Youngest Living Donor Liver Transplant for End-Stage Liver Disease in a 6-Month-Old With a Novel Aggressive Mutation in KIF12 Gene.

BACKGROUND: Kinesin family member 12 (KIF12) mutation-related cholestatic disorder represents a rare subtype of progressive familial intrahepatic cholestasis (PFIC), referred to as PFIC Type 8, with only 21 reported cases globally to date. METHODS: Here, we present a unique case of a 6-month-old boy diagnosed with homozygous KIF12 gene mutation, who successfully underwent a living donor liver transplant at our center for end-stage liver disease. RESULTS: This case marks the youngest patient of KIF12-related cholestatic disorder necessitating a liver transplant to date. The child initially presented with neonatal cholestasis and then developed infantile hepatic decompensation. Our report discusses the diagnostic process and management strategies employed. It underscores the importance of prompt diagnosis through clinical suspicion, biochemical parameters, and genetic testing, as well as the adoption of suitable management strategies, including the early contemplation of liver transplant in such exceptional and rare cases of genetic intrahepatic cholestasis. CONCLUSION: KIF12-related genetic disease should be considered in neonatal cholestasis cases with high gamma glutamyl transpeptidase to differentiate from conditions like biliary atresia. Favorable outcomes post liver transplant stress the importance of early genetic testing and referral to liver transplant centers for unresponsive patients, potentially saving lives.

Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods.

Suppressing vascular endothelial growth factor (VEGF), its receptor (VEGFR2), and the VEGF/VEGFR2 signaling cascade system to inhibit angiogenesis has emerged as a possible cancer therapeutic target. The present work was designed to discover and evaluate bioactive phytochemicals from the Clerodendrum inerme (L.) Gaertn plant for their anti-angiogenic potential. Molecular docking of twenty-one phytochemicals against the VEGFR-2 (PDB ID: 3VHE) protein was performed, followed by ADMET profiling and molecular docking simulations. These investigations unveiled two hit compounds, cirsimaritin (- 12.29 kcal/mol) and salvigenin (- 12.14 kcal/mol), with the highest binding energy values when compared to the reference drug, Sorafenib (- 15.14 kcal/mol). Furthermore, only nine phytochemicals (cirsimaritin and salvigenin included) obeyed Lipinski's rule of five and passed ADMET filters. Molecular dynamics simulations run over 100 ns revealed that the protein-ligand complexes remained stable with minimal backbone fluctuations. The binding free energy values of cirsimaritin (- 52.35 kcal/mol) and salvigenin (- 55.89 kcal/mol), deciphered by MM-GBSA analyses, further corroborated the docking interactions. The HOMO-LUMO band energy gap (ΔE) was calculated using density-functional theory (DFT) and substantiated using density of state (DOS) spectra. The chemical reactivity analyses revealed that salvigenin exhibited the highest chemical softness value (6.384 eV), the lowest hardness value (0.07831 eV), and the lowest ΔE value (0.1566 eV), which implies salvigenin was less stable and chemically more reactive than cirsimaritin and sorafenib. These findings provide further evidence that cirsimaritin and salvigenin have the ability to prevent angiogenesis and the development of cancer. Nevertheless, more in vitro and in vivo confirmation is necessary.

Ineffective ventilation in a very low birth weight infant with H-type Tracheoesophageal Fistula with bilateral chemical pneumonitis. A lesson learned.

Tracheoesophageal fistula (TEF) with or without associated esophageal atresia (EA) in the neonate is challenging to diagnose and manage its complications like aspiration, respiratory distress, and other associated anomalies. To stabilize, ventilate and prepare for surgical correction, understanding the H-nature of disease and anticipation of problems and their management will improve survival. We present a newborn with tracheoesophageal fistula without atresia from resource-limited settings and lessons we learned from the case.

Unveiling the persistent threat: recent insights into Listeria monocytogenes adaptation, biofilm formation, and pathogenicity in foodborne infections.

