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1.
Immunity ; 49(1): 93-106.e7, 2018 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-29958804

RESUMEN

There is a growing body of research on the neural control of immunity and inflammation. However, it is not known whether the nervous system can regulate the production of inflammatory myeloid cells from hematopoietic progenitor cells in disease conditions. Myeloid cell numbers in diabetic patients were strongly correlated with plasma concentrations of norepinephrine, suggesting the role of sympathetic neuronal activation in myeloid cell production. The spleens of diabetic patients and mice contained higher numbers of tyrosine hydroxylase (TH)-expressing leukocytes that produced catecholamines. Granulocyte macrophage progenitors (GMPs) expressed the ß2 adrenergic receptor, a target of catecholamines. Ablation of splenic sympathetic neuronal signaling using surgical, chemical, and genetic approaches diminished GMP proliferation and myeloid cell development. Finally, mice lacking TH-producing leukocytes had reduced GMP proliferation, resulting in diminished myelopoiesis. Taken together, our study demonstrates that catecholamines produced by leukocytes and sympathetic nerve termini promote GMP proliferation and myeloid cell development.


Asunto(s)
Diabetes Mellitus/fisiopatología , Células Progenitoras de Granulocitos y Macrófagos/citología , Células Progenitoras de Granulocitos y Macrófagos/metabolismo , Mielopoyesis , Neuroinmunomodulación , Sistema Nervioso Simpático/metabolismo , Antagonistas de Receptores Adrenérgicos beta 2/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Diabetes Mellitus/sangre , Modelos Animales de Enfermedad , Femenino , Humanos , Leucocitos/enzimología , Leucocitos/metabolismo , Masculino , Ratones , Células Mieloides/citología , Mielopoyesis/efectos de los fármacos , Neuroinmunomodulación/efectos de los fármacos , Norepinefrina/sangre , Transducción de Señal/efectos de los fármacos , Bazo/citología , Bazo/inervación , Bazo/metabolismo , Sistema Nervioso Simpático/efectos de los fármacos
2.
Brief Bioinform ; 24(5)2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37478372

RESUMEN

Access to accurate viral genomes is important to downstream data analysis. Third-generation sequencing (TGS) has recently become a popular platform for virus sequencing because of its long read length. However, its per-base error rate, which is higher than next-generation sequencing, can lead to genomes with errors. Polishing tools are thus needed to correct errors either before or after sequence assembly. Despite promising results of available polishing tools, there is still room to improve the error correction performance to perform more accurate genome assembly. The errors, particularly those in coding regions, can hamper analysis such as linage identification and variant monitoring. In this work, we developed a novel pipeline, HMMPolish, for correcting (polishing) errors in protein-coding regions of known RNA viruses. This tool can be applied to either raw TGS reads or the assembled sequences of the target virus. By utilizing profile Hidden Markov Models of protein families/domains in known viruses, HMMPolish can correct errors that are ignored by available polishers. We extensively validated HMMPolish on 34 datasets that covered four clinically important viruses, including HIV-1, influenza-A, norovirus, and severe acute respiratory syndrome coronavirus 2. These datasets contain reads with different properties, such as sequencing depth and platforms (PacBio or Nanopore). The benchmark results against popular/representative polishers show that HMMPolish competes favorably on error correction in coding regions of known RNA viruses.


Asunto(s)
COVID-19 , Virus ARN , Virus , Humanos , Análisis de Secuencia de ADN/métodos , Genoma , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
3.
Mol Biol Rep ; 51(1): 296, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38340202

RESUMEN

Circular RNAs (circRNAs) are a unique family of endogenous RNAs devoid of 3' poly-A tails and 5' end caps. These single-stranded circRNAs, found in the cytoplasm, are synthesized via back-splicing mechanisms, merging introns, exons, or both, resulting in covalently closed circular loops. They are profusely expressed across the eukaryotic transcriptome and offer heightened stability against exonuclease RNase R compared to linear RNA counterparts. This review endeavors to provide a comprehensive overview of circRNAs' characteristics, biogenesis, and mechanisms of action. Furthermore, aimed to shed light on the potential of circRNAs as significant biomarkers in various cancer types. It has been performed an exhaustive literature review, drawing on recent studies and findings related to circRNA characteristics, synthesis, function, evaluation techniques, and their associations with oncogenesis. CircRNAs are intricately associated with tumor progression and development. Their multifaceted roles encompass gene regulation through the sponging of proteins and microRNAs, controlling transcription and splicing, interacting with RNA binding proteins (RBPs), and facilitating gene translation. Due to these varied roles, circRNAs have become a focal point in tumor pathology investigations, given their promising potential as both biomarkers and therapeutic agents. CircRNAs, due to their unique biogenesis and multifunctionality, hold immense promise in the realm of oncology. Their stability, widespread expression, and intricate involvement in gene regulation underscore their prospective utility as reliable biomarkers and therapeutic targets in cancer. As our understanding of circRNAs deepens, advanced techniques for their detection, evaluation, and manipulation will likely emerge. These advancements might catalyze the translation of circRNA-based diagnostics and therapeutics into clinical practice, potentially revolutionizing cancer care and prognosis.


