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1.
Nature ; 578(7793): 112-121, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32025012

RESUMEN

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1-7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.


Asunto(s)
Variación Genética , Genoma Humano/genética , Neoplasias/genética , Reordenamiento Génico/genética , Genómica , Humanos , Mutagénesis Insercional , Telomerasa/genética
2.
Nature ; 578(7793): 102-111, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32025015

RESUMEN

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.


Asunto(s)
Genoma Humano/genética , Mutación/genética , Neoplasias/genética , Roturas del ADN , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Mutación INDEL
3.
Blood ; 142(18): 1556-1569, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37624927

RESUMEN

Cardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown to limit platelet reactivity by activating the prostacyclin receptor. Here, we demonstrated the synthesis of a novel analog of 12-HETrE, known as CS585. Human blood and mouse models of hemostasis and thrombosis were assessed for the ability of CS585 to attenuate platelet activation and thrombosis without increasing the risk of bleeding. Human platelet activation was assessed using aggregometry, flow cytometry, western blot analysis, total thrombus formation analysis system, microfluidic perfusion chamber, and thromboelastography. Hemostasis, thrombosis, and bleeding assays were performed in mice. CS585 was shown to potently target the prostacyclin receptor on the human platelet, resulting in a highly selective and effective mechanism for the prevention of platelet activation. Furthermore, CS585 was shown to inhibit platelet function in human whole blood ex vivo, prevent thrombosis in both small and large vessels in mouse models, and exhibit long-lasting prevention of clot formation. Finally, CS585 was not observed to perturb coagulation or increase the risk of bleeding in the mouse model. Hence, CS585 represents a new validated target for the treatment of thrombotic diseases without the risk of bleeding or off-target activation observed with other prostaglandin receptor agonists.


Asunto(s)
Oxilipinas , Trombosis , Animales , Humanos , Ratones , Receptores de Epoprostenol , Oxilipinas/farmacología , Oxilipinas/uso terapéutico , Activación Plaquetaria , Plaquetas , Hemostasis , Hemorragia , Agregación Plaquetaria
4.
Pediatr Blood Cancer ; 71(8): e31090, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38807260

RESUMEN

BACKGROUND: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. METHODS: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. RESULTS: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. CONCLUSION: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.


Asunto(s)
ARN Helicasas DEAD-box , Neoplasias Renales , Blastoma Pulmonar , Sistema de Registros , Ribonucleasa III , Sarcoma , Humanos , ARN Helicasas DEAD-box/genética , Ribonucleasa III/genética , Blastoma Pulmonar/patología , Blastoma Pulmonar/terapia , Blastoma Pulmonar/genética , Blastoma Pulmonar/mortalidad , Masculino , Femenino , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/terapia , Neoplasias Renales/mortalidad , Preescolar , Niño , Lactante , Sarcoma/genética , Sarcoma/patología , Sarcoma/terapia , Tasa de Supervivencia , Pronóstico , Adolescente , Estudios de Seguimiento
7.
Int J Phytoremediation ; 26(2): 178-192, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37409646

RESUMEN

In the present study, we report the chemical modification of the dried and fallen pine needles (PNs) via a simple protocol using KMnO4 oxidation. The oxidized PNs (OPNs) were evaluated as adsorbents using some cationic and anionic dyes. The successful synthesis of OPNs adsorbent was characterized by various techniques to ascertain its structural attributes. The adsorbent showed selectivity for the cationic dyes with 96.11% removal (Pr) for malachite green (MG) and 89.68% Pr for methylene blue (MB) in 120 min. Kinetic models namely, pseudo-first order, pseudo-second order, and Elovich were applied to have insight into adsorption. Additionally, three adsorption isotherms, i.e., Langmuir, Freundlich, and Temkin were also applied. The dye adsorption followed a pseudo-second-order kinetic model with R2 > 0.99912 for MG and R2 > 0.9998 for MB. The adsorbent followed the Langmuir model with a maximum adsorption capacity (qm) of 223.2 mg/g and 156.9 mg/g for MG and MB, respectively. Furthermore, the OPNs showed remarkable regeneration and recyclability up to nine adsorption-desorption cycles with appreciable adsorption for both the dyes. The use of OPNs as an adsorbent for the removal of dyes from wastewater, therefore, provides an ecologically benign, low-cost, and sustainable solution.


