Microscopic pathways of transition from low-density to high-density amorphous phase of water.

In recent years, much attention has been devoted to understanding the pathways of phase transition between two equilibrium condensed phases (such as liquids and solids). However, the microscopic pathways of transition involving non-equilibrium, non-diffusive amorphous (glassy) phases still remain poorly understood. In this work, we have employed computer simulations, persistence homology (a tool rooted in topological data analysis), and machine learning to probe the microscopic pathway of pressure-induced non-equilibrium transition between the low- and high-density amorphous (LDA and HDA, respectively) ice phases of the TIP4P/2005 and ST2 water models. Using persistence homology and machine learning, we introduced a new order parameter that unambiguously identifies the LDA- and HDA-like local environments. The LDA phase transitions continuously and collectively into the corresponding HDA phase via a pre-ordered intermediate phase during the isothermal compression. The local order parameter susceptibilities show a maximum near the transition pressure (P*)-suggesting maximum structural heterogeneities near P*. The HDA-like clusters are structurally ramified and spatially delocalized inside the LDA phase near the transition pressure. We also found manifestations of the first-order low-density to high-density liquid transition in the sharpness of the order parameter change during the LDA to HDA transition. We further investigated the (geometrical) structures and topologies of the LDA and HDA ices formed via different protocols and also studied the dependence of the (microscopic) pathway of phase transition on the protocol followed to prepare the initial LDA phase. Finally, the method adopted here to study the phase transition pathways is not restricted to the system under consideration and provides a robust way of probing phase transition pathways involving any two condensed phases at both equilibrium and out-of-equilibrium conditions.

Comparative Study of Spinal, Epidural, and Sequential Combined Spinal Epidural Anesthesia in Geriatric Patients for Transurethral Resection of the Prostate.

BACKGROUND:  Sequential combined spinal epidural anesthesia (CSEA) is probably the greatest advancement in the central neuraxial block in this decade for geriatric patients due to the potential advantages of both spinal and epidural anesthesia. This study was designed to compare the clinical effects of sequential CSEA versus spinal and epidural anesthesia in geriatric patients undergoing transurethral resection of the prostate (TURP). METHODS:  Ninety patients aged 65 to 80 years were randomly allocated into three groups of 30 each. Group A (n=30) patients were administered spinal anesthesia with 2.5 ml of 0.5% hyperbaric bupivacaine, group B (n=30) received epidural anesthesia with 15 ml of 0.5% isobaric bupivacaine, and group C (n=30) received sequential CSEA with 1 ml of 0.5% hyperbaric bupivacaine and 6 ml of 0.5% isobaric bupivacaine given through epidural route to extend the block up to T10. Patients were observed for hemodynamic parameters, sensory and motor block, total dose required to establish the desired level, and patient satisfaction score. RESULTS: None of the patients were excluded in the study. Group A patients reported rapid onset of sensory block (3.08±11.57 minutes) compared to group B (11.57±1.48 minutes), and group C (5.47±1.25 minutes). The onset of motor block was expeditious in group A (8.08±1.0 minutes) compared to group B (20.33±1.86 minutes) and group C (15.53±1.31 minutes). Patients in group B had maximum hemodynamic stability but with delayed onset and were technically more complex than group A. Patients in group C were hemodynamically more stable than group A. They had a faster onset of action with decreased doses of local anesthetic drug required compared to group B. CONCLUSION: Sequential CSEA is a safe, effective, and reliable technique that combines the advantages of both spinal and epidural while minimizing their disadvantages. It has the advantage of stable hemodynamic parameters along with the provision of prolongation analgesia for geriatric patients undergoing TURP surgery.

Continuous-Flow High-Pressure Homogenization of Blueberry Juice Enhances Anthocyanin and Ascorbic Acid Stability during Cold Storage.

