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1.
Circulation ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38923439

ABSTRACT

BACKGROUND: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

2.
J Environ Manage ; 352: 120137, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38266527

ABSTRACT

Using circular bio-based building materials is considered a promising solution to reduce the environmental impacts of the construction industry. To identify the pros and cons of these materials, it is essential to investigate their sustainability performance. However, the previous sustainability assessment studies are heterogeneous regarding the assessment methods and objectives, highlighting the need for a review to identify and analyse these aspects. Moreover, there is still a lack of studies reviewing the methodological issues and implications of the assessment methods, as well as the current end-of-life scenarios and circularity options for these materials. To address these gaps, this study conducts a systematic and critical review of a sample of 97 articles. The results indicate that Life Cycle Assessment (LCA) is the most frequently applied method, yet most studies are cradle-to-gate analyses of materials. Otherwise, very few studies consider the end-of-life phase, and most of the end-of-life scenarios analysed are unsustainable and have low circularity levels. The analysis also highlights the methodological issues of the assessment methods used, with a particular focus on LCA, such as a lack of consensus on system boundaries, functional units, and databases for facilitating sustainability assessments associated with the use of circular bio-based building materials. Two primary recommendations emerge from the analysis. Firstly, for LCA studies, it is recommended to increase transparency and harmonisation in assessments to improve the comparability of results. Besides, to overcome data availability issues, it is recommended to use data from multiple sources and conduct sensitivity and uncertainty analyses. Secondly, more sustainability assessments (including the three pillars) considering the whole life cycle with more sustainable end-of-life scenarios and circularity options for these materials should be conducted.


Subject(s)
Construction Industry , Environment , Construction Materials
3.
Emerg Infect Dis ; 26(11): e1-e14, 2020 11.
Article in English | MEDLINE | ID: mdl-32917290

ABSTRACT

We report key epidemiologic parameter estimates for coronavirus disease identified in peer-reviewed publications, preprint articles, and online reports. Range estimates for incubation period were 1.8-6.9 days, serial interval 4.0-7.5 days, and doubling time 2.3-7.4 days. The effective reproductive number varied widely, with reductions attributable to interventions. Case burden and infection fatality ratios increased with patient age. Implementation of combined interventions could reduce cases and delay epidemic peak up to 1 month. These parameters for transmission, disease severity, and intervention effectiveness are critical for guiding policy decisions. Estimates will likely change as new information becomes available.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Disease Transmission, Infectious/statistics & numerical data , Models, Statistical , Models, Theoretical , Pneumonia, Viral/epidemiology , COVID-19 , Coronavirus Infections/transmission , Humans , Pandemics , Pneumonia, Viral/transmission , SARS-CoV-2
4.
Theor Biol Med Model ; 13(1): 20, 2016 11 09.
Article in English | MEDLINE | ID: mdl-27829439

ABSTRACT

BACKGROUND: Florida State has reported autochthonous transmission of Zika virus since late July 2016. Here we assessed the transmissibility associated with the outbreak and generated a short-term forecast. METHODS: Time-dependent dynamics of imported cases reported in the state of Florida was approximated by a logistic growth equation. We estimated the reproduction number using the renewal equation in order to predict the incidence of local cases arising from both local and imported primary cases. Using a bootstrap method together with the logistic and renewal equations, a short-term forecast of local and imported cases was carried out. RESULTS: The reproduction number was estimated at 0.16 (95 % Confidence Interval: 0.13, 0.19). Employing the logistic equation to capture a drastic decline in the number of imported cases expected through the course of 2016, together with the low estimate of the local reproduction number in Florida, the expected number of local reported cases was demonstrated to show an evident declining trend for the remainder of 2016. CONCLUSIONS: The risk of local transmission in the state of Florida is predicted to dramatically decline by the end of 2016.


