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1.
ACS Omega ; 9(13): 15547-15555, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38585110

ABSTRACT

Hydrogen getters consisting of 1,4-bis[phenylethynyl] benzene (DEB) and a carbon-supported palladium catalyst (Pd/C) have been used to mitigate the accumulation of unwanted hydrogen gas in a sealed system. Here, we report the formulation of a composite resin consisting of silicone polymer plus DEB-Pd/C as an active getter material and the additive manufacturing of silicone getter composites with a high getter content (up to 50 wt %). NMR and DSC studies suggest no reaction between the silicone polymer resin and DEB even at elevated curing temperatures (75 °C). Getter composites with varying amounts of getter and filler were formulated, and their rheological properties were studied. The two composite resins with good printability parameters and different getter contents were chosen to make 3D-printed samples. The hydrogen absorption capacity of these samples was studied at a low hydrogen pressure of 750 mTorr of pure hydrogen. The getter composite with 50 wt% of getter showed normalized DEB conversion of 83%, with the hydrogen adsorption capacity of 100.2 mL of H2 per gram of polymer getter composite.

2.
J Nepal Health Res Counc ; 21(4): 651-658, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38616598

ABSTRACT

BACKGROUND: Vaccination against COVID-19 for Nepalese was initiated in January 2021 for various age groups. People were anxious about receiving the vaccines and were concerned about the safety profile of the vaccine they received. In this study, we have tried to observe the Adverse Events Following Immunization of two different vaccines namely COVISHIELD (ChAdOx1 nCOV-19) and VERO CELL (CZ02 strain), used in different phases of vaccination by the government of Nepal. METHODS: We conducted a cross-sectional study among people who received COVID-19 vaccines in this study using a self-administered questionnaire.  Data was cleaned and then exported to IBM SPSS v.20 for analysis, Chi-square test was used to see the association between different variables and a p-value<0.05 was considered statistically significant. RESULTS: Out of 303 respondents, all had received the first and 270 participants had received the second dose of the COVID-19 vaccine, among which, 133 (43.89%) reported at least one side effect after the first dose of vaccination while 58 (21.48%) had self-reported side effects after the second dose of vaccination. Seventeen percent of the respondents had COVID-19 infection within the past 3 months before receiving COVID-19 vaccine. Three percent of participants had re-infection with COVID-19 after receiving the first or the second dose of the COVID-19 vaccine. Among participants who experienced adverse events, 42% and 62.1% of participants experienced mild adverse events following the first dose and second dose of the vaccine, respectively.  Conclusions: The adverse events following immunization for both vaccines after both doses of vaccination were quite low, with 43.89% of participants reporting side effects after the first dose and 21.48% of participants reporting side effects after the second dose. Adverse events were most frequently reported within 24 hours of vaccination and were mostly mild. There was no statistical significance of adverse events between both vaccines.


Subject(s)
COVID-19 , ChAdOx1 nCoV-19 , Chlorocebus aethiops , Animals , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , Vero Cells , Nepal/epidemiology , Immunization Programs
3.
ACS Macro Lett ; 13(1): 28-33, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38100721

ABSTRACT

We report a rapid postgrafting reaction to prepare alkyl ammonium functionalized polycarbazoles from a commercially available monomer. This novel synthetic approach provides benefit to preparing the high molecular weight quaternized polycarbazoles within 1 h of Friedel-Crafts polycondensation, avoiding the synthesis and purification step to prepare a functionalized monomer. The postgrafting reaction produces hexyl alkyl ammonium functionalized polycarbazole with 100% grafting degree. However, the postgrafting reaction produced only 60% grafting with propyl alkyl ammonium due to the competitive elimination reaction because of the higher acidity of ß-hydrogen in the propyl alkyl group resulting from the proximity of the bromide and ammonium groups. The hexyl alkyl ammonium functionalized polycarbazole has a high hydroxide conductivity of 103 mS cm-1 at 80 °C and showed excellent alkaline stability with less than 3% loss of ion group after 1 M NaOH treatment at 80 °C for 500 h. This study highlights that the postgrafting reaction provides a pathway for the scale-up synthesis of quaternized aryl ether-free polyaromatics.

