Publications in paediatric critical care medicine: Trends from Pakistan.

Objective: To analyse the characteristics of research published from Pakistan on paediatric critical care medicine. METHODS: The exploratory study was conducted at the Aga Khan University, Karachi from July 2021 to March 2022, and comprised a comprehensive search on MedLine, Google Scholar and PakMediNet databases for literature from Pakistan pertaining to paediatric critical care medicine published between January 2010 and December 2021. The search was done using appropriate key words. Conference abstracts and papers authored by paediatric intensivists with unrelated topics were excluded. Data was extracted on a structured spreadsheet, and was subjected to bibliometric analysis. Data was analysed using SPSS 20. RESULTS: Of the 7,514 studies identified, 146(1.94%) were analysed. These were published in 51 journals with a frequency of 13.3 per year. There were 107(73.3%) original articles, 96(65.8%) were published in PubMed-indexed journals, and 35(24%) were published in locally indexed journals. Further, 100(69.4%) papers were published from 5 paediatric intensive care units in Karachi, and 81(56%) were contributed by a single private-sector hospital. The total citation count was 1072, with 2(1.4%) papers receiving >50 citations. There was a linear trend with some skewing and an annual growth rate of >15%. Conclusion: Publications from Pakistan related to paediatric critical care medicine showed positive linear growth. There was a paucity of multicentre studies, randomised controlled trials, and high-impact publications.

Nitric oxide confers cadmium tolerance in fragrant rice by modulating physio-biochemical processes, yield attributes, and grain quality traits.

Cadmium (Cd) stress causes serious disruptions in plant metabolism, physio-biochemical processes, crop yield, and quality characters. Nitric oxide (NO) improves the quality features and nutritional contents of fruit plants. However, how NO confers Cd toxicity in fragrant rice plants, is sparse. Hence, the present study investigated the effects of 50 µM NO donor sodium nitroprusside (SNP) on physio-biochemical processes, plant growth attributes, grain yield, and quality traits of fragrant rice under Cd stress (100 mg kg-1 soil). The results revealed that Cd stress diminished rice plant growth, impaired photosynthetic apparatus and antioxidant defense system, and deteriorated the grain quality traits. However, foliar application of SNP mitigated Cd stress by improving plant growth and gas exchange attributes. Higher electrolyte leakage (EL) was accompanied with elevated levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) under Cd stress; however, exogenous application of SNP reduced them. The activities and relative expression levels of enzymatic antioxidants; superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) and non-enzymatic antioxidants, glutathione (GSH) contents were reduced by Cd stress, while SNP application regulated their activity and transcript abundances. SNP application improved fragrant rice grain yield and 2-acetyl-1-pyrroline content by 57.68 % and 75.54 % respectively, which is concomitant with higher biomass accumulation, photosynthetic efficiency, photosynthetic pigment contents, and an improved antioxidant defense system. Collectively, our results concluded that SNP application regulated the fragrant rice plant physio-biochemical processes, yield traits and grain quality characters under Cd-affected soil.

Safety huddles in paediatric intensive care unit: Implementation and staff perception in a resource limited setting.

Objective: To evaluate the perception, knowledge, empowerment and comfort level of critical care staff in relation to the implementation of safety huddles in paediatric intensive care unit of a tertiary care hospital. METHODS: The descriptive cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from September 2020 to February 2021, and comprised physicians, nurses and paramedics who were part of the safety huddle. Staff perception regarding this activity was evaluated using open-ended questions that were scored on a Likert scale. Data was analysed using STATA 15. RESULTS: Of the 50 participants, 27(54%) were females and 23(46%) were males. Overall, 26(52%) subjects were aged 20-30 years age, while 24(48%) were aged 31-50 years. Of the total, 37(74%) subjects strongly agreed that safety huddle had been routinely held in the unit since initiation; 42(84%) felt comfortable sharing their concerns about patient safety; and 37(74%) considered the huddles worthwhile. Majority 42(84%) felt more empowered through huddle participation. Moreover, 45(90%) participants strongly agreed that daily huddle helped them in becoming clearer about their responsibilities. For safety risk assessment, 41(82%) participants acknowledged that safety risks had been assessed and modified in routine huddles. Conclusion: Safety huddle was found to be a powerful tool to create a safe environment in a paediatric intensive care unit where all team members can speak up freely about patient safety.

