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1.
PLoS Pathog ; 17(12): e1010105, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34874976

RESUMO

HIV-1 replication within the central nervous system (CNS) impairs neurocognitive function and has the potential to establish persistent, compartmentalized viral reservoirs. The origins of HIV-1 detected in the CNS compartment are unknown, including whether cells within the cerebrospinal fluid (CSF) produce virus. We measured viral RNA+ cells in CSF from acutely infected macaques longitudinally and people living with early stages of acute HIV-1. Active viral transcription (spliced viral RNA) was present in CSF CD4+ T cells as early as four weeks post-SHIV infection, and among all acute HIV-1 specimens (N = 6; Fiebig III/IV). Replication-inactive CD4+ T cell infection, indicated by unspliced viral RNA in the absence of spliced viral RNA, was even more prevalent, present in CSF of >50% macaques and human CSF at ~10-fold higher frequency than productive infection. Infection levels were similar between CSF and peripheral blood (and lymph nodes in macaques), indicating comparable T cell infection across these compartments. In addition, surface markers of activation were increased on CSF T cells and monocytes and correlated with CSF soluble markers of inflammation. These studies provide direct evidence of HIV-1 replication in CD4+ T cells and broad immune activation in peripheral blood and the CNS during acute infection, likely contributing to early neuroinflammation and reservoir seeding. Thus, early initiation of antiretroviral therapy may not be able to prevent establishment of CNS viral reservoirs and sources of long-term inflammation, important targets for HIV-1 cure and therapeutic strategies.


Assuntos
Linfócitos T CD4-Positivos/virologia , Sistema Nervoso Central/virologia , Líquido Cefalorraquidiano/virologia , Infecções por HIV/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Animais , HIV-1 , Humanos , Macaca mulatta , RNA Viral/líquido cefalorraquidiano , Vírus da Imunodeficiência Símia
2.
PLoS Pathog ; 16(9): e1008764, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881968

RESUMO

To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/prevenção & controle , Vacinas contra a SAIDS/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Adolescente , Adulto , Animais , Anticorpos Neutralizantes/imunologia , Método Duplo-Cego , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/imunologia , Adulto Jovem
3.
Proc Natl Acad Sci U S A ; 116(47): 23760-23771, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31676548

RESUMO

Elimination of dysfunctional mitochondria via mitophagy is essential for cell survival and neuronal functions. But, how impaired mitophagy participates in tissue-specific vulnerability in the brain remains unclear. Here, we find that striatal-enriched protein, Rhes, is a critical regulator of mitophagy and striatal vulnerability in brain. In vivo interactome and density fractionation reveal that Rhes coimmunoprecipitates and cosediments with mitochondrial and lysosomal proteins. Live-cell imaging of cultured striatal neuronal cell line shows Rhes surrounds globular mitochondria, recruits lysosomes, and ultimately degrades mitochondria. In the presence of 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, Rhes disrupts mitochondrial membrane potential (ΔΨ m ) and promotes excessive mitophagy and cell death. Ultrastructural analysis reveals that systemic injection of 3-NP in mice promotes globular mitochondria, accumulation of mitophagosomes, and striatal lesion only in the wild-type (WT), but not in the Rhes knockout (KO), striatum, suggesting that Rhes is critical for mitophagy and neuronal death in vivo. Mechanistically, Rhes requires Nix (BNIP3L), a known receptor of mitophagy, to disrupt ΔΨ m and promote mitophagy and cell death. Rhes interacts with Nix via SUMO E3-ligase domain, and Nix depletion totally abrogates Rhes-mediated mitophagy and cell death in the cultured striatal neuronal cell line. Finally, we find that Rhes, which travels from cell to cell via tunneling nanotube (TNT)-like cellular protrusions, interacts with dysfunctional mitochondria in the neighboring cell in a Nix-dependent manner. Collectively, Rhes is a major regulator of mitophagy via Nix, which may determine striatal vulnerability in the brain.


