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1.
Sci Rep ; 14(1): 13519, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866903

RESUMEN

Scientists and engineers encounter considerable environmental and economic obstacles stemming from the depletion of crude oil or petroleum fossil fuel reservoirs. To mitigate this challenge, alternative solutions like bio-oil-modified binder derived from biomass have been innovated. This research aims to examine the feasibility of using bio-oil-modified binder obtained from cotton stalk waste as a modifier. Various mechanical and physical tests, including penetration, softening point, ductility, and dynamic shear rheometer tests, were conducted on asphalt binder incorporating 5% and 10% bio-oil-modified binder. Wheel tracker, four-point beam fatigue, and dynamic modulus tests were used to evaluate asphalt mixture performance, including rutting, fatigue, and dynamic stiffness. A rolling bottle test (RBT) and asphalt binder bond strength (BBS) were used to assess moisture susceptibility. A bio-oil-modified binder enhanced ductility and penetration characteristics while reducing the softening point. With the addition of a bio-oil-modified binder, stiffness was reduced in parameters such as complex shear modulus and phase angle. In fact, for both specimens containing 5% and 10% bio-oil-modified binder, statistically significant differences were observed among the measured samples. As a result of this reduced stiffness, the modified asphalt binder is more suitable for low-temperature applications. Additionally, 5.8% increased at 10% and 3.1% at 5% CS. Bio-oil-modified binder, compared to virgin mixtures, supports equal rut resistance. However, the RBT and BBS tests revealed that the addition of bio-oil-modified binder increased the susceptibility of conventional asphalt binder to moisture. The findings suggest that bio-oil-modified binder can enhance asphalt binder properties in low-temperature regions, but further research is needed to improve moisture resistance.

2.
Proc Natl Acad Sci U S A ; 121(23): e2315363121, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38805281

RESUMEN

Regulatory T cells (Tregs) are central in controlling immune responses, and dysregulation of their function can lead to autoimmune disorders or cancer. Despite extensive studies on Tregs, the basis of epigenetic regulation of human Treg development and function is incompletely understood. Long intergenic noncoding RNAs (lincRNA)s are important for shaping and maintaining the epigenetic landscape in different cell types. In this study, we identified a gene on the chromosome 6p25.3 locus, encoding a lincRNA, that was up-regulated during early differentiation of human Tregs. The lincRNA regulated the expression of interleukin-2 receptor alpha (IL2RA), and we named it the lincRNA regulator of IL2RA (LIRIL2R). Through transcriptomics, epigenomics, and proteomics analysis of LIRIL2R-deficient Tregs, coupled with global profiling of LIRIL2R binding sites using chromatin isolation by RNA purification, followed by sequencing, we identified IL2RA as a target of LIRIL2R. This nuclear lincRNA binds upstream of the IL2RA locus and regulates its epigenetic landscape and transcription. CRISPR-mediated deletion of the LIRIL2R-bound region at the IL2RA locus resulted in reduced IL2RA expression. Notably, LIRIL2R deficiency led to reduced expression of Treg-signature genes (e.g., FOXP3, CTLA4, and PDCD1), upregulation of genes associated with effector T cells (e.g., SATB1 and GATA3), and loss of Treg-mediated suppression.


Asunto(s)
Factores de Transcripción Forkhead , Subunidad alfa del Receptor de Interleucina-2 , ARN Largo no Codificante , Linfocitos T Reguladores , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Epigénesis Genética , Regulación de la Expresión Génica , Diferenciación Celular/genética
3.
Appl Microbiol Biotechnol ; 108(1): 25, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38157005

RESUMEN

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant; however, it is a persistent organic pollutant as well as affects the human thyroid hormones and causes cancer. However, the degradation of HBCD has received little attention from researchers. Due to its bioaccumulative and hazardous properties, an appropriate strategy for its remediation is required. In this study, we investigated the biodegradation of HBCD using Shewanella oneidensis MR-1 under optimized conditions. The Box-Behnken design (BBD) was implemented for the optimization of the physical degradation parameters of HBCD. S. oneidensis MR-1 showed the best degradation performance at a temperature of 30 °C, pH 7, and agitation speed of 115 rpm, with an HBCD concentration of 1125 µg/L in mineral salt medium (MSM). The strain tolerated up to 2000 µg/L HBCD. Gas chromatography-mass spectrometry analysis identified three intermediates, including 2-bromo dodecane, 2,7,10-trimethyldodecane, and 4-methyl-1-decene. The results provide an insightful understanding of the biodegradation of HBCD by S. oneidensis MR-1 under optimized conditions and could pave the way for further eco-friendly applications. KEY POINTS: • HBCD biodegradation by Shewanella oneidensis • Optimization of HBCD biodegradation by the Box-Behnken analysis • Identification of useful metabolites from HBCD degradation.


