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1.
Indian J Crit Care Med ; 28(Suppl 2): S42-S58, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39234231

RESUMEN

Dengue is one of the commonest causes of undifferentiated acute febrile illness in India as well as South East Asia. Nearly two-fifths of the world population is at risk of infection, and nearly 96 million infections reported worldwide, it is a major cause of concern across the globe. The ISCCM leadership felt that there have been no new directives/guidelines except the MOH guidelines for the management of dengue fever since 2014. Under the auspices of the Indian Society of Critical Care Medicine (ISCCM), an expert group of 14 intensivists from across the country, was formed. The task force members formulated questions that needed to be answered. These questions were validated by the members of ISCCM attending research conclave 2023. All the members systematically searched PubMed, MEDLINE, and Science Direct for original articles on different aspects of dengue management between January 1, 2000, and July 1, 2023. From the collected articles, duplicates were removed. Based on the evidence collected, the expert group members prepared statements/answers to the questions. Since most of the evidence is of moderate to low quality, a consensus was generated amongst the members of the task force. Each statement was agreed upon by 70% of the task force. The statements presented in the article are consensus statements as answers to queries raised. How to cite this article: Bhalla A, Singh H, Suri V, Yaddanapudi L, Poddar B, Ghawat R, et al. ISCCM Position Statement: Management of Severe Dengue in Intensive Care Unit. Indian J Crit Care Med 2024;28(S2):S42-S58.

2.
Chem Commun (Camb) ; 60(68): 9062-9065, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39101859

RESUMEN

The first metal-catalyzed (2+4) annulation of 5-alkenyl thiazolones and α,α-dicyanoalkylidenes has been developed via vinylogous Michael/cyclization/isomerization reaction. This (2+4) annulation reaction is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst, delivering enantioenriched spiro[cyclohexenamines-thiazolone] having contiguous quaternary and tertiary stereocenters in good to excellent yield (up to 80%) and excellent stereoselectivities (up to 97% ee and >20 : 1 dr). This methodology has high functional group tolerance and produces a broad range of enantioenriched products under mild reaction conditions.

3.
Org Biomol Chem ; 22(33): 6847, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39129532

RESUMEN

Correction for 'Professor (Dr) Sukh Dev: an iconic scientist with an innate sixth sense who radicalized natural product synthesis & organic chemistry' by Harry Kochat et al., Org. Biomol. Chem., 2024, 22, 5466-5469, https://doi.org/10.1039/D4OB90071E.

4.
Rom J Ophthalmol ; 68(2): 170-172, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006324

RESUMEN

Aim: To describe the case of a patient with Marfan syndrome who had bilateral superonasal lens subluxation. Method: The case of a male patient, aged 18, who complained of having impaired vision in both eyes (BE) since he was a toddler, was presented. On examination of the patient, features suggestive of Marfan syndrome were revealed, as well as bilateral intraocular lens subluxation. Results: The patient was refracted and glasses were recommended, which improved his vision. The patient was referred to the cardiology, orthopedic, and dental departments for a multidisciplinary approach to prevent complications and further management. Discussion: Lens subluxation is frequently presented as a primary clinical manifestation of Marfan syndrome. It can vary from asymptomatic, which is seen only after pupillary dilation, to significant subluxation, in which the equator of the lens in the pupillary axis causes diplopia or decreased vision. Conclusion: This case underscored the importance of considering the rare feature of Marfan syndrome.


Asunto(s)
Subluxación del Cristalino , Síndrome de Marfan , Agudeza Visual , Humanos , Síndrome de Marfan/complicaciones , Síndrome de Marfan/diagnóstico , Subluxación del Cristalino/etiología , Subluxación del Cristalino/diagnóstico , Masculino , Adolescente
5.
Rom J Ophthalmol ; 68(2): 166-169, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006321