Listeriosis is a severe disease caused by the foodborne pathogen Listeria monocytogenes, posing a significant risk to vulnerable populations such as the elderly, pregnant women, and newborns. While relatively uncommon, it has a high global mortality rate of 20-30%. Recent research indicates that smaller outbreaks of the more severe, invasive form of the disease occur more frequently than previously thought, despite the overall stable infection rates of L. monocytogenes over the past 10 years. The ability of L. monocytogenes to form biofilm structures on various surfaces in food production environments contributes to its persistence and challenges in eradication, potentially leading to contamination of food and food production facilities. To address these concerns, this review focuses on recent developments in epidemiology, risk evaluations, and molecular mechanisms of L. monocytogenes survival in adverse conditions and environmental adaptation. Additionally, it covers new insights into strain variability, pathogenicity, mutations, and host vulnerability, emphasizing the important events framework that elucidates the biochemical pathways from ingestion to infection. Understanding the adaptation approaches of L. monocytogenes to environmental stress factors is crucial for the development of effective and affordable pathogen control techniques in the food industry, ensuring the safety of food production.

Nitric oxide: An emerging warrior of plant physiology under abiotic stress.

The natural environment of plants comprises a complex set of various abiotic stresses and their capability to react and survive under this anticipated changing climate is highly flexible and involves a series of balanced interactions between signaling molecules where nitric oxide becomes a crucial component. In this article, we focussed on the role of nitric oxide (NO) in various signal transduction pathways of plants and its positive impact on maintaining cellular homeostasis under various abiotic stresses. Besides this, the recent data on interactions of NO with various phytohormones to control physiological and biochemical processes to attain abiotic stress tolerance have also been considered. These crosstalks modulate the plant's defense mechanism and help in alleviating the negative impact of stress. While focusing on the diverse functions of NO, an effort has been made to explore the functions of NO-mediated post-translational modifications, such as the N-end rule pathway, tyrosine nitration, and S-nitrosylation which revealed the exact mechanism and characterization of proteins that modify various metabolic processes in stressed conditions. Considering all of these factors, the present review emphasizes the role of NO and its interlinking with various phytohormones in maintaining developmental processes in plants, specifically under unfavorable environments.

Domino liver transplantation for maple syrup urine disease in children: A single-center case series.

BACKGROUND: Domino liver transplant (DLT) represents another type of liver donor to expand the donor pool. Recent reports of successful DLT in children with maple syrup urine disease (MSUD) show promising long-term outcomes. METHODS: It was a retrospective study. All children with MSUD were paired with either recipients with end-stage liver disease (ESLD) or non-MSUD metabolic disease. Each pair underwent simultaneous liver transplant (LT), where the MSUD recipient received the graft from a living-related donor and the liver explanted from the MSUD donor was transplanted to the respective paired domino recipient. We report our experience regarding the techniques and outcomes of DLT at our center. RESULTS: Eleven children with MSUD and 12 respective DLT recipients were enrolled, one of which was domino split-liver transplantation. DLT recipients included seven ESLD, two propionic acidemia (PA), one glycogen storage disease(GSD) type-1, one GSD type-3, and one Citrullinemia. Post-LT ICU and hospital stays were comparable (p > .05). Patient and graft survival was 100% and 66.6% in the MSUD group and DLT recipients at a mean follow-up of 13.5 and 15 months. There was no death in the MSUD group as compared to four in the DLT group. The amino acid levels rapidly normalized after the LT in the children with MSUD and they tolerated the normal unrestricted diet. No vascular, biliary, or graft-related complications were seen in the post-transplant period. No occurrence of MSUD was noted in DLT recipients. CONCLUSION: DLTs have excellent post-surgical outcomes. DLT should be strongly considered and adopted by transplant programs worldwide to circumvent organ shortage.

Quality Management of Probiotics: Ensuring Safety and Maximizing Health Benefits.

