Genome-wide expression analysis of novel heat-responsive microRNAs and their targets in contrasting wheat genotypes at reproductive stage under terminal heat stress.

Introduction: Heat stress at terminal stage of wheat is critical and leads to huge yield losses worldwide. microRNAs (miRNAs) play significant regulatory roles in gene expression associated with abiotic and biotic stress at the post-transcriptional level. Methods: In the present study, we carried out a comparative analysis of miRNAs and their targets in flag leaves as well as developing seeds of heat tolerant (RAJ3765) and heat susceptible (HUW510) wheat genotypes under heat stress and normal conditions using small RNA and degradome sequencing. Results and discussion: A total of 84 conserved miRNAs belonging to 35 miRNA families and 93 novel miRNAs were identified in the 8 libraries. Tae-miR9672a-3p, tae-miR9774, tae-miR9669-5p, and tae-miR5048-5p showed the highest expression under heat stress. Tae-miR9775, tae-miR9662b-3p, tae-miR1120a, tae-miR5084, tae-miR1122a, tae-miR5085, tae-miR1118, tae-miR1130a, tae-miR9678-3p, tae-miR7757-5p, tae-miR9668-5p, tae-miR5050, tae-miR9652-5p, and tae-miR9679-5p were expressed only in the tolerant genotype, indicating their role in heat tolerance. Comparison between heat-treated and control groups revealed that 146 known and 57 novel miRNAs were differentially expressed in the various tissues. Eight degradome libraries sequence identified 457 targets of the differentially expressed miRNAs. Functional analysis of the targets indicated their involvement in photosynthesis, spliceosome, biosynthesis of nucleotide sugars and protein processing in the endoplasmic reticulum, arginine and proline metabolism and endocytosis. Conclusion: This study increases the number of identified and novel miRNAs along with their roles involved in heat stress response in contrasting genotypes at two developing stages of wheat.

Structure of a novel form of phosphopantetheine adenylyltransferase from Klebsiella pneumoniae at 2.59 Å resolution.

Phosphopantetheine adenylyltransferase (EC. 2.7.7.3, PPAT) catalyzes the penultimate step of the multistep reaction in the coenzyme A (CoA) biosynthesis pathway. In this step, an adenylyl group from adenosine triphosphate (ATP) is transferred to 4'-phosphopantetheine (PNS) yielding 3'-dephospho-coenzyme A (dpCoA) and pyrophosphate (PPi). PPAT from strain C3 of Klebsiella pneumoniae (KpPPAT) was cloned, expressed and purified. It was crystallized using 0.1 M HEPES buffer and PEG10000 at pH 7.5. The crystals belonged to tetragonal space group P41212 with cell dimensions of a = b = 72.82 Å and c = 200.37 Å. The structure was determined using the molecular replacement method and refined to values of 0.208 and 0.255 for Rcryst and Rfree factors, respectively. The structure determination showed the presence of three crystallographically independent molecules A, B and C in the asymmetric unit. The molecules A and B are observed in the form of a dimer in the asymmetric unit while molecule C belongs to the second dimer whose partner is related by crystallographic twofold symmetry. The polypeptide chain of KpPPAT folds into a ß/α structure. The conformations of the side chains of several residues in the substrate binding site in KpPPAT are significantly different from those reported in other PPATs. As a result, the modes of binding of substrates, phosphopantetheine (PNS) and adenosine triphosphate (ATP) differ considerably. The binding studies using fluorescence spectroscopy indicated a KD value of 3.45 × 10-4 M for ATP which is significantly lower than the corresponding values reported for PPAT from other species.

A simulation-based approach to target Zika virus RNA-dependent RNA polymerase with marine compounds for antiviral development.