Assuntos
Proteínas de Ligação ao GTP/fisiologia , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Mitofagia/fisiologia , Animais , Linhagem Celular , Corpo Estriado/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Lisossomos/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Nitrocompostos/farmacologia , Propionatos/farmacologia
4.
Electrophoresis ; 40(9): 1353-1364, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30767247

RESUMO

This study examined 266 individuals from various populations including African American, East Asian, South Asian, European, and mixed populations to evaluate the ForenSeq™ Signature Prep Kit Primer Mix B. Focus was placed on phenotypic and biogeographical ancestry predictions by Illumina's Universal Analysis Software (UAS). These outcomes were compared to those obtained through web-tools developed at the Erasmus Medical Center (EMC) and available from the Forensic Resource/Reference on Genetics-knowledge base (FROG-kb), as well as to eye color predictions by the 8-plex system. Due to drop-outs, predictions for eye and hair color by UAS failed for various samples in each run. By including reads below thresholds, predictions could be obtained for all samples through the web-tools. Eye and hair color predictions for African Americans, East Asians, and South Asians showed no errors. Difficulties however, were noted in intermediate (neither blue nor brown) eye color predictions. These were mitigated by the 8-plex system through exclusion of one eye color (e.g. "not brown"). Additionally, notable discrepancies were observed in hair color predictions, where some black/dark-brown haired individuals were predicted to have blond hair. Overall, ancestry predictions were more accurate by FROG-kb compared to UAS, which did not predict South Asian ancestry, particularly Indian individuals.


Assuntos
Cor de Olho , Cor de Cabelo , Grupos Raciais , Software , Impressões Digitais de DNA , Etnicidade , Humanos , Internet , Fenótipo
5.
Electrophoresis ; 38(6): 846-854, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27943350

RESUMO

This study assesses the performance of Illumina's MiSeq FGx System for forensic genomics by systematically analyzing single source samples, evaluating concordance, sensitivity and repeatability, as well as describing the quality of the reported outcomes. DNA from 16 individuals (9 males/7 females) in nine separate runs showed consistent STR profiles at DNA input ≥400 pg, and two full profiles were obtained with 50 pg DNA input. However, this study revealed that the outcome of a single sample does not merely depend on its DNA input but is also influenced by the total amount of DNA loaded onto the flow cell from all samples. Stutter and sequence or amplification errors can make the identification of true alleles difficult, particularly for heterozygous loci that show allele imbalance. Sequencing of 16 individuals' STRs revealed genetic variations at 14 loci at frequencies suggesting improvement of mixture deconvolution. The STR loci D1S1656 and DXS10103 were most susceptible to drop outs, and D22S1045 and DYS385a-b showed heterozygote imbalance.  Most stutters were typed at TH01 and DYS385a-b, while amplification or sequencing errors were observed mostly at D7S820 and D19S433. Overall, Illumina's MiSeq FGx System produced reliable and repeatable results.  aSTRs showed fewer drop outs than the Y- and X-STRs.


Assuntos
Impressões Digitais de DNA/métodos , DNA/análise , Alelos , Eletroforese Capilar/métodos , Feminino , Genética Forense , Variação Genética , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Análise de Sequência
8.
Mol Phylogenet Evol ; 73: 10-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24440815

RESUMO

Potato (Solanum tuberosum) is an important non-cereal crop throughout the world and is highly recommended for ensuring global food security. Owing to the complexities in genetics and inheritance pattern of potato, the conventional method of cross breeding for developing improved varieties has been difficult. Identification and tagging of desirable traits with informative molecular markers would aid in the development of improved varieties. Insertional polymorphism of copia-like and gypsy-like long terminal repeat retrotransposons (RTN) were investigated among 47 potato varieties from India using Inter-Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon Microsatellite Amplified Polymorphism (REMAP) marker techniques and were compared with the DNA profiles obtained with simple sequence repeats (SSRs). The genetic polymorphism, efficiency of polymorphism and effectiveness of marker systems were evaluated to assess the extent of genetic diversity among Indian potato varieties. A total of 139 polymorphic SSR alleles, 270 IRAP and 98 REMAP polymorphic bands, showing polymorphism of 100%, 87.9% and 68.5%, respectively, were used for detailed characterization of the genetic relationships among potato varieties by using cluster analysis and principal coordinate analysis (PCoA). IRAP analysis resulted in the highest number of polymorphic bands with an average of 15 polymorphic bands per assay unit when compared to the other two marker systems. Based on pair-wise comparison, the genetic similarity was calculated using Dice similarity coefficient. The SSRs showed a wide range in genetic similarity values (0.485-0.971) as compared to IRAP (0.69-0.911) and REMAP (0.713-0.947). A Mantel's matrix correspondence test showed a high positive correlation (r=0.6) between IRAP and REMAP, an intermediate value (r=0.58) for IRAP and SSR and the lowest value (r=0.17) for SSR and REMAP. Statistically significant cophenetic correlation coefficient values, of 0.961, 0.941 and 0.905 were observed for REMAP, IRAP and SSR, respectively. The widespread presence and distinct DNA profiles for copia-like and gypsy-like RTNs in the examined genotypes indicate that these elements are active in the genome and may have even contributed to the potato genome organization. Although the three marker systems were capable of distinguishing all the 47 varieties; high reproducibility, low cost and ease of DNA profiling data collection make IRAP and REMAP markers highly efficient whole-genome scanning molecular probes for population genetic studies. Information obtained from the present study regarding the genetic association and distinctiveness provides an useful guide for selection of germplasm for plant breeding and conservation efforts.