4.
Polymers (Basel) ; 15(21)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37960014

ABSTRACT

Although fumed silica/siloxane suspensions are commonly employed in additive manufacturing technology, the interplay between shelf life, storage conditions, and printability has yet to be explored. In this work, direct ink writing (DIW) was used to print unique three-dimensional structures that required suspensions to retain shape and form while being printed onto a substrate. Suspensions containing varying concentrations of hydrophobic and hydrophilic silica were formulated and evaluated over a time span of thirty days. Storage conditions included low (8%) and high (50%) relative humidity and temperatures ranging from 4 °C to 25 °C. The shelf life of the suspensions was examined by comparing the print quality of pristine and aged samples via rheology, optical microscopy, and mechanical testing. Results showed a significant decrease in printability over time for suspensions containing hydrophilic fumed silica, whereas the printability of suspensions containing hydrophobic fumed silica remained largely unchanged after storage. The findings in this work established the following recommendations for extending the shelf life and printability of suspensions commonly used in DIW technology: (1) higher fumed silica concentrations, (2) low humidity and low temperature storage environments, and (3) the use of hydrophobic fumed silica instead of hydrophilic fumed silica.

5.
Hum Vaccin Immunother ; 19(2): 2239680, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37539816

ABSTRACT

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.


Subject(s)
COVID-19 , Humans , Child , COVID-19/prevention & control , COVID-19/epidemiology , Pandemics/prevention & control , Nepal/epidemiology , Infection Control , Clinical Trials, Phase III as Topic
6.
Cell Rep ; 42(5): 112435, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37104088

ABSTRACT

Organelle interactions play a significant role in compartmentalizing metabolism and signaling. Lipid droplets (LDs) interact with numerous organelles, including mitochondria, which is largely assumed to facilitate lipid transfer and catabolism. However, quantitative proteomics of hepatic peridroplet mitochondria (PDM) and cytosolic mitochondria (CM) reveals that CM are enriched in proteins comprising various oxidative metabolism pathways, whereas PDM are enriched in proteins involved in lipid anabolism. Isotope tracing and super-resolution imaging confirms that fatty acids (FAs) are selectively trafficked to and oxidized in CM during fasting. In contrast, PDM facilitate FA esterification and LD expansion in nutrient-replete medium. Additionally, mitochondrion-associated membranes (MAM) around PDM and CM differ in their proteomes and ability to support distinct lipid metabolic pathways. We conclude that CM and CM-MAM support lipid catabolic pathways, whereas PDM and PDM-MAM allow hepatocytes to efficiently store excess lipids in LDs to prevent lipotoxicity.


Subject(s)
Fatty Acids , Lipid Metabolism , Fatty Acids/metabolism , Liver/metabolism , Lipid Droplets/metabolism , Proteome/metabolism
7.
JNMA J Nepal Med Assoc ; 61(266): 755-757, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-38289781

ABSTRACT

Introduction: Poisoning occurs when substances are ingested, inhaled, or absorbed through skin contact in quantities that are harmful to the body. Knowledge of the pattern and prevalence of paediatric poisoning will help us quantify the burden of poisoning. The aim of the study was to find out the prevalence of poisoning among children visiting the Paediatric Emergency Department in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among children visiting the Paediatric Emergency Department in a tertiary care centre. Data from 1 January 2020 to 31 December 2021 was collected between 15 April 2022 to 25 April 2022 from medical records. Ethical approval was taken from the Institutional Review Committee. Children aged 0 to 14 years old were included in the study. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 12,488 children, 162 (1.30%) (1.10-1.50, 95% Confidence Interval) had poisoning. Pesticides and insecticides were the most common agents involved in poisoning 39 (24.07%). Conclusions: The prevalence of poisoning was found to be lower than other studies done in similar settings. Keywords: children; Nepal; poisoning.


