Publications by authors named "Arnab Ghosh"

313 Publications

Gas transfer model for a multistage vortex aerator: A novel oxygen transfer system for dissolved oxygen improvement.

J Environ Manage 2022 Jul 14;319:115704. Epub 2022 Jul 14.

Department of Civil Engineering, Dong-A University, 37 Nakdong-daero Saha-gu, Busan, 49315, Republic of Korea.

A novel aerator for enhancing the oxygen transfer rate and efficiency, named multistage vortex aerator (MVA), was developed. It uses vortex flow in repeated stages to increase the gas-liquid interfacial area and to decrease the thickness of the stagnant layer at the interface between the two phases. The basic characteristics of oxygen transfer using this aerator were investigated using the American Society of Civil Engineers standard procedure. The MVA could rapidly transfer oxygen to water to a concentration higher than 40 mg/L in 60 min owing to the effect of high purity oxygen, additional pressure induced by water and gas, and vortex flow dynamics. A gas transfer model was developed for describing the non-steady state operation of the aerator. This model is based on the mass and molar balances of oxygen in gas and water. It could successfully simulate the DO change inside the aerator. This study can help better understand the oxygen transfer mechanism and evaluate the performance of the new aerator at the various temperatures, pressures, and gas compositions found in diverse environmental systems.
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http://dx.doi.org/10.1016/j.jenvman.2022.115704DOI Listing
July 2022

Validation of a noninvasive aMMP-8 point-of-care diagnostic methodology in COVID-19 patients with periodontal disease.

Clin Exp Dent Res 2022 Jul 11. Epub 2022 Jul 11.

Department of Internal Medicine, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.

Objectives: The aim of this study was to validate an active matrix metalloproteinase (MMP-8) point-of-care diagnostic tool in COVID-19 patients with periodontal disease.

Subjects, Materials, And Methods: Seventy-two COVID-19-positive and 30 COVID-19-negative subjects were enrolled in the study. Demographic data were recorded, periodontal examination carried out, and chairside tests run for evaluating the expression of active MMP-8 (aMMP-8) in the site with maximum periodontal breakdown via gingival crevicular fluid sampling as well as via a mouth rinse-based kit for general disease activity. In COVID-19-positive patients, the kits were run again once the patients turned COVID-19 negative.

Results: The overall (n = 102) sensitivity/specificity of the mouthrinse-based kits to detect periodontal disease was 79.41%/36.76% and that of site-specific kits was 64.71%/55.88% while adjusting for age, gender, and smoking status increased the sensitivity and specificity (82.35%/76.47% and 73.53%/88.24, respectively). Receiver operating characteristic (ROC) analysis for the adjusted model revealed very good area under the ROC curve 0.746-0.869 (p < .001) and 0.740-0.872 (p < .001) (the aMMP-8 mouth rinse and site-specific kits, respectively). No statistically significant difference was observed in the distribution of results of aMMP-8 mouth rinse test (p = .302) and aMMP-8 site-specific test (p = .189) once the subjects recovered from COVID-19.

Conclusions: The findings of the present study support the aMMP-8 point-of-care testing (PoCT) kits as screening tools for periodontitis in COVID-19 patients. The overall screening accuracy can be further increased by utilizing adjunctively risk factors of periodontitis. The reported noninvasive, user-friendly, and objective PoCT diagnostic methodology may provide a way of stratifying risk groups, deciding upon referrals, and in the institution of diligent oral hygiene regimens.
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http://dx.doi.org/10.1002/cre2.589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350191PMC
July 2022

Essential oil nebulization in mild COVID-19(EONCO): Early phase exploratory clinical trial.

J Ayurveda Integr Med 2022 Jul 6:100626. Epub 2022 Jul 6.

Department of Pharmacology, PGIMER, Chandigarh.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids.

Aim: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19.

Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10.

Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034).

Conclusion: EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.
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http://dx.doi.org/10.1016/j.jaim.2022.100626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257088PMC
July 2022

Society of General Internal Medicine Position Statement on Social Risk and Equity in Medicare's Mandatory Value-Based Payment Programs.

J Gen Intern Med 2022 Jun 29. Epub 2022 Jun 29.

Maine Medical Center Research Institute, Scarborough, ME, USA.

The Affordable Care Act (2010) and Medicare Access and CHIP Reauthorization Act (2015) ushered in a new era of Medicare value-based payment programs. Five major mandatory pay-for-performance programs have been implemented since 2012 with increasing positive and negative payment adjustments over time. A growing body of evidence indicates that these programs are inequitable and financially penalize safety-net systems and systems that care for a higher proportion of racial and ethnic minority patients. Payments from penalized systems are often redistributed to those with higher performance scores, which are predominantly better-financed, large, urban systems that serve less vulnerable patient populations - a "Reverse Robin Hood" effect. This inequity may be diminished by adjusting for social risk factors in payment policy. In this position statement, we review the literature evaluating equity across Medicare value-based payment programs, major policy reports evaluating the use of social risk data, and provide recommendations on behalf of the Society of General Internal Medicine regarding how to address social risk and unmet health-related social needs in these programs. Immediate recommendations include implementing peer grouping (stratification of healthcare systems by proportion of dual eligible Medicare/Medicaid patients served, and evaluation of performance and subsequent payment adjustments within strata) until optimal methods for accounting for social risk are defined. Short-term recommendations include using census-based, area-level indices to account for neighborhood-level social risk, and developing standardized approaches to collecting individual socioeconomic data in a robust but sensitive way. Long-term recommendations include implementing a research agenda to evaluate best practices for accounting for social risk, developing validated health equity specific measures of care, and creating policies to better integrate healthcare and social services.
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http://dx.doi.org/10.1007/s11606-022-07698-9DOI Listing
June 2022

Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine.