RESUMEN

Aim: To report a case of cytomegalovirus (CMV) neuroretinitis observed in an immunocompetent patient. Materials and methods: The patient presented with a complaint of diminution of vision in both eyes (BE) and had a traumatic cataract in the right eye (RE). Fundus examination of the left eye (LE) revealed an active white, fluffy lesion with an overlying retinal hemorrhage patch with a macular star. The diagnosis of CMV neuroretinitis was established, and the patient commenced treatment with valganciclovir. Results: The patient exhibited no underlying risk factors. Subsequently, a positive response to oral valganciclovir treatment was observed. Discussion: Cytomegalovirus (CMV) neuroretinitis is typically associated with immunocompromised individuals, such as those with HIV/AIDS. The patient's presentation with a traumatic cataract in the right eye and a distinctive fundus appearance in the left eye posed a diagnostic challenge. The absence of common risk factors for CMV infection necessitated a thorough examination and consideration of rare infectious etiologies. The positive response to valganciclovir reinforces its efficacy in managing CMV-related ocular conditions. This case emphasized the necessity for ophthalmologists to maintain a high index of suspicion for CMV and other unusual pathogens when faced with neuroretinitis in patients who do not present with typical systemic immunosuppressive conditions. Early diagnosis and appropriate antiviral therapy prevent potential complications and preserve vision in such atypical presentations. Conclusion: This case underscores the importance of considering rare infectious agents in immunocompetent patients when encountering neuroretinitis, particularly in the absence of typical symptoms or signs of the disease. Abbreviations: CMV = Cytomegalovirus, BE = Both eyes, RE = Right eye, LE = Left eye, CBC = Complete Blood Count, ESR = Erythrocyte Sedimentation Rate, VDRL = Venereal Disease Research Laboratory, FTA-ABS = Fluorescent Treponemal Antibody Absorption, PPD = Purified Protein Derivative, ANA = Anti-Nuclear Antibodies, RF = Rheumatoid Factor, ACE = Anti Converting Enzyme, Ig G = Immunoglobulin G, HSV = Herpes simplex virus.


Asunto(s)
Antivirales , Retinitis por Citomegalovirus , Citomegalovirus , Inmunocompetencia , Humanos , Retinitis por Citomegalovirus/diagnóstico , Retinitis por Citomegalovirus/tratamiento farmacológico , Antivirales/uso terapéutico , Citomegalovirus/aislamiento & purificación , Masculino , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/virología , Infecciones Virales del Ojo/tratamiento farmacológico , Agudeza Visual , Angiografía con Fluoresceína/métodos , Valganciclovir/uso terapéutico , Fondo de Ojo , Tomografía de Coherencia Óptica/métodos
6.
J Org Chem ; 89(14): 10148-10162, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38959521

RESUMEN

An organocatalytic enantio- and diastereoselective synthesis of hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted α-amino allenoates, exhibiting both axial and central chirality, has been accomplished via cascade dearomatization-cyclization reaction. The γ-addition to ß,γ-alkynyl-α-imino esters provides a library of densely substituted highly enantioenriched allenes in high yields and excellent stereoselectivities. In addition, the scope of this methodology has been extended to tryptophol as well. A scale-up reaction and synthetic transformations of the products were performed to demonstrate the practical usefulness of this approach.

8.
Anal Methods ; 16(27): 4551-4560, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38912555

RESUMEN

In this paper, a coumarin-based Schiff base chemosensor has been synthesized and developed to detect Cu2+ and Zn2+ ions in nanomolar concentrations. The probe selectively distinguishes Cu2+ and Zn2+ from among several metal ions in DMF : H2O (7 : 3, v/v, pH 7.4) HEPES buffer. The structure of the probe and its sensing behavior were investigated by FT-IR, UV-vis, fluorescence, HRMS, and NMR analyses, along with X-ray crystallography and computational studies. CIH detects Zn2+ and Cu2+ using different strategies: CHEF-induced fluorescence enhancement and paramagnetic fluorescence quenching, respectively. Job's plots show a 1 : 1 binding interaction between CIH and Cu2+ or Zn2+ ions. The binding constant values for Cu2+ (1.237 × 105 M-1) and Zn2+ (1.24 × 104 M-1) suggest a better ability for Cu2+ to interact with CIH than Zn2+. An extremely high sensitivity of the probe was highlighted by its very low detection limits (LOD) of 5.36 nM for Cu2+ and 3.49 nM for Zn2+. The regeneration of the probe with the addition of EDTA in its complexes allows the formation of molecular logic gates. CIH has been successfully employed in mitotracking and intracellular detection of Zn2+ and Cu2+ in SiHa cells.