Assuntos
Impressões Digitais de DNA/métodos , Variação Genética/genética , Repetições de Microssatélites/genética , Retroelementos/genética , Solanum tuberosum/genética , Alelos , Impressões Digitais de DNA/economia , Marcadores Genéticos/genética , Genótipo , Filogenia , Polimorfismo Genético/genética , Análise de Sequência de DNA/economia
9.
Indian J Exp Biol ; 52(6): 664-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24956898

RESUMO

Recent work on the venation patterning and morphogenesis of leaf/leaflet has posed the question how different are these in tendrils, which are another type of vegetative lateral organ. Here, the venation patterns of leaflets, stipules and tendrils were compared in the model species, P. sativum. Unlike reticulated venation in leaflets and stipules, venation in tendrils comprised of one or more primary veins. A few secondaries were attached to a primary vein, mostly distally. Bilaterally symmetrical secondary veins were rare. The primary veins in tendrils were daughter strands from dichotomously divided mother veins in rachis, connected finally to vascular strands in stem. A tendril received primary vein from one or more mother strands. Some mother strands contributed primary veins to proximal, distal and terminal domain tendrils of af leaf. The tendrils shared the multi-primary vein character with stipules. Vein redundancy provided a mechanism for survival of tendril/leaf against injury to some of the veins/mother veins. The presence of aborted primary veins that did not reach apex, rows of cambium cells attached to primary vein(s) at apex, the pattern of attachment of primary veins to mother veins and cessation of vein growth in apical direction in aborted tendrils of af lld genotype indicated that the growth of primary veins and tendril was acropetal. Loss-of-function of AF extended the repression of TL and MFP genes on leaflet development from distal and apical domains to proximal domain of leaves in af mutants.


Assuntos
Pisum sativum/citologia , Folhas de Planta/citologia , Feixe Vascular de Plantas/citologia , Genes de Plantas , Genótipo , Pisum sativum/genética , Pisum sativum/crescimento & desenvolvimento , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Feixe Vascular de Plantas/genética , Feixe Vascular de Plantas/crescimento & desenvolvimento
10.
Forensic Sci Int Genet ; 69: 102995, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38065030

RESUMO

Massively parallel sequencing (MPS) techniques were developed approximately 15 years ago. Meanwhile, several MPS kits for forensic identification, phenotypic information, ancestry, and mitochondrial DNA analysis have been developed and their use has been established. Sequencing short tandem repeats (STRs) has certain advantages over the currently used length-based genotyping methods, which are based on PCR amplification followed by capillary electrophoresis (CE). MPS is more discriminative and includes the possibility of testing high numbers of targets (> 100), different types of markers [STRs and single nucleotide polymorphisms (SNPs)], as well as the use of smaller amplicons (< 300 bp). This study evaluated in 24 experimental runs the Precision ID GlobalFiler™ NGS STR panel v2 from ThermoFisher, which targets 31 autosomal STRs, amelogenin, and three Y-markers (one STR, SRY, and Yindel). Single-source samples were used in 18 experimental runs, for systematic evaluation. These included assessing library preparation benchmark conditions, limited DNA input, as well as testing repeatability, number of samples per run, and degraded DNA samples. Full profiles were consistently obtained from as little as 50 pg DNA input. Using the optional recovery PCR method improved outcomes for samples with low DNA input. Full profiles were also obtained from severely degraded DNA samples with degradation indices (DI) of > 60. In addition, six experimental runs were performed testing various two-person mixtures with mixture ratios ranging from 1:20 to 20:1. Major and minor contributors were distinguishable by their read counts (coverage), because less DNA input yielded lower read counts, analogous to the traditional CE technology, where less DNA produces lower peak heights. Mixture ratios of approximately 1:1 were indistinguishable, while a greater imbalance, i.e., higher mixture ratios, made the mixture more distinguishable between major and minor contributors. Based on this information, the highest success rate of correctly deconvoluted four-allelic loci was from mixtures with 1:3 ratios. At higher mixture ratios, the drop-out rate of the minor contributor increased, reducing the number of four-allelic loci.