Subject(s)
Disease Outbreaks/statistics & numerical data , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Zika Virus/physiology , Florida/epidemiology , Humans , Time Factors , Zika Virus Infection/virology
5.
Int J Pharm ; 661: 124386, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942182

ABSTRACT

Postoperative tissue adhesion is a well-recognized and common complication. Despite ongoing developments in anti-adhesion agents, complete prevention remains a challenge in clinical practice. Colorectal cancer necessitates both adhesion prevention and postoperative chemotherapy. Accordingly, drug-loading into an anti-adhesion agent could be employed as a treatment strategy to maximize the drug effects through local application and minimize side effects. Herein, we introduce an anti-adhesion agent that functions as a drug delivery system by loading drugs within an emulsion that forms a gel matrix in the presence of polysaccharides, xanthan gum, and pectin. Based on the rheological analysis, the xanthan gum-containing emulsion gel formed a gel matrix with suitable strength and mucosal adhesiveness. In vitro dissolution tests demonstrated sustained drug release over 12 h, while in vivo pharmacokinetic studies revealed a significant increase in the Tmax (up to 4.03 times) and area under the curve (up to 2.62 times). However, most of the drug was released within one day, distributing systemically and raising toxicity concerns, thus limiting its efficacy as a controlled drug delivery system. According to in vivo anti-adhesion efficacy evaluations, the xanthan gum/pectin emulsion gels, particularly F2 and F3, exhibited remarkable anti-adhesion capacity (P < 0.01). The emulsion gel formulation exhibited no cytotoxicity against fibroblasts or epithelial cell lines. Thus, the xanthan gum/pectin emulsion gel exhibits excellent anti-adhesion properties and could be developed as a drug delivery system.

6.
Liquids (Basel) ; 3(4): 456-468, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38711572

ABSTRACT

Lyotropic liquid crystals (LLCs) are liquids that have crystalline structures. LLCs as drug delivery systems that can deliver hydrophobic, hydrophilic, and amphiphilic agents. Due to their unique phases and structures, LLCs can protect both small molecules and biologics from the gastrointestinal tract's harsh environment, thus making LLCs attractive as carriers for oral drug delivery. In this review, we discuss the advantages of LLCs and LLCs as oral formulations targeting intestinal lymphatic transport. In oral LLC formulations, the relationship between the micelle compositions and the resulting LLC structures as well as intestinal transport and absorption were determined. In addition, we further demonstrated approaches for the enhancement of intestinal lymphatic transport: (1) lipid-based LLCs promoting chylomicron secretion and (2) the design of LLC nanoparticles with M cell-triggered ligands for targeting the M cell pathway. In this review, we introduce LLC drug delivery systems and their characteristics. Our review focuses on recent approaches using oral LLC drug delivery strategies targeting the intestinal lymphatic system to enhance drug bioavailability.

7.
Taiwan J Ophthalmol ; 13(2): 168-183, 2023.
Article in English | MEDLINE | ID: mdl-37484617

ABSTRACT

Artificial intelligence (AI) has been widely used in ophthalmology for disease detection and monitoring progression. For glaucoma research, AI has been used to understand progression patterns and forecast disease trajectory based on analysis of clinical and imaging data. Techniques such as machine learning, natural language processing, and deep learning have been employed for this purpose. The results from studies using AI for forecasting glaucoma progression however vary considerably due to dataset constraints, lack of a standard progression definition and differences in methodology and approach. While glaucoma detection and screening have been the focus of most research that has been published in the last few years, in this narrative review we focus on studies that specifically address glaucoma progression. We also summarize the current evidence, highlight studies that have translational potential, and provide suggestions on how future research that addresses glaucoma progression can be improved.

8.
Pharmaceutics ; 15(3)2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36986767

ABSTRACT

(1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)-a new anticoagulation drug-has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10-6 cm/s across Caco-2 colonic cells), thus resulting in a low oral bioavailability of <50%; (2) Methods: To solve the drawbacks of conventional APX products, a novel SD of APX in Soluplus® was prepared, characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy techniques and evaluated for its solubility, intestinal permeability and pharmacokinetic performance. (3) Results: The crystallinity of the prepared APX SD was confirmed. The saturation solubility and apparent permeability coefficient increased 5.9 and 2.54 times compared to that of raw APX, respectively. After oral administration to the rats, the bioavailability of APX SD was improved by 2.31-fold compared to that of APX suspension (4) Conclusions: The present study introduced a new APX SD that potentially exhibits better solubility and permeability, thus increasing APX's bioavailability.

