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Chronic hepatitis B, a major cause of liver disease and cancer, affects >250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative hepatitis B virus (HBV) therapies are underway, consisting of combinations of multiple novel agents with or without nucleos(t)ide reverse-transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, along with subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives, and regulatory agencies. This Viewpoints article outlines areas of consensus within our multistakeholder group for stopping finite therapies in chronic hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, predefined stopping criteria, predefined retreatment criteria, duration of investigational therapies, and follow-up after stopping therapy. Future research of unmet needs are discussed.
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Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Vírus da Hepatite B/genética , Resultado do Tratamento , Biomarcadores , Antígenos de Superfície da Hepatite B , DNA Viral , Hepatite B/tratamento farmacológicoRESUMO
This study aims to identify clinically meaningful sex differences in efficacy and selected safety adverse events for the treatment of chronic hepatitis C virus infection (HCV) or HIV/HCV co-infection in those receiving combination direct-acting antiviral (DAA) regimens. Our assessment was based on adult trial participants treated at the approved DAA dosage and treatment duration from 40 phase 3 clinical trials submitted to the FDA. Female enrollment ranged from 11% to 54% (overall mean 38%). Females with HCV genotype (GT) 1 or 3 infection had statistically significant higher unadjusted or covariant-adjusted odds of achieving sustained virologic response at post-treatment Week 12 (SVR12) compared with males. Odds ratios favouring females were observed among Whites and those ≥40 years of age with HCV GT1 or 3 infections, and among those ≥50 years of age, non-cirrhotic and those with HCV GT3 infection who were treatment-experienced. These differences were not clinically relevant due to the high SVR12 rate achieved by females and males, overall or in subgroups. No differences were observed in SVR12 rates between HCV GT1 mono-infected and HCV GT1/ HIV-1 co-infected participants. Numerically, more females reported headache, fatigue and nausea compared to males, but the differences were small and predominately Grade 1 or 2 severity. Discontinuation rates for any reason or due to an adverse event were low and similar between the sexes. Our study demonstrated females successfully complete DAA regimens and achieve high SVR12 rates despite numerically higher adverse events for certain commonly reported events.
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Infecções por HIV , Hepatite C Crônica , Hepatite C , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/efeitos adversos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Caracteres Sexuais , Resposta Viral Sustentada , Resultado do Tratamento , Ensaios Clínicos Fase III como AssuntoRESUMO
What physiological role does a slow hyperpolarization-activated ion channel with mixed cation selectivity play in the fast world of neuronal action potentials that are driven by depolarization? That puzzling question has piqued the curiosity of physiology enthusiasts about the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are widely expressed across the body and especially in neurons. In this review, we emphasize the need to assess HCN channels from the perspective of how they respond to time-varying signals, while also accounting for their interactions with other co-expressing channels and receptors. First, we illustrate how the unique structural and functional characteristics of HCN channels allow them to mediate a slow negative feedback loop in the neurons that they express in. We present the several physiological implications of this negative feedback loop to neuronal response characteristics including neuronal gain, voltage sag and rebound, temporal summation, membrane potential resonance, inductive phase lead, spike triggered average, and coincidence detection. Next, we argue that the overall impact of HCN channels on neuronal physiology critically relies on their interactions with other co-expressing channels and receptors. Interactions with other channels allow HCN channels to mediate intrinsic oscillations, earning them the "pacemaker channel" moniker, and to regulate spike frequency adaptation, plateau potentials, neurotransmitter release from presynaptic terminals, and spike initiation at the axonal initial segment. We also explore the impact of spatially non-homogeneous subcellular distributions of HCN channels in different neuronal subtypes and their interactions with other channels and receptors. Finally, we discuss how plasticity in HCN channels is widely prevalent and can mediate different encoding, homeostatic, and neuroprotective functions in a neuron. In summary, we argue that HCN channels form an important class of channels that mediate a diversity of neuronal functions owing to their unique gating kinetics that made them a puzzle in the first place.