Assuntos
Impressões Digitais de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Impressões Digitais de DNA/métodos , Análise de Sequência de DNA , Técnicas de Genotipagem , DNA Mitocondrial/genética , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único
11.
J Biomol Struct Dyn ; : 1-11, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38415708

RESUMO

Kirsten rat sarcoma (KRAS) stands out as the most prevalent mutated oncogene, playing a crucial role in the initiation and progression of various cancer types, including colorectal, lung and pancreatic cancer. The oncogenic modifications of KRAS are intricately linked to tumor development and are identified in 22% of cancer patients. This has spurred the necessity to explore inhibition mechanisms, with the aim of investigating and repurposing existing drugs for diagnosing cancers dependent on KRAS G12C In this investigation, 26 nucleoside-based drugs were collected from literature to assess their effectiveness against KRAS G12C. The study incorporates in-silico molecular simulations and molecular docking examinations of these nucleoside-derived drugs with the KRAS G12C protein using Protein Data Bank (PDB) ID: 5V71. The docking outcomes indicated that two drugs, Azacitidine and Ribavirin, exhibited substantial binding affinities of -8.7 and -8.3 kcal/mol, respectively. These drugs demonstrated stability in binding to the active site of the protein during simulation studies. Root mean square deviation (RMSD) analyses indicated that the complexes closely adhered to an equilibrium RMSD value ranging from 0.17 to 0.2 nm. Additionally, % occupancies, bond angles and the length of hydrogen bonds were calculated. These findings suggest that Azacitidine and Ribavirin may potentially serve as candidates for repurposing in individuals with KRAS-dependent cancers.Communicated by Ramaswamy H. Sarma.

12.
Front Cell Dev Biol ; 12: 1353860, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601081

RESUMO

Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in pre-clinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients.

13.
Indian J Exp Biol ; 51(7): 492-501, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23898547

RESUMO

In the wild type P. sativum, each of the adult plant stem nodes, bears a pair of sessile foliaceous stipules and a petiolated unipinnately compound leaf of 4 to 6 leaflets and 7-9 tendrils. The stipule-reduced (st) and cochleata (coch) single null mutants and coch st double null mutant differ fom the wild type in respectively having sessile stipules of much reduced size, petiolated simple and/or compound leaf-like stipules and no stipules. It is also known that coch leaves are somewhat bigger than st and wild type leaves. Here, pleiotropic phenotype of coch st double mutant was investigated. The morphologies of stipules and leaf were quantified in the field grown plants and microcultured shoots, latter in the presence and absence of gibberellic acid and N-1-naphthylphthalamic acid. The observations showed that as compared to the corresponding plants or shoots of COCH ST (WT) genotype, (a) coch st plants bore leaves in which all the organs were hypertrophied; (b) full complement of leaflets and 3-5 tendrils were formed on leaf; (c) the microcultured coch st shoots were taller despite lower number of nodes, and (d) they also produced leaves in which all the organs were bigger and the ratio of leaflets/tendrils was higher. It was concluded that in coch st double mutant (a) ST function is essential for stipule primordium differentiation, in the absence of COCH function and (b) absence of negative feedback loops between simple stipules and compound leaf for metabolite utilization allows hypertrophied growth in leaves.


Assuntos
Genes de Plantas/genética , Mutação/genética , Pisum sativum/crescimento & desenvolvimento , Folhas de Planta/crescimento & desenvolvimento , Células Cultivadas , Regulação da Expressão Gênica de Plantas , Giberelinas/farmacologia , Hipertrofia , Morfogênese , Pisum sativum/efeitos dos fármacos , Pisum sativum/genética , Fenótipo , Reguladores de Crescimento de Plantas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética
14.
Indian J Exp Biol ; 51(6): 421-34, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23926690