Despite significant efforts, currently, there is no particular drug available to treat Zika virus (ZIKV) infection, highlighting the urgent need for effective therapeutic interventions. To identify putative inhibitors of the ZIKV RdRp protein's RNA binding function, the present study applied an extensive in-silico drug discovery methodology. The initial phase involved virtual screening using Lipinski's rule of five as a filter, ensuring the selection of molecules with favorable pharmacokinetic properties. This process yielded 238 compounds with promising docking scores, ranging from -6.0 to -7.48 kcal/mol, indicative of their potential binding affinity to the ZIKV RdRp. To refine the selection, these compounds underwent a re-docking process, comparing their binding energies with a reference molecule known for its inhibitory action against RdRp. Remarkably, five compounds, labeled CMNPD30598, CMNPD27464, CMNPD25971, CMNPD27444, and CMNPD16599, demonstrated superior re-docking energies compared to the reference, suggesting a stronger interaction with the RdRp allosteric site. Subsequent molecular dynamics (MD) simulations provided insights into the stability of these complexes over time, reinforcing their potential as RdRp inhibitors. Additionally, the calculation of free binding energies and principal component analysis (PCA) of the free energy landscape offered a deeper understanding of the binding dynamics and energetics. This study not only highlights the utility of marine fungi compounds in antiviral drug discovery but also showcases the power of computational tools in identifying novel therapeutics. The identified compounds represent promising candidates for further experimental validation and development as ZIKV RdRp inhibitors.Communicated by Ramaswamy H. Sarma.

Impact of weight reduction on structural and functional parameters of the optic nerve in idiopathic intracranial hypertension.

PURPOSE: To evaluate the effect of weight reduction on the structural and functional parameters of the optic nerve in established cases of papilledema in Idiopathic Intracranial Hypertension (IIH). METHODS: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2019 to February 2021. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER), structural parameters (RNFL, GCL-IPL, and optic disc height), and clinical grading of papilledema were measured at baseline and every 6 weeks for 6 months. All patients underwent medical (oral acetazolamide) and diet therapy. RESULTS: Mean body mass index (BMI) at presentation was 26.32 ± 3.52 kg/m² and the mean change in BMI over 6 months was 1.27 ± 0.50 kg/m². 67% of eyes had papilledema of grades 2-3 at the presentation. At the end of 6 months, 75% of eyes had grade 1 papilledema while 13% showed complete resolution. A reduction of 5.32 ± 3.58 in mean deviation (r = 0.316; p-value 0.01) and gain in VER P100 amplitude of 4.2 ± 2.7 µV (r = 0.40; p-value 0.003) were noted over 6 months with reduction in BMI over 6 months. A statistically significant reduction in optic disc height (ODH) was noticed with BMI reduction over 6 months (p = 0.0007; r = 0.45).A reduction of 1.72 ± 0.90 kg/m² (equivalent to 6.53% weight loss) in BMI was associated with a four-grade change in clinical grading of papilledema. CONCLUSION: Reduction in BMI had a significant impact on both structural and functional parameters of the optic nerve in IIH. The involvement of a well-certified dietician should be an integral part of treatment in IIH.

Impact of subgingival instrumentation on systemic inflammation and serum bone resorption marker in premenopausal women with periodontitis: a prospective interventional study.

OBJECTIVES: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. METHOD AND MATERIALS: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). RESULTS: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. CONCLUSION: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health.

Manipulating epigenetic diversity in crop plants: Techniques, challenges and opportunities.