Asunto(s)
Cobre , Cumarinas , Colorantes Fluorescentes , Bases de Schiff , Zinc , Zinc/análisis , Zinc/química , Cumarinas/química , Cobre/análisis , Cobre/química , Humanos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Bases de Schiff/química , Límite de Detección , Espectrometría de Fluorescencia/métodos , Imagen Óptica/métodos
9.
Org Lett ; 26(23): 4932-4937, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38825803

RESUMEN

Herein we report the first use of p-quinone diimide for the aminative dearomatization of 2,3-disubstituted indoles to furnish C3 aza-quaternary chiral indolenines. This approach, which proceeds via an electrophilic 1,6-addition of p-quinone diimide, allows the synthesis of an array of optically active aza-quaternary indolenines with high yields and excellent enantioselectivities. A one-pot approach of the same has also been established to further improve the synthetic accessibility of this protocol.

10.
J Fluoresc ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38724868

RESUMEN

Solvatochromic studies in conjunction with NCQDs and analysis of material at different pH levels provide valuable insights about the process of metal ion sensing. Metal ion sensing holds significant importance in various fields like environment monitoring, biomedical diagnostics and various industrial purpose. The detection of metal ions by mixing the nitrogen-doped quantum dots (NCQDs) in the solvent at different pH levels for the analysis of the photoluminescence spectra is the unique property to achieve selective metal ion detection. In present study, the synthesis of NCQDs was performed by the use of flowers of Tecoma stans. The synthesis of NCQDs to best of our knowledge using flowers of Tecoma stans as natural carbon source via hydrothermal process has been done for the first time. The NCQDs exhibit absorption bands ranging from 190 to 450 nm, with the energy band gap varying from 3.55 to 5.42 eV when mixed with different solvent such as, 1-4 dioxane, acetone, acetonitrile, ethyl- acetate, ethanol, methanol and toluene. The fluorescence spectra exhibited highly intense range from approximately 390 to 680 nm across various solvents. XRD analysis further confirmed the crystalline nature of the particles with an average size of 6.96 nm. Different peak positions of the FTIR spectra support functional groups having C-H stretching, C = O (carbonyl) stretching, and C = C stretching vibrations. In the study a notable solvatochromic shift was observed, indicating sensitivity to change in solvent polarity. Additionally, the investigation of the ratio of ground to excited state dipole moment based on solvatochromic shift yielded a value of 3.30. This provide valuable information about optical and electronic properties of NCQDs. Overall, our study sheds light on the unique properties of NCQDs synthesized from Tecoma stans flowers and their potential applications in metal ion sensing, pH probing, and solvent polarity studies.

11.
PLoS One ; 19(4): e0299785, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38598442

RESUMEN

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 µg TPF g-1 soil hr-1), arylsulfatase activity (82.8 µg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.


Asunto(s)
Suelo , Triticum , Triticum/genética , Agua/análisis , Clorofila , Biomasa , Grano Comestible/química
12.
Indian J Ophthalmol ; 72(5): 722-727, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38648434

RESUMEN

PURPOSE: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). METHODS: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. RESULTS: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME. CONCLUSION: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME.


Asunto(s)
Inhibidores de la Angiogénesis , Retinopatía Diabética , Fóvea Central , Inyecciones Intravítreas , Edema Macular , Ranibizumab , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Tomografía de Coherencia Óptica/métodos , Ranibizumab/administración & dosificación , Ranibizumab/uso terapéutico , Edema Macular/tratamiento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiología , Edema Macular/fisiopatología , Agudeza Visual/fisiología , Masculino , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/complicaciones , Estudios Prospectivos , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Persona de Mediana Edad , Fóvea Central/patología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios de Seguimiento , Mácula Lútea/patología , Biomarcadores , Anciano , Segmento Externo de las Células Fotorreceptoras Retinianas/patología
13.
ACS Appl Bio Mater ; 7(5): 3271-3282, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38654595

