Emergence of SARS-CoV-2 Omicron Variant JN.1 in Tamil Nadu, India - Clinical Characteristics and Novel Mutations.

In December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.

Investigation of Levan-derived Nanoparticles of Dolutegravir: A Promising Approach for the Delivery of anti-HIV Drug as Milk Admixture.

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100% release, whereas the unprocessed drug exhibited only 50% release at the end of 24 hours. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV.

Insects to the rescue? Insights into applications, mechanisms, and prospects of insect-driven remediation of organic contaminants.

Traditional and emerging contaminants pose significant human and environmental health risks. Conventional physical, chemical, and bioremediation techniques have been extensively studied for contaminant remediation. However, entomo- or insect-driven remediation has received limited research and public attention. Entomo-remediation refers to the use of insects, their associated gut microbiota, and enzymes to remove or mitigate organic contaminants. This novel approach shows potential as an eco-friendly method for mitigating contaminated media. However, a comprehensive review of the status, applications, and challenges of entomo-remediation is lacking. This paper addresses this research gap by examining and discussing the evidence on entomo-remediation of various legacy and emerging organic contaminants. The results demonstrate the successful application of entomo-remediation to remove legacy organic contaminants such as persistent organic pollutants. Moreover, entomo-remediation shows promise in removing various groups of emerging contaminants, including microplastics, persistent and emerging organic micropollutants (e.g., antibiotics, pesticides), and nanomaterials. Entomo-remediation involves several insect-mediated processes, including bio-uptake, biotransfer, bioaccumulation, and biotransformation of contaminants. The mechanisms underlying the biotransformation of contaminants are complex and rely on the insect gut microbiota and associated enzymes. Notably, while insects facilitate the remediation of contaminants, they may also be exposed to the ecotoxicological effects of these substances, which is often overlooked in research. As an emerging field of research, entomo-remediation has several knowledge gaps. Therefore, this review proposes ten key research questions to guide future perspectives and advance the field. These questions address areas such as process optimization, assessment of ecotoxicological effects on insects, and evaluation of potential human exposure and health risks.

Production and characterization of microbial levan using sugarcane (Saccharum spp.) juice and chicken feather peptone as a low-cost alternate medium.

An alternate medium consisting of sugarcane juice (SJ) (Saccharum spp.) and chicken feather peptone (CFP) was employed for microbial synthesis of levan. SJ has considerable amounts of vital minerals, vitamins, and amino acids in addition to its major constituent, sucrose. Meanwhile, CFP is also a rich source of essential nutrients such as amino acids, micro and macro elements. Amino acids present in SJ and CFP, such as glutamic acid, arginine, aspartic acid, asparagine and elements such as Ca, Mg favoured the cell growth and levan production. In this present work, levan was produced using Bacillus subtilis MTCC 441 in five different media, namely, sucrose along with defined nutrients (M1), Sugarcane Juice without nutrients (M2), SJ with defined nutrients (M3), SJ along with chicken feather peptone (M4) and sucrose without nutrient (M5). Alternative nutrient medium using SJ and CFP (M4) showed a promising levan yield of 0.32 ± 0.01 g of levan/g of sucrose consumed, which is 64% of the theoretical levan yield possible. Levan produced was characterized using Nuclear Magnetic Resonance (NMR) and Gel Permeation Chromatography (GPC). There is a change in low molecular weight fractions of levan obtained from SJ and CFP medium compared to the defined medium. Produced levan from the composite medium exhibited strong antioxidant activity and was biocompatible when tested against endothelial cells. The substrate cost was 20% lower than the cost of defined medium. Thus, a composite medium made of SJ and CFP can serve as an alternate low-cost medium for microbial fermentation.

The Implementation of HIV Self-Testing in Resource-Limited Settings Where the HIV Disease Burden is High.