Sci Transl Med 2022 06 15;14(649):eaba4380. Epub 2022 Jun 15.

Department of Oncology, National Center for Cancer Immune Therapy, Herlev Hospital, Herlev 2730, Denmark.

The majority of JAK2-negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin (), resulting in a common carboxyl-terminal mutant fragment (CALR), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALR-specific T cells are rare in patients with CALR MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALR MPN from two independent cohorts. We observed that MHC-I alleles that present CALR neoepitopes with high affinity are underrepresented in patients with CALR MPN. We speculated that this was due to an increased chance of immune-mediated tumor rejection by individuals expressing one of these MHC-I alleles such that the disease never clinically manifested. As a consequence of this MHC-I allele restriction, we reasoned that patients with CALR MPN would not efficiently respond to a CALR fragment cancer vaccine but would when immunized with a modified CALR heteroclitic peptide vaccine approach. We found that heteroclitic CALR peptides specifically designed for the MHC-I alleles of patients with CALR MPN efficiently elicited a CALR cross-reactive CD8 T cell response in human peripheral blood samples but not to the matched weakly immunogenic CALR native peptides. We corroborated this effect in vivo in mice and observed that C57BL/6J mice can mount a CD8 T cell response to the CALR fragment upon immunization with a CALR heteroclitic, but not native, peptide. Together, our data emphasize the therapeutic potential of heteroclitic peptide-based cancer vaccines in patients with CALR MPN.
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http://dx.doi.org/10.1126/scitranslmed.aba4380DOI Listing
June 2022

PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin.

Blood Adv 2022 Jun 6. Epub 2022 Jun 6.

Center for RNA Science and Therapeutics, Case Western Reserve University, United States.

The fetal to adult hemoglobin switching around birth involves an expression shift from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the physiological and clinical relevance of this switch, its post-transcriptional regulation is poorly understood. Here, we identify Pumilo-1 (PUM1), an RNA binding protein with no previously reported functions in erythropoiesis, as a direct post-transcriptional regulator of β-globin switching. PUM1, whose expression is regulated by the erythroid master transcription factor, Erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin mRNA, and reduces γ-globin (HBG1) mRNA stability and translational efficiency, which culminates in reduced γ-globin protein levels. Knockdown of PUM1 leads to a robust increase in fetal hemoglobin (~22% HbF), without affecting β-globin levels in human erythroid cells. Importantly, targeting PUM1 does not limit erythropoiesis progression, providing a potentially safe and effective treatment strategy in sickle cell anemia and β-thalassemia. In support of this idea, we report elevated fetal hemoglobin levels in the absence of anemia, in an individual with a novel heterozygous PUM1 mutation in the RNA binding domain (p.(His1090Profs*16); c.3267_3270delTCAC), suggesting that PUM1 mediated post-transcriptional regulation is a critical player during human hemoglobin switching.
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http://dx.doi.org/10.1182/bloodadvances.2021006730DOI Listing
June 2022

Mucinous Carcinoma of the Skin: A Case Report.

JNMA J Nepal Med Assoc 2022 Apr 15;60(248):402-405. Epub 2022 Apr 15.

Department of Surgery, Manipal College of Medical Sciences, Pokhara, Kaski, Nepal.

Primary mucinous carcinoma of the skin is a rare malignant neoplasm showing predilection to the periorbital region. These tumours are indolent and low-grade, with a tendency for local, sometimes multiple, recurrences. Distinguishing between these primary neoplasms and the more frequent metastatic mucinous deposits on the skin from primaries in the breast and gastrointestinal tract constitutes a diagnostic dilemma. In this case report, we have put forth the findings of a 70-year-old male who presented with a slow-growing periorbital swelling and was subsequently diagnosed with mucinous adenocarcinoma. An extensive workup in search of another primary tumour failed to show a primary malignancy elsewhere and the diagnosis of primary mucinous adenocarcinoma of the skin was rendered.

Keywords: case reports; mucinous carcinoma; Nepal; sialomucins.
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http://dx.doi.org/10.31729/jnma.7415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252249PMC
April 2022

A Huge Mesenteric Lymphangioma Presenting as a Small Bowel Volvulus in a Paediatric Patient: A Case Report.

Case Rep Pathol 2022 17;2022:3033705. Epub 2022 May 17.

Department of Pathology, Manipal College of Medical Sciences, Pokhara, Nepal.

