Tag: nevin manimala

Nanomedicine (Lond). 2022 Jun 1. doi: 10.2217/nnm-2022-0043. Online ahead of print.

ABSTRACT

Background: Combination antiretroviral therapy has significantly advanced HIV-1 infection treatment. However, HIV-1 remains persistent in the brain; the inaccessibility of the blood-brain barrier allows for persistent HIV-1 infections and neuroinflammation. Nanotechnology-based drug carriers such as nanodiscoidal bicelles can provide a solution to combat this challenge. Methods: This study investigated the safety and extended release of a combination antiretroviral therapy drug (tenofovir)-loaded nanodiscs for HIV-1 treatment in the brain both in vitro and in vivo. Result: The nanodiscs entrapped the drug in their interior hydrophobic core and released the payload at the desired location and in a controlled release pattern. The study also included a comparative pharmacokinetic analysis of nanodisc formulations in in vitro and in vivo models. Conclusion: The study provides potential applications of nanodiscs for HIV-1 therapy development.

PMID:35642549 | DOI:10.2217/nnm-2022-0043

mSphere. 2022 Jun 1:e0002322. doi: 10.1128/msphere.00023-22. Online ahead of print.

ABSTRACT

Trypanosoma brucei, the causative agent of human and animal African trypanosomiasis, cycles between a mammalian host and a tsetse fly vector. The parasite undergoes huge changes in morphology and metabolism during adaptation to each host environment. These changes are reflected in the different transcriptomes of parasites living in each host. However, it remains unclear whether chromatin-interacting proteins help mediate these changes. Bromodomain proteins localize to transcription start sites in bloodstream parasites, but whether the localization of bromodomain proteins changes as parasites differentiate from bloodstream to insect stages remains unknown. To address this question, we performed cleavage under target and release using nuclease (CUT&RUN) against bromodomain protein 3 (Bdf3) in parasites differentiating from bloodstream to insect forms. We found that Bdf3 occupancy at most loci increased at 3 h following onset of differentiation and decreased thereafter. A number of sites with increased bromodomain protein occupancy lie proximal to genes with altered transcript levels during differentiation, such as procyclins, procyclin-associated genes, and invariant surface glycoproteins. Most Bdf3-occupied sites are observed throughout differentiation. However, one site appears de novo during differentiation and lies proximal to the procyclin gene locus housing genes essential for remodeling surface proteins following transition to the insect stage. These studies indicate that occupancy of chromatin-interacting proteins is dynamic during life cycle stage transitions and provide the groundwork for future studies on the effects of changes in bromodomain protein occupancy. Additionally, the adaptation of CUT&RUN for Trypanosoma brucei provides other researchers with an alternative to chromatin immunoprecipitation (ChIP). IMPORTANCE The parasite Trypanosoma brucei is the causative agent of human and animal African trypanosomiasis (sleeping sickness). Trypanosomiasis, which affects humans and cattle, is fatal if untreated. Existing drugs have significant side effects. Thus, these parasites impose a significant human and economic burden in sub-Saharan Africa, where trypanosomiasis is endemic. T. brucei cycles between the mammalian host and a tsetse fly vector, and parasites undergo huge changes in morphology and metabolism to adapt to different hosts. Here, we show that DNA-interacting bromodomain protein 3 (Bdf3) shows changes in occupancy at its binding sites as parasites transition from the bloodstream to the insect stage. Additionally, a new binding site appears near the locus responsible for remodeling of parasite surface proteins during transition to the insect stage. Understanding the mechanisms behind host adaptation is important for understanding the life cycle of the parasite.

PMID:35642518 | DOI:10.1128/msphere.00023-22

mSphere. 2022 Jun 1:e0091821. doi: 10.1128/msphere.00918-21. Online ahead of print.

