-
The New England Journal of Medicine Apr 2023A 48-year-old man with long-standing type 2 diabetes mellitus (recent glycated hemoglobin level, 6.5%) and chronic kidney disease (baseline creatinine level, 3.3 mg per...
A 48-year-old man with long-standing type 2 diabetes mellitus (recent glycated hemoglobin level, 6.5%) and chronic kidney disease (baseline creatinine level, 3.3 mg per deciliter [292 mol per liter]; glomerular filtration rate, 24 ml per minute per 1.73 m of body-surface area) presented to his primary care physician with a 3-month history of numbness, tingling, and faint violaceous discoloration of the tips of multiple fingers and toes. His physical examination showed reduced light-touch sensation in a glove-and-stocking distribution; the radial and pedal pulses were palpable. The vitamin B level was 260 pg per milliliter (192 pmol per liter; normal range, 190 to 950 pg per milliliter [140 to 701 pmol per liter]). He did not smoke tobacco, drink alcohol, or use illicit drugs. One month later, a nontraumatic wound developed on the left foot. The ankle–brachial index (ABI) was 1.2 on both sides (normal range, 0.91 to 1.3). Wound care was initiated for a presumed neuropathic ulcer.
PubMed: 37018496
DOI: 10.1056/NEJMcps2210419 -
MedRxiv : the Preprint Server For... Jun 2023To compare the frequency of replication-competent virologic rebound with and without nirmatrelvir-ritonavir treatment for acute COVID-19. Secondary aims were to estimate...
OBJECTIVE
To compare the frequency of replication-competent virologic rebound with and without nirmatrelvir-ritonavir treatment for acute COVID-19. Secondary aims were to estimate the validity of symptoms to detect rebound and the incidence of emergent nirmatrelvir-resistance mutations after rebound.
DESIGN
Observational cohort study.
SETTING
Multicenter healthcare system in Boston, Massachusetts.
PARTICIPANTS
We enrolled ambulatory adults with a positive COVID-19 test and/or a prescription for nirmatrelvir-ritonavir.
EXPOSURES
Receipt of 5 days of nirmatrelvir-ritonavir treatment versus no COVID-19 therapy.
MAIN OUTCOME AND MEASURES
The primary outcome was COVID-19 virologic rebound, defined as either (1) a positive SARS-CoV-2 viral culture following a prior negative culture or (2) two consecutive viral loads ≥4.0 log copies/milliliter after a prior reduction in viral load to <4.0 log copies/milliliter.
RESULTS
Compared with untreated individuals (n=55), those taking nirmatrelvir-ritonavir (n=72) were older, received more COVID-19 vaccinations, and were more commonly immunosuppressed. Fifteen individuals (20.8%) taking nirmatrelvir-ritonavir experienced virologic rebound versus one (1.8%) of the untreated (absolute difference 19.0% [95%CI 9.0-29.0%], P=0.001). In multivariable models, only N-R was associated with VR (AOR 10.02, 95%CI 1.13-88.74). VR occurred more commonly among those with earlier nirmatrelvir-ritonavir initiation (29.0%, 16.7% and 0% when initiated days 0, 1, and ≥2 after diagnosis, respectively, P=0.089). Among participants on N-R, those experiencing rebound had prolonged shedding of replication-competent virus compared to those that did not rebound (median: 14 vs 3 days). Only 8/16 with virologic rebound reported worsening symptoms (50%, 95%CI 25%-75%); 2 were completely asymptomatic. We detected no post-rebound nirmatrelvir-resistance mutations in the NSP5 protease gene.
CONCLUSIONS AND RELEVANCE
Virologic rebound occurred in approximately one in five people taking nirmatrelvir-ritonavir and often occurred without worsening symptoms. Because it is associated with replication-competent viral shedding, close monitoring and potential isolation of those who rebound should be considered.
PubMed: 37425934
DOI: 10.1101/2023.06.23.23288598 -
Scientific Reports Jan 2021Calcium added to dentifrices can complex with fluoride ions to reduce intra-oral bioavailability and therefore efficacy in preventing dental caries. Six commercially...
Calcium added to dentifrices can complex with fluoride ions to reduce intra-oral bioavailability and therefore efficacy in preventing dental caries. Six commercially available dentifrices containing different types of calcium and fluoride were analyzed for total and bioavailable fluoride levels by adding 10 g of dentifrice to 30 mL of distilled deionized water and mixing vigorously for 1 min to simulate toothbrushing. One milliliter of the dentifrice/water slurry was immediately centrifuged and the supernatant removed for bioavailable fluoride analysis and the mixed slurry prior to centrifugation used for total fluoride analysis using a modified microdiffusion method. The concentration of fluoride was determined using a fluoride ion-selective electrode calibrated with internal fluoride standards. All the dentifrices had similar total fluoride concentrations to those indicated on their labels (94% to 105%). However, only one dentifrice that contained calcium in the form of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) had almost 100% (97%) of fluoride in bioavailable form. The other dentifrices contained calcium carbonate and they exhibited significantly (p < 0.001) lower bioavailable fluoride levels (27% to 61%), through the generation of poorly soluble fluoride phases. The saliva biomimetic CPP, as CPP-ACP, in a dentifrice stabilised calcium and fluoride ions to maintain fluoride's bioavailability.