Lymphangioma is a benign tumor characterized by proliferation of thin-walled lymphatic spaces. Lymphangioma of the small-bowel mesentery is rare, with an incidence of 1 : 250,000, representing less than 1% of all lymphangiomas. The predilection of the tumor is in the head and neck (70%), axillary (20%), and internal organs (10%). They are usually asymptomatic but can cause acute abdominal symptoms due to complications such as volvulus, bleeding, or lymphangioma rupture that require emergent surgery. Here, we report a case of mesenteric lymphangioma (ML) of a small bowel in a paediatric patient who presented with pain abdomen on and off which increased in severity and later had features of subacute intestinal obstruction. He underwent explorative laparotomy, and the mass was excised completely along with the part of small intestine. Pathological analysis of the surgical specimen confirmed the diagnosis of ML of the small intestine. The postoperative recovery was uneventful, and the patient was discharged after ten days of hospital stay. Though benign in nature, ML may cause acute abdominal symptoms that require emergent surgery. Therefore, it has to be kept in differential diagnosis of the acute abdominal condition.
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http://dx.doi.org/10.1155/2022/3033705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130006PMC
May 2022

Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer.

iScience 2022 May 27;25(5):104317. Epub 2022 Apr 27.

National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India.

Cancer cell state transitions emerged as powerful mechanisms responsible for drug tolerance and overall poor prognosis; however, evidences were largely missing in oral cancer. Here, by multiplexing phenotypic markers of stem-like cancer cells (SLCCs); CD44, CD24 and aldehyde dehydrogenase (ALDH), we characterized diversity among multiple oral tumor tissues and cell lines. Two distinct patterns of spontaneous transitions with stochastic bidirectional interconversions on 'ALDH-axis', and unidirectional non-interconvertible transitions on 'CD24-axis' were observed. Interestingly, plastic 'ALDH-axis' was harnessed by cells to adapt to a Cisplatin tolerant state. Furthermore, phenotype-specific RNA sequencing suggested the possible maintenance of intermediate hybrid cell states maintaining stemness within the differentiating subpopulations. Importantly, survival analysis with subpopulation-specific gene sets strongly suggested that cell-state transitions may drive non-genetic heterogeneity, resulting in poor prognosis. Therefore, we have described the phenotypic-composition of heterogeneous subpopulations critical for global tumor behavior in oral cancer; which may provide prerequisite knowledge for treatment strategies.
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http://dx.doi.org/10.1016/j.isci.2022.104317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114525PMC
May 2022

Fine-needle aspiration cytology diagnosis of aspergilloma - A case report.

Clin Case Rep 2022 May 12;10(5):e05826. Epub 2022 May 12.

Manipal College of Medical Sciences Pokhara Nepal.

Fine-needle aspiration cytology, a simple and inexpensive technique can aid in early diagnosis of aspergilloma. Here, we present a case of 55-years-old female with a past history of pulmonary tuberculosis and a right-lung cavitary lesion, diagnosed as aspergilloma.
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http://dx.doi.org/10.1002/ccr3.5826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097039PMC
May 2022

Glucocorticoid Receptor β Isoform Predominates in the Human Dysplastic Brain Region and Is Modulated by Age, Sex, and Antiseizure Medication.

Int J Mol Sci 2022 Apr 29;23(9). Epub 2022 Apr 29.

Cerebrovascular Research, Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

The glucocorticoid receptor (GR) at the blood-brain barrier (BBB) is involved in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD); however, the roles of GR isoforms GRα and GRβ in the dysplastic brain have not been revealed. We utilized dysplastic/epileptic and non-dysplastic brain tissue from patients who underwent resective epilepsy surgery to identify the GRα and GRβ levels, subcellular localization, and cellular specificity. BBB endothelial cells isolated from the dysplastic brain tissue (EPI-ECs) were used to decipher the key BBB proteins related to drug regulation and BBB integrity compared to control and transfected GRβ-overexpressed BBB endothelial cells. GRβ was upregulated in dysplastic compared to non-dysplastic tissues, and an imbalance of the GRα/GRβ ratio was significant in females vs. males and in patients > 45 years old. In EPI-ECs, the subcellular localization and expression patterns of GRβ, Hsp90, CYP3A4, and CYP2C9 were consistent with GRβ+ brain endothelial cells. Active matrix metalloproteinase levels and activity increased, whereas claudin-5 levels decreased in both EPI-ECs and GRβ+ endothelial cells. In conclusion, the GRβ has a major effect on dysplastic BBB functional proteins and is age and gender-dependent, suggesting a critical role of brain GRβ in dysplasia as a potential biomarker and therapeutic target in epilepsy.
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http://dx.doi.org/10.3390/ijms23094940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099578PMC
April 2022

Comparison of Multisystem Inflammatory Syndrome (MIS-C) and Dengue in Hospitalized Children.

Indian J Pediatr 2022 May 5. Epub 2022 May 5.

Pediatric Emergency and Intensive Care Units, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.

Objective: Multisystem inflammatory syndrome (MIS-C) in children is a febrile illness that has overlapping presentation with other locally prevalent illnesses. Clinicolaboratory profile of children admitted with MIS-C and dengue were compared to understand their presentation at the outset.

Methods: This was a retrospective study of children ≤ 12 y admitted with MIS-C (WHO definition) or laboratory-confirmed dengue between August 2020 and January 2021 at a tertiary center in North India.