In resource-limited settings, there is growing evidence that HIV testing is lacking among high-risk key populations such as men having sex with men, injection drug users, and transgenders largely due to stigma, discrimination, and lack of confidentiality. Findings from recent studies among high-risk key populations and the general population from various regions including resource-limited settings support the need for wider accessibility of HIV self-testing (HIV-ST) to reach those who may not otherwise have access to testing. Therefore, HIV-ST has untapped potential as a strategy to improve access to HIV testing and to increase testing frequency among key high-risk populations and their partners. Though HIV-ST has emerged as a safe, acceptable, and effective way to reach people, there are several roadblocks to implementing the HIV-ST policy, and fast-track policy implementation needs to be necessitated with newer or modified strategic plans.

Bioprospecting of aqueous phase from pyrolysis of plant waste residues to disrupt MRSA biofilms.

Methicillin resistant Staphylococcus aureus (MRSA) infections have increased at an alarming rate, recently. In India, stubble burning and air pollution due to the burning of agricultural and forest residues have also increased over the past decade causing environmental and health hazards. This work evaluates the anti-biofilm property of the aqueous phase obtained from pyrolysis of wheat straw (WS AQ) and pine cone (PC AQ) against an MRSA isolate. The WS AQ and PC AQ compositions were determined by GC-MS analysis. The minimum inhibitory concentration was found to be 8% (v v-1) and 5% (v v-1) for WS AQ and PC AQ, respectively. The eradication of biofilms was performed on hospital contact surfaces namely, stainless steel and polypropylene and found to be 51% and 52% for WS AQ and PC AQ, respectively. Compounds identified from the aqueous phase of WS and PC docked against AgrA protein showed good binding scores.

Waste to drugs: identification of pyrolysis by-products as antifungal agents against Cryptococcus neoformans.

The fungi, Cryptococcus neoformans cause major infections such as cryptococcal meningitis and cryptococcosis. Therefore, we explored the use of Thioredoxin reductase (Trr1) from C. neoformans as a gene target for the development of novel antifungal agents. Trr1 plays an essential role in the survival in the oxidative environment of macrophages and is important for the virulence of C. neoformans. During the thermochemical conversion (pyrolysis) of lignocellulosic biomass (LCB), a cocktail of compounds is produced by the decomposition and degradation. In general, LCB-derived cocktail of compounds is a rich source of aromatic compounds that have been shown to be antifungal in nature. Usually, the aqueous phase produced during biomass pyrolysis is generally regarded as waste. Here, we used Parthenium hysterophorus biomass as the antifungal source and obtained the aqueous phase after pyrolysis. Using GC-MS analysis of the aqueous phase collected from P. hysterophorus biomass revealed the presence of a large number of aromatic and organic compounds. Using virtual screening, the compounds present in the aqueous phase were docked against Trr1 using GLIDE. Two promising candidates were analyzed further by performing molecular dynamics simulation using GROMACS, to establish stable interactions. We validated the computational results with clustering analysis. We report that 2,4-Di-tertbutyl phenol and 1H-Pyrazole, 4-ethyl-3,5-dimethyl have a potent antifungal property and we postulate that they could be a potent antifungal agent against Trr1 of C. neoformans.

Antibacterial drugs and cyclodextrin inclusion complexes: a patent review.

INTRODUCTION: Bacterial antibiotic resistance occurs when bacteria mutate and escape the effect of antibiotics, which makes the antibiotics no longer effective in treating infections. New solutions for bacterial infections are a persistent need including the identification of drugs with better pharmacological profiles, more potent, and safer. Cyclodextrins inclusion complexes have been able to improve the physicochemical and pharmacological properties of the formulation molecules, resulting in new alternatives with better efficacy. AREAS COVERED: The patents analyzed in the review used treatments based on antibiotics already on the market, natural products, and synthesized molecules composed of the formulation with cyclodextrins. The combination between cyclodextrin and nanostructures also were presented in the patents review process. Moreover, inclusion complexes have been an alternative in developing treatment mainly in China by the pharmaceutical industries in several countries such as Germany, Hungary, the United States of America, Japan and China. EXPERT OPINION: This review is broad and complete since it considers the first patent involving cyclodextrins and antibacterial drugs. Therefore, the various inclusion complexes and antibacterial drugs alternatives presented in this review offer therapeutic options to fight bacterial infections. If shown to be effective, these drugs may be extremely important in the current clinical practice.