ABSTRACT

A fundamental question in biology is why some species tend to occur together in the same locations, while others are never observed coexisting. This question becomes particularly relevant for microorganisms thriving in the highly diluted waters of high mountain lakes, where biotic interactions might be required to make the most of an extreme environment. We studied a high-throughput gene data set of alpine lakes (>220 Pyrenean lakes) with cooccurrence network analysis to infer potential biotic interactions, using the combination of a probabilistic method for determining significant cooccurrences and coexclusions between pairs of species and a conceptual framework for classifying the nature of the observed cooccurrences and coexclusions. This computational approach (i) determined and quantified the importance of environmental variables and spatial distribution and (ii) defined potential interacting microbial assemblages. We determined the properties and relationships between these assemblages by examining node properties at the taxonomic level, indicating associations with their potential habitat sources (i.e., aquatic versus terrestrial) and their functional strategies (i.e., parasitic versus mixotrophic). Environmental variables explained fewer pairs in bacteria than in microbial eukaryotes for the alpine data set, with pH alone explaining the highest proportion of bacterial pairs. Nutrient composition was also relevant for explaining association pairs, particularly in microeukaryotes. We identified a reduced subset of pairs with the highest probability of species interactions (“interacting guilds”) that significantly reached higher occupancies and lower mean relative abundances in agreement with the carrying capacity hypothesis. The interacting bacterial guilds could be more related to habitat and microdispersal processes (i.e., aquatic versus soil microbes), whereas for microeukaryotes trophic roles (osmotrophs, mixotrophs, and parasitics) could potentially play a major role. Overall, our approach may add helpful information to guide further efforts for a mechanistic understanding of microbial interactions in situ. IMPORTANCE A fundamental question in biology is why some species tend to occur together in the same locations, while others are never observed to coexist. This question becomes particularly relevant for microorganisms thriving in the highly diluted waters of high mountain lakes, in which biotic interactions might be required to make the most of an extreme environment. Microbial metacommunities are too often only studied in terms of their environmental niches and geographic barriers since they show inherent difficulties to quantify biological interactions and their role as drivers of ecosystem functioning. Our study highlights that telling apart potential interactions from both environmental and geographic niches may help for the initial characterization of organisms with similar ecologies in a large scope of ecosystems, even when information about actual interactions is partial and limited. The multilayered statistical approach carried out here offers the possibility of going beyond taxonomy to understand microbiological behavior in situ.

PMID:35642514 | DOI:10.1128/msphere.00918-21

Hosp Pediatr. 2022 Jun 1:e2021006420. doi: 10.1542/hpeds.2021-006420. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe maternal knowledge, attitudes, and practices related to marijuana use and breastfeeding, and determine their association with knowledge about potential harmful effects of marijauna use while breastfeeding.

METHODS: Cross-sectional study design, using a 48-item survey, including previously validated questions, of postpartum mothers at a single urban, academic hospital from 2018 to 2019. Mothers ≥ 18 years with a newborn ≥ 35 weeks’ gestation were eligible. Descriptive statistics were tabulated, and associations were tested by using χ2 analysis.

RESULTS: Of 46 participants, 57% reported marijuana use, and 13% use within the past 12 months. The large majority (87%) knew that use while breastfeeding may be harmful to the infant, whereas just 46% knew that marijuana or THC is found in breast milk. Only 35% received prenatal and 30% postnatal counseling on the risks of marijuana use while breastfeeding. Those aware compared to those unaware that marijuana use during pregnancy may cause learning and behavior problems were more likely to know that use while breastfeeding may be harmful to the infant (75% vs. 25%, P = .03). Those reporting prenatal HCP discussion about the risks of marijuana use while breastfeeding compared to those without such counseling were more likely to know that marijuana/ or HC is found in breast milk (69% vs. 33%, P = .02).

CONCLUSIONS: The majority of mothers were aware that marijuana use while breastfeeding may be harmful to the infant, but a minority received counseling about the risks of marijuana use while breastfeeding.

PMID:35642492 | DOI:10.1542/hpeds.2021-006420

Hepatology. 2022 Jun 1. doi: 10.1002/hep.32594. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: The impact of disease progression in non-alcoholic fatty liver disease (NAFLD) on liver outcomes remains poorly understood. We aimed to investigate NAFLD progression using longitudinal liver stiffness measurements (LSM) by serial MREs and the association with liver outcomes.

METHODS: All adult NAFLD patients who underwent at least 2 serial MREs for clinical evaluation at Mayo Clinic, Rochester between 2007-2019 were identified from the institutional database. Progression and regression were defined based on LSM change of 19% above or below 19% of initial LSM, respectively, based on QIBA consensus. The association between change in LSM and liver-related outcomes occurring after the last MRE was examined using time-to-event analysis.