Asunto(s)
MicroARNs , Neoplasias , Humanos , ARN Circular/genética , ARN/genética , ARN/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/genética , Neoplasias/terapia , Neoplasias/diagnóstico , Biomarcadores , Regulación de la Expresión Génica
4.
Nutr Metab Cardiovasc Dis ; 34(6): 1554-1558, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38664128

RESUMEN

BACKGROUND AND AIMS: The rising prevalence of metabolic syndrome (MetS) is a matter of serious concern worldwide. Hyperuricemia has been observed as an independent risk factor in the development of MetS and each of its individual components in different populations. This study aims to determine the association of hyperuricemia with MetS and its individual components in a Pakistani cohort. METHODS AND RESULTS: A cross-sectional study was performed in a public sector hospital in Faisalabad, Pakistan. Total 204 participants were studied along with their anthropometric measurements and blood sample analysis for clinically important parameters. MetS was defined according to the NCEP-criteria. Independent sample t-test, Binomial logistic regression and Linear regression analyses were used to determine the association between hyperuricemia and metabolic syndrome. The prevalence of MetS and hyperuricemia in our study was 42.6% and 31.9% respectively. As compared to the normo-uricemic group, the hyperuricemic group had a significantly higher systolic blood pressure, BMI and lower HDL-C level (p < 0.05). After adjusting for age, gender, BMI and LDL-C, hyperuricemia was observed to increase the risk of MetS, increased systolic blood pressure and reduce HDL-C respectively by 1.34, 1.23 and 1.20 folds respectively. CONCLUSION: In this study, a significant association between hyperuricemia and metabolic syndrome, systolic hypertension, blood glucose and decreased HDL-C was observed.


Asunto(s)
Biomarcadores , Hiperuricemia , Síndrome Metabólico , Ácido Úrico , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/sangre , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Hiperuricemia/diagnóstico , Pakistán/epidemiología , Masculino , Femenino , Estudios Transversales , Prevalencia , Adulto , Persona de Mediana Edad , Factores de Riesgo , Biomarcadores/sangre , Ácido Úrico/sangre , Presión Sanguínea , Hipertensión/epidemiología , Hipertensión/diagnóstico , Hipertensión/sangre , Índice de Masa Corporal , Modelos Lineales , Modelos Logísticos , Oportunidad Relativa , Adulto Joven , Medición de Riesgo
5.
Reprod Domest Anim ; 59(3): e14551, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38462999

RESUMEN

Cryopreservation is one of the reliable techniques for long-term storage of sperm. The success of this technique depends on the choice of cryoprotectant; therefore, a plethora of literature has reported the effects of different cryoprotective agents so far. Kappa-carrageenan (κ-carrageenan) is a hydrocolloid polysaccharide extracted from red marine seaweed. Its unique property makes it a promising option as a non-colligative cryoprotectant. The current study aims to evaluate the cryoprotective effect of k-carrageenan along with glycerol on ram sperm quality both after equilibration and freezing. Nine Kajli rams were utilized in this experiment for semen collection through an artificial vagina maintained at 42°C. Qualified samples were diluted in tris egg yolk glycerol (TEYG) extender containing different concentrations of k-carrageenan as 0 mg/mL (control), 0.2, 0.5, 0.8 and 1 mg/mL. Post-thaw assessment was done at 37°C after 24 h of storage, which showed a significant improvement (p < .05) in sperm viability, motility, membrane and acrosome integrity in an extender containing k-carrageenan at a concentration of 0.5 mg/mL compared to control. It is concluded from the current study that the combination of glycerol and 0.5 mg/mL concentration of k-carrageenan improved the sperm post-thaw quality.