Blueberries (Vaccinium section Cyanococcus) have a wealth of bioactive compounds, including anthocyanins and other antioxidants, that offer significant health benefits. Preserving these compounds and maintaining the sensory and nutritional qualities of blueberry products such as juice during cold market storage is critical to meet consumer expectations for nutritious, safe, and minimally processed food. In this study, we compared the effects of two preservation processing techniques, high-temperature short-time (HTST) and continuous flow high-pressure homogenization (CFHPH), on blueberry juice quality during storage at 4 °C. Our findings revealed that inlet temperature (Tin) of CFHPH processing at 4 °C favored anthocyanin retention, whereas Tin at 22 °C favored ascorbic acid retention. After 45 days of storage, CFHPH (300 MPa, 1.5 L/min, 4 °C) juice retained up to 54% more anthocyanins compared to control at 0 day. In contrast, HTST treatment (95 °C, 15 s) initially increased anthocyanin concentrations but led to their subsequent degradation over time, while also significantly degrading ascorbic acid. Furthermore, CFHPH (300 MPa, 4 °C) juice had significantly lower polyphenol oxidase activity (>80% less than control), contributing to the overall quality of the juice. This innovative processing technique has the potential to improve commercial blueberry juice, and help meet the rising demand for healthy and appealing food choices.

The role of RIPK1 in chronic obstructive pulmonary disease.

Necroptosis has emerged as one of the crucial pathological processes involved in the regulation of cell death and inflammation in chronic obstructive pulmonary disease (COPD). Airway epithelial necroptosis is closely linked to COPD pathogenesis. Necroptotic lung cells can release damage-associated molecular patterns (DAMPs) that can initiate a robust inflammatory response. However, the underlying mechanism of necroptosis in COPD is still not clearly understood. Therefore, we aimed to explore the roles and mechanisms of receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-mediated necroptosis in the regulation of inflammatory responses in COPD to provide insights into RIPK1-inhibitor drug discovery efforts and their therapeutic benefits in COPD.

Lindane and Cetrimide lotion poisoning in an adult patient: A case report on an uncommon ingestion.

Lindane induces severe side effects, including fatality, while Cetrimide causes esophageal damage. With no antidotes available, our patient ingested both, requiring prompt gastric lavage and comprehensive treatment.

Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis.

INTRODUCTION: Common mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing the social determinants of mental health may represent a key strategy for effectively preventing CMHCs. However, no systematic reviews have evaluated the effectiveness of these combined intervention strategies for preventing CMHCs. METHODS AND ANALYSIS: This systematic review will include randomised controlled trials (RCTs) focused on the effectiveness of interventions that combine preventive psychological interventions with interventions that address the social determinants of mental health in LMICs. Primary outcome is the frequency of depression, anxiety or PTSD at postintervention as determined by a formal diagnostic tool or any other standardised criteria. We will search Epistemonikos, Cochrane Controlled Trials Register (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL, Global Index Medicus, ClinicalTrials.gov (Ctgov), International Clinical Trials Registry Platform (ICTRP). Two reviewers will independently extract the data and evaluate the risk of bias of included studies using the Cochrane risk of bias tool 2. Random-effects meta-analyses will be performed, and certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This study uses data from published studies; therefore, ethical review is not required. Findings will be presented in a published manuscript. TRIAL REGISTRATION NUMBER: CRD42023451072.

Isolation, Characterization, and Expression Analysis of NAC Transcription Factor from Andrographis paniculata (Burm. f.) Nees and Their Role in Andrographolide Production.