RESULTS: A total of 128 participants underwent serial MREs (53% female, median age 59 years). The median time between paired MREs was 3.4 (range 1-10.7) years. NAFLD progression (LSM of +0.61 kPa/year) was identified in 17 patients (13.3%). NAFLD regression (-0.40 kPa/year) occurred in 35 patients (27.3%). Stable LSM was noted in 76 participants (59.4%). In NAFLD without cirrhosis at baseline (n=75), cirrhosis development occurred in 14% of LSM progressors and 2.9% of non-progressors (p=0.059) over a median 2.7 years of follow-up from the last MRE. Among those with compensated cirrhosis at baseline MRE (n=29), decompensation or death occurred in 100% of LSM progressors and 19% of non-progressors (p<0.001) over a median 2.5 years of follow-up after the last MRE.

CONCLUSION: Noninvasive monitoring of LSM by conventional MRE is a promising method of longitudinal NAFLD monitoring and risk estimation of liver-related outcomes in NAFLD.

PMID:35642504 | DOI:10.1002/hep.32594

Biomark Med. 2022 Jun 1. doi: 10.2217/bmm-2022-0139. Online ahead of print.

ABSTRACT

Aim: Helicobacter pylori (Hp) infection has a connection with metabolic syndrome (MetS). Pepsinogen II (PGII) is a marker for gastric epithelial function. The present research was aimed at determining the associations among serum PGII levels, Hp infection and MetS in healthy subjects. Methods: This cross-sectional study enrolled 1242 healthy people, including 545 subjects with asymptomatic Hp infection and 697 subjects without Hp infection. Based on the number of MetS components present, subjects with Hp infection were assigned to the following groups: group 1, no component (126 subjects); group 2, one or two components (260 subjects); and group 3, three or more components (159 subjects). Physical measurements and biochemical indices were recorded. Serum PGII levels were recorded using ELISA. SPSS and GraphPad Prism were used for statistical analyses. Results: Among subjects with Hp infection, serum PGII was evidently downregulated in group 3 compared with group 1 (14.95 ± 8.24 vs 17.97 ± 9.08 μg/l; p = 0.015). Serum PGII levels were correlated with an increased risk of MetS (odds ratio: 0.867; 95% CI: 0.772-0.974; p = 0.016), as indicated by the multivariate logistic regression analysis. Grouping subjects with Hp infection according to quartiles of serum PGII levels identified an evident difference in MetS prevalence among the four quartile-based groups (p = 0.047). Conclusions: Among healthy subjects with asymptomatic Hp infection, serum PGII levels were lower in those with MetS than in those without MetS. Serum PGII levels showed an independent and negative correlation with the risk of MetS in healthy subjects with Hp infection.

PMID:35642469 | DOI:10.2217/bmm-2022-0139

Glob Chang Biol. 2022 Jun 1. doi: 10.1111/gcb.16280. Online ahead of print.

ABSTRACT

Livestock contributes approximately one-third of global anthropogenic methane (CH₄ ) emissions. Quantifying the spatial and temporal variations of these emissions is crucial for climate change mitigation. Although country-level information is reported regularly through national inventories and global databases, spatially-explicit quantification of century-long dynamics of CH₄ emissions from livestock has been poorly investigated. Using the Tier 2 method adopted from the 2019 Refinement to 2006 IPCC guidelines, we estimated CH₄ emissions from global livestock at a spatial resolution of 0.083° (~9 km at the equator) during the period 1890-2019. We find that global CH₄ emissions from livestock increased from 31.8 [26.5-37.1] (mean [minimum-maximum of 95% confidence interval) Tg CH₄ yr^-1 in 1890 to 131.7 [109.6-153.7] Tg CH₄ yr^-1 in 2019, a fourfold increase in the past 130 years. The growth in global CH₄ emissions mostly occurred after 1950 and was mainly attributed to the cattle sector. Our estimate shows faster growth in livestock CH₄ emissions as compared to the previous Tier 1 estimates and is ~20% higher than the estimate from FAOSTAT for the year 2019. Regionally, South Asia, Brazil, North Africa, China, the United States, Western Europe, and Equatorial Africa shared the majority of the global emissions in the 2010s. South Asia, tropical Africa, and Brazil have dominated the growth in global CH₄ emissions from livestock in the recent three decades. Changes in livestock CH₄ emissions were primarily associated with changes in population and national income and were also affected by the policy, diet shifts, livestock productivity improvement, and international trade. The new geospatial information on the magnitude and trends of livestock CH₄ emissions identifies emission hotspots and spatial-temporal patterns, which will help to guide meaningful CH₄ mitigation practices in the livestock sector at both local and global scales.