Subject(s)
Emergency Service, Hospital , Pesticides , Humans , Child , Infant, Newborn , Infant , Child, Preschool , Adolescent , Tertiary Care Centers , Cross-Sectional Studies , Nepal/epidemiology
8.
Cureus ; 15(12): e50167, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38186511

ABSTRACT

Thrombocytopenia is a rare but potentially serious complication associated with the use of various medications, including antibiotics. Piperacillin-tazobactam (Zosyn), a commonly used broad-spectrum antibiotic, has been reported as an infrequent cause of drug-induced thrombocytopenia. We present a case of a 65-year-old female with end-stage renal disease (ESRD) on hemodialysis, HIV, and multiple comorbidities who developed rapid-onset thrombocytopenia shortly after receiving Zosyn. The patient's platelet count dropped from a baseline of 291,000/µL on admission to a nadir of 8,000/µL within 36 hours of starting Zosyn. The administration of Zosyn was promptly discontinued, and the patient's platelet count gradually increased to 134,000/µL within two days after discontinuation. The patient had no apparent bleeding manifestations during her hospital stay. Further workup for other causes of thrombocytopenia, including heparin-induced thrombocytopenia (HIT), was negative. This case highlights the importance of vigilance for drug-induced thrombocytopenia in patients receiving Zosyn and the need for prompt recognition and management to prevent potential complications.

9.
J Nepal Health Res Counc ; 21(2): 297-302, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38196224

ABSTRACT

BACKGROUND: Enteric fever is a major public health problem in developing and under developed countries. Case fatality rate without treatment is 10-30% and with appropriate treatment is only 1-4%. Gold standard for diagnosis is isolation of Salmonella enterica from blood or bone marrow. Antibiotics resistance is skyrocketing with emergence of multidrug resistance S. typhi and extensively drug resistant S. typhi. METHODS: The blood culture done in Kanti children hospital in last six years were taken from the data base and the culture positive cases were taken from which the salmonella species positive cases along with the drug sensitivity pattern were used in our study. RESULTS: The culture positivity rate was 2.8% and 7.6% (n=136) among the culture positive cases were Salmonella species. Salmonella typhi (121; 88.9%) was the most frequently isolated species, followed by Salmonella paratyphi A (13; 9.5%) and Salmonella paratyphi B (2;1.4%). Children with age 5-10 years was the most affected age group for infection with Salmonella, 50.0% (n=68). Nalidixic acid is resistant in 89.9% Salmonella typhi; followed by ciprofloxacin (31.8%), ofloxacin (18.2%), ampicillin (9.6%), azithromycin (8.4%), chloramphenicol (8.2%), cotrimoxazole (5.4%), cefixime (4%), ceftriaxone (2.5%) and cefotaxime (0.0%). Cefixime, ceftriaxone, cefotaxime are 100% sensitive to Salmonella paratyphi, followed by cotrimoxazole (92.9%), ofloxacin (81.8%), chloramphenicol (75%), azithromycin (66.7%), ampicillin (60%), ciprofloxacin (50%) and Nalidixic acid (23.1%). CONCLUSIONS: Salmonella species culture isolatation are declining every year. Fluoroquinolones have more resistance than first line drugs of typhoid, azithromycin resistance is rising but 3rd generation cephalosporins are sensitive to Salmonella species.


Subject(s)
Typhoid Fever , Typhoid-Paratyphoid Vaccines , Child , Humans , Child, Preschool , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Typhoid Fever/drug therapy , Typhoid Fever/epidemiology , Typhoid Fever/prevention & control , Azithromycin/pharmacology , Azithromycin/therapeutic use , Cefixime , Ceftriaxone , Nalidixic Acid , Trimethoprim, Sulfamethoxazole Drug Combination , Nepal , Ciprofloxacin , Cefotaxime , Ofloxacin , Ampicillin , Chloramphenicol , Salmonella typhi
10.
J Nepal Health Res Counc ; 20(2): 475-481, 2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36550731

