inhibition, updating, and shifting) are impaired in individuals with internet gaming disorder, as well as to examine the effectiveness of a brief mindfulness intervention on executive function. Methods A total of 82 individuals diagnosed with IGD and 40 non-addicted gamers will be recruited for this study. These participants will be evenly divided into an intervention group and a control group at a ratio of 1:1. The intervention group will undergo a 7-day mindfulness training program focusing on breathing meditation, while the control group will receive progressive muscle relaxation training. Both groups’ outcomes will be assessed at seven different time points. Primary outcome measures will include electroencephalography (EEG) data (band power, functional connectivity, source localization, and N2/P3 amplitudes), behavioral metrics (response times and accuracy from psychological experimental paradigms), physiological indices (specifically heart rate variability), self-reported measures (game craving and mindfulness levels, executive function performance, and impulsivity emphasizing inhibitory control). Secondary outcome measures will encompass anxiety, stress, positive and negative affect, sleep quality, and other indicators such as demographic information, physical and mental health status, and the Big Five personality traits. Discussion This study aims to explore the efficacy of a brief mindfulness intervention on executive function impairments in IGD individuals and to elucidate its underlying neural mechanisms. It is anticipated that the findings will contribute to more targeted intervention strategies for executive function research, offering novel insights into the treatment of IGD and related cognitive dysfunctions. This study is expected to explore the effectiveness of brief mindfulness intervention on IGD and its underlying brain functional mechanisms, particularly providing more targeted intervention strategies for improving executive functions in this population. Trial registration Trial registration number: ChiCTR2400081509, registered on March 4th 2024. Protocol Version1.0.
Image encryption scheme based on thorp shuffle and pseudo dequeue
The glycolytic enzyme PKM2 regulates inflammatory osteoclastogenesis by modulating STAT3 phosphorylation
Voluntarily wheel running protects doxorubicin-induced kidney injury by inhibiting oxidative stress through mitochondrial function
Background Doxorubicin (DOX) has a broad anticancer spectrum and precise anticancer effects, but its clinical application is limited by severe multiorgan toxicity, among which nephrotoxicity is one of the main adverse reactions. In this study, the protective effect of voluntary wheel running on nephrotoxicity induced by DOX was observed, and its mechanism was initially discussed. Methods Forty male C57BL/6 mice were randomly divided into a control group (CTR), a voluntary wheel running group (EX), a doxorubicin model group (DOX) and a doxorubicin combined with voluntary wheel running group (COM). After 2 weeks of exercise, the mice were sacrificed. Serum creatinine (CREA), urea nitrogen (BUN), uric acid (UA), carbon dioxide combining power (CO2-CP), renal tissue apoptosis, oxidative stress and mitochondrial function indicators were assessed. Results Compared with those in the DOX group, the concentrations of CREA, BUN and UA decreased, the number of TUNEL-positive cells in kidney tissue decreased, the expression of antiapoptotic proteins increased, and the expression of proapoptotic proteins decreased in the COM group. In addition, the COM can reduce the ROS and MDA contents in kidney tissue, reduce peroxide accumulation and alleviate mitochondrial respiratory chain damage caused by DOX. Conclusions Voluntary wheel running can improve the mitochondrial function of renal cells and reduce oxidative stress damage, thus playing a protective role against nephrotoxicity caused by DOX. This study provides a new way to reduce the adverse reactions to chemotherapy in combination with the application of chemical drugs.