RESUMEN

A thiazole-based probe, N'-((2-aminothiazol-5-yl)methylene)benzohydrazide (TBH), has been efficiently synthesized and characterized for the selective and sensitive detection of the neurotransmitter epinephrine (EP). The sensing strategy is based on the use of TBH for sequential colorimetric sensing of Ag+ and EP via in situ formation of Ag nanoparticles (Ag NPs) from the TBH-Ag+ complex. The generated Ag NPs lead to a bathochromic shift in absorption maximum and a change in color of the solution from light brown to reddish brown. TBH-Ag+ shows remarkable selectivity toward EP versus other drugs, common cations, anions, and some biomolecules. Moreover, TBH-Ag+ has a low detection limit for EP at 1.2 nM. The coordination of TBH-Ag+ has been proposed based on Job's plot, Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), 1H NMR titration, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDAX), and density functional theory (DFT) studies. The composition and morphology of the generated Ag NPs have been analyzed by XPS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The proposed sensing mechanism for EP has been supported by XPS of Ag after the reaction. Further, the sensitivity of TBH-Ag+ toward EP in brain tissues of an Alzheimer's disease model of mouse has been evaluated. A thorough comparison was done for evaluation of the proposed method.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Colorimetría , Epinefrina , Plata , Tiazoles , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Plata/química , Animales , Ratones , Epinefrina/análisis , Tiazoles/química , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Ensayo de Materiales , Modelos Animales de Enfermedad , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Tamaño de la Partícula , Nanopartículas del Metal/química , Estructura Molecular , Iones/química
14.
World J Crit Care Med ; 13(1): 89026, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38633478

RESUMEN

BACKGROUND: Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb® extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb® haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated. AIM: To formulate/establish specific consensus statements on the use of CytoSorb® haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario. METHODS: We performed a comprehensive literature on CytoSorb® haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb® in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. RESULTS: Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb® for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb® therapy". CONCLUSION: This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb® haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

15.
Chemistry ; 30(20): e202304078, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38311856

RESUMEN

An asymmetric double desymmetrization methodology has been developed for synthesizing densely functionalized chiral cyclopentylcyclohexane scaffolds. We have constructed four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. The methodology has high functional-group tolerance and delivers a broad range of enantioenriched products. This vinylogous Michael addition reaction of prochiral α,α-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst.

16.
Urol Ann ; 16(1): 81-86, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38415232

RESUMEN

Introduction: Nocturnal enuresis (NE) in children is a very common problem managed in pediatric urology. In this study, we present the prevalence of NE in children in Aseer region in Saudi Arabia. Methodology: This study was conducted as a descriptive cross-sectional survey to estimate the prevalence of NE among 555 Saudi children aged 5-15 years in Aseer region in Saudi Arabia. Data collection was done through a questionnaire, which included questions on sociodemographic data, personal knowledge, enuresis-related characteristics, risk factors, and management modalities. Results: This study identified a prevalence of enuresis of 24% of the study population, most of whom were boys. The majority of the parents had a high educational level. Clinical characteristics of the study population showed: 9% have a family history of NE, 2.2% have a history of neurological disorder, 10.0% have a history of urinary tract infections, 66.8% have associated daytime urgency, 67% have urine-holding behavior, and 19.5% have associated daytime enuresis of the study population. Conclusion: Our study found that 24% of children in the Aseer region in Saudi Arabia have NE. Our study finding helps us to understand the prevalence of NE in Aseer region in Saudi Arabia, and this can be applied to other regions in the kingdom. Furthermore, this finding helps us to understand the need to raise awareness in the community about NE and the need to educate the nonpediatric urologist health-care provider about the best management practice for NE.

17.
J Org Chem ; 89(2): 1264-1274, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38175926

RESUMEN

An organocatalytic asymmetric cascade Michael-acyl transfer reaction of 2-hydroxynitrostyrenes and monofluorinated ß-diketones has been developed employing a cooperative catalytic system. A combination of quinine-derived bifunctional squaramide catalyst and achiral hydrogen bond donor cocatalyst was found to be the most effective for this reaction and provided the fluorinated acyl transfer products in high yields with good diastereo- and excellent enantioselectivities. Synthetic transformations have been demonstrated, including the synthesis of functionalized 2,3-dihydrobenzofurans and 1-pyrroline.