We have carried out the chemical modification of the dried and fallen pine needles (PNs) via a simple protocol using KMnO4 oxidation. The oxidized PNs (OPNs) were evaluated as adsorbents using some cationic and anionic dyes and the adsorbent showed selectivity for the cationic dyes. As far as the authors are aware, no such report has been documented in the literature wherein an adsorbent based on oxidized PNs with a simple protocol has been used for dye removal.


Asunto(s)
Colorantes , Contaminantes Químicos del Agua , Colorantes/química , Biodegradación Ambiental , Aguas Residuales , Colorantes de Rosanilina , Cationes/química , Adsorción , Cinética , Azul de Metileno/química , Contaminantes Químicos del Agua/química
8.
Indian J Public Health ; 68(2): 326-328, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38953829

RESUMEN

With the introduction of the novel coronavirus in late 2019, the healthcare system of every country in the world experienced many challenges. In India, every healthcare organization has prepared itself to fight against these global challenges. This study aims to describe the challenges faced during the COVID-19 pandemic and how we dealt with the pandemic successfully. This narrative analysis study was made in a 960-bedded teaching hospital during the pandemic. The challenges were identified from the minutes of meetings, circulars issued, and various strategic decisions made to combat the pandemic. The challenges faced by the institute were categorized into nine different categories: infrastructural, human resource, hospital operations, and others. Lack of knowledge during the initial days of the pandemic, need for round-theclock situational management, and day-to-day operation needed aggressive training and adherence to the guidelines. Gaps identified in areas like inventory, infection control, logistics, etc., were quickly addressed, and processes were created as per the nation's changing guidelines. This study revealed strategies to manage the pandemic by optimally utilizing available resources with good teamwork and situational leadership.


Asunto(s)
COVID-19 , Centros de Atención Terciaria , India/epidemiología , COVID-19/epidemiología , Humanos , Centros de Atención Terciaria/organización & administración , SARS-CoV-2 , Pandemias , Hospitales de Enseñanza/organización & administración , Control de Infecciones/organización & administración , Control de Infecciones/métodos
9.
Crit Care Med ; 51(11): 1449-1460, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37294145

RESUMEN

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.


Asunto(s)
Lesión Renal Aguda , Choque Séptico , Desequilibrio Hidroelectrolítico , Niño , Preescolar , Femenino , Humanos , Masculino , Soluciones Cristaloides , Fluidoterapia/efectos adversos , Fluidoterapia/métodos , Resucitación/métodos , Solución Salina , Choque Séptico/terapia , Desequilibrio Hidroelectrolítico/terapia , Lactante
10.
Biophys J ; 121(8): 1512-1524, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35278426

RESUMEN

Antimicrobial peptides are promising therapeutic agents to mitigate the global rise of antibiotic resistance. They generally act by perturbing the bacterial cell membrane and are thus less likely to induce resistance. Because they are membrane-active molecules, it is critical to verify and understand their potential action toward eukaryotic cells to help design effective and safe drugs. In this work, we studied the interaction of two antimicrobial peptides, aurein 1.2 and caerin 1.1, with red blood cell (RBC) membranes using in situ 31P and 2H solid-state NMR (SS-NMR). We established a protocol to integrate up to 25% of deuterated fatty acids in the membranes of ghosts, which are obtained when hemoglobin is removed from RBCs. Fatty acid incorporation and the integrity of the lipid bilayer were confirmed by SS-NMR and fluorescence confocal microscopy. Leakage assays were performed to assess the lytic power of the antimicrobial peptides. The in situ perturbation of the ghost membranes by aurein 1.2 and caerin 1.1 revealed by 31P and 2H SS-NMR is consistent with membrane perturbation through a carpet mechanism for aurein 1.2, whereas caerin 1.1 acts on RBCs via pore formation. These results are compatible with fluorescence microscopy images of the ghosts. The peptides interact with eukaryotic membranes following similar mechanisms that take place in bacteria, highlighting the importance of hydrophobicity when determining such interactions. Our work bridges model membranes and in vitro studies and provides an analytical toolbox to assess drug toxicity toward eukaryotic cells.