Waste tire particles as efficient materials towards hexavalent chromium removal: Characterisation, adsorption behaviour, equilibrium, and kinetic modelling.

The growing demand for vehicles is increasing every year, and this paves the way for the environmental problem for the generation of the waste tire (WT) and associated disposal after their end life. On the other direction, effluent from tannery and electroplating industries contented with a higher concentration of chromium, which is a toxic pollutant, induces mutation effects. In this work, the approach of reutilization of waste tires as adsorbent is reported towards the sequestrations of hexavalent chromium (Cr(VI)) from the simulated system. The waste tire sample is activated using orthophosphoric acid (H3PO4) and utilized for adsorption studies. Adsorption studies are performed with native tire sample (NTP) and activated tire sample (ATP). About 96.5% of Cr(VI) adsorption efficiency was attained using ATP and at the optimal adsorption solution pH 2.0. The adsorbent performed relatively well in wide a range of initial solution pH tested in the present research. The experimental data analysis of Cr(VI) adsorption onto NTP and ATP revealed the best fit with the kinetic model of pseudo-second-order. Further, the equilibrium data were analysed using two-parameter isotherms, relatively the Langmuir isotherm best represented in both NTP and ATP. ATP demonstrated with higher Cr(VI) removal performance with an adsorption capacity of 102.90 mg/g, according to the Langmuir model. The proposed idea of utilizing waste tire particles as adsorbents in the treatment of Cr(VI) contaminated water offers valuable guidance towards further investigations in the directions of dynamic adsorption and effluent treatment.

α-Amylase inhibition, cytotoxicity and influence of the in vitro gastrointestinal digestion on the bioaccessibility of phenolic compounds in the peel and seed of Theobroma grandiflorum.

The aim of this work was to evaluate the bioaccessibility, cytotoxicity, antioxidant and antidiabetic potential of peel and seeds of cupuassu (Theobroma grandiflorum). Thus, the extracts of cupuassu were evaluated for inhibition of α-amylase, cytotoxicity, and bioaccessibility after gastrointestinal digestion and probiotic fermentation (Lactobacillus delbrueckii, Lactobacillus jhonsoni, Lactobacillus rhamus and Bifidobacterium longum). Digestion increased concentrations of phenolics, showing bioaccessibility of up to 274.13% (total phenolics) and 1105.15% (ORAC). ß-carotene, quinic, tartaric, malic, citric, epicatechin, ethyl gallate, epigallocatechin gallate, gallic acid, pyrocatechol, vanillin, ramnetine were the main compounds while the epicatechin, ethyl gallate, gallic acid and pyrocatechol were the major effective phenolic compounds. The extracts did not show toxic effects and the cupuassu seeds showed 97% inhibition of α-amylase and 47.91% bioaccessibility of pyrocatechol. This study suggests that cupuassu extracts are sources of natural antioxidants with promising antidiabetic potential, and probiotics are able to increase phenolic compounds, responsible for health benefits.

Anti-inflammatory and modulatory effects of steroidal saponins and sapogenins on cytokines: A review of pre-clinical research.

BACKGROUND: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models. PURPOSE: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines. STUDY DESIGN AND METHODS: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved. RESULTS: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways. CONCLUSION: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

Role of direct and indirect social and spatial ties in the diffusion of HIV and HCV among people who inject drugs: a cross-sectional community-based network analysis in New Delhi, India.