Transcriptional cascades in the regulation of 2-AP biosynthesis under Zn supply in fragrant rice.

Transcription factors (TFs) regulate gene expression to control certain genetic programs, such as growth and development, phytohormone regulation, and environmental stresses. 2-acetyl-1-pyrroline (2-AP) is the key element involved in aroma biosynthesis pathway, and the application of micronutrients can increase the 2-AP levels. However, little is known about the micronutrient-induced TFs involved in 2-AP biosynthesis. Here, we identify a number of TF families in two fragrant rice varieties, "Meixiangzhan-2" (M) and "Xiangyaxiangzhan" (X), in response to Zinc (Zn) application through transcriptomic analysis. A total of ~678 TFs were identified and grouped into 26 TF families, each of which was found to be involved in numerous signaling pathways. The WRKY TF family was found to be the most abundant, followed by bHLH and MYB. Furthermore, members of the WRKY, bHLH, MYB, ERF, HSF, MADS-box, NFY, and AP2 TF families were significantly upregulated and may be involved in the transcriptional regulation of aroma biosynthesis. In brief, this study enhances our understanding of the molecular mechanism of 2-AP biosynthesis and highlights the key TFs potentially involved in the production of aroma in fragrant rice.

Genome wide analysis of DWARF27 genes in soybean and functional characterization of GmD27c reveals eminent role of strigolactones in rhizobia interaction and nodulation in Glycine max.

BACKGROUND: Strigolactones (SLs) are newly identified hormones and their biosynthesis is stimulated under phosphate deprivation and accomplished by the action of several enzymes, including the beta-carotene isomerase DWARF27 (D27). Expression of D27 is well renowned to respond to phosphate insufficiency. However, the identification and functional analysis of the carotenoid isomerase D27 genes are not elucidated in soybean. METHODS AND RESULTS: A total of six D27 genes were identified in the soybean genome and designated on the basis of chromosomal localization. According to the findings, these genes were irregularly distributed on chromosomes, and segmental repetition led to the expansion of the soybean GmD27 gene family. Based on a neighbor-joining phylogenetic tree, the predicted D27 proteins of soybean were divided into three clades. Based on RNA seq data analysis, GmD27 genes were differently expressed in various tissues but GmD27c was the highest. Therefore, GmD27c was chosen for the additional functional study due to its rather obvious transcription in nodulation and roots. RT-qPCR results showed that GmD27c was highly expressed in different nodule stages and in response to rhizobia infection. Functional characterization of GmD27c revealed that overexpression of GmD27c led to higher nodule number, while GmD27c knockdown caused fewer nodules compared to GUS control. Furthermore, GmD27c overexpressed and knockdown lines oppositely regulated the expression of numerous nodulation genes, which are vital for the development of nodules. CONCLUSION: This study not only discovered that SL biosynthesis and signaling pathway genes are conserved, but it also revealed that SL biosynthesis gene GmD27c and legume rhizobia have close interactions in controlling plant nodule number.

Molecular cloning, characterization and expression analysis of two 12-oxophytodienoate reductases (NtOPR1 and NtOPR2) from Nicotiana tabacum.

BACKGROUND: 12-oxophytodienoic acid (OPDA) is a signaling molecule involved in defense and stress responses in plants. 12-oxophytodienoate reductase (OPR) is involved in the biosynthesis of jasmonic acid and trigger the conversion of OPDA into 3-oxo-2(2'[Z]-pentenyl)-cyclopentane-1-octanoic acid (OPC-8:0). METHODS AND RESULTS: Sequence analysis revealed that Nicotiana tabacum 12-oxophytodienoate reductase 1 (OPR1) and OPR2 encoded polypeptides of 375 and 349 amino acids with molecular masses of 41.67 and 39.04 kilodaltons (kDa), respectively, while the deduced protein sequences of NtOPR1 and NtOPR2 showed high homology with other 12-oxophytodienoate reductases. BLAST (Basic local alignment search tool) analysis revealed that both NtOPRs belong to the family of Old Yellow Enzymes (OYE), and analysis of genomic DNA structure indicated that both genes include 5 exons and 4 introns. Phylogenetic analysis using MEGA X showed that NtOPR1 and NtOPR2 shared a close evolutionary relationship with Nicotiana attenuata 12-oxophytodienoate reductases. In silico analysis of subcellular localization indicated the probable locations of NtOPR1 and NtOPR2 to be the cytoplasm and the peroxisome, respectively. Tissue-specific expression assays via qRT-PCR revealed that NtOPR1 and NtOPR2 genes were highly expressed in Nicotiana tabacum roots, temperately expressed in leaves and flowers, while low expression was observed in stem tissue. CONCLUSIONS: Presently, two 12-oxophytodienoate reductase genes (NtOPR1 and NtOPR2) were cloned and comprehensively characterized. Our findings provide comprehensive analyses that may guide future deep molecular studies of 12-oxophytodienoate reductases in Nicotiana tabacum.