Results: A total of 84 children (MIS-C - 40; dengue - 44) were included. The mean (SD) age [83.5 (39) vs. 91.6 (35) mo] was comparable. Rash (72.5% vs. 22.7%), conjunctival injection (60% vs. 2.3%), oral mucocutaneous changes (27.5% vs. 0) and gallop rhythm (15% vs. 0) were seen more frequently with MIS-C, while petechiae [29.5% vs. 7.5%], myalgia (38.6% vs. 10%), headache (22.7% vs. 2.5%), and hepatomegaly (68.2% vs. 27.5%) were more common with dengue. Children with MIS-C had significantly higher C-reactive protein (124 vs. 3.2 mg/L) and interleukin 6 (95.3 vs. 20.7 ng/mL), while those with dengue had higher hemoglobin (12 vs. 10.2 g/dL) lower mean platelet count (26 vs. 140 × 10/L), and greater elevation in aspartate (607 vs. 44 IU/L) and alanine (235.5 vs. 56 IU/L) aminotransferases. The hospital stay was longer with MIS-C; however, PICU stay and mortality were comparable.

Conclusion: In hospitalized children with acute febrile illness, the presence of mucocutaneous features and highly elevated CRP could distinguish MIS-C from dengue. The presence of petechiae, hepatomegaly, and hemoconcentration may favor a diagnosis of dengue.
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http://dx.doi.org/10.1007/s12098-022-04184-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068862PMC
May 2022

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

JAMA Oncol 2022 07;8(7):1053-1058

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes.

Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT).

Design, Setting, And Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose.

Interventions: Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines.

Main Outcomes And Measures: Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines.

Results: This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]).

Conclusions And Relevance: In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.
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http://dx.doi.org/10.1001/jamaoncol.2022.0752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026224PMC
July 2022

Egg-yolk core-shell mesoporous silica nanoparticles for high doxorubicin loading and delivery to prostate cancer cells.

Nanoscale 2022 May 16;14(18):6830-6845. Epub 2022 May 16.

Global Innovative Centre for Advanced Nanomaterials, Faculty of Engineering and Built Environment, The University of Newcastle, Callaghan, 2308, NSW, Australia.

Mesoporous silica-based nanoparticles (MSNs) have gained rapid interest as a drug delivery system (DDS) and demonstrated their versatility in delivering drugs for the treatment of various cancers. However, the drug loading efficiency of MSNs is low and is usually improved by improving textural properties through complicated synthesis methods or by post synthesis modification of the surface that can result in the loss of surface area and modify its drug release properties. In this study, we report a direct single-step synthesis of MSNs with a unique egg-yolk core-shell morphology, large pore volume and a hydrophilic surface, decorated with nitrogen rich surface functionalities for increasing its drug loading capacity. This combination of excellent textural properties and surface functionalisation was achieved by a simple soft templating method using dual surfactants and the silica sources assisted by employing either triethylamine (TEA) or triethanolamine (TEO) as the hydrolysis agent. The morphology and well-ordered mesoporous structure can simply be tuned by changing the pH of the synthesis medium that affects the self-assembly mechanism of the micelles. HRTEM image of samples clearly revealed an egg-yolk core-shell morphology with a thin mesoporous silica shell. The optimised MSN samples synthesized at a pH of 11 using either TEA or TEO depicted a higher doxorubicin (Dox) loading capacity of 425 μg mg and 481 μg mg respectively, as compared to only 347 μg mg for MSN samples due to the uniform distribution of nitrogen functionalities. The anticancer activity of Dox loaded MSNs evaluated in two different prostate cancer cell lines (PC-3 and LNCaP) showed a higher cytotoxicity of the drug loaded on optimised MSN samples as compared to pristine MSNs without affecting the cellular uptake of the particles. These results suggest that the unique single-step synthesis and functionalisation method resulted in successfully achieving higher drug loading in egg-yolk core-shell nitrogen functionalised MSNs and could be implemented as an effective carrier of chemotherapeutic drugs.
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http://dx.doi.org/10.1039/d2nr00783eDOI Listing
May 2022

The gene encodes RET protein, which triggers intracellular signaling pathways for enteric neurogenesis, and mutation results in Hirschsprung's disease.

AIMS Neurosci 2022 16;9(1):128-149. Epub 2022 Mar 16.

Department of Anatomy, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Karnataka, 576104, India.

Enteric neurons and ganglia are derived from vagal and sacral neural crest cells, which undergo migration from the neural tube to the gut wall. In the gut wall, they first undergo rostrocaudal migration followed by migration from the superficial to deep layers. After migration, they proliferate and differentiate into the enteric plexus. Expression of the Rearranged During Transfection () gene and its protein RET plays a crucial role in the formation of enteric neurons. This review describes the molecular mechanism by which the gene and the RET protein influence the development of enteric neurons. Vagal neural crest cells give rise to enteric neurons and glia of the foregut and midgut while sacral neural crest cells give rise to neurons of the hindgut. Interaction of RET protein with its ligands (glial cell derived neurotrophic factor (GDNF), neurturin (NRTN), and artemin (ARTN)) and its co-receptors (GDNF receptor alpha proteins (GFRα1-4)) activates the Phosphoinositide-3-kinase-protein kinase B (PI3K-PKB/AKT), RAS mitogen-activated protein kinase (RAS/MAPK) and phospholipase Cγ (PLCγ) signaling pathways, which control the survival, migration, proliferation, differentiation, and maturation of the vagal and sacral neural crest cells into enteric neurons. Abnormalities of the gene result in Hirschsprung's disease.
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http://dx.doi.org/10.3934/Neuroscience.2022008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941195PMC
March 2022

Computational prediction of the molecular mechanism of statin group of drugs against SARS-CoV-2 pathogenesis.

Sci Rep 2022 04 14;12(1):6241. Epub 2022 Apr 14.