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We report anesthesia management of sclerotherapy for vascular malformations (VMs) of the upper airway and face of pediatric patients conducted under sedation using a high-flow nasal cannula (HFNC) oxygen delivery system. Sclerotherapy procedures were carried out in six patients (five males, one female; age group: 5-12 years). The patients were sedated with midazolam, fentanyl, ketamine, and graded doses of propofol along with continuous oxygen delivery using HFNC. There were no episodes of oxygen desaturation, tongue fall or obstruction of the airway, interruption of procedure for assisted ventilation, and postoperative nausea and vomiting (PONV). Only two patients showed transient apnea for 10 and 15 s but did not require ventilatory assistance. HFNC provides effective oxygenation in pediatric patients undergoing sclerotherapy of VMs of the upper airway and face under sedation.
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Impact of glycerol on the physico-functional, morphological, mechanical, and rehydration properties of corn starch-based aerogel has been investigated. The aerogel was prepared from hydrogel (sol-gel method) using solvent exchange and supercritical CO2 drying. Glycerol-infused aerogel had a more connected, denser structure (0.38-0.45 g/cm3), enhanced hygroscopic behavior, and was reusable up to eight times in terms of its capacity to absorb water after being drawn from the soaked sample. However, the inclusion of glycerol reduced the aerogel's porosity (75.89-69.91 %) and water absorption rate (WAR; 118.53-84.64 %) but enhanced its percentage shrinkage (75.03-77.99 %) and compressive strength (26.01-295.06 N). The most effective models for describing the rehydration behavior of aerogel were determined to be the Page, Weibull, and Modified Peleg models. Glycerol addition improved the internal strength of the aerogel so could be recycled without significant change in the physical characteristics of the aerogel. By effectively eliminating the condensed moisture that was developed inside the packing owing to the transpiration of fresh spinach leaves, the aerogel extended the storage life of the leaves by up to eight days. The glycerol-based aerogel has the potential to be employed as a carrier matrix for various chemicals and a moisture scavenger.
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Glicerol , Amido , Amido/química , Spinacia oleracea , Zea mays , ÁguaRESUMO
Ethnomedicinal plants are a rich reservoir of active compounds with potent pharmacological properties. Therefore, plants could serve as a source for the discovery of active antimicrobial and antioxidant agents and are focused because of their low toxicity, economic viability, easy availability, etc. In this regard, phytochemical analyses, viz. ß-carotene, total sugar, reducing sugar, vitamin C, total carotenoids, protein, total phenolic content (TPC), and total flavonoid content (TFC) of 20 ethnomedicinal plants of North East India (NEI) were evaluated in this study. The antibacterial activity against human pathogens and antioxidant potential of plant extracts was also demonstrated. The minimum inhibitory concentration (MIC80), minimum bactericidal concentration (MBC), and total antibacterial activity (TAA) of the active extracts were evaluated against Pseudomonas aeruginosa and Chromobacterium violaceum. The active extracts were also examined for antibiofilm as well as anti-pyocyanin activities against P. aeruginosa and anti-QS activity against C. violaceum at sub-MICs. The study demonstrated variable concentration of phytochemicals of the extracts, viz. ß-carotene (0.29-8.91 mg g-1), total sugar (2.92-30.6 mM), reducing sugar (0.44-14.5 mM), vitamin C (8.41-31.3 mg g-1), total carotenoids (14.9-267.0 mg g-1), protein (5.65-283 mg g-1), TPC (5.32-31.0 mg GAE/g DW), and TFC (1.74-68.2 mg QE/g DW). The plant extracts also exhibited potent antioxidant and antibacterial activities against both Gram-positive and Gram-negative bacteria. Some of the extracts also demonstrated significant biofilm inhibition and eradication, anti-pyocyanin, and anti-QS activities at sub-MICs. The selected ethnomedicinal plants are rich in phytochemicals and demonstrated potent antioxidant, antibacterial, and antibiofilm activities, thus could serve as the important source of novel antioxidant and antimicrobial agents.