Consumption of probiotics, which are beneficial live microorganisms, has received a lot of attention because of their potential to improve health and wellness. Robust quality control measures are necessary to ensure the safety of probiotics and maximize their health effects. This review delves into the topic of quality management in probiotics, highlighting the significance of sticking to strict guidelines from manufacture to storage to distribution. Probiotic quality standards, Good Manufacturing Practices (GMP) implementation, quality control and testing techniques, and documentation and traceability systems are all discussed in detail. The importance of taking precautions to avoid microbial contamination, meeting all applicable regulations, and clearly marking and packaging probiotic products is also emphasized. In addition, it reviews the clinical evidence supporting the possible health advantages of probiotics and investigates the processes through which probiotics enhance health. The review continues by stressing the significance of educating and informing consumers about probiotics and their proper use in order to maximize health benefits. Probiotics' potential health benefits can be maximized and consumer faith in these helpful microbes can be bolstered by adopting thorough quality management measures to ensure their safety, efficacy, and consistency.

Chemical constituents and strong larvicidal activity of Solanum xanthocarpum among selected plants extracts against the malaria, filaria, and dengue vectors.

BACKGROUND & OBJECTIVES: The role of mosquitoes is instrumental in the transmission of various diseases. Mosquitoe-borne diseases account for a significant share of the global burden of total infectious diseases. Vector control is the principal method for the control of these mosquito-borne diseases. Plant-derived insecticides serve as an effective alternative to chemical insecticides. The present study has been undertaken to assess the larvicidal potential of methanol and petroleum ether extracts of leaves of Solanum xanthocarpum, Parthenium hysterophorus, Manihot esculenta, and Chamaecyparis obtusa. METHODS: Larvicidal activity was tested against the early four-stage instar larvae of laboratory-reared susceptible strains of the malaria vector, Anopheles stephensi, dengue fever vector, Aedes aegypti, and the lymphatic filariasis vector, Culex quinquefasciatus at 20 to 120 ppm concentrations. Further, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectroscopy (GC-MS) analyses were carried out to identify the bioactive compounds present in the methanolic leaf extracts of Solanum xanthocarpum for designing a larvicidal product in future. RESULTS: After 72 h of exposure high larvicidal activities were observed in methanolic and petroleum ether leaves extract of S. xanthocarpum against An. stephensi, Ae. aegypti and Cx. quinquefasciatus. The larvicidal activities for methanol and petroleum ether leaf extract of S. xanthocarpum with LC50 = 09.201 and 12.435 ppm and LC90 = 21.578 and 27.418 ppm for An. stephensi; LC50 = 11.450 and 10.026 ppm and LC90 = 26.328 and 22.632 ppm for Ae. aegypti and LC50 = 12.962 and 13.325 ppm and LC90 = 26.731 and 30.409 ppm for Cx. quinquefasciatus, respectively, were found to be most effective. GC-MS analysis revealed 43 compounds, amongst these phytol (13.09%), 3-allyl-2-methoxy phenol (9.55%), (9Z, 12Z)-9, 12-octadecadienoyl chloride (7.93%), linoleic acid (5.45%), alpha-tocospiro B (5.08%) and hexadecanoic acid (4.35%) were identified as major compounds. INTERPRETATION & CONCLUSION: Present work showed that leaf extracts of S. xanthocarpum are a source of potential natural candidate that possess several phytochemicals which can be explored further for the development of ecologically safer mosquito control products.

Hydrometeorological field instrumentation in Lesser Himalaya to advance research for future water and food security.

Hydrometeorological monitoring and continuous data collection in ungauged mountainous regions are exciting and challenging for water resource planners compared to the measurement in plain areas. Lesser Himalayas in the mountainous areas face the insufficiency of continuous hydrometeorological data, hindering our understanding of hydrological processes and hampering integrated water resources management. This present study focuses on the setup of the field instruments for collecting hydrometeorological data and analyzing continuously collected data at Aglar watershed to assess hydrometeorological parameters' spatial and temporal distribution. The instrumentation includes monitoring one sub-surface flow, five stream flows, four rain gauges, and one automatic weather station. The relationship between the stage and the discharge was established based on the collected data for three streams. The analyzed seasonal rainfall revealed 726.7 mm of rain occurred during the monsoon with an intensity of less than 16 mm/day. The Paligaad sub-watershed displayed a flashy response towards the rainfall events, whereas the Upper Aglar exhibited a wide range of dampening runoff responses for different rainfall events. The monitored sub-surface flow varies annually, and during the monsoon season, interflow and baseflow hydrograph decayed more rapidly at the rate of 0.04 day-1 and 0.78 day-1, respectively. The installed AWS has been used to measure crop water requirements and plan for better strategies to cope with future food and water security. The high-frequency generated data will help answer the queries related to hydrological responses of different watershed characteristics.