Asunto(s)
Retardadores de Llama , Hidrocarburos Bromados , Shewanella , Humanos , Biodegradación Ambiental , Hidrocarburos Bromados/química , Hidrocarburos Bromados/metabolismo , Shewanella/metabolismo , Retardadores de Llama/metabolismo
4.
Ir J Med Sci ; 193(3): 1665-1670, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38114866

RESUMEN

PURPOSE: To describe the anatomical, visual, and safety results of full-thickness macular hole (FTMH) repair surgery and determine factors influencing outcomes. PATIENTS AND METHODS: A retrospective chart review was performed on all patients who underwent primary FTMH repair surgery by a single surgeon over a 3-year period. For comparisons, Snellen visual acuity (VA) was converted to logMAR equivalent. Anatomical hole closure, visual improvement, and final VA of ≤ 0.30 logMAR were the primary outcome measures. RESULTS: Twenty eyes of 19 patients were included. Mean patient age was 69 years (range 55 to 80 years) and 74% were female. Mean minimum linear diameter (MLD) was 440 µm (range 170 µm to 1200 µm). Mean duration of symptoms before surgery was 16 weeks (range 3 to 39 weeks). 100% of eyes achieved successful anatomical FTMH closure. Mean VA improved from 1.03 ± 0.43 logMAR (Snellen 6/60) preoperatively to 0.35 ± 0.22 logMAR (Snellen 6/15) postoperatively (p = 0.0001). Patients with worse preoperative VA gained more vision than those with better preoperative VA (p = 0.01). Eyes operated on within 4 months of symptom onset were more than twice as likely to achieve a postoperative VA of ≤ 0.30 logMAR (Snellen 6/12 or better) compared to eyes with a longer duration of symptoms (p = 0.03). CONCLUSION: FTMH repair surgery was safe and effective, with outcomes comparing favourably with published international studies. All patients benefited from surgery regardless of symptom duration, presenting VA or FTMH size. However, surgery performed within 4 months of symptom-onset was particularly beneficial, highlighting the need for prompt referral and surgery.


Asunto(s)
Perforaciones de la Retina , Agudeza Visual , Humanos , Perforaciones de la Retina/cirugía , Perforaciones de la Retina/fisiopatología , Femenino , Anciano , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Resultado del Tratamiento , Vitrectomía/métodos , Irlanda , Factores de Tiempo
5.
Biotechnol Biofuels Bioprod ; 16(1): 191, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38072928

RESUMEN

BACKGROUND: While representing a model bacterium and one of the most used chassis in biomanufacturing, performance of Escherichia coli is often limited by severe stresses. A super-robust E. coli chassis that could efficiently tolerant multiple severe stresses is thus highly desirable. Sterols represent a featured composition that distinguishes eukaryotes from bacteria and all archaea, and play a critical role in maintaining the membrane integrity of eukaryotes. All sterols found in nature are directly synthesized from (S)-2,3-oxidosqualene. However, in E. coli, (S)-2,3-oxidosqualene is not present. RESULTS: In this study, we sought to introduce (S)-2,3-oxidosqualene into E. coli. By mining and recruiting heterologous enzymes and activation of endogenous pathway, the ability of E. coli to synthesize (S)-2,3-oxidosqualene was demonstrated. Further analysis revealed that this non-native chemical confers E. coli with a robust and stable cell membrane, consistent with a figurative analogy of wearing an "Iron Man's armor"-like suit. The obtained Iron Man E. coli (IME) exhibited improved tolerance to multiple severe stresses, including high temperature, low pH, high salt, high sugar and reactive oxygen species (ROS). In particular, the IME strain shifted its optimal growth temperature from 37 °C to 42-45 °C, which represents the most heat-resistant E. coli to the best of our knowledge. Intriguingly, this non-native chemical also improved E. coli tolerance to a variety of toxic feedstocks, inhibitory products, as well as elevated synthetic capacities of inhibitory chemicals (e.g., 3-hydroxypropionate and fatty acids) due to improved products tolerance. More importantly, the IME strain was effectively inhibited by the most commonly used antibiotics and showed no undesirable drug resistance. CONCLUSIONS: Introduction of the non-native (S)-2,3-oxidosqualene membrane lipid enabled E. coli to improve tolerance to various stresses. This study demonstrated the effectiveness of introducing eukaryotes-featured compound into bacteria for enhancing overall tolerance and chemical production.