Background: People who inject drugs (PWID) account for some of the most explosive human immunodeficiency virus (HIV) and hepatitis C virus (HCV) epidemics globally. While individual drivers of infection are well understood, less is known about network factors, with minimal data beyond direct ties. Methods: 2512 PWID in New Delhi, India were recruited in 2017-19 using a sociometric network design. Sampling was initiated with 10 indexes who recruited named injection partners (people who they injected with in the prior month). Each recruit then recruited their named injection partners following the same process with cross-network linkages established by biometric data. Participants responded to a survey, including information on injection venues, and provided a blood sample. Factors associated with HIV/HCV infection were identified using logistic regression. Results: The median age was 26; 99% were male. Baseline HIV prevalence was 37.0% and 46.8% were actively infected with HCV (HCV RNA positive). The odds of prevalent HIV and active HCV infection decreased with each additional degree of separation from an infected alter (HIV AOR: 0.87; HCV AOR: 0.90) and increased among those who injected at a specific venue (HIV AOR: 1.50; HCV AOR: 1.69) independent of individual-level factors (p<0.001). In addition, sociometric factors, for example, network distance to an infected alter, were statistically significant predictors even when considering immediate egocentric ties. Conclusions: These data demonstrate an extremely high burden of HIV and HCV infection and a highly interconnected injection and spatial network structure. Incorporating network and spatial data into the design/implementation of interventions may help interrupt transmission while improving efficiency. Funding: National Institute on Drug Abuse and the Johns Hopkins University Center for AIDS Research.

Understanding the social and spatial relationships that connect people is a key element to stop the spread of infectious diseases. These networks are particularly relevant to combat epidemics among populations that are hard to reach with public health interventions. Network-based approaches, for example, can help to stop HIV or hepatitis C from spreading amongst populations that use injectable drugs. Yet how social and geographic connections such as acquaintances, injection partners, or preferred drug use places impact the risk of infection is still poorly mapped out. To address this question, Clipman et al. focused on people who inject drugs in New Delhi, India, a population heavily impacted by HIV and hepatitis C. Over 2500 people were recruited, each participant inviting their injection partners to also take part. The volunteers answered survey questions, including where they used drugs, and provided a blood sample to be tested. The results showed that, even after adjusting for individual risk factors, where people used drugs and with whom affected their risk of becoming infected with HIV and hepatitis C. In terms of social ties, the likelihood of HIV and hepatitis C infection decreased by about 13% for each person separating a given individual from an infected person. However, geographical networks also had a major impact. Injecting at a popular location respectively increased the odds of HIV and hepatitis C infection by 50% and 69%. In fact, even if the participant was not using drugs at these specific places, having an injection partner who did was enough to increase the risk for disease: for each person separating an individual from the location, the likelihood of being infected with HIV and hepatitis C decreased by respectively 14% and 10%. The results by Clipman et al. highlight how the relationships between physical spaces and social networks contribute to the spread of dangerous diseases amongst people who inject drugs. Ultimately, this knowledge may help to shape better public health interventions that would take into account the importance of geographical locations.

Pharmaceutical agents for treatment of leishmaniasis: a patent landscape.

INTRODUCTION: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Worldwide, approximately 1.5-2 million new cases of leishmaniasis and 20,000-30,000 deaths occurs each year. Effective treatment for all forms of leishmaniasis have numerous adverse effects contributing to poor adherence and/or treatment interruption by the patient. Development of novel therapies, as multitarget drugs, for example, can contribute to accelerate discover safer, more active, and patient-compliant drugs for leishmaniasis treatment. AREAS COVERED: In this review, authors summarize pharmaceutical agents for treatment of leishmaniasis developed between 2014 and 2019, which includes synthetic and natural drugs for specific treatments, as well as considering new approaches and strategies using drug delivery system. EXPERT OPINION: Universities or public research institutes produced most of the patents related to pharmaceutical agents for treatment of leishmaniasis in this review, and the majority of the inventions disclosed did not conduct clinical trials. In other words, there is still a lot of investment to be done for the identification of new drugs.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Volatile profiling and UHPLC-QqQ-MS/MS polyphenol analysis of Passiflora leschenaultii DC. fruits and its anti-radical and anti-diabetic properties.