Epigenetic modifications act as conductors of inheritable alterations in gene expression, all while keeping the DNA sequence intact, thereby playing a pivotal role in shaping plant growth and development. This review article presents an overview of techniques employed to investigate and manipulate epigenetic diversity in crop plants, focusing on both naturally occurring and artificially induced epialleles. The significance of epigenetic modifications in facilitating adaptive responses is explored through the examination of how various biotic and abiotic stresses impact them. Further, environmental chemicals are explored for their role in inducing epigenetic changes, particularly focusing on inhibitors of DNA methylation like 5-AzaC and zebularine, as well as inhibitors of histone deacetylation including trichostatin A and sodium butyrate. The review delves into various approaches for generating epialleles, including tissue culture techniques, mutagenesis, and grafting, elucidating their potential to induce heritable epigenetic modifications in plants. In addition, the ground breaking CRISPR/Cas is emphasized for its accuracy in targeting specific epigenetic changes. This presents a potent tools for deciphering the intricacies of epigenetic mechanisms. Furthermore, the intricate relationship between epigenetic modifications and non-coding RNA expression, including siRNAs and miRNAs, is investigated. The emerging role of exo-RNAi in epigenetic regulation is also introduced, unveiling its promising potential for future applications. The article concludes by addressing the opportunities and challenges presented by these techniques, emphasizing their implications for crop improvement. Conclusively, this extensive review provides valuable insights into the intricate realm of epigenetic changes, illuminating their significance in phenotypic plasticity and their potential in advancing crop improvement.

Genome-wide identification of DCL, AGO, and RDR gene families in wheat (Triticum aestivum L.) and their expression analysis in response to heat stress.

Key components of the RNA interference (RNAi) pathway include the Dicer-like (DCL), Argonaute (AGO), and RNA-dependent RNA polymerase (RDR) gene families. While these components have been studied in various plant species, their functional validation in wheat remains unexplored particularly under heat stress. In this study, a comprehensive genome-wide analysis to identify, and characterize DCL, AGO, and RDR genes in wheat and their expression patterns was carried out. Using phylogenetic analysis with orthologous genes from Arabidopsis and rice, we identified a total of 82 AGO, 31 DCL, and 31 RDR genes distributed across the 21 chromosomes of wheat. To understand the regulatory network, a network analysis of miRNAs that target RNA-silencing genes was performed. Our analysis revealed that 13 miRNAs target AGO genes, 8 miRNAs target DCL genes, and 10 miRNAs target RDR genes at different sites, respectively. Additionally, promoter analysis of the RNA-silencing genes was done and identified the presence of 132 cis-elements responsive to stress and phytohormones. To examine their expression patterns, we performed RNA-seq analysis in the flag leaf samples of wheat exposed to both normal and heat stress conditions. To understand the regulation of RNA silencing, we experimentally analysed the transcriptional changes in response to gradient heat stress treatments. Our results showed constitutive expression of the AGO1, AGO9, and DCL2 gene families, indicating their importance in the overall biological processes of wheat. Notably, RDR1, known to be involved in small interfering RNA (siRNA) biogenesis, exhibited higher expression levels in wheat leaf tissues. These findings suggest that these genes may play a role in responses to stress in wheat, highlighting their significance in adapting to environmental challenges. Overall, our study provides additional knowledge to understand the mechanisms underlying heat stress responses and emphasizes the essential roles of these gene families in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01362-0.

Genome-wide identification and expression analysis of the NHX gene family under salt stress in wheat (Triticum aestivum L).

Salt stress affects plant growth and development, resulting in the loss of crop yield across the world, and sodium-proton antiporters (NHXs) are one of the genes known to promote salt tolerance in transgenic plants. In this study, we conducted a comprehensive genome-wide analysis and expression profile of NHX genes in wheat under salinity stress. We identified 30 TaNHX genes in wheat based on the Na+/H+ exchanger domain, with all genes containing an amiloride motif except one, a known for inhibiting Na+ ions in plants. Phylogenetic analysis classified these genes into three classes with subfamilies: 12 were localized in vacuoles, while 18 were in the endoplasmic reticulum and plasma membrane. Promoter analysis revealed stress-related cis-acting elements, indicating their potential role in abiotic stress tolerance. The non-synonymous (Ka)/synonymous (Ks) ratios highlighted that the majority of TaNHX genes experienced robust purifying selection throughout their evolutionary history. Transcriptomis data analysis and qRT-PCR demonstrated distinct expression patterns for TaNHX genes across various tissues when subjected to salt stress. Additionally, we predicted 20 different miRNA candidates targeting the identified TaNHX genes. Protein-protein interaction prediction revealed NHX6's involvement in the SOS1 pathway, while NHX1 gene exhibit proton antiporter activity. Molecular dynamics (MD) simulations were also conducted to examine the interactions of TaNHX1, TaNHX2, and TaNHX3. These results represent a significant advancement in our understanding of the molecular mechanisms governing Na+ transporters. This may also offer promising avenues for future studies aimed at unraveling the intricate details of their biological roles and applications.