Asunto(s)
Preservación de Semen , Semen , Masculino , Ovinos , Animales , Carragenina/farmacología , Glicerol/farmacología , Motilidad Espermática , Espermatozoides , Crioprotectores/farmacología , Criopreservación/veterinaria , Criopreservación/métodos , Oveja Doméstica , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Suplementos Dietéticos
6.
J Pak Med Assoc ; 74(5): 939-945, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38783444

RESUMEN

Objective: To review available medical literature to elucidate the association between childhood sexual abuse and the development of irritable bowel syndrome later in life. METHODS: This systematic review was conducted from January to August 2022 and comprised a literature search on Medline (via PubMed), Scopus, Embase, Web of Science, and Google Scholar databases for relevant studies published between 2001 and 2021. The Newcastle-Ottawa scale was used to determine the quality of the studies. Data on the prevalence of irritable bowel syndrome were meta-analysed using a Mantel-Haenszel random-effects model in RevMan 5.4.1. RESULTS: Of the 7 observational studies analyzed in detail, 5 (71.4%) had a case-control design, and 2 (28.6%) were crosssectional studies. Overall, there were 3156 subjects. The prevalence of irritable bowel syndrome in the childhood sexual abuse group was 51.86% (334/644), while it was 36.74% (923/2512) in the non-childhood sexual abuse group. The pooled odds ratio, indicating the association between childhood sexual abuse and irritable bowel syndrome, was 1.87 (95% confidence interval: 1.56-2.26). The study quality was rated as good in 3 (42.8%) cases, fair in 3 (42.8%), and poor in 1 (14.3%). Conclusion: Childhood sexual abuse was found to be significantly associated with the development of irritable bowel syndrome later in life, further strengthening the argument that childhood sexual abuse can lead to long-term detriments extending into adulthood. However, there was no existing literature found that stratified other aspects of irritable bowel syndrome, including symptom severity and childhood sexual abuse being the exclusive cause of irritable bowel syndrome.


Asunto(s)
Abuso Sexual Infantil , Síndrome del Colon Irritable , Síndrome del Colon Irritable/epidemiología , Humanos , Abuso Sexual Infantil/estadística & datos numéricos , Abuso Sexual Infantil/psicología , Prevalencia , Niño
7.
Curr Opin Nephrol Hypertens ; 32(2): 153-164, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36683540

RESUMEN

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy remain a highly morbid condition that affects both the mother and fetus, complicate approximately 10% of pregnancies worldwide, and contribute to immediate and long-term cardiovascular outcomes. There is still much to learn regarding pathogenesis and treatment goals. RECENT FINDINGS: There is updated information on the pathogenesis of preeclampsia and treatment thresholds for HTN in pregnancy. l-Kynurenine, a metabolite of the essential amino acid l-tryptophan, has been implicated in preeclampsia as decreased levels were found in a uninephrectomized pregnant mouse model of preeclampsia, where replacement of l-kynurenine rescued the preeclamptic state. Further, data from CHIPS (The Control of HTN in Pregnancy Study) and CHAP (Chronic HTN and Pregnancy) trials demonstrate not only the safety of lowering blood pressure to either a diastolic goal of 85 mmHg (CHIPS) or less than 160/105 mmHg (CHAP) without detriment to the fetus but the CHAPS trial has also shown a decrease in the rate of preeclampsia in the treatment group. SUMMARY: We will summarize the different types of hypertensive disorders in pregnancy, updates on the pathogenesis of preeclampsia, and appropriate HTN management based on the latest evidence in order to better care for mother and child.


Asunto(s)
Hipertensión , Preeclampsia , Embarazo , Femenino , Animales , Ratones , Humanos , Preeclampsia/terapia , Quinurenina , Hipertensión/tratamiento farmacológico , Feto
8.
Artículo en Inglés | MEDLINE | ID: mdl-36280225