National Institute of Biomedical Genomics, PO NSS, Kalyani, West Bengal, 741251, India.

Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro, Helicase, and the Spike proteins ( wild type and mutants from different VOCs) were performed using the Schrodinger docking tool. We observed that fluvastatin and pitavastatin showed fair, binding affinities to RNA polymerase and 3-CL-Pro, whereas fluvastatin showed the strongest binding affinity to the helicase. Fluvastatin also showed the highest affinity for the Spike and a fair docking score for other spike variants. Additionally, molecular dynamics simulation confirmed the formation of a stable drug-protein complex between Fluvastatin and target proteins. Thus our study shows that of all the statins, fluvastatin can bind to multiple target proteins of SARS-CoV-2, including the spike-mutant proteins. This property might contribute to the potent antiviral efficacy of this drug.
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http://dx.doi.org/10.1038/s41598-022-09845-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009757PMC
April 2022

Respiratory viral infections other than SARS CoV-2 among the North Indian patients presenting with acute respiratory illness during the first COVID-19 wave.

Virusdisease 2022 Mar 6;33(1):57-64. Epub 2022 Apr 6.

Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012 India.

Acute respiratory infections due to viral or bacterial etiology can cause 60 deaths per one lakh population. Viral etiology is more common as compared to bacterial, but lack of definite diagnosis leads to increased usage of empirical antibiotics. During the first wave of the COVID-19 pandemic, there was a need to identify co-infections especially in severe acute respiratory illness (SARI) patients to identify it as one of the cofactors for increased severity of illness and to identify the causative agents in COVID-19 negative individuals. The SARS CoV-2 real time PCR was carried out using ICMR approved kits and the other respiratory viruses were detected using the multiplex commercially available real time  kit. A total of 186 patients presenting with either SARI (89.8%) or influenza like illness (10.2%) were included in the study. Out of these, 43 (23.1%) were positive for SARS CoV-2 RNA and 2 (4.6%) patients with SARI showed concomitant infection with either human rhinovirus or human respiratory syncytial virus . Out of 143 patients negative for SARS CoV-2, 35 (24.5%) were positive for one or more microbial infections and 28 (19.6%) infected with other respiratory viral infection most common being human rhinovirus. The results suggest that viral coinfections are significantly higher among COVID-19 negative individuals (24.5% vs 4.6%) presenting with respiratory illness as compared to COVID-19 positive individuals possibly due to viral interference and competitive advantage of SARS-CoV-2 in modulating the host immunity. Further detailed research is required for the understanding of mechanisms of viral co-infection.
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http://dx.doi.org/10.1007/s13337-022-00761-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985743PMC
March 2022

Comparing Hospital Length of Stay Risk-Adjustment Models in US Value-Based Physician Payments.

Qual Manag Health Care 2022 Apr 4. Epub 2022 Apr 4.

Departments of Medicine (Drs Ghosh, Lee, and Shapiro) and Population Health Sciences (Drs Ibrahim and Ancker), Weill Cornell Medical College, Cornell University, New York, New York.

Backgroung And Objectives: Under the Affordable Care Act, the US Centers for Medicare & Medicaid Services created Physician Value-Based Payment Modifier Program and its successor the Merit-Based Incentive Payment System to tie physician payments to quality and cost. The addition of hospital length of stay (LOS) to these value-based physician payment models reflects its increasing importance as a metric of health care cost and efficiency and its association with adverse health outcomes. This study compared the Centers for Medicare & Medicaid Services-endorsed LOS risk-adjustment methodology with a novel methodology that accounts for pre-hospitalization clinical, socioeconomic status (SES), and admission-related factors as influential factors of hospital LOS.

Methods: Using the 2014 New York, Florida, and New Jersey State Inpatient Database, we compared the observed-to-expected LOS of 2373102 adult admissions for 742 medical and surgical diagnosis-related groups (DRGs) by 3 models: (a) current risk-adjustment model (CRM), which adjusted for age, sex, number of chronic conditions, Elixhauser comorbidity score, and DRG severity weight, (b) CRM but modeling LOS using a generalized linear model (C-GLM), and (c) novel risk-adjustment model (NRM), which added to the C-GLM covariates for race/ethnicity, SES, discharge destination, weekend admission, and individual intercepts for DRGs instead of severity weights.

Results: The NRM disadvantaged physicians for fewer medical and surgical DRGs, compared with both the C-GLM and CRM models (medical DRGs: 0.49% vs 13.17% and 10.89%, respectively; surgical DRGs: 0.30% vs 13.17% and 10.98%, respectively). In subgroup analysis, the NRM reduced the proportion of physician-penalizing DRGs across all racial/ethnic and socioeconomic groups, with the highest reduction among Whites, followed by low SES patients, and the lowest reduction among Hispanic patients.

Conclusions: After accounting for pre-hospitalization socioeconomic and clinical factors, the adjusted LOS using the NRM was lower than estimates from the current Centers for Medicare & Medicaid Services-endorsed model. The current model may disadvantage physicians serving communities with higher socioeconomic risks.
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http://dx.doi.org/10.1097/QMH.0000000000000363DOI Listing
April 2022

Integrative analysis of genomic and transcriptomic data of normal, tumour, and co-occurring leukoplakia tissue triads drawn from patients with gingivobuccal oral cancer identifies signatures of tumour initiation and progression.