ABSTRACT

BACKGROUND: The second wave of COVID-19 pandemic hit all age groups with different presentations and outcomes. This study aimed to explore the clinical characteristics, investigational findings, hospital outcomes along with a ninety days telephonic follow-up of COVID-19 infection in children. METHODS: A longitudinal descriptive study among COVID-19 RT-PCR positive hospital-admitted children was conducted during the second wave of the pandemic from 15 Mar 2021 to 15 Oct 2021 at Kanti Children's Hospital. Demographics, clinical characteristics, oxygen saturation, comorbidities, need of oxygen, need of ventilator, laboratory investigations, admission to intensive care unit, duration of hospital stay and patient's outcome (improved and discharged or death) were recorded. A follow up at ninety days from discharge was also done via telephonic call to inquire for any illness and hospital admission. RESULTS: Among the 156 admitted children, males and females were 54.5% and 45.5% with a median age of 15 months and Inter quartile range (IQR) of 63. Thirty-six (23.1%) were underweight and 31 (19.9%) had comorbidities. The most common presenting symptoms were fever 115 (73.7%), cough 50 (32.1%) and vomiting 38 (24.4%). The median (IQR) length of hospital stay was 15 (range of 11-20) days. Oxygen use was seen among 35 (22.4%) cases and 36 (23.1%) cases were admitted to the ICU. Ventilator was required for 7 (4.5%) cases. The number of deaths was 9 (5.8%) during hospital stay. After discharge from the hospital during the ninety days follow-up, 117 children had no health problems while 42 reported having some health problems and 5 died after discharge. CONCLUSIONS: In the second wave of the pandemic, only symptomatic children were admitted. Respiratory and gastrointestinal symptoms were common among the admitted cases. The majority of admitted cases had a good outcome and had no other health problems attributable to COVID-19 till ninety days of follow-up.


Subject(s)
COVID-19 , Male , Female , Humans , Child , Infant , COVID-19/epidemiology , Patient Discharge , Pandemics , SARS-CoV-2 , Nepal , Treatment Outcome , Oxygen
11.
Inorg Chem ; 61(44): 17746-17758, 2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36282246

ABSTRACT

To provide new insights for understanding the influence of B site cations on the structure in chlorometallate materials of the form ABn+Cln+2, we report novel organic-inorganic hybrid metallates (OIHMs) incorporating histammonium (HistNH3) dications and various transition-metal and main group B site cations. Single crystals of OIHMs with the basic formula (HistNH3Mn+Cln+2, M = Fe, Co, Ni, Cu, Zn, Cd, Hg, Sb, Sn, Pb, Bi) were grown and their structures characterized by single-crystal X-ray crystallography. HistNH3CoCl4, HistNH3ZnCl4, and HistNH3SbCl5 were crystallized in a non-centrosymmetric space group and were subsequently studied with piezoresponse force microscopy (PFM). While bulk measurements of crystals and poly(vinylidene difluoride) (PVDF)/metallate composite films exhibited low bulk response values, the surface-measured local response values using PFM were 5.17 pm/V for HistNH3CoCl4, 22.6 pm/V for HistNH3ZnCl4, and 2.9 pm/V for HistNH3SbCl5 compared with 2.50 pm/V for PVDF reference samples. The magnitudes of the d33 coefficient, net dipole, and cation-Cl bond dipole obtained from the density functional theory calculations confirm the higher response in HistNH3ZnCl4 compared to HistNH3CoCl4. Density of states and crystal orbital Hamilton population analysis indicate that the higher net dipole in HistNH3ZnCl4 compared to HistNH3CoCl4 is due to the lower hybridization of the M-Cl bond.

12.
Nucleic Acids Res ; 50(13): e78, 2022 07 22.
Article in English | MEDLINE | ID: mdl-35524554

ABSTRACT

The dynamic rearrangement of chromatin is critical for gene regulation, but mapping both the spatial organization of chromatin and its dynamics remains a challenge. Many structural conformations are too small to be resolved via conventional fluorescence microscopy and the long acquisition time of super-resolution photoactivated localization microscopy (PALM) precludes the structural characterization of chromatin below the optical diffraction limit in living cells due to chromatin motion. Here we develop a correlative conventional fluorescence and PALM imaging approach to quantitatively map time-averaged chromatin structure and dynamics below the optical diffraction limit in living cells. By assigning localizations to a locus as it moves, we reliably discriminate between bound and unbound dCas9 molecules, whose mobilities overlap. Our approach accounts for changes in DNA mobility and relates local chromatin motion to larger scale domain movement. In our experimental system, we show that compacted telomeres move faster and have a higher density of bound dCas9 molecules, but the relative motion of those molecules is more restricted than in less compacted telomeres. Correlative conventional and PALM imaging therefore improves the ability to analyze the mobility and time-averaged nanoscopic structural features of locus specific chromatin with single molecule sensitivity and yields unprecedented insights across length and time scales.