The Impacts and Changes Related to the Cancer Drug Resistance Mechanism.

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Assessment of pathogen removal efficiency of vertical flow constructed wetland treating septage.

Septage refers to the semi-liquid waste material that accumulates in septic tanks and other onsite sanitation systems. It is composed of a complex mixture of human excreta, wastewater, and various solid particles. Septage is a potential source of water pollution owing to presence of high organic content, significant pathogen concentrations, and a range of nutrients like nitrogen and phosphorus. The harmful impacts of septage pollution poses significant risks to public health through the contamination of drinking water sources, eutrophication of water bodies and spread of water borne diseases. Conventional septage treatment technologies often face limitations such as high operational costs, energy requirements, and the need for extensive infrastructure. Therefore, with an aim to treat septage through an alternative cost effective and energy-efficient technology, a laboratory-scale constructed wetland (CW) system (0.99 m2) consisting of a sludge drying bed and a vertical flow wetland bed was utilized for the treatment of septage. The sludge drying bed and vertical flow beds were connected in series and filled with a combination of gravel with varying sizes (ranging from 5 to 40 mm) and washed sand. Canna indica plants were cultivated on both beds to facilitate phytoremediation process. The system was operated with intermittent dosing of 30 Ltrs of septage every day for 2 months. The HRT of the system was fixed at 48 h. The average inlet loads of Biochemical Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), and Total Suspended Solids (TSS) were measured as 150 ± 65.7 g m-2 day-1, 713 ± 443.9 g m-2 day-1, and 309 ± 66.3 g m-2 day-1, respectively. After treatment, the final effluent had an average load of 6 g m-2 day-1 for BOD5, 15 g m-2 day-1 for COD, and 51 g m-2 day-1 for TSS, indicating that the CW system achieved an average removal efficiency of 88% for BOD, 87% for COD, and 65% for TSS. The average load of total coliforms and helminthes eggs in the influent was recorded as 4 × 108 Colony-Forming Units (CFU) m-2 day-1 and 3 × 107 eggs m-2 day-1, respectively. However, the CW system demonstrated significant effectiveness in reducing microbial contamination, with an average removal efficiency of 99% for both total coliforms and helminthes eggs. The vertical flow constructed wetland system, equipped with pretreatment by sludge drying bed, has proven to be efficient in treatment of septage.

Genome-wide identification and expression analysis of the GRAS gene family under abiotic stresses in wheat (Triticum aestivum L.).

The GRAS transcription factors are multifunctional proteins involved in various biological processes, encompassing plant growth, metabolism, and responses to both abiotic and biotic stresses. Wheat is an important cereal crop cultivated worldwide. However, no systematic study of the GRAS gene family and their functions under heat, drought, and salt stress tolerance and molecular dynamics modeling in wheat has been reported. In the present study, we identified the GRAS gene in Triticum aestivum through systematically performing gene structure analysis, chromosomal location, conserved motif, phylogenetic relationship, and expression patterns. A total of 177 GRAS genes were identified within the wheat genome. Based on phylogenetic analysis, these genes were categorically placed into 14 distinct subfamilies. Detailed analysis of the genetic architecture revealed that the majority of TaGRAS genes had no intronic regions. The expansion of the wheat GRAS gene family was proven to be influenced by both segmental and tandem duplication events. The study of collinearity events between TaGRAS and analogous orthologs from other plant species provided valuable insights into the evolution of the GRAS gene family in wheat. It is noteworthy that the promoter regions of TaGRAS genes consistently displayed an array of cis-acting elements that are associated with stress responses and hormone regulation. Additionally, we discovered 14 miRNAs that target key genes involved in three stress-responsive pathways in our study. Moreover, an assessment of RNA-seq data and qRT-PCR results revealed a significant increase in the expression of TaGRAS genes during abiotic stress. These findings highlight the crucial role of TaGRAS genes in mediating responses to different environmental stresses. Our research delved into the molecular dynamics and structural aspects of GRAS domain-DNA interactions, marking the first instance of such information being generated. Overall, the current findings contribute to our understanding of the organization of the GRAS genes in the wheat genome. Furthermore, we identified TaGRAS27 as a candidate gene for functional research, and to improve abiotic stress tolerance in the wheat by molecular breeding.