RESUMEN

Hibernating Spermophilus dauricus is resistant to muscle atrophy. Comprehensive transcriptome and proteome time-course analyses based on Metascape can further reveal the underlying processes (pre-hibernation stage, PRE; torpor stage, TOR; interbout arousal stage, IBA; and post-hibernation stage, POST). Transcriptome analysis showed that the cellular responses to growth factor stimulus and discrete oxygen levels continuously changed during hibernation. Proteomic analysis showed that neutrophil degranulation, sulfur compound metabolic process, and generation of precursor metabolites and energy continuously changed during hibernation. Molecular complex detection (MCODE) analysis in both transcriptome and proteome indicated that smooth muscle contraction was involved in the POST versus IBA stage, and peroxisome proliferator-activated receptor delta (Ppard), Myc proto-oncogene (Myc), Sp1 transcription factor (Sp1), and nuclear factor Kappa B subunit 1 (NFκB1) are the common TFs during the hibernation process. Integrated transcriptome and proteome analyses found 18 molecules in the TOR versus PRE stage, 1 molecule in the IBA versus TOR stage, and 16 molecules in the POST versus IBA stage. Among these molecules, carnitine palmitoyltransferase 1A (Cpt1a), SET and MYND domain containing 2 (Smyd2), four and a half LIM domains 1(Fhl1), reactive oxygen species modulator 1 (Romo1), and translocase of the inner mitochondrial membrane 50 (Timm50) were testified by Western blot. In conclusion, novel muscle atrophy resistance mechanisms can be deciphered by time-course transcriptome and proteome analyses based on Metascape.


Asunto(s)
Hibernación , Sciuridae , Animales , Sciuridae/fisiología , Transcriptoma , Proteómica , Proteoma/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Hibernación/fisiología
9.
Sensors (Basel) ; 23(12)2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37420791

RESUMEN

As criminal activity increasingly relies on digital devices, the field of digital forensics plays a vital role in identifying and investigating criminals. In this paper, we addressed the problem of anomaly detection in digital forensics data. Our objective was to propose an effective approach for identifying suspicious patterns and activities that could indicate criminal behavior. To achieve this, we introduce a novel method called the Novel Support Vector Neural Network (NSVNN). We evaluated the performance of the NSVNN by conducting experiments on a real-world dataset of digital forensics data. The dataset consisted of various features related to network activity, system logs, and file metadata. Through our experiments, we compared the NSVNN with several existing anomaly detection algorithms, including Support Vector Machines (SVM) and neural networks. We measured and analyzed the performance of each algorithm in terms of the accuracy, precision, recall, and F1-score. Furthermore, we provide insights into the specific features that contribute significantly to the detection of anomalies. Our results demonstrated that the NSVNN method outperformed the existing algorithms in terms of anomaly detection accuracy. We also highlight the interpretability of the NSVNN model by analyzing the feature importance and providing insights into the decision-making process. Overall, our research contributes to the field of digital forensics by proposing a novel approach, the NSVNN, for anomaly detection. We emphasize the importance of both performance evaluation and model interpretability in this context, providing practical insights for identifying criminal behavior in digital forensics investigations.


Asunto(s)
Redes Neurales de la Computación , Máquina de Vectores de Soporte , Algoritmos
10.
Heart Lung Circ ; 32(10): 1178-1188, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37743220

RESUMEN

BACKGROUND: There is a dearth of comprehensive studies examining the burden and trends of hypertensive heart disease (HHD) and high systolic blood pressure (SBP) among the Australian population. We aimed to explore the burden of HHD and high SBP, and how they changed over time from 1990 to 2019 in Australia. METHODS: We analysed data from the Global Burden of Disease study in Australia. We assessed the prevalence, mortality, disability-adjusted life-years (DALY), years lived with disability (YLD) and years of life lost (YLL) attributable to HHD and high SBP. Data were presented as point estimates with 95% uncertainty intervals (UI). We compared the burden of HHD and high SBP in Australia with World Bank defined high-income countries and six other comparator countries with similar sociodemographic characteristics and economies. RESULTS: From 1990 to 2019, the burden of HHD and high SBP in Australia reduced. Age standardised prevalence rate of HHD was 119.3 cases per 100,000 people (95% UI 86.6-161.0) in 1990, compared to 80.1 cases (95% UI 57.4-108.1) in 2019. Deaths due to HDD were 3.4 cases per 100,000 population (95% UI 2.6-3.8) in 1990, compared to 2.5 (95% UI 1.9-3.0) in 2019. HHD contributed to 57.2 (95% UI 46.6-64.7) DALYs per 100,000 population in 1990 compared to 38.4 (95% UI 32.0-45.2) in 2019. Death rates per 100,000 population attributable to high SBP declined significantly over time for both sexes from 1990 (155.6 cases; 95% UI 131.2-177.0) to approximately one third in 2019 (53.8 cases; 95% UI 43.4-64.4). Compared to six other countries in 2019, the prevalence of HHD was highest in the USA (274.3%) and lowest in the UK (52.6%), with Australia displaying the third highest prevalence. Australia ranked second in term of lowest rates of deaths and third for lowest DALYs respectively due to high SBP. From 1990-2019, Australia ranked third best for reductions in deaths and DALYs due to HHD and first for reductions in deaths and DALYs due to high SBP. CONCLUSION: Over the past three decades, the burden of HHD in Australia has reduced, but its prevalence remains relatively high. The contribution of high SBP to deaths, DALYs and YLLs also reduced over the three decades.