Subject(s)
Chromatin , DNA , Molecular Imaging/methods , CRISPR-Associated Protein 9/metabolism , Chromosomes , DNA/chemistry , DNA/genetics , Molecular Dynamics Simulation , Single Molecule Imaging/methods
13.
Hum Vaccin Immunother ; 18(5): 2051413, 2022 11 30.
Article in English | MEDLINE | ID: mdl-35353657

ABSTRACT

Due to the inherent complex nature of clinical trials, individual's willingness to participate and hence, enrollment in a clinical trial maybe challenging. When it comes to vaccine clinical trial in children, informed consent needs to be secured from the parents or legally acceptable representatives (LARs). Some of the factors which contribute to hesitancy in taking part in clinical trials are based on the level of education, living standards, part of the world they live, associated burden of disease, fear of different procedures in clinical trial, side effects, limited understanding, limited time, and mistrust with Investigational product. This study included 201 parents/LARs, who approached Kanti Children Hospital site in Kathmandu with the interest to get their children enrolled in a vaccine clinical trial with objectives of describing the reasons for agreeing or disagreeing to participate in the vaccine clinical trial, factors affecting decision making, and finding the major concerns of parents/LARs. The acceptance for the study vaccine was 136 (67.7%) whereas denial was 65 (32.3%). This study showed that age, education level, family structure, advice from family and friends, and medical guidance play important roles in willingness of parents to get their child enrolled in the trial. If a proper counseling is done, fear of blood sampling is not a big factor which is contrary to the belief among clinical researchers. Safety of vaccine, frequency of injections, and cost of vaccine were the main concerns of the parents, which need to be addressed extensively while planning for any clinical trial in children.


Subject(s)
Clinical Trials as Topic , Patient Participation , Vaccines , Child , Developing Countries , Humans , Informed Consent/psychology , Nepal , Parents/psychology , Patient Participation/psychology , Vaccines/administration & dosage , Vaccines/adverse effects
14.
ACS Appl Bio Mater ; 5(2): 545-551, 2022 02 21.
Article in English | MEDLINE | ID: mdl-35113537

ABSTRACT

The reliance on antibiotics and antimicrobials to treat bacterial infectious diseases is threatened by the emergence of antibiotic resistance and multi-drug-resistant organisms, thus having the potential to greatly impact human health. Thus, the discovery and development of antimicrobials capable of acting on antibiotic-resistant bacteria is a major area of significance in scientific research. Herein, we present the development of a eumelanin-inspired antimicrobial capable of killing methicillin-resistant Staphylococcus aureus (MRSA). By ligating quaternary ammonium-functionalized "arms" to a eumelanin-inspired indole with intrinsic antimicrobial activity, an antimicrobial agent with enhanced activity was prepared. This resulting antimicrobial, EIPE-1, had a minimum inhibitory concentration of 16 µg/mL (17.1 µM) against a clinical isolate of MRSA obtained from an adult cystic fibrosis patient. The biocidal activity occurred within 30 min of exposure and resulted in changes to the bacterial cell surface as visualized with a scanning electron microscope. Taken together, these studies demonstrate that EIPE-1 is effective at killing MRSA.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Adult , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Drug Resistance, Microbial , Humans , Microbial Sensitivity Tests
15.
Nat Commun ; 13(1): 142, 2022 01 10.
Article in English | MEDLINE | ID: mdl-35013231

ABSTRACT

The establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation.