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Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/química , Antioxidantes/farmacologia , Antioxidantes/análise , beta Caroteno , Bactérias , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Extratos Vegetais/química , Plantas , Anti-Infecciosos/farmacologia , Flavonoides/farmacologia , Flavonoides/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Fenóis/farmacologia , Biofilmes , Ácido Ascórbico , Açúcares , ÍndiaRESUMO
INTRODUCTION: On 4 February, 2020, the Secretary of the Department of Health and Human Services declared a public health emergency related to coronavirus disease 2019 (COVID-19), and on 27 March, 2020 declared circumstances existed to justify the authorization of the emergency use of drug and biological products (hereafter, "drugs") for COVID-19. At the outset of the pandemic with uncertainty relating to the virus, many drugs were being used to treat or prevent COVID-19, resulting in the US Food and Drug Administration's (FDA's) need to initiate heightened surveillance across these drugs. OBJECTIVE: We aimed to describe the FDA's approach to monitoring the safety of drugs to treat or prevent COVID-19 across multiple data sources and the subsequent actions taken by the FDA to protect public health. METHODS: The FDA conducted surveillance of adverse event and medication error data using the FDA Adverse Event Reporting System, biomedical literature, FDA-American College of Medical Toxicology COVID-19 Toxicology Investigators Consortium Pharmacovigilance Project Sub-registry, and the American Association of Poison Control Centers National Poison Data System. RESULTS: From 4 February, 2020, through 31 January, 2022, we identified 22,944 unique adverse event cases worldwide and 1052 unique medication error cases domestically with drugs to treat or prevent COVID-19. These were from the FDA Adverse Event Reporting System (22,219), biomedical literature (1107), FDA-American College of Medical Toxicology COVID-19 Toxicology Investigator's Consortium Sub-registry (638), and the National Poison Data System (32), resulting in the detection of several important safety issues. CONCLUSIONS: Safety surveillance using near real-time data was critical during the COVID-19 pandemic because the FDA monitored an unprecedented number of drugs to treat or prevent COVID-19. Additionally, the pandemic prompted the FDA to accelerate innovation, forging new collaborations and leveraging data sources to conduct safety surveillance to respond to the pandemic.
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COVID-19 , Venenos , Humanos , Estados Unidos/epidemiologia , Preparações Farmacêuticas , Pandemias , United States Food and Drug Administration , FarmacovigilânciaRESUMO
Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, which have been implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic physiologically constrained parametric search to identify the cellular mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We used heterogeneous model populations to ensure that our conclusions were not biased by parametric choices in a single hand-tuned model. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneities in synaptic plasticity profiles obtained with two different induction protocols. However, among the disparate forms of neural-circuit heterogeneities, our analyses demonstrated the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. We found that strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult neurogenesis-induced heterogeneities in neural structure were accounted for. Importantly, our analyses showed that it was not imperative that the manifestation of neural-circuit heterogeneities must translate to heterogeneities in plasticity profiles. Specifically, despite the expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable across all models through synergistic interactions among these heterogeneities. We assessed the parametric combinations required for the manifestation of such degeneracy in the expression of plasticity profiles. We found that immature cells showed physiological plasticity profiles despite receiving afferent inputs with weak synaptic strengths. Thus, the high intrinsic excitability of immature granule cells was sufficient to counterbalance their low excitatory drive in the expression of plasticity profile degeneracy. Together, our analyses demonstrate that disparate forms of neural-circuit heterogeneities could mechanistically drive plasticity heterogeneity, but also caution against treating neural-circuit heterogeneities as proxies for plasticity heterogeneity. Our study emphasizes the need for quantitatively characterizing the relationship between neural-circuit and plasticity heterogeneities across brain regions.
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Giro Denteado , Neurogênese , Adulto , Giro Denteado/fisiologia , Humanos , Neurogênese/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologiaRESUMO
Plasticity in the brain is ubiquitous. How do neurons and networks encode new information and simultaneously maintain homeostasis in the face of such ubiquitous plasticity? Here, we unveil a form of neuronal plasticity in rat hippocampal granule cells, which is mediated by conjunctive changes in HCN, inward-rectifier potassium, and persistent sodium channels induced by theta-modulated burst firing, a behaviorally relevant activity pattern. Cooperation and competition among these simultaneous changes resulted in a unique physiological signature: sub-threshold excitability and temporal summation were reduced without significant changes in action potential firing, together indicating a concurrent enhancement of supra-threshold excitability. This form of intrinsic plasticity was dependent on calcium influx through L-type calcium channels and inositol trisphosphate receptors. These observations demonstrate that although brain plasticity is ubiquitous, strong systemic constraints govern simultaneous plasticity in multiple components-referred here as plasticity manifolds-thereby providing a cellular substrate for concomitant encoding and homeostasis in engram cells.