Asunto(s)
Carga Global de Enfermedades , Cardiopatías , Masculino , Femenino , Humanos , Años de Vida Ajustados por Calidad de Vida , Presión Sanguínea , Australia/epidemiología
11.
Environ Monit Assess ; 195(9): 1047, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37589892

RESUMEN

Lead (Pb) is a non-essential metal with high toxicity, is persistent, is not biodegradable, and has no known biological function. It is responsible for severe health and environmental issues that need appropriate remediation. Therefore, microbes have thrived in a lead-contaminated environment without exhibiting any negative impacts. The present study aimed to examine the toxic effects of lead on animals and the isolation, identification, and characterization of lead-resistant bacterial strains and their biodegradation potential. After oral administration of lead for 4 weeks, mice showed an elevated level of leukocytes and a decrease in TEC, Hb, PCV, MCV, MCH, and MCHC levels. However, a decline in body weight and inflammation and oxidative stress was observed in liver tissues. To remediate toxic heavy metal, lead-resistant bacterial strains were isolated, among which Enterobacter exhibited maximum degradation potential at high lead concentrations. It was identified by molecular basis and after 16S rRNA sequencing, and 99% resemblance was observed with Enterobacter cloacae. FT-IR analysis of the bacteria illustrated the presence of functional groups, including hydroxyl, carboxyl group, sulfide, and amino groups, on the bacterial cell surface involved in the adsorption of lead. Moreover, electron microscopy (SEM) revealed the morphological and physiochemical changes in the bacterial cell after biosorption, indicating the interaction of Cu ions with functional groups. To summarize, the findings show the highly toxic effects of lead on animals and humans and its effective biodegradation by the bacterial strains in the lead-contaminated environment. This biological strategy can be an ideal alternative to remediate heavy metals from contaminated sites to clean up the environment.


Asunto(s)
Plomo , Metales Pesados , Humanos , Animales , Ratones , Biodegradación Ambiental , ARN Ribosómico 16S , Espectroscopía Infrarroja por Transformada de Fourier , Monitoreo del Ambiente , Metales Pesados/toxicidad
12.
Vet Med (Praha) ; 68(6): 238-245, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37982002

RESUMEN

The present study was aimed at measuring the concentration of aflatoxin M1 (AFM1) in the milk of Holstein Friesian cows, its effect on the milk quality and seasonal trends, as well as to investigate the efficacy of a commercial clay-based toxin binder. For this purpose, milk samples from dairy cows (n = 72) were collected and assayed for AFM1 before employing a clay-based toxin binder. The milk samples (n = 72) were collected from selected animals, revealing that 69.4% of the milk samples had AFM1 levels above the United States permissible limit (0.5 µg/kg). The incidence of AFM1 in milk during the winter and summer was 82.5% and 53.1%, respectively. Owing to the presence of AFM1, the level of milk fat, solids-not-fat, and protein were found to be low. Subsequently, the affected animals were divided into two groups, i.e., AFM1 positive control (n = 10) and the experimental group (n = 40). The experimental group of animals were fed the clay-based toxin binder at 25 g/animal/day. A progressive decrease of 19.8% in the AFM1 levels was observed on day 4 and on day 7 (53.6%) in the treatment group. Furthermore, the fat, solids-non-fat and protein increased significantly in the milk. In conclusion, a high level of AFM1 contamination occurs in the milk in Pakistan, affecting the quality of the milk production. Clay-based toxin binders may be used to ensure the milk quality and to protect the animal and consumer health.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38147285

RESUMEN

This review is engaged in determining the capability of plant pollen as a significant source of evidence for the linkage between suspects and crime location in forensic sciences. Research and review articles were collected from Google Scholar, the Web of Science, and PubMed. Articles were searched using specific keywords such as "Forensic Palynology," "Pollen metabarcoding," "Plant forensics," and "Pollen" AND "criminal investigation." Boolean logic was also utilized to narrow the articles to be included in this review article. Through the literature and exploratory research, it has been observed in the current study that with advancements in technology, forensic palynology has found its application in creating an association between the crime scene and suspected individuals to have a link to it, as pollen DNA is a long-lasting investigative tool that can effectively help forensic investigations. Moreover, the literature shows that the DNA of pollen and spores has helped forensic scientists link suspects to crime scenes, and the introduction of pollen DNA metabarcoding tools has eased the efforts of palynologists to analyze pollen DNA. The introduction of DNA metabarcoding techniques to analyze pollen from plants has helped identify the geological locations of the plants and ultimately identify the culprit.