Subject(s)
Cell Lineage/genetics , Epigenesis, Genetic , G-Quadruplexes , Histones/metabolism , Human Embryonic Stem Cells/metabolism , Pluripotent Stem Cells/metabolism , Protein Processing, Post-Translational , Biomarkers/metabolism , Cell Differentiation , Cell Line , DNA/genetics , DNA/metabolism , DNA Methylation , Enhancer Elements, Genetic , Gene Expression , Histones/genetics , Human Embryonic Stem Cells/cytology , Humans , Nanog Homeobox Protein/genetics , Nanog Homeobox Protein/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nestin/genetics , Nestin/metabolism , Octamer Transcription Factor-3/genetics , Octamer Transcription Factor-3/metabolism , PAX6 Transcription Factor/genetics , PAX6 Transcription Factor/metabolism , Pluripotent Stem Cells/cytology , Promoter Regions, Genetic , Receptors, Nerve Growth Factor/genetics , Receptors, Nerve Growth Factor/metabolism , Transcription Factor AP-2/genetics , Transcription Factor AP-2/metabolism
16.
Sensors (Basel) ; 21(22)2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34833660

ABSTRACT

Advancements in electrode technologies to both stimulate and record the central nervous system's electrical activities are enabling significant improvements in both the understanding and treatment of different neurological diseases. However, the current neural recording and stimulating electrodes are metallic, requiring invasive and damaging methods to interface with neural tissue. These electrodes may also degrade, resulting in additional invasive procedures. Furthermore, metal electrodes may cause nerve damage due to their inherent rigidity. This paper demonstrates that novel electrically conductive organic fibers (ECFs) can be used for direct nerve stimulation. The ECFs were prepared using a standard polyester material as the structural base, with a carbon nanotube ink applied to the surface as the electrical conductor. We report on three experiments: the first one to characterize the conductive properties of the ECFs; the second one to investigate the fiber cytotoxic properties in vitro; and the third one to demonstrate the utility of the ECF for direct nerve stimulation in an in vivo rodent model.


Subject(s)
Nanotubes, Carbon , Electric Conductivity , Electric Stimulation , Electrodes
17.
J Nepal Health Res Counc ; 19(2): 349-354, 2021 Sep 06.
Article in English | MEDLINE | ID: mdl-34601529

ABSTRACT

BACKGROUND: COVID-19 pandemic hit all age group with different presentations and outcome. This study aimed at exploring the clinical characteristics, investigational findings, hospital outcome along with 90 days follow up of COVID-19 infection in children. METHODS: This was longitudinal descriptive study among hospital admitted children with COVID-19 RT-PCR positive during first wave of Pandemic with 90 days telephonic follow up. Demographic and clinical characteristics, comorbidities, SPO2, investigations, need of oxygen , PICU admission, need of ventilator, outcome (improved and discharged, death) and duration of hospital stay were recorded and 90 days telephonic follow up was performed for any illness and hospital admission. RESULTS: Out of 65 children admitted, male 44 (67.7%) and female 21 (32.3%), median age was 23 months ( IQR 6 days -14 years) with 52( 80.0%) without any comorbid conditions. The common signs were Fever 40(61.5%) vomiting 15 (23.1%) and Cough 11(16.9%).Thirteen (20.0%) children has platelets count less than 150000 and 16(24.6%) had C - reactive protein Positive .Mean duration of hospital stay 8 days (Range 1 -44 days), 20( 30.8% ) needed oxygen , 20(30.8%) needed Pediatric intensive care unit (PICU)admission and 6 (9.2%), needed ventilator. Forty seven (72.3%) recovered and discharged with death of 6.2% (n=4). Fifty six children (75.4%) has not experienced any problem after COVID -19 and only 2 children needed hospital admission in 90 days telephone follow up. CONCLUSIONS: In the first wave of the pandemic, Respiratory and Gastrointestinal symptoms were common presentation with few Severe and critical cases. Majority had good outcome. Majority has no other related illness till 90 days after discharge.