9.
Int J Pharm ; 646: 123426, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37729976

ABSTRACT

Delivering protein drugs through dry powder inhalation (DPI) remains a significant challenge. Liposomes offer a promising solution, providing protection for proteins from external environment and controlled release capabilities. Furthermore, the use of non-ionic surfactants plays a crucial role in protecting the activity of proteins because of how the surfactants positioning themselves at the liquid-gas interface during the spray-drying process. In this study, lysozyme-loaded liposomal DPI formulations were prepared using various non-ionic surfactants, including polysorbate 80, poloxamer 188, poloxamer 407, and sucrose stearate. Lysozyme solution and 1,2-distearoyl-sn-glycero-3-phosphatidylcholine liposomes were subjected through high-pressure homogenization to form lysozyme-loaded liposomes. Formulations of homogenized lysozyme liposomes were spray-dried and further characterized. The particle size of reconstituted liposomal lysozyme DPI was from 129.5 to 816.9 nm. The formulations showed encapsulation efficiency up to 32.5% with zeta potential value of around - 30 mV, and spherical structures were observed. The aerosol dispersion performance of the dry powder inhalers was evaluated with emitted doses reaching up to 103% and fine particle fractions up to 28.4%. Significantly higher lysozyme activity was confirmed in formulation with drug to PS 80 ratio of 1: 0.5 w/w (92.1%) compared to that of formulation containing no surfactant (59.8%). The formulation stood out as the only formulation that maintained protein activity while demonstrating good aerosol performance.

10.
Front Cell Neurosci ; 17: 1321632, 2023.
Article in English | MEDLINE | ID: mdl-38283751

ABSTRACT

The etiology of schizophrenia (SCZ) is multifactorial, and depending on a host of genetic and environmental factors. Two putative SCZ susceptibility genes, Disrupted-in-Schizophrenia-1 (DISC1) and reelin (RELN), interact at a molecular level, suggesting that combined disruption of both may lead to an intensified SCZ phenotype. To examine this gene-gene interaction, we produced a double mutant mouse line. Mice with heterozygous RELN haploinsufficiency were crossed with mice expressing dominant-negative c-terminal truncated human DISC1 to produce offspring with both mutations (HRM/DISC1 mice). We used an array of behavioral tests to generate a behavioral phenotype for these mice, then examined the prefrontal cortex and hippocampus using western blotting and immunohistochemistry to probe for SCZ-relevant molecular and cellular alterations. Compared to wild-type controls, HRM/DISC1 mice demonstrated impaired pre-pulse inhibition, altered cognition, and decreased activity. Diazepam failed to rescue anxiety-like behaviors, paradoxically increasing activity in HRM/DISC1 mice. At a cellular level, we found increased α1-subunit containing GABA receptors in the prefrontal cortex, and a reduction in fast-spiking parvalbumin positive neurons. Maturation of adult-born neurons in the hippocampus was also altered in HRM/DISC1 mice. While there was no difference in the total number proliferating cells, more of these cells were in immature stages of development. Homozygous DISC1 mutation combined with RELN haploinsufficiency produces a complex phenotype with neuropsychiatric characteristics relevant to SCZ and related disorders, expanding our understanding of how multiple genetic susceptibility factors might interact to influence the variable presentation of these disorders.

11.
Per Med ; 20(5): 425-433, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37623819

ABSTRACT

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.


Subject(s)
Noninvasive Prenatal Testing , Pregnancy , Female , Infant, Newborn , Humans , Vietnam , Prenatal Diagnosis
12.
Per Med ; 20(6): 467-475, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37937420

ABSTRACT

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex (TSC2 c.4154G>A) and Alagille syndrome (JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.