Andrographis paniculata (Burm. f.) Nees is an important medicinal plant known for its bioactive compound andrographolide. NAC transcription factors (NAM, ATAF1/2, and CUC2) play a crucial role in secondary metabolite production, stress responses, and plant development through hormonal signaling. In this study, a putative partial transcript of three NAC family genes (ApNAC83, ApNAC21 22 and ApNAC02) was used to isolate full length genes using RACE. Bioinformatics analyses such as protein structure prediction, cis-acting regulatory elements, and gene ontology analysis were performed. Based on in silico predictions, the diterpenoid profiling of the plant's leaves (five-week-old) and the real-time PCR-based expression analysis of isolated NAC genes under abscisic acid (ABA) treatment were performed. Additionally, the expression analysis of isolated NAC genes under MeJA treatment and transient expression in Nicotiana tabacum was performed. Full-length sequences of three members of the NAC transcription factor family, ApNAC83 (1102 bp), ApNAC21 22 (996 bp), and ApNAC02 (1011 bp), were isolated and subjected to the promoter and gene ontology analysis, which indicated their role in transcriptional regulation, DNA binding, ABA-activated signaling, and stress management. It was observed that ABA treatment leads to a higher accumulation of andrographolide and 14-deoxyandrographolide content, along with the upregulation of ApNAC02 (9.6-fold) and the downregulation of ApNAC83 and ApNAC21 22 in the leaves. With methyl jasmonate treatment, ApNAC21 22 expression decreased, while ApNAC02 increased (1.9-fold), with no significant change being observed in ApNAC83. The transient expression of the isolated NAC genes in a heterologous system (Nicotiana benthamiana) demonstrated their functional transcriptional activity, leading to the upregulation of the NtHMGR gene, which is related to the terpene pathway in tobacco. The expression analysis and heterologous expression of ApNAC21 22 and ApNAC02 indicated their role in andrographolide biosynthesis.

Mining genomic regions associated with agronomic and biochemical traits in quinoa through GWAS.

Quinoa (Chenopodium quinoa Willd.), an Andean crop, is a facultative halophyte food crop recognized globally for its high nutritional value and plasticity to adapt to harsh conditions. We conducted a genome-wide association study on a diverse set of quinoa germplasm accessions. These accessions were evaluated for the following agronomic and biochemical traits: days to 50% flowering (DTF), plant height (PH), panicle length (PL), stem diameter (SD), seed yield (SY), grain diameter (GD), and thousand-grain weight (TGW). These accessions underwent genotyping-by-sequencing using the DNBSeq-G400R platform. Among all evaluated traits, TGW represented maximum broad-sense heritability. Our study revealed average SNP density of ≈ 3.11 SNPs/10 kb for the whole genome, with the lowest and highest on chromosomes Cq1B and Cq9A, respectively. Principal component analysis clustered the quinoa population in three main clusters, one clearly representing lowland Chilean accessions, whereas the other two groups corresponded to germplasm from the highlands of Peru and Bolivia. In our germplasm set, we estimated linkage disequilibrium decay to be ≈ 118.5 kb. Marker-trait analyses revealed major and consistent effect associations for DTF on chromosomes 3A, 4B, 5B, 6A, 7A, 7B and 8B, with phenotypic variance explained (PVE) as high as 19.15%. Nine associations across eight chromosomes were also found for saponin content with 20% PVE by qSPN5A.1. More QTLs were identified for PL and TGW on multiple chromosomal locations. We identified putative candidate genes in the genomic regions associated with DTF and saponin content. The consistent and major-effect genomic associations can be used in fast-tracking quinoa breeding for wider adaptation across marginal environments.

Exploring kidney dialysis costs in the United States: a scoping review.

AIMS: The increasing prevalence of end-stage renal disease (ESRD) in the United States (US) represents a considerable economic burden due to the high cost of dialysis treatment. This review examines data from real-world studies to identify cost drivers and explore areas where dialysis costs could be reduced. METHODS: We identified and synthesized evidence published from 2016-2023 reporting direct dialysis costs in adult US patients from a comprehensive literature search of MEDLINE, Embase, and grey literature sources (e.g. US Renal Data System reports). RESULTS: Most identified data related to Medicare expenditures. Overall Medicare spending in 2020 was $29B for hemodialysis and $2.8B for peritoneal dialysis (PD). Dialysis costs accounted for almost 80% of total Medicare expenditures on ESRD beneficiaries. Private insurance payers consistently pay more for dialysis; for example, per person per month spending by private insurers on outpatient dialysis was estimated at $10,149 compared with Medicare spending of $3,364. Dialysis costs were higher in specific high-risk patient groups (e.g. type 2 diabetes, hepatitis C). Spending on hemodialysis was higher than on PD, but the gap in spending between PD and hemodialysis is closing. Vascular access costs accounted for a substantial proportion of dialysis costs. LIMITATIONS: Insufficient detail in the identified studies, especially related to outpatient costs, limits opportunities to identify key drivers. Differences between the studies in methods of measuring dialysis costs make generalization of these results difficult. CONCLUSIONS: These findings indicate that prevention of or delay in progression to ESRD could have considerable cost savings for Medicare and private payers, particularly in patients with high-risk conditions such as type 2 diabetes. More efficient use of resources is needed, including low-cost medication, to improve clinical outcomes and lower overall costs, especially in high-risk groups. Widening access to PD where it is safe and appropriate may help to reduce dialysis costs.