J Pathol 2022 Aug 21;257(5):593-606. Epub 2022 Apr 21.

National Institute of Biomedical Genomics, Kalyani, India.

A thickened, white patch - leukoplakia - in the oral cavity is usually benign, but sometimes (in ~9% of individuals) it progresses to malignant tumour. Because the genomic basis of this progression is poorly understood, we undertook this study and collected samples of four tissues - leukoplakia, tumour, adjacent normal, and blood - from each of 28 patients suffering from gingivobuccal oral cancer. We performed multiomics analysis of the 112 collected tissues (four tissues per patient from 28 patients) and integrated information on progressive changes in the mutational and transcriptional profiles of each patient to create this genomic narrative. Additionally, we generated and analysed whole-exome sequence data from leukoplakia tissues collected from 11 individuals not suffering from oral cancer. Nonsynonymous somatic mutations in the CASP8 gene were identified as the likely events to initiate malignant transformation, since these were frequently shared between tumour and co-occurring leukoplakia. CASP8 alterations were also shown to enhance expressions of genes that favour lateral spread of mutant cells. During malignant transformation, additional pathogenic mutations are acquired in key genes (TP53, NOTCH1, HRAS) (41% of patients); chromosomal-instability (arm-level deletions of 19p and q, focal-deletion of DNA-repair pathway genes and NOTCH1, amplification of EGFR) (77%), and increased APOBEC-activity (23%) are also observed. These additional alterations were present singly (18% of patients) or in combination (68%). Some of these alterations likely impact immune-dynamics of the evolving transformed tissue; progression to malignancy is associated with immune suppression through infiltration of regulatory T-cells (56%), depletion of cytotoxic T-cells (68%), and antigen-presenting dendritic cells (72%), with a concomitant increase in inflammation (92%). Patients can be grouped into three clusters by the estimated time to development of cancer from precancer by acquiring additional mutations (range: 4-10 years). Our findings provide deep molecular insights into the evolutionary processes and trajectories of oral cancer initiation and progression. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5900DOI Listing
August 2022

Association between city-wide lockdown and COVID-19 hospitalization rates in multigenerational households in New York City.

PLoS One 2022 30;17(3):e0266127. Epub 2022 Mar 30.

Department of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, New York, United States of America.

Background: City-wide lockdowns and school closures have demonstrably impacted COVID-19 transmission. However, simulation studies have suggested an increased risk of COVID-19 related morbidity for older individuals inoculated by house-bound children. This study examines whether the March 2020 lockdown in New York City (NYC) was associated with higher COVID-19 hospitalization rates in neighborhoods with larger proportions of multigenerational households.

Methods: We obtained daily age-segmented COVID-19 hospitalization counts in each of 166 ZIP code tabulation areas (ZCTAs) in NYC. Using Bayesian Poisson regression models that account for spatiotemporal dependencies between ZCTAs, as well as socioeconomic risk factors, we conducted a difference-in-differences study amongst ZCTA-level hospitalization rates from February 23 to May 2, 2020. We compared ZCTAs in the lowest quartile of multigenerational housing to other quartiles before and after the lockdown.

Findings: Among individuals over 55 years, the lockdown was associated with higher COVID-19 hospitalization rates in ZCTAs with more multigenerational households. The greatest difference occurred three weeks after lockdown: Q2 vs. Q1: 54% increase (95% Bayesian credible intervals: 22-96%); Q3 vs. Q1: 48% (17-89%); Q4 vs. Q1: 66% (30-211%). After accounting for pandemic-related population shifts, a significant difference was observed only in Q4 ZCTAs: 37% (7-76%).

Interpretation: By increasing house-bound mixing across older and younger age groups, city-wide lockdown mandates imposed during the growth of COVID-19 cases may have inadvertently, but transiently, contributed to increased transmission in multigenerational households.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266127PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967012PMC
March 2022

Hsp90 in Human Diseases: Molecular Mechanisms to Therapeutic Approaches.

Cells 2022 03 12;11(6). Epub 2022 Mar 12.

Department of Inflammation and Immunity, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA.

The maturation of hemeprotein dictates that they incorporate heme and become active, but knowledge of this essential cellular process remains incomplete. Studies on chaperon Hsp90 has revealed that it drives functional heme maturation of inducible nitric oxide synthase (iNOS), soluble guanylate cyclase (sGC) hemoglobin (Hb) and myoglobin (Mb) along with other proteins including GAPDH, while globin heme maturations also need an active sGC. In all these cases, Hsp90 interacts with the heme-free or apo-protein and then drives the heme maturation by an ATP dependent process before dissociating from the heme-replete proteins, suggesting that it is a key player in such heme-insertion processes. As the studies on globin maturation also need an active sGC, it connects the globin maturation to the NO-sGC (Nitric oxide-sGC) signal pathway, thereby constituting a novel NO-sGC-Globin axis. Since many aggressive cancer cells make Hbβ/Mb to survive, the dependence of the globin maturation of cancer cells places the NO-sGC signal pathway in a new light for therapeutic intervention. Given the ATPase function of Hsp90 in heme-maturation of client hemeproteins, Hsp90 inhibitors often cause serious side effects and this can encourage the alternate use of sGC activators/stimulators in combination with specific Hsp90 inhibitors for better therapeutic intervention.
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http://dx.doi.org/10.3390/cells11060976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946885PMC
March 2022

Biomarkers in Neurodegenerative Diseases.