Subject(s)
Prenatal Diagnosis , Thanatophoric Dysplasia , Pregnancy , Female , Humans , Vietnam , Thanatophoric Dysplasia/diagnosis , Thanatophoric Dysplasia/genetics , Receptor, Fibroblast Growth Factor, Type 3
13.
Pharmaceutics ; 14(8)2022 Jul 26.
Article in English | MEDLINE | ID: mdl-35893805

ABSTRACT

Significant improvements in the wettability and dissolution rate of celecoxib (CEL), a poorly soluble selective cyclooxygenase-2 (COX-2) inhibitor, have been shown by Huyn et al., 2019 by combining the binary pharmaceutical compositions including CEL and one of the two co-formers, adipic acid (ADI) and saccharin (SAC), into eutectic mixtures (EM). Purpose: In this study, we developed a therapeutic eutectic system for CEL which is a promising approach for oral delivery to enhance bioavailability. CEL EM were synthesized by novel techniques including supercritical CO2 techniques and new tablet formulations were purposed. Methods: CEL EM were synthesized by evaporation crystallization method, spray drying, supercritical fluid (SCF) techniques. The CEL EM particles were then characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope, and particle size analysis. Dissolution studies were carried out. With a quality by design approach, a statistical method through design of experiment and data analysis by JMP® (SAS institute) was applied to CEL EM immediate release tablet formulation development. Results: CEL EM produced by spray drying technique, supercritical fluid (SCF) techniques were identified and characterized. The enhancement of dissolution was observed for SCF processed samples. The design space for CEL-ADI EM IR tablet and control limits for individual parameters were determined.

14.
Pharmaceutics ; 14(1)2022 Jan 16.
Article in English | MEDLINE | ID: mdl-35057101

ABSTRACT

Donepezil (DPZ) is generally administered orally to treat Alzheimer's disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.

15.
Int J Pharm ; 621: 121771, 2022 Jun 10.
Article in English | MEDLINE | ID: mdl-35487401

ABSTRACT

Although the first-choice treatment for colorectal cancer is cytoreductive surgery combined with chemotherapy, post-surgical peritoneal adhesion and extant malignancy can cause fatal complications. Studies examining hydrogel-based postoperative anti-adhesion treatments are still limited. In this study, several formulations of 5-fluorouracil (5-FU) loaded into hyaluronic acid (HA) and kappa-carrageenan (kCGN)-poloxamer 407 (P407)-based cross-linked hydrogels were prepared and evaluated in vitro and in vivo for their efficacy in preventing adhesion. These hydrogels met a set of desired specifications such as thermosensitive behavior, strong elasticity at body temperature (tan δ < 1.0 at 37 °C), and ability to encapsulate hydrophilic drug and deliver it in a sustained released manner. Our secondary purpose is to provide in situ 5-FU for additional local antitumor effect when the anti-adhesion agent is spread over the tumor site. Over 60% of the total loaded drug was released within 4 h, and about 80% of 5-FU was released after three days. Both the Higuchi and Korsmeyer-Peppas models showed that the mechanism of sustained drug release involved diffusion. The constructed hydrogels were evaluated for in vivo intra-abdominal anti-adhesion barrier efficiency; the HA/kCGN 1%/3% w/v hydrogel formulation showed the best anti-adhesion effect in this preclinical study using Sprague-Dawley rat models.


Subject(s)
Hydrogels , Poloxamer , Animals , Carrageenan , Fluorouracil , Hyaluronic Acid , Rats , Rats, Sprague-Dawley , Temperature , Tissue Adhesions/drug therapy , Tissue Adhesions/prevention & control
16.
Taiwan J Obstet Gynecol ; 61(2): 372-377, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35361405

ABSTRACT

OBJECTIVE: To report an extremely rare case of atrioventricular discordance and ventriculoarterial concordance associated with a ventricular septal defect which was diagnosed prenatally. CASE REPORT: By fetal echocardioraphy at 20 weeks' gestation, we diagnosed a rare case of atrioventricular discordance and ventriculoarterial concordance associated with a ventricular septal defect. This is the first case reported from Vietnam prenatally. We present our management of this pregnancy and the baby's neonatal course. This rare anomaly remains a challenge for the baby's early neonatal course before initial neonatal discharge. CONCLUSION: A combined multidisciplinary and individualized approach for the optimal management of this complicated pregnancy and further neonatal surgical treatment plans for the baby are recommended.