Tuberculosis treatment spills the beans on Wilson's disease and more.

Drug-induced liver injury (DILI) is an unwarranted problem and has been a scourge in the treatment of tuberculosis (TB) infection in general and children in particular. Usually, when the Antituberculosis treatment (ATT) regime is temporarily interrupted and modified, DILI subsides, and the whole treatment can be completed under supervision. We report a case of ATT-induced DILI not improving despite modification in the ATT regime, which ultimately led to the revealing of a yet unreported constellation of syndromes that included Wilson Disease, 46 XX gonadal dysgenesis, and Mayer Rokitansky Kuster Hauser (MRKH) Syndrome.

Mosquito larvicidal potential of Solanum xanthocarpum leaf extract derived silver nanoparticles and its bio-toxicity on non-target aquatic organism.

BACKGROUND & OBJECTIVES: Mosquitoes are insects of public health importance that act as a vector to transmit various vector-borne diseases in humans including dengue, malaria, filariasis and yellow fever. The continually employed synthetic insecticides have developed resistance in mosquitoes. Nano-based botanical insecticides can be considered as the best alternative due to several advantages like being simple, non-pathogenic, biodegradable and safe to the environment. The present work reported the maximum larvicidal potential of green synthesized silver nanoparticles (AgNPs) derived from the leaf extract of Solanum xanthoearpum against the third instar larvae of Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus over its crude leaf extract. METHODS: The synthesis of AgNPs was done by adding leaf extract into silver nitrate solution in a conical flask. The characterization of AgNPs was done using different techniques such as UV-Vis, SEM, TEM, XRD, DLS and SAED. FT-IR analysis was done to find out the compound responsible for bio-reduction of silver nitrate. Larvicidal activity of AgNPs was checked against An. stephensi, Ae. aegypti, and Cx. quinquefasciatus according to WHO standard protocol and toxicity was evaluated against Poecilia reticulate. RESULTS: A change in colour was observed indicating the synthesis of AgNPs which was further confirmed by a strong surface plasmon resonance peak at 421nm under the UV-Vis spectrum. SEM and TEM micrographs exhibited that the most common shape of AgNPs was spherical. XRD spectrum showed crystalline nature of silver nanoparticles. FT-IR spectrum showed the presence of various functional groups such as carboxyl and hydroxyl which might be responsible for bio-reduction and capping of silver nanoparticles. Further, silver nanoparticles were very effective against An. stephensi, Ae. aegypti, and Cx. quinquefasciatus with LC50 and LC90 values of 1.90, 2.36, 2.93, 3.82, 4.31 and 7.63 ppm, respectively, as compared to aqueous leaf extract after 72 h of exposure and were non-toxic against non-target organism P. retieulata. Interpretation & eonelusion: From the above finding, it can be concluded that fabricated AgNPs can be promising eco-friendly tools for controlling mosquito vectors.

Experimental study on infiltration pattern: opportunities for sustainable management in the Northern region of India.