14.
Medicina (Kaunas) ; 59(7)2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37512028

RESUMEN

Background and Objectives: The increase in antimicrobial resistance (AMR) across countries has seriously impacted the effective management of infectious diseases, with subsequent impact on morbidity, mortality and costs. This includes Pakistan. Antimicrobial surveillance activities should be mandatory to continually assess the extent of multidrug-resistant bacteria and the implications for future empiric prescribing. The objective of this retrospective observational study was to monitor the susceptibility pattern of microbes in Pakistan. Materials and Methods: Clinical samples from seven laboratories in Punjab, Pakistan were collected between January 2018 and April 2019, with Punjab being the most populous province in Pakistan. The isolates were identified and their antimicrobial susceptibility was tested using the Kirby-Bauer disc diffusion assay and micro broth dilution methods. The antibiotics assessed were those typically prescribed in Pakistan. Results: In total, 2523 bacterial cultural reports were studied. The most frequently isolated pathogens were Staphylococcus aureus (866, 34.3%), followed by Escherichia coli (814, 32.2%), Pseudomonas aeruginosa (454, 18.0%) and Klebsiella pneumoniae (269, 10.7%). Most pathogens were isolated from pus (1464, 58.0%), followed by urine (718, 28.5%), blood (164, 6.5%) and sputum (81, 3.2%). Conclusions: The findings suggest that current antimicrobial options are severally restricted in Pakistan due to the emergence of multidrug-resistant pathogens. This calls for urgent actions including initiating antimicrobial stewardship programs to enhance prudent prescribing of antibiotics. This includes agreeing on appropriate empiric therapy as part of agreed guidelines, in line with the WHO EML and AWaRe book, whilst awaiting culture reports. This is alongside other measures to reduce inappropriate antimicrobial prescribing and reverse the threat of rising AMR.


Asunto(s)
Antiinfecciosos , Infecciones Estafilocócicas , Humanos , Pakistán/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana Múltiple , Escherichia coli
15.
Pak J Med Sci ; 39(2): 409-416, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36950438

RESUMEN

Objective: To identify the genetic variants in the CYP1B1 gene associated with Primary Congenital Glaucoma (PCG) and to predict its pathological effect. Method: A descriptive study was conducted in the time period of nine months (September 2021-May 2022) after the ethical approval was taken from The Children Hospital and Institute of Child Health (CH & ICH). Two milliliters of the blood sample from PCG-affected individuals were collected in EDTA vacutainers and genomic DNA was extracted by a phenol-chloroform method. The semi-quantification of extracted DNA was done by agarose gel electrophoresis. PCR amplification was performed by specific primers of CYP1B1 gene then termination sequencing (di-deoxy) was done to detect the genetic variants. Different bioinformatics tools such as BLAST, Ensembl, Clustal Omega, Polyphen and SIFT were used for the further analysis of mutation causing the disease. Result: A total of 85% of patients were bilaterally affected, while 15% were unilaterally affected. Mutation analysis identified five non related known variants. Two missense mutations (c.355 G/T p.A119S and c.685G/A p.E229K) occurred in 94% patients and intragenic SNP occurred in 29% patients along with the 1% somatic (c.693C/A p.F231L) and stop gained mutation (c.840C/A p.C280*). Conclusion: Genetic analysis in the current study showed that 85% of PCG affected patients were due to the CYP1B1 mutation, and disease heterogeneity might be reduced through genetic counseling.