PMID:35642457 | DOI:10.1111/gcb.16280

J Med Virol. 2022 Jun 1. doi: 10.1002/jmv.27898. Online ahead of print.

ABSTRACT

A prospective cohort study was conducted during the Delta and Omicron SARS-CoV-2 epidemic waves from paired nasopharyngeal swab (NPS) and saliva samples taken from 624 participants. The study aimed to assess if any differences among participants from both waves could be observed and if any difference in molecular diagnostic performance could be observed among the two sample types. Samples were transported immediately to the laboratory to ensure the highest possible sample quality without any freezing and thawing steps before processing. Nucleic acids from saliva and NPS were prospectively extracted and SARS-CoV-2 was detected using rtRT-PCR. All observed results were statistically analyzed. Although the results obtained with NP and saliva agreed overall, higher viral loads were observed in NP swabs regardless of the day of specimen collection in both SARS-CoV-2 epidemic waves. No significant difference could be observed between the two epidemic waves characterized by Delta or Omicron SARS-CoV-2. To note, Delta infection resulted in higher viral loads both in NP and saliva and more symptoms, including rhinorrhea, cough, and dyspnea, whereas Omicron wave patients more frequently reported sore throat. An increase in the mean log RNA of SARS-CoV-2 was observed with the number of expressed symptoms in both waves, however, the difference was not significant. Data confirmed that results from saliva were concordant with those from NP swabs, although saliva proved to be a challenging sample with frequent inhibitions that required substantial retesting. This article is protected by copyright. All rights reserved.

PMID:35642439 | DOI:10.1002/jmv.27898

J R Soc Interface. 2022 Jun;19(191):20220018. doi: 10.1098/rsif.2022.0018. Epub 2022 Jun 1.

ABSTRACT

Multicellular life forms have evolved many times on our planet, suggesting that this is a common evolutionary innovation. Multiple advantages have been proposed for the emergence of multicellularity (MC). In this paper, we address the problem of how the first precondition for MC, namely ‘stay together’, might have occurred under spatially limited resources exploited by a population of unicellular agents. Using a minimal model of evolved cell-cell adhesion among growing and dividing cells that exploit a localized resource with a given size, we show that a transition occurs at a critical resource size separating a phase of evolved multicellular aggregates from a phase where unicellularity (UC) is favoured. The two phases are separated by an intermediate domain where both UC and MC can be selected by evolution. This model provides a minimal approach to the early stages that were required to transition from individuality to cohesive groups of cells associated with a physical cooperative effect: when resources are present only in a localized portion of the habitat, MC is a desirable property as it helps cells to keep close to the available local nutrients.

PMID:35642429 | DOI:10.1098/rsif.2022.0018

Turk Patoloji Derg. 2022 Jun 1. doi: 10.5146/tjpath.2022.01578. Online ahead of print.

ABSTRACT

OBJECTIVE: Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The early stage of MF is a difficult diagnostic case, as it is often confused with many benign inflammatory dermatoses (BID). The study aimed to evaluate the diagnostic utility of TOX, FOXP3, CDD4 and GATA3 in differentiating early stages of MF from histologically overlapping BID lesions.

MATERIAL AND METHOD: A retrospective cross-sectional study was performed, in which immunohistochemistry (IHC) was used to evaluate the expression of TOX, FOXP3, CD4 and GATA3 in formalin-fixed paraffin-embedded (FFPE) sections of skin lesions from 30 cases with BID and 30 patients with early-stage MF.

RESULTS: The association between TOX expression and early-stage MF was statistically significant (P < 0.001). TOX had the highest sensitivity of 96.77% and accuracy of 85.71% in diagnosis of MF; followed by CD4 with sensitivity of 85.71% and accuracy of 78.95%; and then, GATA3 with sensitivity of 76.7% and finally FOXP3 with sensitivity of 70.0%.

CONCLUSION: TOX is suggested to be of higher diagnostic value in the early stages of MF than the conventionally used CD4 and other markers examined.

PMID:35642346 | DOI:10.5146/tjpath.2022.01578