Physiologically Based Pharmacokinetic modelling of drugs in pregnancy: A mini-review on availability and limitations.

Physiologically based pharmacokinetic (PBPK) modelling in pregnancy is a relatively new approach that is increasingly being used to assess drug systemic exposure in pregnant women to potentially inform dosing adjustments. Physiological changes throughout pregnancy are incorporated into mathematical models to simulate drug disposition in the maternal and fetal compartments as well as the transfer of drugs across the placenta. This mini-review gathers currently available pregnancy PBPK models for drugs commonly used during pregnancy. In addition, information about the main PBPK modelling platforms used, metabolism pathways, drug transporters, data availability and drug labels were collected. The aim of this mini-review is to provide a concise overview, demonstrate trends in the field, highlight understudied areas and identify current gaps of PBPK modelling in pregnancy. Possible future applications of this PBPK approach are discussed from a clinical, regulatory and industry perspective.

Evaluation of change in objective cyclotorsion after various inferior oblique-weakening procedures.

PURPOSE: To study the effect of four types of inferior oblique-weakening procedures on ocular torsion: inferior oblique recession (IOR), recession and antero-positioning (RAP), anterior transposition as practiced by Elliot and Nankin (EN), and anterior and nasal transposition (ANT). METHODS: The medical records of 72 consecutive patients >10 years of age undergoing inferior oblique weakening for primary or secondary inferior oblique overaction (IOOA) with or without horizontal rectus surgery were reviewed retrospectively. The 106 included eyes were assigned to one of the four groups according to the type of inferior oblique-weakening procedure. The severity of IOOA and the amount of V pattern guided the choice of procedure. IOOA, disk-fovea angle (DFA), and the amount of V pattern were recorded preoperatively. Measurements were repeated postoperatively at 1 week, 4 weeks, and 3 months. Change in the DFA was used to study the change in objective cyclotorsion in all four groups. RESULTS: A significant incyclotorsional shift was seen in all four groups at postoperative 3 months. The mean reduction in excyclotorsion 3 months postoperatively was 3.65° ± 4.84° for IOR, 5.31° ± 4.64° for RAP, 6.10° ± 3.89° for EN, and 16.62° ± 8.72° ANT; it was significantly higher in the ANT group compared with the other three groups. Reduction in DFA was also correlated with preoperative DFA overall, and for all procedures except IOR (P ≤ 0.005). CONCLUSIONS: All four inferior oblique-weakening procedures reduced excyclotorsion; the largest reductions in our study were seen in cases treated using ANT of the inferior oblique.

Rifampicin-induced ER stress and excessive cytoplasmic vacuolization instigate hepatotoxicity via alternate programmed cell death paraptosis in vitro and in vivo.