Subject(s)
Echocardiography , Heart Septal Defects, Ventricular , Female , Fetus , Heart Septal Defects, Ventricular/diagnostic imaging , Heart Septal Defects, Ventricular/surgery , Humans , Infant , Infant, Newborn , Pregnancy , Prenatal Diagnosis , Ultrasonography, Prenatal
17.
Taiwan J Obstet Gynecol ; 58(5): 645-649, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31542086

ABSTRACT

OBJECTIVE: Duchenne Muscular Dystrophy is an X-linked recessive disorder characterized by progressive muscular degeneration, patients often develop cardiac failure in the later stage and death occurs before 20 years of age. For a disease with poor postnatal prognosis such as Duchenne Muscular Dystrophy (DMD), providing the carrier mother with the option of prenatal diagnosis in a subsequent pregnancy is accepted practice in many places where termination of pregnancy is allowed. Though methods of direct sequencing such as Sanger's sequencing has been widely used, Next-Generation Sequencing is been increasingly replacing most of its application. For the DMD gene, being the longest gene in the human genome, methods of direct sequencing is often unpractical and time-consuming, instead, STR analysis for linkage analysis would be a cost-effective option and have been used routinely for prenatal diagnosis of DMD. The diagnostic significance of the STRs is based on several criteria, the most important one being the heterozygosity of the locus, power of discrimination (PD) and power of exclusion (PE). MATERIAL AND METHODS: In this study, we investigated the feasibility of application and diagnostic value of 6 STR loci (DSTR49, DSTR50, DXS1036, DXS1067, DXS890, DXS9907) in the proximity of the DMD gene, 66 healthy individuals were recruited for STR analysis and 5 cases of prenatal diagnosis for carrier mother were performed. RESULT: Allele frequency, heterozygosity, polymorphic information content, the power of discrimination and exclusion and Hardy-Weinberg equilibrium were analyzed and calculated for the 6 STR loci. 5 of these loci (DSTR49, DSTR50, DXS1067, DXS890, DXS9907) were found practical and useful for preimplantation Genetic diagnosis (PGD) and prenatal diagnosis. All 5 cases of prenatal diagnosis using the method had informative STR results and correct diagnosis. CONCLUSION: We concluded that our protocol of STR analysis can be applied for prenatal diagnosis and pre-implantation genetic diagnosis of DMD with high confidence and accuracy, especially in clinical settings where diagnostic resources are more limited.


Subject(s)
Genetic Loci/genetics , High-Throughput Nucleotide Sequencing/methods , Microsatellite Repeats/genetics , Muscular Dystrophy, Duchenne/diagnosis , Prenatal Diagnosis/methods , Adult , Feasibility Studies , Female , Gene Frequency , Genetic Linkage/genetics , Genetic Markers , Humans , Multiplex Polymerase Chain Reaction/methods , Muscular Dystrophy, Duchenne/embryology , Muscular Dystrophy, Duchenne/genetics , Pregnancy , Preimplantation Diagnosis/methods , Sensitivity and Specificity
18.
ACS Chem Biol ; 13(6): 1426-1437, 2018 06 15.
Article in English | MEDLINE | ID: mdl-29763292

ABSTRACT

Nature is a prolific producers of bioactive natural products with an array of biological activities and impact on human and animal health. But with great power comes great responsibility, and the organisms that produce a bioactive compound must be resistant to its biological effects to survive during production/accumulation. Microorganisms, particularly bacteria, have developed different strategies to prevent self-toxicity. Here, we review a few of the major mechanisms including the mechanism of resistance with a focus on self-resistant protein variants, target proteins that contain amino acid substitutions to reduce the binding of the bioactive natural product, and therefore its inhibitory effects are highlighted in depth. We also try to identify some future avenues of research and challenges that need to be addressed.


Subject(s)
Biological Products/metabolism , Drug Resistance, Bacterial/physiology , Protein Isoforms/physiology , Animals , Bacterial Physiological Phenomena/genetics , Drug Resistance, Bacterial/genetics , Fungi/genetics , Fungi/physiology , Multigene Family/genetics , Plant Physiological Phenomena/genetics , Protein Isoforms/genetics , Vertebrates/genetics , Vertebrates/physiology
19.
Ann Epidemiol ; 28(5): 273-280, 2018 05.
Article in English | MEDLINE | ID: mdl-29361358