The infiltration process plays a key role in designing groundwater recharge, irrigation, and drainage systems, and contamination evaluation is controlled by numerous factors, among which soil physical properties and land use & land cover (LULC) are the prime factors. A comprehensive understanding of the spatial water infiltration characteristics over the soil, which is site-specific and more complex due to non-uniformity, could enhance the agriculture water use efficiency and mitigate water-related issues. The present study deals with the measurement of field infiltration characteristics using a mini disc infiltrometer in all 24 blocks of Gaya district, Bihar, which covers a wide spectrum of soil types. Results showed that the average cumulative infiltration rate (IR) for the study area varies between 0.38 and 2.20 cm/min with an average rate of 1.16 cm/min. The initial IR among all blocks was found to be high but decreased gradually with each successive reading. Moreover, the land use under forest cumulative IR was more than the cumulative IR for urban and grassland. Eight blocks (33.3%) have an IR more than the average infiltration of the area, which is good for storing the water in the aquifer and suggested constructing a recharge structure. Further investigation revealed a small IR in the inundated area, because of the maximum soil water table. The ready-to-use map showing the IR for the district was prepared, which could be used by any decision-taking during the high or low rainfall, for understanding the hydrological process, development of any reference guide for farmers for increasing the agriculture productivity and soil-water management.

Broadband infrared photodetector based on nanostructured MoSe2-Si heterojunction extended up to 2.5 µm spectral range.

Transition metal dichalcogenides (TMDs) and their heterojunctions are drawing immense research interest for various applications including infrared detection. They are being studied with different semiconductor materials to explore their heterojunction properties. In this regard, we report a MoSe2/Si heterojunction broadband photodiode which is highly sensitive for a wide spectral range from 405 nm to 2500 nm wavelength with the maximum responsivity of ∼522 mA W-1 for 1100 nm of incident light. The hydrothermal synthesis approach leads to the imperfect growth of the MoSe2, creating defects in the lattice, which was confirmed by x-ray photo-spectroscopy. These sub-bandgap defects caused high optical absorption of the SWIR light as observed in the absorption spectra. The speed of the device ranges to 18/10 µs for 10 kHz modulated light. Furthermore, the photodetector has been fully operational even at zero bias voltage, making it a potential contender for self-powered photodetection.

Comparative evaluation of biting force and chewing efficiency of all-on-four treatment concept with other treatment modalities in completely edentulous individuals.

AIM: To compare and evaluate biting force and chewing efficiency of all-on-four treatment concept, implant-supported overdenture, and conventional complete denture. SETTINGS AND DESIGN: Invivo - comparative study. MATERIALS AND METHODS: A total of 12 edentulous patients were included in the study and conventional complete dentures were fabricated. Patients were divided into two groups. In Group 1, complete dentures were replaced with implant-supported overdenture, and in Group 2, complete dentures were replaced with hybrid denture supported by all-on-four treatment concept. The biting force was assessed using a bite force sensor and electromyographic recordings were made by electromyogram for masticatory muscles when chewing three different consistencies of foods. STATISTICAL ANALYSIS USED: The data was statistically analyzed using software SPSS version 22.0. Paired t-test was used for intra-group comparison and unpaired t-test was used for intergroup comparison. RESULTS: The difference in biting force and chewing efficiency for all-on-four treatment concept was statistically significant for overdenture and complete denture. The highest biting force and chewing efficiency were observed for all-on-four treatment concept, followed by implant-supported overdenture and complete denture. CONCLUSION: The study concluded that the completely edentulous individuals with atrophic posterior alveolar ridges can be rehabilitated successfully with improved biting force and chewing efficiency by All-on-four treatment concept.

Proteomic approach and expression analysis revealed the differential expression of predicted leptospiral proteases capable of ECM degradation.

Leptospira, the causative agent of leptospirosis is known to have many proteases with potential to degrade extracellular matrix. However, a multipronged approach to identify, classify, characterize and elucidate their role has not been attempted. Our proteomic approach using high-resolution LC-MS/MS analysis of Triton X-114 fractions of Leptospira interrogans resulted in the identification of 104 proteases out of 130 proteases predicted by MEROPS. In Leptospira approximately 3.5% of the genome complements for proteases, which include catalytic types of metallo-, serine-, cysteine-, aspartic-, threonine- and asparagine- peptidases. Comparison of proteases from different serovars revealed that M04, M09B, M14A, M75, M28A, A01 and U73 protease families are exclusively present in pathogenic form. The M23 and S33 protease families are represented with >14 members in Leptospira. The differential expression under physiological temperature (37 °C) and osmolarity (300 mOsM) showed that proteases belonging to the catalytic type of Metallo-peptidases are upregulated significantly in pathogenic conditions. In silico prediction and characterization of the proteases revealed that several proteases are membrane anchored and secretory, classical as well as non-classical system. The study demonstrates the diversity and complexity of proteases, while maintaining conservation across the serovars in Leptospira and their differential expression under pathogenic conditions.