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There have been unprecedented advances in the identification of new treatment targets for chronic hepatitis B that are being developed with the goal of achieving functional cure in patients who would otherwise require lifelong nucleoside analogue treatment. Many of the new investigational therapies either directly target the immune system or are anticipated to impact immunity indirectly through modulation of the viral lifecycle and antigen production. While new viral biomarkers (HBV RNA, HBcAg, small, middle, large HBs isoforms) are proceeding through validation steps in clinical studies, immunological biomarkers are non-existent outside of clinical assays for antibodies to HBs, HBc and HBe. To develop clinically applicable immunological biomarkers to measure mechanisms of action, inform logical combination strategies, and guide clinical management for use and discontinuation of immune-targeting drugs, immune assays must be incorporated into phase I/II clinical trials. This paper will discuss the importance of sample collection, the assays available for immunological analyses, their advantages/disadvantages and suggestions for their implementation in clinical trials. Careful consideration must be given to ensure appropriate immunological studies are included as a primary component of the trial with deeper immunological analysis provided by ancillary studies. Standardising immunological assays and data obtained from clinical trials will identify biomarkers that can be deployed in the clinic, independently of specialised immunology laboratories.
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Hepatite B Crônica , Hepatite B , Biomarcadores , DNA Viral/genética , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , HumanosRESUMO
Maturity determination of pomelo fruits having health-benefiting attributes is an important issue to enhance the quality of harvesting. Here, an interdigitated electrode (IDE) based sensor is introduced to detect its maturity by determining the naringin content. The sensor was made by depositing amberlite IRA-400 as a sensing layer on IDE patterned PCB substrate at room temperature with hydrothermal and spin-coating techniques. The sensor exhibits excellent selectivity for naringin, high sensitivity of 0.008 µA for 10 ppb of naringin, and reusability up to 3-4 times for naringin quantification in maturity testing of fruits. The pomelo fruits start to mature when maximum values of current response and naringin content are found at 140 DAFS. The naringin content decreases as maturity progresses and maximum phytochemical attributes were obtained at 180-220 DAFS. The IDE sensor assures an appropriate period of plucking of pomelo fruits improving harvesting practices and trade of citrus fruits.
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Citrus , Flavanonas , Eletrodos , FrutasRESUMO
Owing to their health-boosting properties and other appreciable properties, citrus fruit is widely consumed and commercialized worldwide. Destination markets around the world vary in their fruit quality requirements and are also highly influenced by climatic conditions, agronomical and postharvest practices. Hence, harvesting decisions are arduous. Maturity indices in citrus fruit are highly variable and dependent on the species and varieties, growing regions, and destination markets. For decades, determination of the maturity of citrus fruit and predicting the near time of harvesting was a challenge for producers, researchers, and food safety agencies. Thus, the current review provides a correlation between maturity and internal components and an overview of techniques of maturity determination for citrus fruits. Also, stress has been given to the destructive and nondestructive methods to determine the maturity level of different citrus species. The techniques presented in this review portray continuous productiveness as an excellent quality assessment, particularly as ripening and maturity analysis tools for citrus fruits. Traditional techniques are time-consuming, laborious, costly, destructive, and tedious. Thus, these nondestructive techniques hold great potential to replace conventional procedures.
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Citrus , FrutasRESUMO
In the present study, sonication assisted debittering of pomelo fruit juice was carried out and the effect of sonication along with resin/enzyme on the chemical, phytochemical and volatile composition of juice was also investigated. The optimum conditions for sonication coupled debittering using resin were 50â¯kHz, 2â¯min, and 45â¯â while 50â¯kHz, 60â¯min, and 60â¯â were obtained for enzyme hydrolysis. Sonication treatment not only reduced the debittering time but also enhanced the adsorption and hydrolysis of naringin by 17% and 20% in resin and enzyme respectively. In addition, enzymatic activity was also improved and weakened C-O bonds in naringin. At the same time, sonication significantly affected the bioactive compounds of juice, chemical composition, and volatile compounds of juice. Flavor compounds including octanal, linalool, citral, and ethyl butyrate were enhanced by sonication-assisted enzymatic treated juice.