Asunto(s)
Péptidos Catiónicos Antimicrobianos , Péptidos Antimicrobianos , Péptidos Catiónicos Antimicrobianos/metabolismo , Membrana Eritrocítica/metabolismo , Membrana Dobles de Lípidos/química , Espectroscopía de Resonancia Magnética/métodos
11.
J Natl Compr Canc Netw ; 20(3): 285-308, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35276674

RESUMEN

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.


Asunto(s)
Linfadenopatía Inmunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/patología , Linfadenopatía Inmunoblástica/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia
12.
Langmuir ; 2021 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-34339205

RESUMEN

Protein S100A10 participates in different cellular mechanisms and has different functions, especially at the membrane. Among those, it forms a ternary complex with annexin A2 and the C-terminal of AHNAK and then joins the dysferlin membrane repair complex. Together, they act as a platform enabling membrane repair. Both AHNAK and annexin A2 have been shown to have membrane binding properties. However, the membrane binding abilities of S100A10 are not clear. In this paper, we aimed to study the membrane binding of S100A10 in order to better understand its role in the cell membrane repair process. S100A10 was overexpressed by E. coli and purified by affinity chromatography. Using a Langmuir monolayer as a model membrane, the binding parameters and ellipsometric angles of the purified S100A10 were measured using surface tensiometry and ellipsometry, respectively. Phosphorus-31 solid-state nuclear magnetic resonance spectroscopy was also used to study the interaction of S100A10 with lipid bilayers. In the presence of a lipid monolayer, S100A10 preferentially interacts with unsaturated phospholipids. In addition, its behavior in the presence of a bilayer model suggests that S100A10 interacts more with the negatively charged polar head groups than the zwitterionic ones. This work offers new insights on the binding of S100A10 to different phospholipids and advances our understanding of the parameters influencing its membrane behavior.

13.
Radiographics ; 41(7): 2136-2156, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34623944

RESUMEN

The fields of both radiology and radiation oncology have evolved considerably in the past few decades, resulting in an increased ability to delineate between tumor and normal tissue to precisely target and treat vertebral metastases with radiation therapy. These scientific advances have also led to improvements in assessing treatment response and diagnosing toxic effects related to radiation treatment. However, despite technological innovations yielding greatly improved rates of palliative relief and local control of osseous spinal metastases, radiation therapy can still lead to a number of acute and delayed posttreatment complications. Treatment-related adverse effects may include pain flare, esophageal toxic effects, dermatitis, vertebral compression fracture, radiation myelopathy, and myositis, among others. The authors provide an overview of the multidisciplinary approach to the treatment of spinal metastases, indications for surgical management versus radiation therapy, various radiation technologies and techniques (along with their applications for spinal metastases), and current principles of treatment planning for conventional and stereotactic radiation treatment. Different radiologic criteria for assessment of treatment response, recent advances in radiologic imaging, and both common and rare complications related to spinal irradiation are also discussed, along with the imaging characteristics of various adverse effects. Familiarity with these topics will not only assist the diagnostic radiologist in assessing treatment response and diagnosing treatment-related complications but will also allow more effective collaboration between diagnostic radiologists and radiation oncologists to guide management decisions and ensure high-quality patient care. ©RSNA, 2021.