AIMS: Rifampicin-induced hepatotoxicity is a primary cause of drug-induced liver injury (DILI), posing a significant challenge to its continued clinical application. Moreover, the mechanism underlying rifampicin-induced hepatotoxicity remains unclear. MAIN METHODS: Human hepatocyte line-17 (HHL-17) cells were treated with an increasing dose of rifampicin for 24 h, and male Wistar rats were given rifampicin [150 mg/kg body weight (bw)] orally for 28 days. Viability assay, protein expression, and cell death assays were analyzed in vitro. Moreover, liver serum markers, body/organ weight, H&E staining, protein expression, etc., were assayed in vivo. KEY FINDINGS: Rifampicin induced a dose-dependent hepatotoxicity in HHL-17 cells (IC50; 600 µM), and increased the serum levels of liver injury markers, e.g., alanine transaminase (ALT) and aspartate transaminase (AST) in rats. Rifampicin-induced cell death was non-apoptotic and non-necroptotic both in vitro and in vivo. Further, excessive cellular vacuolization and reduced expression of Alix protein confirmed the induction of paraptosis both in vitro and in vivo. In addition, a significant increase in the endoplasmic reticulum (ER) stress markers (e.g., BiP, CHOP, and total polyubiquitinated proteins) was detected, demonstrating the induction of ER stress and altered protein homeostasis. Interestingly, rifampicin-induced hepatotoxicity was associated with the inhibition of autophagy and enhanced reactive oxygen species (ROS) generation in HHL-17 cells. Furthermore, inhibition of protein synthesis by cycloheximide (CHX) suppressed paraptosis by alleviating rifampicin-induced ER stress and ROS generation. SIGNIFICANCE: Rifampicin-induced hepatotoxicity involves ER stress-driven paraptosis as a novel mechanism of its toxicity that may be targeted to protect liver cells from rifampicin toxicity.

Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity.

Homocysteine (Hcy), produced physiologically in all cells, is an intermediate metabolite of methionine and cysteine metabolism. Hyperhomocysteinemia (HHcy) resulting from an in-born error of metabolism that leads to accumulation of high levels of Hcy, is associated with vascular damage, neurodegeneration and cognitive decline. Using a HHcy model in neuronal cells, primary cortical neurons and transgenic zebrafish, we demonstrate diminished autophagy and Hcy-induced neurotoxicity associated with mitochondrial dysfunction, fragmentation and apoptosis. We find this mitochondrial dysfunction is due to Hcy-induced proteotoxicity leading to ER stress. We show this sustained proteotoxicity originates from the perturbation of upstream autophagic pathways through an aberrant activation of mTOR and that protetoxic stress act as a feedforward cues to aggravate a sustained ER stress that culminate to mitochondrial apoptosis in HHcy model systems. Using chemical chaperones to mitigate sustained ER stress, Hcy-induced proteotoxicity and consequent neurotoxicity were rescued. We also rescue neuronal lethality by activation of autophagy and thereby reducing proteotoxicity and ER stress. Our findings pave the way to devise new strategies for the treatment of neural and cognitive pathologies reported in HHcy, by either activation of upstream autophagy or by suppression of downstream ER stress. Video Abstract.

Clinical Profile, Radiological Findings, and Risk Factors Associated with Pneumonia among Children Admitted in Dhulikhel Hospital.

BACKGROUND: Pneumonia is the commonest lung disease which is a major cause of mortality and morbidity in young children and is a common acute respiratory infection. The presentation varies among the cases. The study was done to know the risk factors, clinical profile, radiological findings, and short-term outcome of the admitted patients with pneumonia between six months to sixteen years at Dhulikhel Hospital. METHODS: A hospital based observational prospective cross-sectional study done in 65 cases over the period of 17 months in children admitted with pneumonia at Pediatrics department of Dhulikhel Hospital. Socio-demographic variables, clinical profile, radiological profile, diagnosis, and short-term outcome were collected and analyzed using descriptive statistics. RESULTS: Out of 65 patients, 76.9% cases were children between six months to five years. The most common clinical presentation was fever (98.5%) followed by cough (86.2%). Crepitation (78.5%) and subcostal retraction (29.2%) were common clinical findings. Disseminated intravascular coagulation, thrombocytopenia, sepsis, and right heart failure were associated with mortality. The requirement of mechanical ventilation, oxygenation, and inotrope support was more likely to have fatal outcome. CONCLUSIONS: Fever and cough were the most common clinical presentation and right middle zone consolidation was the most common finding in children admitted with pneumonia.