Authors:
Arnab Ghosh

Biomedicines 2022 Jan 20;10(2). Epub 2022 Jan 20.

Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.

An increasing number of people are affected by various neurodegenerative diseases each year, impacting the quality of life of millions of people worldwide [...].
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http://dx.doi.org/10.3390/biomedicines10020215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868590PMC
January 2022

Benign Skin Neoplasms among the Histopathological Specimens of Skin Neoplasm in a Teaching Hospital: A Descriptive Cross-sectional Study.

JNMA J Nepal Med Assoc 2021 Nov 15;59(243):1106-1110. Epub 2021 Nov 15.

Department of Pathology, Manipal Teaching Hospital, Pokhara, Nepal.

Introduction: Skin tumors are relatively uncommon malignancies worldwide, but its incidence has been progressively increased over the last few decades. Skin tumor belongs to a diverse group of neoplasms arising from the epidermis, adnexal structures and dermis rendering the classification difficult. The study aims to find out the prevalence of benign skin neoplasm among the histopathological specimens of skin neoplasm of a teaching hospital.

Methods: A descriptive cross-sectional study among the hospital records of histopathological samples of skin neoplasm in the Department of Pathology of a tertiary care center from January 2017 to December 2020. Ethical approval was taken from the Institutional Review Committee (Ref: MEMG/IRC/427/GA). Convenient sampling was done. Data were entered in Microsoft Excel and analyzed using Statistical Package for the Social Sciences version 21 software. Point estimate at 95% Confidence Interval was calculated with frequency and descriptive statistics.

Results: Out of total skin neoplasm samples, 121 (57.34%) (50.67-64.01 at 95% Confidence Interval) benign skin neoplasms were present. Among them, the majority were keratinocytic tumor 81 (66.9%) followed by skin appendageal 23 (19.0%) and melanocytic tumors 17 (14.0%). Acrochordan 18 (14.9%) and pilomatricoma 12 (9.9%) were the predominant keratinocytic and appendageal neoplasms respectively. Most of the cases occurred in head and neck region 64 (52.9%).

Conclusions: The study concluded that the prevalence of benign skin neoplasm was slightly lower compared to the other studies. Most of the benign skin neoplasms were keratinocytic tumors followed by appendageal and melanocytic tumors. Acrochordan was the commonest benign keratinocytic tumor.
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http://dx.doi.org/10.31729/jnma.6086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124324PMC
November 2021

Non-neoplastic Lesions of Gallbladder Among Cholecystectomy Specimens of a Tertiary Care Center: A Descriptive Cross-sectional Study.

JNMA J Nepal Med Assoc 2021 Oct 15;59(242):970-974. Epub 2021 Oct 15.

Department of Pathology, Manipal College of Medical Science, Pokhara, Nepal.

Introduction: Gallbladder diseases are prevalent worldwide and present with a diverse histopathological spectrum. Mucosal irritation and chronic inflammation is considered as an important etiological factor for the mechanical or functional dysfunction of emptying of the gallbladder. This study aims to find the prevalence of non-neoplastic lesions of gallbladder among cholecystectomy specimens of a tertiary care center.

Methods: A descriptive cross-sectional study was conducted in the Department of Pathology, of a tertiary care center from January 2005 to December 2020. Ethical approval was taken from the Institutional Review Committee. All the patients who had undergone cholecystectomy procedures which showed non-neoplastic lesions were enrolled in the study. Convenient sampling was done. Statistical Package for Social Sciences version 21 and Microsoft Excel were used for data analysis. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data.

Results: Out of 4914 cholecystectomy specimens, 4852 (98.73%) (95% Confidence Interval= 98.42- 99.04) were non-neoplastic lesions. There were 1252 (25.8%) males and 3600 (74.2%) females with a male to female ratio of 1:2.87. Age ranged from 2 to 89 years with a mean age of 45±14.48 years. Gallbladder lesions were observed maximum in age group 41-50 years with 1200 (24.7%) cases. Among the non-neoplastic lesions, cholecystitis without any specific finding was the most common finding with 3028 (62.4%) cases followed by cholelithiasis with 1478 (30.5%) cases.

Conclusions: The prevalence of non-neoplastic lesions of gallbladder is similar to other studies done in similar setings. Female predominance was noted in non-neoplastic lesions.
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http://dx.doi.org/10.31729/jnma.5861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107806PMC
October 2021

Predictors of life-threatening complications in relatively lower-risk patients hospitalized with COVID-19.

PLoS One 2022 15;17(2):e0263995. Epub 2022 Feb 15.

Department of Medicine, Weill Medical College of Cornell University, New York, New York, United States of America.