Previous papers have studied the cost of treating patients who need dialysis for kidney failure. We reviewed these costs and looked for patterns. Dialysis was the most expensive part of treatment for people with kidney disease who have Medicare. Dialysis with private insurance was much more expensive than with Medicare. People with diabetes experienced higher costs of dialysis than those without diabetes. Dialysis in a hospital costs more than dialysis at home. There are opportunities to reduce the cost of dialysis that should be explored further, such as more use of low-cost medication that can prevent the worsening of kidney disease and reduce the need for dialysis.

Genome-Wide Comparative Analysis of Five Amaranthaceae Species Reveals a Large Amount of Repeat Content.

Amaranthus is a genus of C4 dicotyledonous herbaceous plant species that are widely distributed in Asia, Africa, Australia, and Europe and are used as grain, vegetables, forages, and ornamental plants. Amaranth species have gained significant attention nowadays as potential sources of nutritious food and industrial products. In this study, we performed a comparative genome analysis of five amaranth species, namely, Amaranthus hypochondriacus, Amaranthus tuberculatus, Amaranthus hybridus, Amaranthus palmeri, and Amaranthus cruentus. The estimated repeat content ranged from 54.49% to 63.26% and was not correlated with the genome sizes. Out of the predicted repeat classes, the majority of repetitive sequences were Long Terminal Repeat (LTR) elements, which account for about 13.91% to 24.89% of all amaranth genomes. Phylogenetic analysis based on 406 single-copy orthologous genes revealed that A. hypochondriacus is most closely linked to A. hybridus and distantly related to A. cruentus. However, dioecious amaranth species, such as A. tuberculatus and A. palmeri, which belong to the subgenera Amaranthus Acnida, have formed their distinct clade. The comparative analysis of genomic data of amaranth species will be useful to identify and characterize agronomically important genes and their mechanisms of action. This will facilitate genomics-based, evolutionary studies, and breeding strategies to design faster, more precise, and predictable crop improvement programs.

Peptide-triggered IL-12 and IFN-γ mediated immune response in CD4+ T-cells against Leishmania donovani infection.

Leishmania donovani are intracellular, human blood parasites that cause visceral leishmaniasis or kala-azar. Cell-penetrating peptides (CPPs) have been shown to modulate intracellular processes and cargo delivery, whereas host defense peptides (HDPs) promote proliferation of both naïve and antigen activated CD4+ T-cells. We report newly designed tripeptides that were able to trigger proinflammatory cytokine (IL-12 and IFN-γ) secretion by CD4+CD44+ T-cells in response to Leishmania donovani infection. These peptides can be used to induce antigen specific TH1 responses to combat obstacles of cytotoxicity and drug resistance associated with current anti-leishmanial drugs. Furthermore, these peptides can also be used as adjuvants to develop an effective immunoprophylactic approach for immunity restoration against visceral leishmaniasis.

Prevalence and risk factors for chronic pulmonary aspergillosis in chronic obstructive pulmonary disease patients with acute exacerbations.