Twenty-four phenolic compounds including daidzein, epicatechin and artepillin C were identified in Passiflora leschenaultii DC. fruit by UHPLC-QqQ-MS/MS analysis. The aroma profile has been studied using the HS-SPME/GC-MS which revealed 67 volatile compounds including 13 terpenes, 18 alcoholics, 15 esters, ketones and phenolic acids. Further, the proximate composition, anti-radical and anti-diabetic activities of fruit pulp were also determined. The fresh fruit pulp of P. leschenaultii registered higher total phenolic (691.90 mg GAE/g extract) and tannin (313.81 mg GAE/g extract) contents and it also exhibited maximum DPPH (IC50 of 6.69 µg/ml) and ABTS+ (9760.44 µM trolox equivalent/g extract) scavenging activities. The fresh fruit pulp showed a strong inhibition towards the α-Amylase and α-Glucosidase (IC50 of 32.20 and 19.81 µg/mL, respectively) enzymes. Thus, the work stipulates that phenolic compounds rich P. leschenaultii fruit can serve as a potential nutraceutical, antioxidative and anti-diabetic agent in food and pharmaceutical formulations.

Inflammatory modulation of fluoxetine use in patients with depression: A systematic review and meta-analysis.

There is growing evidence that there is a relationship between major depressive disorder (MDD), also simply known as "depression", and inflammatory processes. Selective serotonin inhibitors, such as fluoxetine, are used as a first-line treatment for depression, and it is hypothesized that its use can reduce levels of proinflammatory cytokines. The aim of this systematic review and meta-analysis is to enable a better understanding of how treatment with the antidepressant fluoxetine modulates inflammation, and the roles of the main cytokines in this process. Risk of bias (RoB) in the included studies was assessed using the Cochrane Risk of Bias Assessment tool for Non-randomized studies (RoBANS). In the meta-analysis, standardized mean difference (SMD) was used as a summary statistic and grouped statistics using the generic inverse variation method in RevMan 5 with random effects model. Heterogeneous changes in cytokine levels were also evaluated from the SMD forest plot of individual studies. After analysis, we observed that fluoxetine was able to decrease TNF-α levels (SMD ± 0.90, 95% CI = 0.16, 1.165, Z ± 2.40, p = 0.02), but not change IL-6 levels (SMD ± 0.37, 95% CI = 0.21, 0.95, Z ± 1.25, p = 0.21).Fluoxetine acts by modulating neuroimmunology, and not only by acting only on the independent restoration of neurotransmission and neuroinflammation pathways.

Antibody avidity-based approach to estimate population-level incidence of hepatitis C.

BACKGROUND & AIMS: Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic. METHODS: An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a maximum likelihood binomial regression model to the probability of appearing recent. Among samples collected ≥2 years post-HCV seroconversion, an individual-level false recent ratio (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators. RESULTS: An avidity index cut-off of <40% resulted in an MDRI of 113 days (95% CI 84-146), and FRRs of 0.4% (95% CI 0.0-1.2), 4.6% (95% CI 2.2-8.3), and 9.5% (95% CI 3.6-19.6) among individuals who were HIV-uninfected, HIV-infected, and HIV-infected with a CD4 count <200/µl, respectively. No variation was seen between HCV genotypes 1 and 3. In hypothetical scenarios of high-risk settings, a sample size of <1,000 individuals could reliably estimate primary HCV incidence. CONCLUSIONS: This cross-sectional approach can estimate primary HCV incidence for the most common genotypes. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce HCV burden. LAY SUMMARY: Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint.

Microneedles as an alternative technology for transdermal drug delivery systems: a patent review.

Introduction: The most conventional drug delivery systems exist with limitations such as drug degradation, toxicity and low bioavailability. Also, hypodermic injections can cause pain, compromising patient compliance. Due to this, transdermal drug delivery systems can minimize several problems associated with conventional drug delivery. The development of microneedle arrays is an approach which allows drug delivery through the skin by improving safety, efficacy, and bioavailability. Hence, several studies have been searching for new ways of treatment using microneedle devices for transdermal drug delivery.Areas covered: All patents were analyzed from European Patent Office and World Intellectual Property Organization databases that reported microneedle arrays using the combined keywords 'microneedle' or 'microneedles' and 'drug delivery systems'. A total of 233 patents were analyzed, out of which 47 selected were microneedle devices for clinical applications.Expert opinion: In past years, there has been a crescent of advances in the development of microneedles as a drug delivery system by researchers and pharmaceutical companies. The authors observed patents related to manufacture of dissolving, hydrogel-forming, solid, hollow, and coated microneedles for ocular and transdermal drug delivery. Finally, the authors noticed patents about new microneedle technologies with potential therapeutic application in several clinical conditions confirmed in clinical tests.