RESUMO

Leaves of P. sativum the double mutant genotype tendril-less (tl) leaflet-development (lld), due to the action of lld mutation, produce many leaflets that are aborted at different stages of development. Morphological, vein pattern and histological observations showed that aborted leaflets became cup/bell/trumpet (cup) shaped because of segmental differentiation in the leaflet primordium. Cup's inside lamina surface was adaxial and outer surfaces of cup and its stem were abaxial. The lld cups were phenotypically homologous to aborted leaves described in Arabidopsis thaliana mutants, angustifolia and those which underexpressed the HD-ZIP III proteins. Leaflet primordium was found to grow and establish three dimensional polarities apex-downwards. Primordium produced lateral outgrowth on one side of midvein. Differentiation, in the outgrowth of secondary veins, whose xylem tissues faced each other, established the adaxial-abaxial polarity. Lateral outgrowth then developed a cavity which got bounded by future adaxial epidermis. Further growth, veinlet formation, differentiation of palisade parenchyma and spongy parenchyma followed. Opening of lateral outgrowth at its outer midline produced a flat leaflet with lateral lamina spans. The structural and functional correspondence between leaflet and simple leaves suggested commonality between leaf and leaflet development mechanisms. A molecular model for the lld led leaflet abortion was also provided.


Assuntos
Genética , Mutação/genética , Pisum sativum/crescimento & desenvolvimento , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Pisum sativum/genética , Pisum sativum/metabolismo , Fenótipo , Folhas de Planta/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo
15.
Indian J Pediatr ; 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37368220

RESUMO

OBJECTIVES: To evaluate diagnostic accuracy of point-of-care Serum Amyloid A (POC-SAA) and its comparison with procalcitonin for diagnosis of neonatal sepsis. METHODS: The present diagnostic accuracy study consecutively recruited neonates with suspected sepsis. Blood samples for sepsis screen, culture, high sensitivity C-reactive protein (CRP) (hs-CRP, as a part of sepsis screen), procalcitonin and POC-SAA were collected before starting antibiotics. The optimum cut-off level of biomarkers (POC-SAA and procalcitonin) was determined by receiver-operating-characteristics curve (ROC) analysis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of POC-SAA and procalcitonin were derived for 'clinical sepsis (neonates with suspected sepsis and either positive sepsis screen and/or blood culture)' and 'culture positive sepsis' (neonates with suspected sepsis and positive blood culture). RESULTS: Seventy-four neonates with mean±SD gestational age of 32.8±3.7 wk were evaluated for suspected sepsis, of which the proportion of 'clinical sepsis' and 'culture positive sepsis' was 37.8% had 16.2%, respectively. At a cut-off of 25.4 mg/L, POC-SAA had sensitivity, specificity, PPV and NPV of 53.6%, 80.4%, 62.5% and 74.0%, respectively for diagnosis of clinical sepsis. The sensitivity, specificity, PPV and NPV of POC-SAA for detection of culture positive sepsis were 83.3%, 61.3%, 29.4% and 95.0%, respectively at a cut-off of 10.3 mg/L. There was no significant difference in the diagnostic accuracy of biomarkers for detection of culture positive sepsis (area under the curve, AUC of POC-SAA vs. procalcitonin vs. hs-CRP: 0.72 vs. 0.85 vs. 0.85; p = 0.21). CONCLUSIONS: POC-SAA is comparable to procalcitonin and hs-CRP for diagnosis of neonatal sepsis.

16.
Indian J Community Med ; 48(5): 692-695, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970157

RESUMO

Introduction: Anthropometric parameters play vital role in monitoring growth in pediatrics. Many etiological factors lead to short stature. So, before assessing the etiological factors short stature needs to be addressed. This study aimed to screen short stature for age in school-going children aged 5 to 16 years in Uttarakhand. Material and Methods: In this cross-sectional observational study, the height (through stadiometer) and weight (through weight machine) of 4189 students of government and private school in Rishikesh (Uttarakhand) aged 5-16 years were measured after the verbal assent of the students and individual's height is in the 3rd percentile for the mean height of a given age, sex, and population group and was considered short stature. The data collection was performed from October 2019 to July 2021. The data were categorized according to different age groups to 5-8 years, 9-12 years, and 13-16 years. The data were recorded in Microsoft (MS) Excel spreadsheet program. Statistical Package for the Social Sciences (SPSS) v23 (IBM Corp.) was used for data analysis. Descriptive statistics were elaborated in the form of means or standard deviations and medians or Interquartile range IQRs for continuous variables and frequencies and percentages for categorical variables. The Chi-square test was used for group comparisons for categorical data. Results: 7.1% of children were short stature (height 143.16 ± 15.09 cm) in the Himalayan belt, and males were more prone to short stature at age of 9-12 years. Conclusion: In the growing phase of children, the etiology of short stature has to be rectified, so the children can achieve such proper growth. Parents and physicians have to assess and monitor the growth of children timely. This study can be a stepping stone for further epidemiological studies.