PubMed: 33420297
DOI: 10.1038/s41598-020-80503-x -
The Saudi Dental Journal Mar 2022This systematic review aimed to evaluate the antiviral effect of mouthwashes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (Review)
Review
OBJECTIVE
This systematic review aimed to evaluate the antiviral effect of mouthwashes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
MATERIAL AND METHODS
An electronic search was performed on PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ProQuest, and Google Scholar, and was complemented by a manual search. Both clinical and studies that focused on the antiviral effect of mouthwashes against SARS-CoV-2 were included. Risk of bias assessment was performed only on the clinical studies using the RoB-2 and ROBINS-I tools.
RESULTS
A total of 907 records were found; after initial selection by title and abstract, 33 full-text articles were selected to be evaluated for eligibility. Finally, a total of 27 studies were included for the qualitative synthesis, including 16 studies and 11 clinical trials. Antiviral effects were evaluated separately for the and clinical studies. In vitro studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, essential oils, cetylpyridinium chloride, and other compounds; studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, essential oils, chlorine dioxide, β-cyclodextrin-citrox, and sorbitol with xylitol. Povidone-iodine, cetylpyridinium chloride, and essential oils were effective , while hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, β-cyclodextrin-citrox, and sorbitol with xylitol were effective . Unclear or high risk of bias was found for almost all clinical studies, and only one study presented with a low risk of bias. No further quantitative analysis was performed.
CONCLUSION
Although povidone-iodine, cetylpyridinium chloride, and essential oils may be an alternative to reduce the viral load and , more studies are needed to determine the real antiviral effect of these different mouthwashes against SARS-CoV-2.This work was not funded. The protocol was registered in PROSPERO (identification number: CRD42021236134).
PubMed: 35125835
DOI: 10.1016/j.sdentj.2022.01.006 -
Science Translational Medicine Jul 2023Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have... (Clinical Trial)
Clinical Trial
Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children ( = 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART. Eleven (44%) children maintained HIV-1 RNA below 400 copies per milliliter through 24 weeks of bNAb-only treatment; 14 (56%) had detectable viremia above 400 copies per milliliter at a median of 4 weeks. Archived HIV-1 provirus susceptible to 10-1074, lower birth HIV-1 DNA reservoir in peripheral blood mononuclear cells, sustained viral suppression throughout early life, and combined negative qualitative HIV-1 DNA polymerase chain reaction and negative HIV-1 serology at entry were associated with maintaining suppression on bNAbs alone. This proof-of-concept study suggests that bNAbs may represent a promising treatment modality for infants and children living with HIV-1. Future studies using newer bNAb combinations with greater breadth and potency are warranted.
Topics: Child; Humans; Anti-Retroviral Agents; Antibodies, Neutralizing; Botswana; Broadly Neutralizing Antibodies; HIV Antibodies; HIV Infections; HIV-1; Leukocytes, Mononuclear; Prospective Studies; Viremia
PubMed: 37406137
DOI: 10.1126/scitranslmed.adh0004 -
Frontiers in Microbiology 2019Viruses are the most abundant biological entities in the biosphere, and have the ability to infect Bacteria, Archaea, and Eukaryotes. The virome is estimated to be at... (Review)
Review
Viruses are the most abundant biological entities in the biosphere, and have the ability to infect Bacteria, Archaea, and Eukaryotes. The virome is estimated to be at least ten times more abundant than the microbiome with 10 viruses per milliliter and 10 viral particles per gram in marine waters and sediments or soils, respectively. Viruses represent a largely unexplored genetic diversity, having an important role in the genomic plasticity of their hosts. Moreover, they also play a significant role in the dynamics of microbial populations. In recent years, metagenomic approaches have gained increasing popularity in the study of environmental viromes, offering the possibility of extending our knowledge related to both virus diversity and their functional characterization. Extreme environments represent an interesting source of both microbiota and their virome due to their particular physicochemical conditions, such as very high or very low temperatures and >1 atm hydrostatic pressures, among others. Despite the fact that some progress has been made in our understanding of the ecology of the microbiota in these habitats, few metagenomic studies have described the viromes present in extreme ecosystems. Thus, limited advances have been made in our understanding of the virus community structure in extremophilic ecosystems, as well as in their biotechnological potential. In this review, we critically analyze recent progress in metagenomic based approaches to explore the viromes in extreme environments and we discuss the potential for new discoveries, as well as methodological challenges and perspectives.