Asunto(s)
Fracturas por Compresión , Oncología por Radiación , Fracturas de la Columna Vertebral , Neoplasias de la Columna Vertebral , Humanos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/radioterapia , Columna Vertebral
14.
Pediatr Crit Care Med ; 22(1): 40-49, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33031352

RESUMEN

OBJECTIVES: To evaluate the functional outcomes in critically ill children with severe sepsis using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale and to evaluate the risk factors for "worse outcomes." DESIGN: Prospective observational cohort study. SETTING: Tertiary care PICU from September 2017 to October 2019. PATIENTS: One hundred twenty-one children with severe sepsis, 2 months to 17 years old, admitted to PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores were recorded at admission, PICU discharge, at 3 months and 1 year after discharge. "New disability" was defined as Pediatric Overall Performance Category and Pediatric Cerebral Performance Category score change "from baseline score" by greater than or equal to 1 category. Risk factors for "worse outcomes" (defined as "death" or "new disability") were evaluated by univariate and multivariate analysis. At admission, 33% (n = 39) had mild to moderate "overall disability" (Pediatric Overall Performance Category) and 26% (n = 32) had mild to moderate "cognitive disability" (Pediatric Cerebral Performance Category). At PICU discharge (n = 89 children), 50.5% (n = 45) had "new disability" in overall function (Pediatric Overall Performance Category scores) and 28% (n = 25) had "new disability" in cognitive function (Pediatric Cerebral Performance Category scores). At 3 months follow-up (n = 85 children), "new disability" at PICU discharge improved in 65% (n = 28/43) and 50% (n = 12/24) of those with "overall disability" (Pediatric Overall Performance Category) and "cognitive disability" (Pediatric Cerebral Performance Category), respectively. At 1-year follow-up (n = 84 children), only 5% (n = 2/43) had residual "new disability" in overall function (Pediatric Overall Performance Category) and 14% (n = 3/21) had residual "new disability" in cognitive function. PICU mortality was 26% (n = 32). The proportion with "worse outcomes" was 64% (n = 77). Risk factors for worse outcomes on univariate analysis included higher Pediatric Index of Mortality-3 scores, day 1 pediatric Sequential Organ Failure Assessment score, receiving cardiopulmonary resuscitation during the ICU stay, and treatments received such as ventilation and Vasoactive-Inotrope Score. On multivariate analysis, only day 1 pediatric Sequential Organ Failure Assessment score and receiving cardiopulmonary resuscitation during the ICU stay were found to be statistically significant. CONCLUSIONS: Children with severe sepsis had significant "new onset" mild to moderate functional disability at PICU discharge, and most of these children recovered within 1 year after PICU discharge. Day 1 pediatric Sequential Organ Failure Assessment score and patient receiving cardiopulmonary resuscitation during the ICU stay were found to be the significant risk factors of "worse outcomes."


Asunto(s)
Alta del Paciente , Sepsis , Niño , Enfermedad Crítica , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Estudios Prospectivos , Sepsis/terapia
15.
Molecules ; 25(8)2020 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-32326252

RESUMEN

Gaining a fundamental insight into the biomolecular recognition of posttranslationally modified histones by epigenetic reader proteins is of crucial importance to understanding the regulation of the activity of human genes. Here, we seek to establish whether trimethylthialysine, a simple trimethyllysine analogue generated through cysteine alkylation, is a good trimethyllysine mimic for studies on molecular recognition by reader proteins. Histone peptides bearing trimethylthialysine and trimethyllysine were examined for binding with five human reader proteins employing a combination of thermodynamic analyses, molecular dynamics simulations and quantum chemical analyses. Collectively, our experimental and computational findings reveal that trimethylthialysine and trimethyllysine exhibit very similar binding characteristics for the association with human reader proteins, thereby justifying the use of trimethylthialysine for studies aimed at dissecting the origin of biomolecular recognition in epigenetic processes that play important roles in human health and disease.