6.
Immunol Lett ; 263: 123-132, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37838026

RESUMEN

Transcriptional repressor, hypermethylated in cancer 1 (HIC1) participates in a range of important biological processes, such as tumor repression, immune suppression, embryonic development and epigenetic gene regulation. Further to these, we previously demonstrated that HIC1 provides a significant contribution to the function and development of regulatory T (Treg) cells. However, the mechanism by which it regulates these processes was not apparent. To address this question, we used affinity-purification mass spectrometry to characterize the HIC1 interactome in human Treg cells. Altogether 61 high-confidence interactors were identified, including IKZF3, which is a key transcription factor in the development of Treg cells. The biological processes associated with these interacting proteins include protein transport, mRNA processing, non-coding (ncRNA) transcription and RNA metabolism. The results revealed that HIC1 is part of a FOXP3-RUNX1-CBFB protein complex that regulates Treg signature genes thus improving our understanding of HIC1 function during early Treg cell differentiation.


Asunto(s)
Terapia de Inmunosupresión , Activación de Linfocitos , Femenino , Embarazo , Humanos , Transporte de Proteínas , Diferenciación Celular/genética , Factores de Transcripción Forkhead/genética , Factores de Transcripción de Tipo Kruppel/genética , Linfocitos T Reguladores
7.
Ann Med Surg (Lond) ; 85(6): 2787-2790, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37363553

RESUMEN

Neurological disorders, especially migraines, pose a significant global burden. This has driven the recent innovative research being conducted in the field of anti-migraine therapies, including the discovery of Zavegepant for the treatment of acute migraine attacks. Zavegepant is a novel, first-in-class, intranasally administered calcitonin gene-related peptide (CGRP) receptor antagonist that has recently been approved for use in acute migraine attacks. Recent randomized controlled trials comparing Zavegepant with a placebo have demonstrated favorable results with respect to primary endpoints, as well as a desirable safety profile. The current first-line therapy consists of oral triptans, which are associated with lower efficacy, weaker safety profile, and an unsatisfactory preference rate among patients. Moreover, the intranasal method of administration is a characteristic advantage of Zavegepant, as patients suffering from acute migraine attacks cannot easily ingest oral medication, due to severe nausea and vomiting. In this mini-review, the efficacy and safety of Zavegepant will be compared with those of alternative treatments available for migraines, including oral triptans, intranasal triptans, and other CGRP antagonists currently available in the market. With currently available research, Zavegepant holds superiority over other forms of treatment and can be included in the current treatment guidelines for migraine attacks. However, further research is necessary to effectively assess Zavegepant's long-term efficacy, safety, tolerability, and drug-drug interactions.

8.
Chemosphere ; 326: 138413, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36925003

RESUMEN

A three-dimensional (3D) macroporous reduced graphene oxide/polypyrrole (rGO/Ppy) hydrogel assembled by bacterial cells was fabricated and applied for microbial fuel cells. By taking the advantage of electroactive cell-induced bioreduction of graphene oxide and in-situ polymerization of Ppy, a facile self-assembly by Shewanella oneidensis MR-1and in-situ polymerization approach for 3D rGO/Ppy hydrogel preparation was developed. This facile one-step self-assembly process enabled the embedding of living electroactive cells inside the hydrogel electrode, which showed an interconnected 3D macroporous structures with high conductivity and biocompatibility. Electrochemical analysis indicated that the self-assembly of cell-embedding rGO/Ppy hydrogel enhanced the electrochemical activity of the bioelectrode and reduced the electron charge transfer resistance between the cells and the electrode. Impressively, extremely high power output of 3366 ± 42 mW m-2 was achieved from the MFC with cell-embedding rGO/Ppy hydrogel rGO/Ppy, which was 8.6 times of that delivered from the MFC with bare electrode. Further analysis indicated that the increased cell loading by the hydrogel and improved electrochemical activity by the rGO/Ppy composite would be the underlying mechanism for this performance improvement. This study provided a facile approach to fabricate the biocompatible and electrochemical active 3D nanocomposites for MFC, which would also be promising for performance optimization of various bioelectrochemical systems.