PubMed: 31749771
DOI: 10.3389/fmicb.2019.02403 -
Biomicrofluidics Nov 2019Inertial microfluidic systems have been arousing interest in medical applications due to their simple and cost-efficient use. However, comparably small sample volumes in... (Review)
Review
Inertial microfluidic systems have been arousing interest in medical applications due to their simple and cost-efficient use. However, comparably small sample volumes in the microliter and milliliter ranges have so far prevented efficient applications in continuous bioprocesses. Nevertheless, recent studies suggest that these systems are well suited for cell separation in bioprocesses because of their facile adaptability to various reactor sizes and cell types. This review will discuss potential applications of inertial microfluidic cell separation systems in downstream bioprocesses and depict recent advances in inertial microfluidics for bioprocess intensification. This review thereby focusses on spiral microchannels that separate particles at a moderate Reynolds number in a laminar flow ( < 2300) according to their size by applying lateral hydrodynamic forces. Spiral microchannels have already been shown to be capable of replacing microfilters, extracting dead cells and debris in perfusion processes, and removing contaminant microalgae species. Recent advances in parallelization made it possible to process media on a liter-scale, which might pave the way toward industrial applications.
PubMed: 31700559
DOI: 10.1063/1.5125264 -
Cardiovascular Drugs and Therapy Apr 2023Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19)....
PURPOSE
Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19). Although our understanding of the pathogenesis of COVID-19 has rapidly evolved, much of the focus has been on the immune mechanisms underlying COVID-19. In addition to immune dysfunction, vascular injury is also associated with COVID-19 and is a major driver of clinical deterioration in SARS-CoV-2 infections. The glycocalyx (GAC), a sugar-based shell that surrounds all mammalian cells, is an important regulator of vascular and immune responses. In sepsis, vascular dysfunction contributes to acute respiratory distress syndrome (ARDS) by altering vessel integrity, promoting thrombosis, and accelerating inflammation, all of which are also present in COVID-19. Observational studies in sepsis have found an association between levels of circulating GAC degradation products with both organ dysfunction and mortality. Although vascular dysfunction is a hallmark of COVID-19, it remains unclear whether GAC disruption occurs in COVID-19 and if GAC disruption contributes to the clinical progression of COVID-19.
METHODS
In this prospective cohort study, we measured the GAC components syndecan-1 (SDC1) and hyaluronan (Hyal) along with inflammatory cytokines in 12 hospitalized COVID-19 patients and 8 healthy controls (HC).
RESULTS
In agreement with other studies, we found that inflammatory cytokines are elevated in hospitalized COVID-19 patients compared with HC [median (IQR), all units picograms per milliliter: IL-6 4.65 (3.32-9.16) vs 0.69 (0.55-0.89), p < 0.001; TNFα 4.49 (1.87-8.03) vs 0.04 (0.04-0.84), p < 0.001]. Additionally, we found that the GAC components SDC1 and Hyal are also elevated in COVID-19 patients [median (IQR), all units picograms per milliliter: SDC1: 247.37 (101.43-458.26) vs 84.8 (52.88-123.59), p = 0.036; Hyal: 26.41 (16.4-35.1) vs 3.01 (1.66-4.61), p < 0.001].
CONCLUSION
We propose that GAC markers offer insights into the pathobiology of COVID-19, potentially guide therapeutic approaches, and could aid in early risk stratification that is particularly beneficial in phasic diseases such as COVID-19.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Prospective Studies; Glycocalyx; Cytokines; Sepsis; Mammals
PubMed: 34792686
DOI: 10.1007/s10557-021-07288-7 -
Journal of Family & Reproductive Health Sep 2022To investigate the effect of cold plasma on Staphylococcus aureus destruction at different treatment times. Staphylococcus aureus was cultured on 4 plates of LB Agar...
To investigate the effect of cold plasma on Staphylococcus aureus destruction at different treatment times. Staphylococcus aureus was cultured on 4 plates of LB Agar medium each at 1.5 × 103 CFU / mL (colony-forming unit per milliliter) and one group was selected as the control group and the other 3 groups were treated with plasma for 5, 7 and 10 minutes. They were incubated for 24 hours at 37 °C. Finally, the number of colonies formed was counted. It was shown that treatment with cold atmospheric plasma significantly reduced bacterial colonies and in comparison to the control plate with a colony count of 1.5 × 10 CFU/mL treatment with air plasma for 10 minutes decreased the Pseudomonas colony count to zero. It was observed that the cold atmospheric plasma jet device manufactured in atomic Energy Organization of Iran can significantly kill bacteria in a short time. Increasing the duration of treatment significantly reduces bacterial colonies.
PubMed: 36569254
DOI: 10.18502/jfrh.v16i3.10583