17.
Indian J Otolaryngol Head Neck Surg ; 75(4): 3925-3928, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37974857

RESUMO

Cavernous hemangioma of orbit is a benign, noninfiltrative, slowly progressive vascular neoplasm. It is usually asymptomatic but patients may present with proptosis and diminished vision due to compression of second cranial nerve, optic nerve. This can be usually diagnosed with the help of clinical examination and computed tomography (CT) or magnetic resonance imaging (MRI). Small sized tumours are worth wait and watch while large ones need surgical excision. In our case report, A 65-year-old male patient presented to the head and neck surgery with proptosis of left eye since 5 years along with decreased vision since 4 years. MDCT scan (orbits plain) suggestive of large solid retroocular, intraconal mass in left orbit leading to proptosis of left eyeball. The patient underwent excision of tumour through a transnasal endoscopic approach. Histopathological examination of the tumour identified as cavernous hemangioma. It is safe and effective way to access and excise the orbital tumours through the transnasal endoscopic approach. It is essential to have experienced surgeon in endoscopic procedures. The patient had satisfactory results at three months follow up and showed no symptoms or relapse on CT scans of orbital region. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03984-y.

18.
J Pharm Bioallied Sci ; 15(Suppl 2): S964-S967, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37694045

RESUMO

Four new dental replacement base tars were evaluated in vitro to determine their mechanical qualities, authentic properties, and biocompatibility. Materials and Methods: In this experiment, we employed SR Triplet HOT (a fiber-developed heat fix tar), Sunflex (a multipurpose force fix sap), Trevalon-Hello (a high-impact heat fix tar), DPI (a digital pigment imaging system), and a variety of other pigments and inks (normal power fix tar). For these models, the ISO specification 1567 for dental substitute base gums called for testing of flexural strength, hardness, impact strength, water sorption and dissolvability, and cytotoxicity. Results: All the strength and mechanical properties tested had a statistically significant difference when intergroup analysis was performed. Conclusion: The exceptional physical and mechanical capabilities of the Sunflex denture base resin, together with its biocompatibility with oral tissues, make it a good candidate for use as a denture base material in routine clinical practice.

19.
Sci Rep ; 13(1): 16532, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37783691

RESUMO

With the expansion of electronic health records(EHR)-linked genomic data comes the development of machine learning-enable models. There is a pressing need to develop robust pipelines to evaluate the performance of integrated models and minimize systemic bias. We developed a prediction model of symptomatic Clostridioides difficile infection(CDI) by integrating common EHR-based and genetic risk factors(rs2227306/IL8). Our pipeline includes (1) leveraging phenotyping algorithm to minimize temporal bias, (2) performing simulation studies to determine the predictive power in samples without genetic information, (3) propensity score matching to control for the confoundings, (4) selecting machine learning algorithms to capture complex feature interactions, (5) performing oversampling to address data imbalance, and (6) optimizing models and ensuring proper bias-variance trade-off. We evaluate the performance of prediction models of CDI when including common clinical risk factors and the benefit of incorporating genetic feature(s) into the models. We emphasize the importance of building a robust integrated pipeline to avoid systemic bias and thoroughly evaluating genetic features when integrated into the prediction models in the general population and subgroups.


Assuntos
Algoritmos , Infecções por Clostridium , Humanos , Simulação por Computador , Registros Eletrônicos de Saúde , Genômica
20.
Photodermatol Photoimmunol Photomed ; 28(3): 162-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22548400

RESUMO

Netherton syndrome (NS) is a rare congenital ichthyosis that is characterized by impaired skin barrier function. Topical medications are cautiously used in NS since toxicity from systemic absorption is a major concern. Narrowband ultraviolet B phototherapy is an alternative therapeutic option that demonstrated its beneficial and practical use in a patient with NS.


Assuntos
Síndrome de Netherton/patologia , Síndrome de Netherton/terapia , Terapia Ultravioleta , Adolescente , Humanos , Masculino
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