Asunto(s)
Fuentes de Energía Bioeléctrica , Fuentes de Energía Bioeléctrica/microbiología , Polímeros/química , Pirroles/química , Hidrogeles , Electrodos
9.
Diseases ; 11(1)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36810539

RESUMEN

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease characterized by light chain deposition in soft tissues and viscera, causing systemic organ dysfunction with an underlying lymphoproliferative disorder. While the kidney is the most affected organ, cardiac and hepatic involvement is also seen with LCDD. Hepatic manifestation can range from mild hepatic injury to fulminant liver failure. Herein, we are presenting a case of an 83-year-old woman with a monoclonal gammopathy of undetermined significance (MGUS), who presented to our institution with acute liver failure progressing to circulatory shock and multiorgan failure. After an extensive workup, a diagnosis of hepatic LCDD was determined. In conjunction with the hematology and oncology department, chemotherapy options were discussed, but given her poor prognosis, the family decided to pursue a palliative route. Though establishing a prompt diagnosis is important for any acute condition, the rarity of this condition, along with paucity of data, makes timely diagnosis and treatment challenging. The available literature shows variable rates of success with chemotherapy for systemic LCDD. Despite chemotherapeutic advances, liver failure in LCDD indicates a dismal prognosis, where further clinical trials are difficult owing to the low prevalence of the condition. In our article, we will also be reviewing previous case reports on this disease.

10.
Ir J Med Sci ; 192(5): 2527-2532, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36658378

RESUMEN

AIM: The aim of this retrospective review was to analyse the frequency of patients presenting with flashes and/or floaters (F/F) on bright versus dark days to the eye emergency department of a tertiary referral hospital (the Mater Misericordiae University Hospital) over a 3-year period. The diagnostic and clinical outcomes of F/F presentations were also analysed. METHODS: This retrospective study assessed eye casualty attendances between January 2018 and December 2020. Solar irradiation (j/cm2) at ground level was retrieved from the records of Met Eireann (Irish National Meteorological Service) via their open access records. A review of electronic patient medical records using the in-house database patient centre was carried out of all patients who attended EED of during the study timeline on the 5 'brightest' and 5 'darkest' days of each year. RESULTS: Seven hundred forty patient presentations were analysed in total. Overall, 16% (n = 119) of all patients that attended EED during the timeframe of the study presented with F/F. One hundred six patients (89%) presented with floaters, 40 patients (34%) presented with flashing lights/photopsia, and 35 patients (29%) presented with both F/F. More patients presented to EED with F/F on bright days when compared with dark days (74 vs 45, p < 0.05). Eighty-nine percent of all patients with F/F presented with monocular floaters. There were more floater presentations during bright when compared with dark days (70 vs 36, p < 0.05). More patients were diagnosed with PVD on bright days when compared with those diagnosed with PVD on dark days (43vs 15, p < 0.05). More RDs were diagnosed on dark days compared with bright days (7 vs 3, p < 0.05). CONCLUSION: This study established that F/F presentations were more likely to present during bright days when compared with dark days. The diagnosis of PVD was more common during bright days, and RDs were diagnosed significantly more frequently on dark days. Although incident solar radiation was correlated with greater floaters/PVD presentation, causation is unlikely, and the duration of PVD may have been longer in patients presenting on bright days (i.e. pseudo-sudden symptoms).