16.
Clin Infect Dis ; 75(1): e44-e49, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35271728

RESUMEN

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.2 sublineage has increased rapidly in Europe and Asia since January 2022. Here, we report the epidemiological and genomic analysis of a large single-source BA.2 outbreak in a housing estate. METHODS: We analyzed the epidemiological information on a community outbreak of BA.2 (STY outbreak). We performed whole viral genome sequencing using the Oxford Nanopore MinION device. We calculated the doubling time of the outbreak within a housing estate. RESULTS: The STY outbreak involved a total of 768 individuals as of 5 February 2022, including 432 residents, visitors, or staff (56.3%) from a single housing estate (KC Estate). The outbreak at the KC Estate had a short doubling time of 1.28 days (95% confidence interval: .560-1.935). The outbreak was promptly controlled with the lockdown of 3 buildings within the housing estate. Whole-genome sequencing was performed for 133 patients in the STY outbreak, including 106 residents of the KC Estate. All 133 sequences from the STY outbreak belonged to the BA.2 sublineage, and phylogenetic analysis showed that these sequences cluster together. All individuals in the STY cluster had the unique mutation C12525T. CONCLUSIONS: Our study highlights the exceptionally high transmissibility of the Omicron variant BA.2 sublineage in Hong Kong, where stringent measures are implemented as part of the elimination strategy. Continual genomic surveillance is crucial in monitoring the emergence of epidemiologically important Omicron sublineages.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Brotes de Enfermedades , Hong Kong/epidemiología , Humanos , Filogenia , SARS-CoV-2/genética
17.
Clin Infect Dis ; 75(1): e76-e81, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35234870

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human and other mammals, including hamsters. Syrian (Mesocricetus auratus) and dwarf (Phodopus sp.) hamsters are susceptible to SARS-CoV-2 infection in the laboratory setting. However, pet shop-related Coronavirus Disease 2019 (COVID-19) outbreaks have not been reported. METHODS: We conducted an investigation of a pet shop-related COVID-19 outbreak due to Delta variant AY.127 involving at least 3 patients in Hong Kong. We tested samples collected from the patients, environment, and hamsters linked to this outbreak and performed whole genome sequencing analysis of the reverse transcription polymerase chain reaction (RT-PCR)-positive samples. RESULTS: The patients included a pet shop keeper (Patient 1), a female customer of the pet shop (Patient 2), and the husband of Patient 2 (Patient 3). Investigation showed that 17.2% (5/29) and 25.5% (13/51) environmental specimens collected from the pet shop and its related warehouse, respectively, tested positive for SARS-CoV-2 RNA by RT-PCR. Among euthanized hamsters randomly collected from the storehouse, 3% (3/100) tested positive for SARS-CoV-2 RNA by RT-PCR and seropositive for anti-SARS-CoV-2 antibody by enzyme immunoassay. Whole genome analysis showed that although all genomes from the outbreak belonged to the Delta variant AY.127, there were at least 3 nucleotide differences among the genomes from different patients and the hamster cages. Genomic analysis suggests that multiple strains have emerged within the hamster population, and these different strains have likely transmitted to human either via direct contact or via the environment. CONCLUSIONS: Our study demonstrated probable hamster-to-human transmission of SARS-CoV-2. As pet trading is common around the world, this can represent a route of international spread of this pandemic virus.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Cricetinae , Brotes de Enfermedades , Femenino , Hong Kong/epidemiología , Humanos , Mamíferos , ARN Viral/genética , SARS-CoV-2/genética
18.
Mol Biol Rep ; 49(6): 5611-5624, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35618939

RESUMEN

BACKGROUND: Salinity stress (SS) is a serious detrimental factor for crop growth and productivity and its intensity it is continuously increasing which is posing serious threat to global food security. Hydrogen peroxide (H2O2) priming has emerged as an excellent strategy to mitigate the adverse impacts of SS. However, the role of H2O2 priming in mitigating the salinity induced toxicity is not fully explored. METHODS AND RESULTS: Therefore, in this context the present study was conducted in complete randomized design (CRD) in factorial combination to determine the impact of H2O2 priming on germination, growth, physiological and biochemical traits, osmo-regulating compounds, hormonal balance and ionic homeostasis. The experiment was based on different levels of SS; control, 6 and 12 dS m-1 SS and priming treatments, control and H2O2 priming (2%). Salinity stress significantly reduced the growth, leaf water status (- 15.55%), calcium (Ca2+), potassium (K+) and magnesium (Mg2+) accumulation and increased malondialdehyde (MDA: + 29.95%), H2O2 (+ 21.48%) contents, osmo-regulating compounds (proline, soluble sugars), indole acetic acid (IAA), anti-oxidant activities (ascorbate peroxidase: APX, catalase: CAT, peroxidase: POD and ascorbic acid: AsA) and accumulation of sodium (Na+) and chloride (Cl-.). H2O2 priming effectively reduced the effects of SS on germination and growth and strengthen the anti-oxidant activities through reduced MDA (- 12.36%) and H2O2 (- 21.13%) and increasing leaf water status (16.90%), soluble protein (+ 71.32%), free amino acids (+ 26.41%), proline (+ 49.18%), soluble sugars (+ 71.02%), IAA (+ 57.59%) and gibberlic acid (GA) (+ 21.11%). Above all, H2O2 priming reduced the massive entry of noxious ions (Na+ and Cl-) while increased the entry of Ca2+, K+ and Mg2+ thus improved the plant performance under SS. CONCLUSION: In conclusion H2O2 priming was proved beneficial for improving maize growth under SS thorough enhanced anti-oxidant activities, photosynthetic pigments, leaf water status, accumulation of osmo-regulating compounds, hormonal balance and ionic homeostasis.