Comprehensive Detoxification Mechanism Assessment of Red Imported Fire Ant (Solenopsis invicta) against Indoxacarb.

The red imported fire ant (Solenopsis invicta) is one of the deadliest invasive ant species that threatens the world by disrupting biodiversity, important functions within a natural ecosystem, and community structure. They are responsible for huge economic losses in the infested countries every year. Synthetic insecticides, especially indoxacarb, have been broadly used to control S. invicta for many years. However, the biochemical response of S. invicta to indoxacarb remains largely undiscovered. Here, we used the sublethal doses of indoxacarb on the S. invicta collected from the eight different cities of Southern China. The alteration in the transcriptome profile of S. invicta following sublethal dosages of indoxacarb was characterized using high-throughput RNA-seq technology. We created 2 libraries, with 50.93 million and 47.44 million clean reads for indoxacarb treatment and control, respectively. A total of 2018 unigenes were regulated after insecticide treatment. Results indicated that a total of 158 differentially expressed genes (DEGs) were identified in the indoxacarb-treated group, of which 100 were significantly upregulated and 58 were downregulated, mostly belonging to the detoxification enzymes, such as AChE, CarE, and GSTs. Furthermore, results showed that most of these DEGs were found in several KEGG pathways, including steroid biosynthesis, other drug metabolizing enzymes, glycerolipid metabolism, chemical carcinogenesis, drug-metabolizing cytochrome P450, glutathione metabolism, glycerophospholipid metabolism, glycolysis/gluconeogenesis, and metabolism of xenobiotics. Together, these findings indicated that indoxacarb causes significant alteration in the transcriptome profile and signaling pathways of S. invicta, providing a foundation for further molecular inquiry.

GmMAX2-D14 and -KAI interaction-mediated SL and KAR signaling play essential roles in soybean root nodulation.

Despite of important functions of strigolactones (SLs) and karrikins (KARs) in plant development, plant-parasite and plant-fungi interactions, their roles in soybean-rhizobia interaction remain elusive. SL/KAR signaling genes GmMAX2a, GmD14s, and GmKAIs are activated by rhizobia infection. GmMAX2a restored atmax2 root hair defects and soybean root hairs were changed in GmMAX2a overexpression (GmMAX2a-OE) or knockdown (GmMAX2a-KD) mutants. GmMAX2a-KD gave fewer, whereas GmMAX2a-OE produced more nodules than GUS hairy roots. Mutation of GmMAX2a in its KD or OE transgenic hairy roots affected the rhizobia infection-induced increases in early nodulation gene expression. Both mutant hairy roots also displayed the altered auxin, jasmonate and abscisic acid levels, as further verified by transcriptomic analyses of their synthetic genes. Overexpression of an auxin synthetic gene GmYUC2a also affected SL and KAR signaling genes. GmMAX2a physically interacted with SL/KAR receptors GmD14s, GmKAIs, and GmD14Ls with different binding affinities, depending on variations in the critical amino acids, forming active D14/KAI-SCFMAX2 complexes. The knockdown mutant roots of the nodule-specifically expressing GmKAIs and GmD14Ls gave fewer nodules, with altered expression of several early nodulation genes. The expression levels of GmKAIs, and GmD14Ls were markedly changed in GmMAX2a mutant roots, so did their target repressor genes GmD53s and GmSMAX1s. Thus, SL and KAR signaling were involved in soybean-rhizobia interaction and nodulation partly through interactions with hormones, and this may explain the different effects of MXA2 orthologs on legume determinate and indeterminate nodulation. The study provides fresh insights into the roles of GmMAX2-mediated SL/KAR signaling in soybean root hair and nodule formation.