ABSTRACT

PURPOSE: Our understanding of the temporal dynamics and age-specific mortality patterns of the 1918-1921 influenza pandemic remains scarce due to lack of detailed respiratory mortality datasets in the United States and abroad. METHODS: We manually retrieved individual death records from Arizona during 1915-1921 and applied time series models to estimate the age specific mortality burden of the 1918-1921 influenza pandemic. We estimated influenza-related excess mortality rates and mortality rate ratio increase over baseline based on pneumonia and influenza (P&I), respiratory, tuberculosis and all-cause death categories. RESULTS: Based on our analysis of 35,151 individual mortality records from Arizona, we identified three successive pandemic waves in spring 1918, fall 1918-winter 1919 and winter 1920. The pandemic associated excess mortality rates per 10,000 population in Arizona was estimated at 83 for P&I, 86 for respiratory causes, 84 for all-causes and 9 for tuberculosis. Age-specific P&I and tuberculosis excess death rates were highest among 25- to 44-year-olds and individuals ≥65 years, respectively. The 25- to 44-year-olds and 5- to 14-year-olds had highest P&I and tuberculosis mortality impact respectively when considering the ratio over background mortality. CONCLUSIONS: The 1918-1921 influenza pandemic killed an estimated 0.8% of the Arizona population in three closely spaced consecutive waves. The mortality impact of the fall 1918 wave in Arizona lies in the upper range of previous estimates reported for other US settings and Europe, with a telltale age distribution of deaths concentrated among young adults. We identified a significant rise in tuberculosis-related mortality during the pandemic, lending support to the hypothesis that tuberculosis was a risk factor for severe pandemic infection. Our findings add to our current understanding of the mortality impact of this pandemic in the US and globally.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human/mortality , Mortality/trends , Pandemics , Adolescent , Age Distribution , Aged , Arizona/epidemiology , Cause of Death , Death Certificates , Female , History, 20th Century , Humans , Influenza, Human/virology , Male , Middle Aged , Mortality/history , Pandemics/history , Risk Factors , Seasons , Young Adult
20.
Congenit Heart Dis ; 13(4): 584-593, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30019378

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Nit-Occlud Lê VSD Coil versus Duct Occluders for percutaneous closure of perimembranous ventricular septal defect (pmVSD). INTRODUCTION: VSD closure using conventional pmVSD occluders has been largely abandoned because of an unacceptable high rate of complete heart block (CHB). The advantages of Duct Occluders and VSD Coil are supposed to reduce the drawbacks of previous devices, especially CHB complications. METHOD: Patients underwent percutaneous pmVSD closure were divided into Coil group (using VSD Coil, n = 71) and DO group (using Duct Occluders, n = 315). Patient demographics, clinical presentations, echocardiography measurements, procedure details and follow-up data were collected. RESULT: The procedure success rate was high in both DO group (95.6%) and Coil group (97.2%, P = .53). The closure rate immediately after procedure in the DO group was higher than that in the Coil group (76.8% vs. 58.0%, P < .01). After 6 months, the closure rate was not significantly different between the 2 groups (DO group 91.3% vs. Coil group 84.1%, P = .07). The mean follow-up time was 61.4 ± 24.1 months. The major complication rate was low in both groups (DO group 1.9% vs. Coil group 1.4%, P = .78). Two patients (0.7%) in the DO group and one patient (1.4%) in the Coil group with CHB needed permanent pacemaker (P = .5). Device embolization (3 patients, 1.0%) and endocarditis (1 patient, 0.3%) occurred only in the DO group. There was no death, disability or other major complications detected in either group. CONCLUSION: Percutaneous pmVSD closure using either Nit-Occlud Lê VSD Coil or Duct Occluders is feasible, safe and efficacious in selected patients. The main problems of Duct Occluders are unsuitable defect anatomy and device embolization while VSD Coil disadvantages are residual shunt and hemolysis.


Subject(s)
Cardiac Catheterization/methods , Cardiac Surgical Procedures/methods , Heart Septal Defects, Ventricular/surgery , Septal Occluder Device , Surgery, Computer-Assisted/methods , Adolescent , Child , Female , Follow-Up Studies , Humans , Male , Prosthesis Design , Radiography, Thoracic , Retrospective Studies , Treatment Outcome
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