Older individuals with chronic health conditions are at highest risk of adverse clinical outcomes from COVID-19, but there is widespread belief that risk to younger, relatively lower-risk individuals is negligible. We assessed the rate and predictors of life-threatening complications among relatively lower-risk adults hospitalized with COVID-19. Of 3766 adults hospitalized with COVID-19 to three hospitals in New York City from March to May 2020, 963 were relatively lower-risk based on absence of preexisting health conditions. Multivariable logistic regression models examined in-hospital development of life-threatening complications (major medical events, intubation, or death). Covariates included age, sex, race/ethnicity, hypertension, weight, insurance type, and area-level sociodemographic factors (poverty, crowdedness, and limited English proficiency). In individuals ≥55 years old (n = 522), 33.3% experienced a life-threatening complication, 17.4% were intubated, and 22.6% died. Among those <55 years (n = 441), 15.0% experienced a life-threatening complication, 11.1% were intubated, and 5.9% died. In multivariable analyses among those ≥55 years, age (OR 1.03 [95%CI 1.01-1.06]), male sex (OR 1.72 [95%CI 1.14-2.64]), being publicly insured (versus commercial insurance: Medicare, OR 2.02 [95%CI 1.22-3.38], Medicaid, OR 1.87 [95%CI 1.10-3.20]) and living in areas with relatively high limited English proficiency (highest versus lowest quartile: OR 3.50 [95%CI 1.74-7.13]) predicted life-threatening complications. In those <55 years, no sociodemographic factors significantly predicted life-threatening complications. A substantial proportion of relatively lower-risk patients hospitalized with COVID-19 experienced life-threatening complications and more than 1 in 20 died. Public messaging needs to effectively convey that relatively lower-risk individuals are still at risk of serious complications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263995PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846540PMC
February 2022

Impacts Infection in Tick Cells.

Int J Environ Res Public Health 2022 01 18;19(3). Epub 2022 Jan 18.

Department of Biological Sciences, Texas Tech University, 2901 Main St., Lubbock, TX 79409, USA.

The specific interactions of members of tick bacterial microbiota and their effects on pathogen transmission remains relatively unexplored. Here, we introduced a novel infection type into tick cells and examined the antipathogenic effects on the intracellular pathogen . An increase in replication was observed in -infected tick cells. However, infection densities decreased when cells were serially passaged and ultimately the infection was lost. Host-cell immune response was also examined as an additional factor that could have affected replication in -infected cells. In early passages post- infection, a decreased immune response was observed, but in later passages of cells with low densities, there was no change in the immune response. The results are discussed in relation to the importance of studying the interactions of the tick microbiota, the host cell, and the pathogen and the development of novel tick and tick-borne disease-control approaches.
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http://dx.doi.org/10.3390/ijerph19031051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834366PMC
January 2022

Electrocatalytic Activity of Polyaniline in Magnesium-Sulfur Batteries.

J Phys Chem Lett 2022 Feb 2;13(5):1337-1343. Epub 2022 Feb 2.

Electrochemical Energy Laboratory, Department of Energy Science and Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

Rechargeable magnesium-sulfur (Mg-S) batteries offer the potential for inexpensive energy storage alternatives to other metal-ion batteries for the grid scale and household applications. Despite all economic and resource advantages, Mg-S battery chemistry suffers from a complicated reaction mechanism and extremely slow reaction kinetics. To improve the kinetics, we improvise a new electrode architecture where a conductive polymer is used along with a carbon network. This report will bring an important insight of electrocatalytic activity of polyaniline, on the basis of free-radical coupling and is a completely new concept in Mg-S battery chemistry. By the combined electron spin resonance spectroscopy, X-ray photoelectron spectroscopy, and fluorescence lifetime measurements, we perceived that the polyaniline anchors the S species from the electrolyte/catholyte through a free-radical-coupling process and thus promotes the reduction to end-discharged products, via a chemical adduct. The concept of free-radical catalysis in Mg/S batteries will open a new knowledge to enhance the active material utilization in the Mg-S batteries.
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http://dx.doi.org/10.1021/acs.jpclett.1c04021DOI Listing
February 2022

NO rapidly mobilizes cellular heme to trigger assembly of its own receptor.

Proc Natl Acad Sci U S A 2022 01;119(4)

Department of Inflammation and Immunity, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195

Nitric oxide (NO) signaling in biology relies on its activating cyclic guanosine monophosphate (cGMP) production by the NO receptor soluble guanylyl cyclase (sGC). sGC must obtain heme and form a heterodimer to become functional, but paradoxically often exists as an immature heme-free form in cells and tissues. Based on our previous finding that NO can drive sGC maturation, we investigated its basis by utilizing a fluorescent sGC construct whose heme level can be monitored in living cells. We found that NO generated at physiologic levels quickly triggered cells to mobilize heme to immature sGC. This occurred when NO was generated within cells or by neighboring cells, began within seconds of NO exposure, and led cells to construct sGC heterodimers and thus increase their active sGC level by several-fold. The NO-triggered heme deployment involved cellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-heme complexes and required the chaperone hsp90, and the newly formed sGC heterodimers remained functional long after NO generation had ceased. We conclude that NO at physiologic levels triggers assembly of its own receptor by causing a rapid deployment of cellular heme. Redirecting cellular heme in response to NO is a way for cells and tissues to modulate their cGMP signaling and to more generally tune their hemeprotein activities wherever NO biosynthesis takes place.
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http://dx.doi.org/10.1073/pnas.2115774119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795550PMC
January 2022

WITHDRAWN: Pulmonary Nocardiosis Caused by Nocardia otitidiscaviarum in an Immunocompromised Patient and Its Review of Literature

Infect Disord Drug Targets 2022 01 18:e180122200336. Epub 2022 Jan 18.

Department of Microbiology, AIIMS Jodhpur.

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn by the publisher.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php

Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
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http://dx.doi.org/10.2174/1871526522666220118123318DOI Listing
January 2022
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