Partitioned Stator Switched Flux Machine: Novel Winding Configurations.

Torque density is one of the major limiting factors in machine design. In this paper, we propose the hybrid excited partitioned stator switched flux machine3 (HE-PSSFM3). In HE-PSSFM3, armature winding is positioned on the outer stator whereas the permanent magnet (PM) and field winding are placed at the inner stator, while the rotor is free from excitation sources and armature winding. Moreover, concentrated field winding is replaced by toroidal winding. The power splitting ratio between two stators/rotor pole combinations is analytically optimized and are validated through genetic algorithm (GA) in order to enhance average torque and flux regulation capability. The electromagnetic characteristics of the improved and initial design are evaluated and compared with existing designs, i.e., HE-PSSFM1 and HE-PSSFM2. The proposed HE-PSSFM3 has achieved high average torque, i.e., 2.0015 Nm, at same armature and field current densities of 5 A/mm2. The results show that the average torques of the proposed design are 35% and 15% greater than HE-PSSFM1 and HE-PSSFM2, respectively. Furthermore, the analysis of various parameters such as flux linkage, flux regulation, electromagnetic performances, cogging torque, back EMF, electromagnetic torque, and torque ripples are investigated using two dimensional (2D) finite element analysis (FEA). Moreover, the simulation results of the proposed design are validated through GA and analytical modeling.

A Multiscale Denoising Framework Using Detection Theory with Application to Images from CMOS/CCD Sensors.

Output from imaging sensors based on CMOS and CCD devices is prone to noise due to inherent electronic fluctuations and low photon count. The resulting noise in the acquired image could be effectively modelled as signal-dependent Poisson noise or as a mixture of Poisson and Gaussian noise. To that end, we propose a generalized framework based on detection theory and hypothesis testing coupled with the variance stability transformation (VST) for Poisson or Poisson⁻Gaussian denoising. VST transforms signal-dependent Poisson noise to a signal independent Gaussian noise with stable variance. Subsequently, multiscale transforms are employed on the noisy image to segregate signal and noise into separate coefficients. That facilitates the application of local binary hypothesis testing on multiple scales using empirical distribution function (EDF) for the purpose of detection and removal of noise. We demonstrate the effectiveness of the proposed framework with different multiscale transforms and on a wide variety of input datasets.

Strigolactones promote rhizobia interaction and increase nodulation in soybean (Glycine max).

Strigolactones (SLs) play an important role in controlling root growth, shoot branching, and plant-symbionts interaction. Despite the importance, the components of SL biosynthesis and signaling have not been unequivocally explored in soybean. Here we identified the putative components of SL synthesis enzymes GmMAX1a and GmMAX4a with tissue expression patterns and were apparently regulated by rhizobia infection and changed during nodule development. GmMAX1a and GmMAX4a were further characterized in soybean nodulation with knockdown transgenic hairy roots. GmMAX1a and GmMAX4a knockdown lines exhibit decreased nodule number and expression levels of several nodulation genes required for nodule development. Hormone analysis showed that GmMAX1a and GmMAX4a knockdown hairy roots had increased physiological level of ABA and JA but significantly decreased auxin content. This study not only revealed the conservation of SL biosynthesis but also showed close interactions between SL and other hormone signaling in controlling plant development and legume-rhizobia interaction.

Functional characterization of soybean strigolactone biosynthesis and signaling genes in Arabidopsis MAX mutants and GmMAX3 in soybean nodulation.