Chronic obstructive pulmonary disease (COPD) patients often experience acute exacerbations requiring hospitalization. Recently, attention has focused on Aspergillus sensitization in the airways of these COPD patients. This study aimed to assess the prevalence of chronic pulmonary aspergillosis (CPA) in COPD patients with acute exacerbations and identify associated risk factors. A cross-sectional descriptive study was conducted at the Jawaharlal Institute of Postgraduate Medical Education and Research from January 2021 to June 2022. Sixty-one COPD patients presenting with acute exacerbations were included. Demographic details, blood investigations, and sputum examinations were performed for all patients. A high-resolution computed tomography thorax was conducted for eligible patients. The prevalence of CPA among patients with an acute exacerbation of COPD was found to be 9.8%, with chronic cavitary pulmonary aspergillosis being the most common presentation (50%). Among post-tubercular COPD patients, the prevalence of CPA was significantly higher at 22.7%. Hemoptysis (p<0.001) and a previous history of tuberculosis (p=0.008) were associated with Aspergillus sensitization. This study highlights the substantial prevalence of CPA in COPD patients with acute exacerbations, particularly in those with a history of tuberculosis. Early recognition and targeted management of CPA in COPD patients may improve outcomes and reduce hospitalization rates. Further large-scale multi-center studies are needed to validate these findings and comprehensively address the impact of CPA on all COPD patients.

Seafloor primary production in a changing Arctic Ocean.

Phytoplankton and sea ice algae are traditionally considered to be the main primary producers in the Arctic Ocean. In this Perspective, we explore the importance of benthic primary producers (BPPs) encompassing microalgae, macroalgae, and seagrasses, which represent a poorly quantified source of Arctic marine primary production. Despite scarce observations, models predict that BPPs are widespread, colonizing ~3 million km2 of the extensive Arctic coastal and shelf seas. Using a synthesis of published data and a novel model, we estimate that BPPs currently contribute ~77 Tg C y-1 of primary production to the Arctic, equivalent to ~20 to 35% of annual phytoplankton production. Macroalgae contribute ~43 Tg C y-1, seagrasses contribute ~23 Tg C y-1, and microalgae-dominated shelf habitats contribute ~11 to 16 Tg C y-1. Since 2003, the Arctic seafloor area exposed to sunlight has increased by ~47,000 km2 y-1, expanding the realm of BPPs in a warming Arctic. Increased macrophyte abundance and productivity is expected along Arctic coastlines with continued ocean warming and sea ice loss. However, microalgal benthic primary production has increased in only a few shelf regions despite substantial sea ice loss over the past 20 y, as higher solar irradiance in the ice-free ocean is counterbalanced by reduced water transparency. This suggests complex impacts of climate change on Arctic light availability and marine primary production. Despite significant knowledge gaps on Arctic BPPs, their widespread presence and obvious contribution to coastal and shelf ecosystem production call for further investigation and for their inclusion in Arctic ecosystem models and carbon budgets.

Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer.

Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined. This study reveals a novel target of FCF and elucidates its downstream signaling events. FCF significantly impairs mitochondrial respiration and mediates metabolic shift toward glycolysis, thus making cells more vulnerable to glycolysis inhibition. Interestingly, FCF's impact on mitochondrial function persists, even in cells lacking septins. Furthermore, the impaired mitochondrial function leads to the degradation of HIF-1α, facilitated by increased cellular oxygen. FCF also induces AMPK activation, suppresses Erk1/2 phosphorylation, and reduces the expression of HER2, ß-catenin, and PD-L1. Endometrial cancer is characterized by metabolic disorders such as diabetes and aberrant HER2/Ras-Erk1/2/ß-catenin signaling. Thus, FCF may hold promise as a potential therapeutic in endometrial cancer.

Suicidal Behavior in Nepali motion pictures of three decades (1990-2020): A content analysis.