Asunto(s)
Perforaciones de la Retina , Desprendimiento del Vítreo , Humanos , Estudios Retrospectivos , Desprendimiento del Vítreo/complicaciones , Desprendimiento del Vítreo/diagnóstico , Perforaciones de la Retina/complicaciones , Perforaciones de la Retina/diagnóstico , Trastornos de la Visión/etiología , Servicio de Urgencia en Hospital
11.
J Coll Physicians Surg Pak ; 32(8): 1042-1046, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35932130

RESUMEN

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aims to determine the genotypic and phenotypic spectrum of the CFTR gene mutations reported in the literature for Pakistani-origin CF patients. Databases were searched for such studies from 1947-2019 for sample size, method of diagnosis, and CFTR gene mutations. The authors identified 12 studies reporting 33 CFTR gene mutations, both intronic as well as exonic in Pakistani origin patients. The most widely tested mutation was D508 with a frequency of 17%-60%. No hotspot zone was identified and not all reported mutations were causing disease. There is a need to identify common mutations in the Pakistani population to develop population-specific CFTR mutations panel. This will enable the researchers to perform phenotype-genotype correlation studies to improve the CF detection rate. Key Words: Cystic fibrosis, Pakistan, Mutations, CFTR.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística , Pueblo Asiatico/genética , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Fibrosis Quística/genética , Genes Reguladores , Humanos , Mutación , Pakistán
12.
J Theor Biol ; 532: 110914, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34582825

RESUMEN

p53 protein plays an essential role in protecting the genomic integrity of mammalian cells. A drastic decrease in the amount of p53 protein has been observed in cancerous cells. By using Nutlin-based small molecule drugs, the concentration of p53 can be restored to the desired level. This paper presents the drug-dosage design for p53 pathway, based on a control-oriented nonlinear model. A chattering free sliding mode control (CFSMC) strategy is employed to track the desired trajectory of p53 concentration for both of its dynamic behaviors, i.e., sustained and oscillatory responses. A gain-scheduled modified Utkin observer (GSMUO) is designed for robust state reconstruction and disturbance estimation. The simulation results show that CFSMC and GSMUO exhibit desired robustness and performance properties in the presence of parametric variations, an input disturbance and measurement noise. Moreover, a comprehensive simulation study, along with a detailed quantitative analysis is performed to compare CFSMC-GSMUO with four different techniques: a sliding mode control (SMC) with an equivalent control based sliding mode observer (SMO) and GSMUO, respectively, and a dynamic sliding mode control (DSMC) with SMO and GSMUO, respectively. The analysis demonstrates that the tracking error and utilization of the control energy is the least in the case of CFSMC-GSMUO as compared to its counterparts.


Asunto(s)
Algoritmos , Proteína p53 Supresora de Tumor , Simulación por Computador , Dinámicas no Lineales
13.
Comput Math Methods Med ; 2021: 6289337, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34675992

RESUMEN

Cancer is among the major public health problems as well as a burden for Pakistan. About 148,000 new patients are diagnosed with cancer each year, and almost 100,000 patients die due to this fatal disease. Lung, breast, liver, cervical, blood/bone marrow, and oral cancers are the most common cancers in Pakistan. Perhaps smoking, physical inactivity, infections, exposure to toxins, and unhealthy diet are the main factors responsible for the spread of cancer. We preferred a novel four-component mixture model under Bayesian estimation to estimate the average number of incidences and death of both genders in different age groups. For this purpose, we considered 28 different kinds of cancers diagnosed in recent years. Data of registered patients all over Pakistan in the year 2012 were taken from GLOBOCAN. All the patients were divided into 4 age groups and also split based on genders to be applied to the proposed mixture model. Bayesian analysis is performed on the data using a four-component exponential mixture model. Estimators for mixture model parameters are derived under Bayesian procedures using three different priors and two loss functions. Simulation study and graphical representation for the estimates are also presented. It is noted from analysis of real data that the Bayes estimates under LINEX loss assuming Jeffreys' prior is more efficient for the no. of incidences in male and female. As far as no. of deaths are concerned again, LINEX loss assuming Jeffreys' prior gives better results for the male population, but for the female population, the best loss function is SELF assuming Jeffreys' prior.