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Citrus fruits exhibit a high level of different phytoconstituents, of which the changes in the different parts of the fruit during ripening have not been thoroughly studied yet. Thus, in this study, we have investigated how different parts of pomelo fruit (Citrus grandis L.) are modified throughout the development of two consecutive growing seasons. In detail, the main phytochemical compounds, such as total phenolic content, total flavonoid content, antioxidant capacity, DPPH free radical scavenging activity, Ferric reducing antioxidant power (FRAP), and naringin and tannin content, were analyzed. A systematic metabolism of these compounds was found during the development of the fruit, but some pomelo tissues showed a fluctuating trend, suggesting a dependence on the different growing season. Focusing on the tissue distribution of these compounds, the fruit membrane contained the highest level of total phenolic and flavonoid content; fruit flavedo displayed the highest antioxidant capacities and FRAP activities, whereas maximum accumulation of naringin was noticed in fruit albedo. Instead, the highest DPPH free radical scavenging activity and tannin contents were found in the pomelo juice. Regarding the distribution of compounds, a possible bias pattern for the accumulation of those compounds has been noticed throughout the fruit development. From the GC-MS analysis, a total of 111 compounds were identified, where 91 compounds were common in both seasons. Overall, these results could be useful for the food processing industry as guidelines for excellent quality foods and for introducing health-beneficial products and components into our daily diets.
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Biological plasticity is ubiquitous. How does the brain navigate this complex plasticity space, where any component can seemingly change, in adapting to an ever-changing environment? We build a systematic case that stable continuous learning is achieved by structured rules that enforce multiple, but not all, components to change together in specific directions. This rule-based low-dimensional plasticity manifold of permitted plasticity combinations emerges from cell type-specific molecular signaling and triggers cascading impacts that span multiple scales. These multiscale plasticity manifolds form the basis for behavioral learning and are dynamic entities that are altered by neuromodulation, metaplasticity, and pathology. We explore the strong links between heterogeneities, degeneracy, and plasticity manifolds and emphasize the need to incorporate plasticity manifolds into learning-theoretical frameworks and experimental designs.
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Aprendizagem , Plasticidade Neuronal , EncéfaloRESUMO
Degeneracy, the ability of multiple structural components to elicit the same characteristic functional properties, constitutes an elegant mechanism for achieving biological robustness. In this study, we sought electrophysiological signatures for the expression of ion-channel degeneracy in the emergence of intrinsic properties of rat hippocampal granule cells. We measured the impact of four different ion-channel subtypes-hyperpolarization-activated cyclic-nucleotide-gated (HCN), barium-sensitive inward rectifier potassium (Kir ), tertiapin-Q-sensitive inward rectifier potassium, and persistent sodium (NaP) channels-on 21 functional measurements employing pharmacological agents, and report electrophysiological data on two characteristic signatures for the expression of ion-channel degeneracy in granule cells. First, the blockade of a specific ion-channel subtype altered several, but not all, functional measurements. Furthermore, any given functional measurement was altered by the blockade of many, but not all, ion-channel subtypes. Second, the impact of blocking each ion-channel subtype manifested neuron-to-neuron variability in the quantum of changes in the electrophysiological measurements. Specifically, we found that blocking HCN or Ba-sensitive Kir channels enhanced action potential firing rate, but blockade of NaP channels reduced firing rate of granule cells. Subthreshold measures of granule cell intrinsic excitability (input resistance, temporal summation, and impedance amplitude) were enhanced by blockade of HCN or Ba-sensitive Kir channels, but were not significantly altered by NaP channel blockade. We confirmed that the HCN and Ba-sensitive Kir channels independently altered sub- and suprathreshold properties of granule cells through sequential application of pharmacological agents that blocked these channels. Finally, we found that none of the sub- or suprathreshold measurements of granule cells were significantly altered upon treatment with tertiapin-Q. Together, the heterogeneous many-to-many mapping between ion channels and single-neuron intrinsic properties emphasizes the need to account for ion-channel degeneracy in cellular- and network-scale physiology.