BACKGROUND: Assessment of the depiction of suicidal behavior in motion pictures would reveal the social representation of suicide that would foster suicide prevention in a country. OBJECTIVES: We aimed to assess how suicidality has been depicted in Nepali movies by scrutinizing their contents against the sociodemographic checklist and WHO media guidelines for suicidal reporting. METHODS: This is a narrative quantitative analysis of suicidal behavior portrayals in the Nepali motion pictures that are publicly and freely accessible. RESULTS: Overall, out of the 573 scrutinized movies, we found ten movies consisting of 11 characters (i.e., the prevalence is 1.75%) showing suicidal behavior. The majority of suicidal behavior was seen in males 6 (54.5%), and the majority of attempters were students 3 (27.3%) or homemakers 2 (18.2%). Suicidal behavior was mostly observed in unmarried people 6 (54.5%). Hanging was the most prevalent method (45.5%), and home (36.4%) and public places (36.4%) were equally the most frequent places of attempt. The consequential risk factors for the attempts were found to be marital problems/premarital affairs (50%), followed by unfulfilled demand/conflict (30%). While all 11 items depicted the method and place of the attempt, two also depicted the complete scene of the attempt. One item used language that normalized suicide as a constructive solution to the problem. None of the pictures publicized any mental health messages or educated the public about suicide prevention. CONCLUSIONS: The minimal adherence of the Nepali motion pictures on the depictions of suicidality with WHO media guidelines indicates urgent need to create awareness among the Nepali film fraternity.

New insights into QTNs and potential candidate genes governing rice yield via a multi-model genome-wide association study.

BACKGROUND: Rice (Oryza sativa L.) is one of the globally important staple food crops, and yield-related traits are prerequisites for improved breeding efficiency in rice. Here, we used six different genome-wide association study (GWAS) models for 198 accessions, with 553,229 single nucleotide markers (SNPs) to identify the quantitative trait nucleotides (QTNs) and candidate genes (CGs) governing rice yield. RESULTS: Amongst the 73 different QTNs in total, 24 were co-localized with already reported QTLs or loci in previous mapping studies. We obtained fifteen significant QTNs, pathway analysis revealed 10 potential candidates within 100kb of these QTNs that are predicted to govern plant height, days to flowering, and plot yield in rice. Based on their superior allelic information in 20 elite and 6 inferior genotypes, we found a higher percentage of superior alleles in the elite genotypes in comparison to inferior genotypes. Further, we implemented expression analysis and enrichment analysis enabling the identification of 73 candidate genes and 25 homologues of Arabidopsis, 19 of which might regulate rice yield traits. Of these candidate genes, 40 CGs were found to be enriched in 60 GO terms of the studied traits for instance, positive regulator metabolic process (GO:0010929), intracellular part (GO:0031090), and nucleic acid binding (GO:0090079). Haplotype and phenotypic variation analysis confirmed that LOC_OS09G15770, LOC_OS02G36710 and LOC_OS02G17520 are key candidates associated with rice yield. CONCLUSIONS: Overall, we foresee that the QTNs, putative candidates elucidated in the study could summarize the polygenic regulatory networks controlling rice yield and be useful for breeding high-yielding varieties.

Folded interferometer to measure coherence-polarization matrix.

We present and experimentally demonstrate a new, to the best of our knowledge, technique to quantitatively measure coherence-polarization (BCP) matrix with correlations of only two Stokes fluctuations. The BCP matrix is a square matrix with four elements that involves two-point correlations among orthogonal polarization components. A theoretical framework of the technique is developed, and its viability is demonstrated by a proof of principle experiment. Experimental tests and measurement of the elements of the BCP matrix of statistically stationary beams are demonstrated.

Detecting topological index of randomly scattered V-point singularities using Stokes correlations.

Topological defects in vector fields constitute polarization singularities that have numerous applications in classical and quantum optics. These beams are inhomogeneously polarized and are shown to self-heal under symmetric amplitude perturbations. Polarization singular beams are characterized using a singularity index that can be detected using Stokes polarimetry or other interferometric and diffraction approaches. However, the information about the singularity index is lost when these beams travel through random scattering media; this results in a spatially fluctuating polarization pattern known as polarization speckle. This paper proposes and experimentally demonstrates a new method to detect the topological index of these randomly scattered V-point singularities using higher-order Stokes correlations in a lensless condition. A detailed theoretical basis is developed, and the performance of the technique is demonstrated by retrieving the signature of polarization singularities with Poincaré-Hopf index |η|=1 and |η|=2. We also demonstrate that by studying the intensity-intensity correlations of the polarization speckle, it is possible to differentiate between different vector beams having the same magnitude as the Poincaré-Hopf index.