An In-vitro Evaluation of Retention Force of All PEEK, All Zirconia and Zirconia-PEEK Telescopic Attachment for Mandibular Overdentures.

The objective of this study is to compare retention capacity of mandibular implant-supported overdenture with all zirconia, zirconia-PEEK, and all PEEK telescopic attachments. Sixty acrylic resin models of mandible were used. Telescopic attachment system was made up of all zirconia, all PEEK, and zirconia-PEEK. Evaluation of retention force was done using universal testing machine. Obtained data were statistically evaluated. Highest initial force value was obtained with zirconia-PEEK group. All PEEK and zirconia-PEEK groups showed significantly decreased final retention values in comparison to their initial values. Zirconia can be regarded as the material of choice for telescopic crown, whereas polyetheretherketone and zirconia-PEEK telescopic crowns showed retention loss over a period of time.

The giant flexoelectric effect in a luffa plant-based sponge for green devices and energy harvesters.

Soft materials that can produce electrical energy under mechanical stimulus or deform significantly via moderate electrical fields are important for applications ranging from soft robotics to biomedical science. Piezoelectricity, the property that would ostensibly promise such a realization, is notably absent from typical soft matter. Flexoelectricity is an alternative form of electromechanical coupling that universally exists in all dielectrics and can generate electricity under nonuniform deformation such as flexure and conversely, a deformation under inhomogeneous electrical fields. The flexoelectric coupling effect is, however, rather modest for most materials and thus remains a critical bottleneck. In this work, we argue that a significant emergent flexoelectric response can be obtained by leveraging a hierarchical porous structure found in biological materials. We experimentally illustrate our thesis for a natural dry luffa vegetable-based sponge and demonstrate an extraordinarily large mass- and deformability-specific electromechanical response with the highest-density-specific equivalent piezoelectric coefficient known for any material (50 times that of polyvinylidene fluoride and more than 10 times that of lead zirconate titanate). Finally, we demonstrate the application of the fabricated natural sponge as green, biodegradable flexible smart devices in the context of sensing (e.g., for speech, touch pressure) and electrical energy harvesting.

Good outcome of surgical treatment for contaminated penile wound due to a fall from stairs: a case report.

Background: Penile trauma due to the associated stigma poses a diagnostic challenge. The causes of isolated penile injuries include zipper injuries (mainly in children), falls, burns, during fellatio, self-mutilation (Klingsor syndrome), and rarely purposeful forceful bending of the erect penis (Taqaandan). Delayed management of penile trauma might increase the risk of infection, rarely leading to sepsis acutely or structural and functional disabilities in the long run. We believe our report is the first to contribute data on a patient with a delayed presentation of contaminated penile wound who recovered well with prompt management. Case Description: A traumatic laceration of the penis due to a fall from stairs is extremely unexpected. Here we present the case of a 14-year-old boy who slipped from the stairs and got an isolated American Association for the Surgery of Trauma (AAST) Grade-1 ventrolateral penile skin laceration. He took home remedies for 10 days before reporting with a contaminated wound. The patient was first managed conservatively with antibiotics [Amoxyclav 625 mg thrice daily (TDS) and Metronidazole 400 mg TDS], wound care, and then treated surgically, helping wound repair. He recovered well after the treatment and retained normal urinary and sexual function. Conclusions: Penile trauma is severely under-reported due to the stigma associated with it. Early diagnosis and prompt management are imperative to limit complications. A detailed history helps to evaluate the exact cause and check out possibilities of sexual assault. Appropriate management in tandem with patient education and an attempt to de-stigmatize the interaction helps favorable long-term outcomes.