Asunto(s)
Cisteína/análogos & derivados , Histonas/química , Lisina/análogos & derivados , Sitios de Unión , Cisteína/síntesis química , Cisteína/química , Epigénesis Genética , Histonas/metabolismo , Humanos , Lisina/síntesis química , Lisina/química , Metilación , Modelos Moleculares , Conformación Molecular , Unión Proteica , Técnicas de Síntesis en Fase Sólida , Relación Estructura-Actividad , Termodinámica
16.
Mol Biol Rep ; 46(5): 5487-5492, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31087246

RESUMEN

The genus Indirana Laurent, 1986 is composed of 14 species which are endemic to the Western Ghats of India. We isolated and evaluated ten polymorphic microsatellite markers in 32 individuals of Indirana semipalmata. The cross amplification test was successful in two Indirana (I. brachytarsus and I. yadera) and one Walkerana (W. leptodactyla, previously known as I. leptodactyla) species endemic to the Western Ghats. The identified markers will be useful for further studies on the conservation genetics of endemic frog species of Western Ghats.


Asunto(s)
Anuros/genética , Repeticiones de Microsatélite/genética , Animales , Marcadores Genéticos/genética , India , Filogenia , Polimorfismo Genético/genética , Especificidad de la Especie
17.
Pediatr Crit Care Med ; 20(3): e122-e129, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30640887

RESUMEN

OBJECTIVES: To evaluate the proportion of children fulfilling "Sepsis-3" definition and International Pediatric Sepsis Consensus Conference definition among children diagnosed to have septic shock and compare the mortality risk between the two groups. DESIGN: Retrospective chart review. SETTING: PICU of a tertiary care teaching hospital from 2014 to 2017. PATIENTS: Children (≤ 17 yr old) with a diagnosis of septic shock at admission or during PICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied both International Pediatric Sepsis Consensus Conference and the new "Sepsis-3" definition (sepsis with hypotension requiring vasopressors and a lactate value of ≥ 2 mmol/L) to identify cases of septic shock by these definitions. Key outcomes such as mortality, proportion attaining shock reversal at 24 hours and organ dysfunction were compared between those fulfilling "Sepsis-3" definitions ("Sepsis-3" group) and those fulfilling "International Pediatric Sepsis Consensus Conference" definition ("International Pediatric Sepsis Consensus Conference" group). A total of 216 patients fulfilled International Pediatric Sepsis Consensus Conference definitions of septic shock. Of these, only 104 (48%; 95% CI, 42-55) fulfilled "Sepsis-3" definition. Children fulfilling "Sepsis-3 plus International Pediatric Sepsis Consensus Conference definitions" ("Sepsis-3 and International Pediatric Sepsis Consensus Conference" group) had lower proportion with shock resolution (61% vs 82%; relative risk, 0.73; 95% CI, 0.62-0.88) and higher risk of multiple organ dysfunction (85% vs 68%; 1.24; 1.07-1.45) at 24 hours. The mortality was 48.5% in "Sepsis-3 and International Pediatric Sepsis Consensus Conference" group as compared with 37.5% in the "International Pediatric Sepsis Consensus Conference only" group (relative risk, 1.3; 95% CI, 0.94-1.75). CONCLUSIONS: Less than half of children with septic shock identified by International Pediatric Sepsis Consensus Conference definitions were observed to fulfill the criteria for shock as per "Sepsis-3" definitions. Lack of difference in the risk of mortality between children who fulfilled "Sepsis-3" definition and those who did not fulfill the definition raises questions on the appropriateness of using this definition for diagnosis of septic shock in children.


Asunto(s)
Indicadores de Salud , Sepsis/diagnóstico , Sepsis/fisiopatología , Niño , Preescolar , Femenino , Hospitales de Enseñanza , Humanos , Unidades de Cuidado Intensivo Pediátrico , Masculino , Puntuaciones en la Disfunción de Órganos , Estudios Retrospectivos , Sepsis/mortalidad , Choque Séptico/diagnóstico , Choque Séptico/mortalidad
18.
Neurol India ; 67(1): 100-104, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30860104