Optimizing lipase production by Bacillus subtilis on cheese whey and evaluating its antimicrobial, antibiofilm, anti virulence and biosafety properties
Abstract This study optimized lipase production using cheese whey, biofilm inhibition, and antibacterial efficacy of Bacillus subtilis (DSM 1088)derived lipase against Staphylococcus aureus (ATCC 6538). Peak lipase activity, growth rate, and inhibitory potential were observed at 48 h and 30 °C. Using Plackett-Burman and Central Composite Designs (PBD and CCD), whey, peptone, and agitation speed were identified as significant factors, achieving optimal lipase activity of 1314 U/mL and an inhibitory zone diameter (IZD) of 48 mm against S. aureus. Partial purification through ammonium sulfate precipitation and dialysis increased partial purified lipase (PPL) activity by twofold and fivefold, respectively. PPL exhibited effective bactericidal properties with a minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of 1/8 and 1/16, confirming a bactericidal effect (MIC/MBC ratio ≤ 2). Biofilm inhibition assays demonstrated 95% biofilm reduction at 80 µg/mL PPL, with SEM imaging revealing significant biofilm matrix disruption. Time-kill assays showed concentration-dependent bactericidal action, while inhibition of hemolysin and protease activities (25–100%) indicated reduced S. aureus pathogenicity. Cytotoxicity assays on normal liver cells showed an IC50 > 300 µg/mL, indicating low toxicity. GC/MS analysis of oil waste before degradation identified predominantly oleic acid 3-hydroxypropyl ester and octadecane derivatives, while after degradation, it revealed enriched free fatty acids including myristic, palmitic, linoleic, and oleic acids, which could enhance antimicrobial efficacy. Molecular docking suggested that PPL inhibits essential bacterial enzymes (folic acid synthetase, RNA polymerase, DNA gyrase), potentially disrupting DNA synthesis and promoting cell death. These findings highlight B. subtilis-derived lipase as a promising bio-agent for combating biofilm-associated, drug-resistant pathogens with clinical and industrial applications.
A novel spider toxin as a selective antagonist of the Kv1 subfamily of voltage-gated potassium channels through gating modulation
Gamifying water crisis management: A serious game for drinking water contamination emergency response
This paper presents a serious game that simulates a water crisis triggered by the spill of an unregulated chemical. The game includes five stakeholder roles representing a chemical manufacturer, resident, water treatment plant, environmental agency, and health department, in addition to a facilitator role. The game seeks to provide players with practical experience of the communication and collaboration needed among different stakeholders to prepare for and respond to water contamination emergencies. Initial findings from game sessions with 41 participants suggest that frequent, proactive, and transparent communication can expedite the decision-making process and resolve the crisis more effectively. The game results also reveal challenges in inter-organizational coordination and communication, highlighting the need for training and standardized communication terminologies and protocols.
Double burden of malnutrition among under-five children in Eastern and Southern African countries
YibN, a bona fide interactor of the bacterial YidC insertase with effects on membrane protein insertion and membrane lipid production
Changes in attitudes of mental health care staff surrounding the implementation of peer support work: A qualitative study
Background The integration of Peer Support Workers (PSWs) in mental health settings may encounter resistance due to the attitudes of Mental Health Workers (MHWs). At the same time, PSWs may initiate changes in the attitudes, as well as in the larger institutional culture. This paper addresses the question of which changes happen and how they occur. Methods This work is part of the ImpPeer-Psy5 study, funded by the German Innovation Fund, which examines the nationwide implementation of PSWs in health insurance-funded mental health care. Data were derived from two qualitative sub-studies: QUAL1encompassed 57 problem-centered interviews conducted with PSWs, MHWs working together with PSWs, and service users; QUAL2 consisted of one focus group and five interviews only with MHWs. Qualitative data were analyzed using a modified thematic analysis adapted to a collaborative research approach. Results The main findings included that working with PSWs makes MHWs better integrate lived experience insights into their caregiving, pay more attention to life contexts, advance towards a more appreciative language, use diagnostic categories more flexibly, and show more openness towards their own affectedness. These changes are reported to be mediated by the simple presence of PSWs, their “role model” function for other staff, or more direct forms of feedback and critique. Conclusion Overall, staff attitudes changed as a result of reflexive processes induced by their interactions with PSWs. This poses a dilemma as changes in MHWs and larger institutions are expected to occur prior to the implementation of peer support work to facilitate their integration. Further research is needed to evaluate whether and how staff training can facilitate the implementation of PSWs by targeting MHWs’ attitudes.