Asunto(s)
Antioxidantes , Salinidad , Antioxidantes/metabolismo , Homeostasis , Peróxido de Hidrógeno/metabolismo , Potasio/metabolismo , Prolina/metabolismo , Azúcares , Agua , Zea mays/metabolismo
19.
Mol Biol Rep ; 49(12): 11255-11271, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35802276

RESUMEN

Salt stress is one of the leading threats to crop growth and productivity across the globe. Salt stress induces serious alterations in plant physiological, metabolic, biochemical functioning and it also disturbs antioxidant activities, cellular membranes, photosynthetic performance, nutrient uptake and plant water uptake and resulting in a significant reduction in growth and production. The application of osmoprotectants is considered as an important strategy to induce salt tolerance in plants. Trehalose (Tre) has emerged an excellent osmolyte to induce salinity tolerance and it got considerable attention in recent times. Under salinity stress, Tre helps to maintain the membrane integrity, and improves plant water relations, nutrient uptake and reduces the electrolyte leakage and lipid per-oxidation. Tre also improves gas exchange characteristics, protects the photosynthetic apparatus from salinity induced oxidative damages and brings ultra-structure changes in the plant body to induce salinity tolerance. Moreover, Tre also improves antioxidant activities and expression of stress responsive proteins and genes and confers salt tolerance in plants. Additionally, Tre is also involved in signaling association with signaling molecules and phytohormones and resultantly improved the plant performance under salt stress. Thus, it is interesting to understand the role of Tre in mediating the salinity tolerance in plants. Therefore, in this review we have summarized the different physiological and molecular roles of Tre to induce salt tolerance in plants. Moreover, we have also provided the information on Tre cross-talk with various osmolytes and hormones, and its role in stress responsive genes and antioxidant activities. Lastly, we also shed light on research gaps that need to be addressed in future studies. Therefore, this review will help the scientists to learn more about the Tre in changing climate conditions and it will also provide new insights to insights that could be used to develop salinity tolerance in plants.


Asunto(s)
Antioxidantes , Trehalosa , Trehalosa/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés Fisiológico/genética , Tolerancia a la Sal/genética , Salinidad , Agua/metabolismo
20.
BMC Cardiovasc Disord ; 22(1): 210, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35538411

RESUMEN

BACKGROUND: With advancements in cancer treatment, the life expectancy of oncology patients has improved. Thus, transcatheter aortic valve replacement (TAVR) may be considered as a feasible option for oncology patients with severe symptomatic aortic stenosis (AS). We aim to evaluate the difference in short- and long-term all-cause mortality in cancer and non-cancer patients treated with TAVR for severe AS. METHODS: Medline, PubMed, and Cochrane Central Register of Controlled Trials were searched for relevant studies. Patients with cancer who underwent treatment with TAVR for severe AS were included and compared to an identical population without cancer. The primary endpoints were short- and long-term all-cause mortality. RESULTS: Of 899 studies included, 8 met inclusion criteria. Cancer patients had significantly higher long-term all-cause mortality after TAVR when compared to patients without cancer (risk ratio [RR] 1.43; 95% confidence interval (CI) 1.26-1.62; P < 0.01). Four studies evaluated short-term mortality after TAVR and demonstrated no difference in it in patients with and without cancer (RR 0.72; 95% CI 0.47-1.08; P = 0.11). CONCLUSION: Patients with cancer and severe AS have higher long-term all-cause mortality after TAVR. However, we found no difference in short-term all-cause mortality when comparing patients with and without cancer. The decision to perform TAVR in cancer patients should be individualized based on life expectancy and existing co-morbidities.


Asunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Neoplasias , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Humanos , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
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