RESUMEN

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disability and is of public health importance. It affects not only the child and the family. It also has direct and indirect cost implications on the nation that are incurred in providing health care, support for education, and rehabilitative services. There is a lack of evidence-based estimate of the population prevalence of ASD in India. Therefore, this systematic review was aimed at determining the prevalence of ASD in the Indian population. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the published studies evaluating the prevalence of ASD in the community setting. A search within the published literature was conducted from different databases (PubMed, OvidSP, and EMBASE). The analysis of data was done using STATA MP12 (StataCorp, College Station, TX, USA). RESULTS: Four studies were included in this systematic review. Of the four included studies, one had studied both urban and rural populations, and the other three had studied the urban populations only. The study from the rural setting showed a pooled percentage prevalence of 0.11 [95% confidence interval (CI) 0.01-0.20] in children aged 1-18 years; and, four studies conducted in the urban setting showed a pooled percentage prevalence of 0.09 (95% CI 0.02-0.16) in children aged 0-15 years. CONCLUSION: The scarcity of high-quality population-based epidemiological studies on ASD in India highlights an urgent need to study the burden of ASD in India. The proper acquisition of data related to the prevailing burden of ASD in India would lead to a better development of rehabilitative services in our country.


Asunto(s)
Trastorno del Espectro Autista/epidemiología , Adolescente , Niño , Preescolar , Femenino , Humanos , India/epidemiología , Lactante , Masculino , Prevalencia
19.
Angew Chem Int Ed Engl ; 58(7): 1990-1994, 2019 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-30569575

RESUMEN

Enzymes often use nucleophilic serine, threonine, and cysteine residues to achieve the same type of reaction; the underlying reasons for this are not understood. While bacterial d,d-transpeptidases (penicillin-binding proteins) employ a nucleophilic serine, l,d-transpeptidases use a nucleophilic cysteine. The covalent complexes formed by l,d-transpeptidases with some ß-lactam antibiotics undergo non-hydrolytic fragmentation. This is not usually observed for penicillin-binding proteins, or for the related serine ß-lactamases. Replacement of the nucleophilic serine of serine ß-lactamases with cysteine yields enzymes which fragment ß-lactams via a similar mechanism as the l,d-transpeptidases, implying the different reaction outcomes are principally due to the formation of thioester versus ester intermediates. The results highlight fundamental differences in the reactivity of nucleophilic serine and cysteine enzymes, and imply new possibilities for the inhibition of nucleophilic enzymes.


Asunto(s)
Antibacterianos/metabolismo , Cisteína/metabolismo , Peptidil Transferasas/metabolismo , beta-Lactamasas/metabolismo , beta-Lactamas/metabolismo , Antibacterianos/química , Cisteína/química , Conformación Molecular , Peptidil Transferasas/química , beta-Lactamasas/química , beta-Lactamas/química
20.
Int J Phytoremediation ; 20(6): 593-598, 2018 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-29688049

RESUMEN

Excess of copper ion (>2 mg/L) in water is toxic to human beings and the ecosystem. Various water treatment technologies for copper remediation have been investigated in the past. Along with industrial effluents, Bordeaux mixture is also a noteworthy copper contamination source in the agricultural ecosystem. In our study, the biosorbent efficiency of dried orange peel was investigated through an environment-friendly process for the removal of cupric ions. Effects of pH, adsorbate concentration, adsorbent dosage, and temperature for the removal of Cu (II) were studied. Slightly acidic environment (pH = 6) was found to be optimum for removal of copper. The equilibrium data were well fitted with the Langmuir and Freundlich isotherms. The surface morphology of the adsorbent was studied using scanning electron microscope. Crystalline nonhomogenous surface was observed after copper adsorption. Desorption study indicated that 0.1N H2SO4 is the best eluent for the removal of adsorbed copper from the powdered dried orange peel.


Asunto(s)
Citrus sinensis , Contaminantes Químicos del Agua/química , Purificación del Agua , Adsorción , Biodegradación Ambiental , Cobre/química , Ecosistema , Concentración de Iones de Hidrógeno , Cinética , Agua
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