18.
3 Biotech ; 14(2): 38, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38261846

RESUMEN

The present report communicates the first complete genome sequence of S-type Mycobacterium avium subsp. paratuberculosis, isolated from an organised goat herd in Uttar Pradesh, India. Bacteria were isolated in pure culture on Herrold's egg yolk medium (HEYM) slants containing mycobactin J from the faecal sample collected per-rectally from a clinical diseased goat, and next-generation sequencing (NGS) revealed that the genome sequence length of the isolated strain named MAP-Gt-9 is 4,509,428 bp with no plasmid DNA, with a GC content of 69.5%, an N50 value of 125,474 bp, and an L50 value of 12, containing 4235 coding DNA sequences (CDSs), 44 tRNAs, 3 ncRNAs and 1 each 5S, 16S, 23S rRNA genes.

19.
J Clin Invest ; 134(7)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38271119

RESUMEN

Loss of BRCA2 (breast cancer 2) is lethal for normal cells. Yet it remains poorly understood how, in BRCA2 mutation carriers, cells undergoing loss of heterozygosity overcome the lethality and undergo tissue-specific neoplastic transformation. Here, we identified mismatch repair gene mutL homolog 1 (MLH1) as a genetic interactor of BRCA2 whose overexpression supports the viability of Brca2-null cells. Mechanistically, we showed that MLH1 interacts with Flap endonuclease 1 (FEN1) and competes to process the RNA flaps of Okazaki fragments. Together, they restrained the DNA2 nuclease activity on the reversed forks of lagging strands, leading to replication fork (RF) stability in BRCA2-deficient cells. In these cells, MLH1 also attenuated R-loops, allowing the progression of stable RFs, which suppressed genomic instability and supported cell viability. We demonstrated the significance of their genetic interaction by the lethality of Brca2-mutant mice and inhibition of Brca2-deficient tumor growth in mice by Mlh1 loss. Furthermore, we described estrogen as inducing MLH1 expression through estrogen receptor α (ERα), which might explain why the majority of BRCA2 mutation carriers develop ER-positive breast cancer. Taken together, our findings reveal a role of MLH1 in relieving replicative stress and show how it may contribute to the establishment of BRCA2-deficient breast tumors.


Asunto(s)
Proteína BRCA2 , Neoplasias Mamarias Animales , Animales , Ratones , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Reparación de la Incompatibilidad de ADN , Replicación del ADN
20.
Indian J Ophthalmol ; 72(4): 565-570, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38189524

RESUMEN

PURPOSE: To compare postoperative cosmesis, mydriasis, fundus visibility, and anterior chamber depth (ACD) in congenital and traumatic iris defects after single-pass four-throw pupilloplasty (SFTP). SETTINGS AND DESIGN: Hospital-based non-randomized interventional study. METHODS: SFTP was done along with phacoemulsification in six patients each with congenital and traumatic iris defects, and the patients were followed for a minimum period of 3 months. The postoperative pupil shape, size, mydriasis, and ACD were compared between the two groups. RESULTS: Tissue approximation was successful in 11 out of 12 patients (91.7%), whereas it failed to do so in one patient with traumatic iris tear (8.3%). A central round pupil was attained in all six patients with congenital defects (group 1), whereas in the traumatic group (group 2), a central round pupil was attained in four cases. Group 1 did not show a significant reduction in horizontal pupil diameter, but group 2 had a significant reduction in pupil diameter postoperatively. Mydriasis and fundus visibility were satisfactory in all cases. There was a significant deepening of ACD in both groups. CONCLUSION: Traumatic mydriasis usually requires SFTP at two opposite poles to achieve a central pupil with a significant reduction in pupil size, whereas congenital coloboma requires SFTP to be done at the site of coloboma with occasional enlargement at the opposite pole if the pupil is eccentric.


Asunto(s)
Extracción de Catarata , Coloboma , Midriasis , Humanos , Midriasis/diagnóstico , Midriasis/etiología , Midriasis/cirugía , Coloboma/cirugía , Iris/cirugía , Pupila , Cámara Anterior/cirugía
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