BACKGROUND: Strigolactones (SLs) play important roles in controlling root growth, shoot branching, and plant-symbionts interaction. Despite the importance, the components of SL biosynthesis and signaling have not been unequivocally explored in soybean. RESULTS: Here we identified the putative components of SL synthetic enzymes and signaling proteins in soybean genome. Soybean genome contains conserved MORE AXILLARY BRANCHING (MAX) orthologs, GmMAX1s, GmMAX2s, GmMAX3s, and GmMAX4s. The tissue expression patterns are coincident with SL synthesis in roots and signaling in other tissues under normal conditions. GmMAX1a, GmMAX2a, GmMAX3b, and GmMAX4a expression in their Arabidopsis orthologs' mutants not only restored most characteristic phenotypes, such as shoot branching and shoot height, leaf shape, primary root length, and root hair growth, but also restored the significantly changed hormone contents, such as reduced JA and ABA contents in all mutant leaves, but increased auxin levels in atmax1, atmax3 and atmax4 mutants. Overexpression of these GmMAXs also altered the hormone contents in wild-type Arabidopsis. GmMAX3b was further characterized in soybean nodulation with overexpression and knockdown transgenic hairy roots. GmMAX3b overexpression (GmMAX3b-OE) lines exhibited increased nodule number while GmMAX3b knockdown (GmMAX3b-KD) decreased the nodule number in transgenic hairy roots. The expression levels of several key nodulation genes were also altered in GmMAX3b transgenic hairy roots. GmMAX3b overexpression hairy roots had reduced ABA, but increased JA levels, with no significantly changed auxin content, while the contrast changes were observed in GmMAX3b-KD lines. Global gene expression in GmMAX3b-OE or GmMAX3b-KD hairy roots also revealed that altered expression of GmMAX3b in soybean hairy roots changed several subsets of genes involved in hormone biosynthesis and signaling and transcriptional regulation of nodulation processes. CONCLUSIONS: This study not only revealed the conservation of SL biosynthesis and signaling in soybean, but also showed possible interactions between SL and other hormone synthesis and signaling during controlling plant development and soybean nodulation. GmMAX3b-mediated SL biosynthesis and signaling may be involved in soybean nodulation by affecting both root hair formation and its interaction with rhizobia.

Multi-scale pixel-based image fusion using multivariate empirical mode decomposition.

A novel scheme to perform the fusion of multiple images using the multivariate empirical mode decomposition (MEMD) algorithm is proposed. Standard multi-scale fusion techniques make a priori assumptions regarding input data, whereas standard univariate empirical mode decomposition (EMD)-based fusion techniques suffer from inherent mode mixing and mode misalignment issues, characterized respectively by either a single intrinsic mode function (IMF) containing multiple scales or the same indexed IMFs corresponding to multiple input images carrying different frequency information. We show that MEMD overcomes these problems by being fully data adaptive and by aligning common frequency scales from multiple channels, thus enabling their comparison at a pixel level and subsequent fusion at multiple data scales. We then demonstrate the potential of the proposed scheme on a large dataset of real-world multi-exposure and multi-focus images and compare the results against those obtained from standard fusion algorithms, including the principal component analysis (PCA), discrete wavelet transform (DWT) and non-subsampled contourlet transform (NCT). A variety of image fusion quality measures are employed for the objective evaluation of the proposed method. We also report the results of a hypothesis testing approach on our large image dataset to identify statistically-significant performance differences.

Short Caco-2 model for evaluation of drug permeability: A sodium valerate-assisted approach.

The human colorectal adenocarcinoma cell line Caco-2, widely used for studying intestinal drug permeability, is typically grown on permeable filter supports and matures in 21 days with frequent media changes. The process is labor-intensive, prone to contamination, and has low throughput, contributing to the overall high utilization cost. Efforts to establish a low-cost, high-throughput, and short-duration model have encountered obstacles, such as weaker tight junctions causing monolayer leaks, incomplete differentiation resulting in low transporter expression, intricate and challenging protocols, and cytotoxicity, limiting the usability. Hence, this study aimed to develop a low-cost, efficient, and short-duration model by addressing the aforementioned concerns by customizing the media and finding a safe differentiation inducer. We generated a new rapid model using sodium valerate, which demonstrated sufficient transporter activity, improved monolayer integrity, and higher levels of differentiation markers than the 21-day model. Furthermore, this model exhibited consistent and reliable results when used to evaluate drug permeability over multiple days of repeated use. This study demonstrates the potential of a sodium valerate-assisted abbreviated model for drug permeability assessment with economic and practical advantages.

Cobalt-doped zinc oxide based memristors with nociceptor characteristics for bio-inspired technology.