Asunto(s)
Teorema de Bayes , Neoplasias/epidemiología , Biología Computacional , Simulación por Computador , Modelos Epidemiológicos , Femenino , Humanos , Incidencia , Funciones de Verosimilitud , Masculino , Modelos Estadísticos , Neoplasias/mortalidad , Pakistán/epidemiología
14.
Clin Ophthalmol ; 15: 1259-1266, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790533

RESUMEN

PURPOSE: To determine the difference in mean corneal endothelial cell density (CECD) between the healthy and diseased eyes of the patients with unilateral pterygium with different morphology patterns by using a non-contact specular microscope (SP2000: Topcon Corporation, Japan) and to find out any relationship between severity of pterygium and daily sunlight exposure with the CECD loss. METHODS: A descriptive cross-sectional prospective study was carried out at Al-Shifa Trust Eye Hospital (ASTEH), Rawalpindi, Pakistan from 21st January 2019 to 22nd January 2020. Two hundred eyes (n= 100 patients) of age range18 -68 years with unilateral pterygium were selected. Necessary demographic data and essential variables like age, smoking status, occupation, and daily direct sunlight exposure were determined. The severity of pterygium (grading) based on its morphology was determined by slit-lamp examination. CECD of each patient was carried out using a non-contact Specular Microscope. The healthy eye (without pterygium) of a patient was considered as control. RESULTS: The age range in this study was 18-68 years, with a mean age of 43.80 ± 24.37 years with a male to female ratio of 1.6:1 (62.00% males vs 38% females). Out of six occupations, the most common occupation was labour/construction work (n=31) followed by farming (n=27). The study reported a mean corneal endothelial cell density (CECD) of 2411.61±143.64 vs 2751.41 ± 123.674 cells/mm2 in diseased and normal eyes, respectively (p-value = 0.0001). CECD was lower in grade 3 pterygium compared to less severe pterygium { grade 3 (Fleshy) =2261 cells/mm2 vs grade 2 (Intermediate)= 2413 cells/mm2 vs grade 1 (Atrophic)=2459 cells/mm2} although this difference between the groups was not found to be significant (p=0.065). No significant association between sunlight exposure and CECD loss was observed (p=0.065). CONCLUSION: This study concluded that the mean corneal endothelial cell density in patients with unilateral pterygium using a non-contact specular microscope were 2411.61±143.64 cells/mm2.

15.
Ann Med Surg (Lond) ; 64: 102251, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33898026

RESUMEN

BACKGROUND: The gold standard screening method of hyperoxaluria in children is using 24-hour urine collection. Urine collection may be cumbersome and challenging for children. Reference intervals (RI) of oxalate for the Pakistani population are not readily available. Therefore we aimed to determine the oxalate to creatinine ratio (Ox: Cr) for Pakistani children <6 years of age. MATERIALS AND METHODS: A cross-sectional study was conducted at Aga Khan University from June 2018 to October 2019. Random urine samples from apparently healthy children < 6 years were collected and stored at -30°C until analysis after adding 6M HCl. Oxalate was measured on Micro lab 300 using a kit based on oxalate oxidase principle, while creatinine was measured by kinetic Jaffe reaction. Data was analyzed by EP evaluator and SPSS 23. Ox: Cr ratio was calculated and reported with 90% confidence interval (CI) and interquartile range (IQR). RESULTS: The mean age of study subjects (n=120) was 29 ±22.3 months with an M: F ratio of 1:1. Children of various ethnicities were included from all over Karachi. The majority of the subjects were Urdu speaking (37.5%). Median Ox: Cr was 0.13(0.10). No significant difference was noted in the median Ox: Cr ratio between various ethnicities (p>0.05). It was significantly different in group I to V which was 0.25 (IQR: 0.06), 0.19 (IQR: 0.11), 0.15 (IQR: 0.04), 0.11 (IQR: 0.06) and 0.08 (IQR: 0.04) respectively (pvalue <0.001). CONCLUSION: The established RIs of Ox: Cr ratio was 0.05-0.34 (90% CI). Ox: Cr ratio showed a declining trend with age. Large scale reference interval studies are encouraged, taking diet and age into consideration.

17.
Plant Physiol Biochem ; 160: 211-217, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33515970

RESUMEN

Citrate is an important intermediate product for the biosynthesis of several metabolites in plants. As two important organs of the citrus plant, fruits and leaves have their own metabolites characteristics; among them, citrate is normally high in fruit juice sacs (JS) and low in leaves. In this study, citrate content and transcript levels of citrate synthesis, transport, storage, and utilization related genes were compared between leaves and fruit JS of Citrus reticulata cv. 'Huagan No. 2', C. grandis cv. 'Hirado Buntan', and C. sinensis cv. 'Anliu'. Results indicated that the citrate content in fruit JS was significantly higher than in leaves of each cultivar. Only the relative mRNA levels of a P-type proton pump gene, CsPH8, was significantly lower in leaves than in fruit JS of three citrus cultivars, while other genes related to citrate biosynthesis, transport, storage, and utilization were highly expressed in leaves as compared to fruit JS. Furthermore, CsPH8 transient and stable transformation in leaves indicated that the change in citrate content is highly consistent with the change of CsPH8 transcript levels. Taken together, our results strongly suggest that the low accumulation of citrate in citrus leaves is mainly due to the low expression level of CsPH8; additionally, the high level of expression of citrate-utilizing genes would prevent citrate accumulation in the leaf organ.