The utility and safety of flexible bronchoscopy in critically ill acute leukemia patients: a retrospective cohort study.

PURPOSE: Flexible bronchoscopy with bronchoalveolar lavage (BAL) is commonly performed in immunocompromised patients. Nevertheless, it remains unclear whether bronchoscopy with BAL leads to changes in medical management or is associated with procedural complications among critically ill acute leukemia (AL) patients. METHODS: We evaluated 71 AL patients who underwent diagnostic bronchoscopy with BAL in the intensive care unit (ICU) between 1 January 2007 and 31 December 2012. We recorded baseline characteristics, vital signs (before, during, and after the procedure), changes in medical management following the procedure, and procedural complications. Using a multivariable logistic regression model, we explored the relationship between patient characteristics and whether bronchoscopy changed management or caused complications. Patient characteristics included as predictors in the regression model were age, sex, immunosuppression status (those undergoing active chemotherapy), and the Acute Physiology And Chronic Health Evaluation II score. RESULTS: The most common indication for ICU admission was respiratory failure (51 patients, 72%), followed by sepsis (14 patients, 20%). Overall, the results obtained from bronchoscopy with BAL were associated with a change in management in 32 patients (45%), most commonly a change in antimicrobial therapy as a result of an infectious pathogen being identified (17 patients, 24%). Complications were documented in nine patients (13%) and included post-procedural hypoxia (six patients, 8%), the need for intubation (one patient, 9% of non-intubated patients), and tracheal perforation (one patient, 1%). No clinically significant changes in patient vital signs were observed during or immediately following the procedure. Patient characteristics did not predict whether bronchoscopy was associated with changes in medical management or procedural complications in multivariable analyses. CONCLUSIONS: Flexible bronchoscopy with BAL is relatively safe and helps to guide medical management among patients with AL admitted to the ICU.

Technological Developments in lncRNA Biology.

It is estimated that more than 90% of the mammalian genome is transcribed as non-coding RNAs. Recent evidences have established that these non-coding transcripts are not junk or just transcriptional noise, but they do serve important biological purpose. One of the rapidly expanding fields of this class of transcripts is the regulatory lncRNAs, which had been a major challenge in terms of their molecular functions and mechanisms of action. The emergence of high-throughput technologies and the development in various conventional approaches have led to the expansion of the lncRNA world. The combination of multidisciplinary approaches has proven to be essential to unravel the complexity of their regulatory networks and helped establish the importance of their existence. Here, we review the current methodologies available for discovering and investigating functions of long non-coding RNAs (lncRNAs) and focus on the powerful technological advancement available to specifically address their functional importance.

High Field Emission Current Density from Patterned Carbon Nanotube Field Emitter Arrays with Random Growth.

High field emission (FE) current density from carbon nanotube (CNT) arrays grown on lithographically patterned silicon substrates is reported. A typical patterned field emitter array consists of bundles of nanotubes separated by a fixed gap and spread over the entire emission area. Emission performance from such an array having randomly oriented nanotube growth within each bundle is reported for different bundle sizes and separations. One typical sample with aligned CNTs within the bundle is also examined for comparison. It is seen that the current density from an array having random nanotube growth within the bundles is appreciably higher as compared to its aligned counterpart. The influence of structure on FE current densities as revealed by Raman spectroscopy is also seen. It is also observed that current density depends on edge length and increases with the same for all samples under study. Highest current density of -100 mA cm(-2) at an applied field of 5 V/µm is achieved from the random growth patterned sample with a bundle size of 2 µm and spacing of 4 µm between the bundles.