Neuromorphic computing is a new field of information technology, which is inspired by the biomimetic properties of the memristor as an electronic synapse and neuron. If there are electronic receptors that can transmit exterior impulses to the internal nervous system, then the use of memristors can be expanded to artificial nerves. In this study, a layer type memristor is used to build an artificial nociceptor in a very feasible and straightforward manner. An artificial nociceptor is demonstrated here through the fabrication and characterization of a cobalt-doped zinc oxide (CZO)/Au based memristor. In order to increase threshold switching performance, the surface effects of the CZO layer are eliminated by adding cobalt cobalt-doped zinc oxide (CZO) layer between the P++-Si and Au electrodes. Allodynia, hyperalgesia, threshold, and relaxation are the four distinct nociceptive behaviours that the device displays based on the strength, rate of relapse, and duration of the external stimuli. The electrons that are trapped in or released from the CZO layer's traps are responsible for these nociceptive behaviours. A multipurpose nociceptor performance is produced by this type of CZO-based device, which is crucial for artificial intelligence system applications such as neural integrated devices with nanometer-sized characteristics.

Reliability and performance of the IRRAflow® system for intracranial lavage and evacuation of hematomas-A technical note.

BACKGROUND: Intraventricular hemorrhage (IVH) is a severe condition with poor outcomes and high mortality. IRRAflow® (IRRAS AB) is a new technology introduced to accelerate IVH clearance by minimally invasive wash-out. The IRRAflow® system performs active and controlled intracranial irrigation and aspiration with physiological saline, while simultaneously monitoring and maintaining a stable intracranial pressure (ICP). We addressed important aspects of the device implementation and intracranial lavage. METHOD: To allow versatile investigation of multiple device parameters, we designed an ex vivo lab setup. We evaluated 1) compatibility between the IRRAflow® catheter and the Silverline f10 bolt (Spiegelberg), 2) the physiological and hydrodynamic effects of varying the IRRAflow® settings, 3) the accuracy of the IRRAflow® injection volumes, and 4) the reliability of the internal ICP monitor of the IRRAflow®. RESULTS: The IRRAflow® catheter was not compatible with Silverline bolt fixation, which was associated with leakage and obstruction. Design space exploration of IRRAflow® settings revealed that appropriate settings included irrigation rate 20 ml/h with a drainage bag height at 0 cm, irrigation rate 90 ml/h with a drainage bag height at 19 cm and irrigation rate 180 ml/h with a drainage bag height at 29 cm. We found the injection volume performed by the IRRAflow® to be stable and reliable, while the internal ICP monitor was compromised in several ways. We observed a significant mean drift difference of 3.16 mmHg (variance 0.4, p = 0.05) over a 24-hour test period with a mean 24-hour drift of 3.66 mmHg (variance 0.28) in the pressures measured by the IRRAflow® compared to 0.5 mmHg (variance 1.12) in the Raumedic measured pressures. CONCLUSION: Bolting of the IRRAflow® catheter using the Medtronic Silverline® bolt is not recommendable. Increased irrigation rates are recommendable followed by a decrease in drainage bag level. ICP measurement using the IRRAflow® device was unreliable and should be accompanied by a control ICP monitor device in clinical settings.

Data-driven nonstationary signal decomposition approaches: a comparative analysis.

Signal decomposition (SD) approaches aim to decompose non-stationary signals into their constituent amplitude- and frequency-modulated components. This represents an important preprocessing step in many practical signal processing pipelines, providing useful knowledge and insight into the data and relevant underlying system(s) while also facilitating tasks such as noise or artefact removal and feature extraction. The popular SD methods are mostly data-driven, striving to obtain inherent well-behaved signal components without making many prior assumptions on input data. Among those methods include empirical mode decomposition and variants, variational mode decomposition and variants, synchrosqueezed transform and variants and sliding singular spectrum analysis. With the increasing popularity and utility of these methods in wide-ranging applications, it is imperative to gain a better understanding and insight into the operation of these algorithms, evaluate their accuracy with and without noise in input data and gauge their sensitivity against algorithmic parameter changes. In this work, we achieve those tasks through extensive experiments involving carefully designed synthetic and real-life signals. Based on our experimental observations, we comment on the pros and cons of the considered SD algorithms as well as highlighting the best practices, in terms of parameter selection, for the their successful operation. The SD algorithms for both single- and multi-channel (multivariate) data fall within the scope of our work. For multivariate signals, we evaluate the performance of the popular algorithms in terms of fulfilling the mode-alignment property, especially in the presence of noise.

Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions.

Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected. But, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. In this study, we assessed the consequences of daily DEHP ingestion (2 and 20 mg/kg diets) in male mice for at least 100 days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. We found the marked depressive behaviors and reduced learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress were increased in plasma and brain tissues. Long-term DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The reduced glutamatergic neurotransmission activity caused by DEHP ingestion was demonstrated using an electrophysiological method. This study revealed that long-term exposure to DEHP is hazardous and can cause neurobehavioral disorders, even at daily exposure levels.

Bioengineering Techniques to Improve Nitrogen Transformation and Utilization: Implications for Nitrogen Use Efficiency and Future Sustainable Crop Production.

Nitrogen (N) is crucial for plant growth and development, especially in physiological and biochemical processes such as component of different proteins, enzymes, nucleic acids, and plant growth regulators. Six categories, such as transporters, nitrate absorption, signal molecules, amino acid biosynthesis, transcription factors, and miscellaneous genes, broadly encompass the genes regulating NUE in various cereal crops. Herein, we outline detailed research on bioengineering modifications of N metabolism to improve the different crop yields and biomass. We emphasize effective and precise molecular approaches and technologies, including N transporters, transgenics, omics, etc., which are opening up fascinating opportunities for a complete analysis of the molecular elements that contribute to NUE. Moreover, the detection of various types of N compounds and associated signaling pathways within plant organs have been discussed. Finally, we highlight the broader impacts of increasing NUE in crops, crucial for better agricultural yield and in the greater context of global climate change.

Intraventricular Lavage vs External Ventricular Drainage for Intraventricular Hemorrhage: A Randomized Clinical Trial.

Importance: Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use. Objective: To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage. Design, Setting, and Participants: This single-blinded, controlled, investigator-initiated 1:1 randomized clinical trial was conducted at Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022, to November 24, 2022. Follow-up duration was 90 days. The trial was set to include 58 patients with intraventricular hemorrhage. Prespecified interim analysis was performed for the first 20 participants. Data were analyzed from February to April 2023. Interventions: Participants were randomized to receive either intraventricular lavage or standard drainage. Main Outcomes and Measures: The main outcome was risk of catheter occlusions. Additional safety outcomes were catheter-related infections and procedure time, length of stay at the intensive care unit, duration of treatment, and 30-day mortality. The main outcome of the prespecified interim analysis was risk of severe adverse events. Efficacy outcomes were hematoma clearance, functional outcome, overall survival, and shunt dependency. Results: A total of 21 participants (median [IQR] age, 67 [59-82] years; 14 [66%] male) were enrolled, with 11 participants randomized to intraventricular lavage and 10 participants randomized to standard drainage; 20 participants (95%) had secondary intraventricular hemorrhage. The median (IQR) Graeb score was 9 (5-11), and the median (IQR) Glasgow Coma Scale score was 6.5 (4-8). The study was terminated early due to a significantly increased risk of severe adverse events associated with intraventricular lavage at interim analysis (risk difference for control vs intervention, 0.43; 95% CI, 0.06-0.81; P = .04; incidence rate ratio for control vs intervention, 6.0; 95% CI, 1.38-26.1; P = .01). The rate of catheter occlusion was higher for intraventricular lavage compared with drainage (6 of 16 patients [38%] vs 2 of 13 patients [7%]; hazard ratio, 4.4 [95% CI, 0.6-31.2]; P = .14), which met the prespecified α = .20 level. Median (IQR) procedure time for catheter placement was 53.5 (33-75) minutes for intraventricular lavage vs 12 (4-20) minutes for control (P < .001). Conclusions and Relevance: This randomized clinical trial of intraventricular lavage vs standard drainage found that intraventricular lavage was encumbered with a significantly increased number of severe adverse events. Caution is recommended when using the device to ensure patient safety. Trial Registration: ClinicalTrials.gov Identifier: NCT05204849.