Asunto(s)
Ácido Cítrico/análisis , Citrus , ATPasas Tipo P/genética , Hojas de la Planta/química , Proteínas de Plantas/genética , Citrus/enzimología , Citrus/genética , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/enzimología
18.
Ann Med Surg (Lond) ; 60: 330-333, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33224485

RESUMEN

BACKGROUND: The evaluation of 24 h urinary oxalate excretion is the gold standard for diagnosing hyperoxaluria in patients with recurrent urolithiasis. However, 24 h urine sample collection is cumbersome. Therefore we aim to see if oxalate to creatinine ratio in random urine sample can be used as an alternative. MATERIALS AND METHODS: A cross-sectional study was conducted at Section of Chemical Pathology, Department of Pathology and Laboratory Medicine Aga Khan University Karachi from 1st February to December 31, 2019. A total of 62 adult patients, 18-60 years of age with history of kidney stones presenting to the clinical laboratory for 24 h urine oxalate estimation were invited to participate in the study after informed consent. Clinical details were recorded on a structured questionnaire and patients were guided to submit 24 h urine and a random spot urine sample. Urinary oxalate was measured on Micro lab 300 using a kit based on oxalate oxidase principle by Trinity Biotech plc, Wicklow, Ireland following standard operating procedures. Urinary creatinine was measured on ADVIA 1800 by Siemens, US using kinetic Jaffe reaction according to the manufacturer's instructions. The data was analyzed on SPSS. RESULTS: In a period of ten months, a total of 62 subjects were recruited; mean age was 32.4 ± 2.6 years. Males were 49 (79.0%) and females were 13 (20.9%). Correlation was found to be (r = 0.289) by Spearman correlation (p value < 0.005). Taking 24 h urinary oxalate as gold standard the sensitivity, specificity, positive predictive value and negative predictive value of spot oxalate to creatinine ratio was 83.3%, 17.8%, 9.8% and 90.9% respectively. CONCLUSION: The random spot urine test cannot replace the 24 h urinary oxalate estimation in patients with urolithiasis.

19.
Int J Surg ; 84: 57-65, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33122153

RESUMEN

BACKGROUND: Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. METHODS: During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. RESULTS: 500 patients underwent surgery with median age 62.5 (IQR 51-71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. CONCLUSION: It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration.


Asunto(s)
COVID-19/mortalidad , Mortalidad Hospitalaria , Servicio de Oncología en Hospital/organización & administración , Servicio de Cirugía en Hospital/organización & administración , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Complicaciones Posoperatorias/epidemiología , SARS-CoV-2 , Medicina Estatal , Reino Unido/epidemiología
20.
J Community Hosp Intern Med Perspect ; 10(3): 279-282, 2020 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-32850079

RESUMEN

Transcatheter aortic valve implantation (TAVR) constitutes an established treatment in inoperable or high perioperative risk patients with severe aortic stenosis. Prosthetic valve endocarditis after ΤΑVR occurs with an incidence of 0.3-1% per patient-year. Infective endocarditis may stem from hematogenous dissemination or contact with infected adherent tissue. Few cases of infective endocarditis after TAVR have been reported. We present an interesting case of a 79-year-old male with a history of severe aortic stenosis status post TAVR greater than one year ago, and pulmonary vein isolation for atrial fibrillation six weeks ago was found to have infective endocarditis with a vegetation on the prosthetic valve leading to multiple embolic strokes as a result of Enterococcus faecalis bacteremia. The patient was not a surgical candidate with his Society of Thoracic Surgery (STS) risk score being 18%; therefore, he was managed conservatively on intravenous antibiotics. Our case had endocarditis from enterococcus bacteremia; however, the patient never had any gastrointestinal or genitourinary procedure.

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