Subject(s)
COVID-19 , Pandemics , Child , Child, Preschool , Female , Hospitals, Pediatric , Humans , Infant , Laboratories , Male , Nepal/epidemiology , SARS-CoV-2
18.
J Chem Phys ; 155(6): 064109, 2021 Aug 14.
Article in English | MEDLINE | ID: mdl-34391355

ABSTRACT

Density functional theory (DFT) and beyond-DFT methods are often used in combination with photoelectron spectroscopy to obtain physical insights into the electronic structure of molecules and solids. The Kohn-Sham eigenvalues are not electron removal energies except for the highest occupied orbital. The eigenvalues of the highest occupied molecular orbitals often underestimate the electron removal or ionization energies due to the self-interaction (SI) errors in approximate density functionals. In this work, we adapt and implement the density-consistent effective potential method of Kohut, Ryabinkin, and Staroverov [J. Chem. Phys. 140, 18A535 (2014)] to obtain SI-corrected local effective potentials from the SI-corrected Fermi-Löwdin orbitals and density in the Fermi-Löwdin orbital self-interaction correction scheme. The implementation is used to obtain the density of states (photoelectron spectra) and HOMO-LUMO gaps for a set of molecules and polyacenes. Good agreement with experimental values is obtained compared to a range of SI uncorrected density functional approximations.

19.
Nat Chem ; 13(7): 626-633, 2021 07.
Article in English | MEDLINE | ID: mdl-34183817

ABSTRACT

DNA-protein interactions regulate critical biological processes. Identifying proteins that bind to specific, functional genomic loci is essential to understand the underlying regulatory mechanisms on a molecular level. Here we describe a co-binding-mediated protein profiling (CMPP) strategy to investigate the interactome of DNA G-quadruplexes (G4s) in native chromatin. CMPP involves cell-permeable, functionalized G4-ligand probes that bind endogenous G4s and subsequently crosslink to co-binding G4-interacting proteins in situ. We first showed the robustness of CMPP by proximity labelling of a G4 binding protein in vitro. Employing this approach in live cells, we then identified hundreds of putative G4-interacting proteins from various functional classes. Next, we confirmed a high G4-binding affinity and selectivity for several newly discovered G4 interactors in vitro, and we validated direct G4 interactions for a functionally important candidate in cellular chromatin using an independent approach. Our studies provide a chemical strategy to map protein interactions of specific nucleic acid features in living cells.


Subject(s)
Alkynes/chemistry , Cross-Linking Reagents/chemistry , DNA-Binding Proteins/metabolism , DNA/metabolism , Diazomethane/chemistry , G-Quadruplexes , Aminoquinolines/chemistry , Cell Line, Tumor , Cross-Linking Reagents/radiation effects , DNA/chemistry , DNA/genetics , DNA-Binding Proteins/chemistry , Diazomethane/radiation effects , HEK293 Cells , Humans , Ligands , Proof of Concept Study , Protein Binding , Ultraviolet Rays
20.
Mol Biol Cell ; 32(17): 1565-1578, 2021 08 15.
Article in English | MEDLINE | ID: mdl-34161133

ABSTRACT

Lipid droplets (LDs) are dynamic organelles for lipid storage and homeostasis. Cells respond to metabolic changes by regulating the spatial distribution of LDs and enzymes required for LD growth and turnover. The small size of LDs precludes the observation of their associated enzyme densities and dynamics with conventional fluorescence microscopy. Here we employ quantitative photo-activated localization microscopy to study the density of the fatty acid (FA) activating enzyme Faa4 on LDs in live yeast cells with single-molecule sensitivity and 30 nm resolution. During the log phase LDs colocalize with the endoplasmic reticulum (ER) where their emergence and expansion are mediated by the highest observed Faa4 densities. During transition to the stationary phase, LDs with a ∼2-fold increased surface area translocate to the vacuolar surface and lumen and exhibit a ∼2.5-fold increase in Faa4 density. The increased Faa4 density on LDs further suggests its role in LD expansion, is caused by its ∼5-fold increased expression level, and is specific to exogenous FA chain-lengths. When lipolysis is induced by refreshed medium, Faa4 shuttles through ER- and lipophagy to the vacuole, where it may activate FAs for membrane expansion and degrade Faa4 to reset its cellular abundance to levels in the log phase.


Subject(s)
Acyl Coenzyme A/metabolism , Lipid Droplets/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Acyl Coenzyme A/physiology , Autophagy , Endoplasmic Reticulum/metabolism , Fatty Acids/metabolism , Homeostasis , Lipid Droplets/physiology , Lipid Metabolism , Lipolysis , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/physiology , Vacuoles/metabolism
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