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Venenos de Abelha/farmacologia , Hipocampo/fisiologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/antagonistas & inibidores , Neurônios/fisiologia , Canais de Potássio/química , Canais de Sódio/química , Animais , Bário/farmacologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Masculino , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Heterogeneities in biological neural circuits manifest in afferent connectivity as well as in local-circuit components such as neuronal excitability, neural structure and local synaptic strengths. The expression of adult neurogenesis in the dentate gyrus (DG) amplifies local-circuit heterogeneities and guides heterogeneities in afferent connectivity. How do neurons and their networks endowed with these distinct forms of heterogeneities respond to perturbations to individual ion channels, which are known to change under several physiological and pathophysiological conditions? We sequentially traversed the ion channels-neurons-network scales and assessed the impact of eliminating individual ion channels on conductance-based neuronal and network models endowed with disparate local-circuit and afferent heterogeneities. We found that many ion channels differentially contributed to specific neuronal or network measurements, and the elimination of any given ion channel altered several functional measurements. We then quantified the impact of ion-channel elimination on response decorrelation, a well-established metric to assess the ability of neurons in a network to convey complementary information, in DG networks endowed with different forms of heterogeneities. Notably, we found that networks constructed with structurally immature neurons exhibited functional robustness, manifesting as minimal changes in response decorrelation in the face of ion-channel elimination. Importantly, the average change in output correlation was dependent on the eliminated ion channel but invariant to input correlation. Our analyses suggest that neurogenesis-driven structural heterogeneities could assist the DG network in providing functional resilience to molecular perturbations.
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BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes. METHODS: We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point. RESULTS: We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P = .001), 0.30 for HCC (95% CI, 0.20-0.44; P < .001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P < .001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics. CONCLUSIONS: In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , DNA Viral , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , HumanosRESUMO
Bitterness and tartness are one of the crucial reasons for the poor commerciality of Pomelo fruits. The present study intends to optimize the process variables such as resin concentration (Amberlite IRA-400) (3-10 g), time exposure (10-60 s), and stirring speed (300-1000 rpm) for removal of naringin content and tartness using response surface methodology. All the independent variables have shown a significant effect on naringin content, titrable acidity, and vitamin C content of pomelo juice. The optimized process variables for debittering and deacidification were 3.27 g resin concentration, 60 s time and 1000 rpm stirring speed, and the naringin content and titrable acidity at these optimized conditions were 0.22 mg ml-1 and 0.64% citric acid equivalent respectively. The treated juice under optimum conditions was analyzed for physicochemical properties where pH, clarity, and L* value of juice increased. In contrast, total soluble solids, vitamin C content, and a* value decreased slightly. The finding of present investigation will be helpful to improve the commercial acceptability of the sour variety of citrus fruit juice.
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In the present study, an innovative cold plasma treatment was used as a tool to fortify the white rice. The amounts of ferrous sulphate and ascorbic acid were optimized for improving the bioavailability of iron. White rice samples were treated with plasma at a constant voltage of 20 kV for varying time (10 min and 15 min). The exposure time of plasma was selected based on the surface characteristics, hydrophilicity and thermal properties. Significant improvement was observed in the characteristics of hydrophilicity, surface energy, cooking time and hardness of plasma-treated rice. Plasma treated rice was fortified with the optimum concentrations of iron and ascorbic acid solution. Optimum concentrations of iron and ascorbic acid per 100 g of rice (862.93 mg and 1398.27 mg) were found by conducting experiments using Central Composite Design of Response Surface Methodology. Further, rice was blended with untreated rice in the ratio of 1:100 and 1:200 and was packed in LDPE and PP pouches and was stored at ambient temperature for further storage analysis. The in vitro bioavailability of iron was significantly higher in the plasma-treated fortified rice at both 1.35 and 7.5 pH than in the control sample, and plasma treatment significantly reduced the rate of oxidation of iron during storage.