Anti-Inflammatory Activity of Limonene in the Prevention and Control of Injuries in the Respiratory System: A Systematic Review.

INTRODUCTION: The pulmonary inflammatory response results from exposure to injurious factors and is associated with oxidative stress, which intensifies the pathological reaction. In this context, limonene, a monoterpene found in citrus fruits, can be a therapeutic alternative for the treatment of this pathology, as it presents known anti-inflammatory and antioxidant actions. OBJECTIVE: The purpose of this article is to provide an overview of the anti-inflammatory activity of limonene and its capacity to prevent and control respiratory system injuries. SEARCH STRATEGY: A comprehensive literature search of the Cochrane, Scopus, MEDLINE-PubMed, Web of Science, and Lilacs databases was performed using the keywords: "limonene", "lung", "pulmonary", "airway", "trachea", "lung injury", "respiratory system", "respiratory tract diseases". SELECTION CRITERIA: Studies on the use of limonene in disorders of the respiratory system, published until August 2019, were included. Those that did not use limonene alone or treated lesions in different systems other than the respiratory system, without targeting its anti-inflammatory action were excluded. In addition, review articles, meta-analyses, abstracts, conference papers, editorials/letters and case reports were also excluded. RESULTS: Of the 561 articles found, 64 were in the Cochrane database, 235 in Scopus, 99 in Web of science, 150 in PubMed and 13 in Lilacs. After completing the systematic steps, 25 articles were selected for full reading, after which 7 papers remained in the review. An article was added after a manual literature search, resulting in a total of 8 papers. There was a high level of agreement on inclusion/exclusion among the researchers who examined the papers (Kappa index > 88%). CONCLUSION: Limonene has effective anti-inflammatory activity in both preventing and controlling respiratory system injuries.

Psychosocial Barriers to Viral Suppression in a Community-based Sample of Human Immunodeficiency Virus-infected Men Who Have Sex With Men and People Who Inject Drugs in India.

BACKGROUND: Little is known about the impact of psychosocial factors and substance use on viral suppression among human immunodeficiency virus (HIV)-infected key populations in resource-limited settings. Accordingly, we examined the association and interactions between depression, alcohol use, and recreational drug use on viral suppression among men who have sex with men (MSM) and people who inject drugs (PWID) in India. METHODS: MSM and PWID were recruited across India using respondent-driven sampling (RDS). Correlates of viral suppression were determined using Poisson regression models incorporating RDS-II weights. Two-way multiplicative interactions were assessed with separate models of all combinations of the 3 variables of interest using interaction terms; 3-way interactions were evaluated by stratifying 2-way interactions by the third variable. RESULTS: Among 1454 treatment-eligible HIV-infected MSM and 1939 PWID, older age (adjusted prevalence ratio [aPR], 1.14 for MSM; 1.41 for PWID) and higher HIV treatment literacy (aPR, 1.58 for MSM; 3.04 for PWID) were positively associated with viral suppression. Among MSM, there was evidence of a synergistic negative association between severe depression and recreational drug use (aPR, 0.37 [95% confidence interval {CI}, .16-.84]), alcohol dependence and recreational drug use (aPR, 0.45 [95% CI, .20-.99]), and severe depression, alcohol dependence, and recreational drug use (aPR, 0.23 [95% CI, .09-.57]). Among PWID, daily injection (aPR, 0.51 [95% CI, .31-.82]) was the primary barrier to suppression. CONCLUSIONS: Incorporating psychosocial and harm-reduction services into differentiated care models targeting MSM and PWID in low-resource settings is critical to achieving the 90-90-90 HIV/AIDS targets.