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Κυριακή 24 Ιουλίου 2022

Sustained within-season vaccine effectiveness against influenza-associated hospitalization in children: Evidence from the New Vaccine Surveillance Network, 2015-2016 through 2019-2020

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited.
Methods
We conducted a prospective, test-negative study of children 6 months–17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression.
Results
Of 8,430 children, 4,653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were v accinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs. 57%, p < 0.001); overall VE against hospitalization was 53% (95% CI: 46%-60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%-12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4,000, p = 0.275). Odds of hospitalization increased 2.9% (95% CI: -5.4%-11.8%) and 9.6% (95% CI: -7.0%-29.1%) per month in children ≤8 years (n = 3,084) and 9-17 years (n = 916), respectively. These findings were not statistically significant.
Conclusions
We observed minimal, not statistically significant within-season declines in VE. Vaccination following current ACIP guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.
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Nano or No-No? Hydroxyapatite Particle Size Matters…

alexandrossfakianakis shared this article with you from Inoreader

In this article, we're going to take a deep dive into hydroxyapatite. We'll cover what it is, how beneficial it is to help stop tooth decay, and the potential risks of nano-hydroxyapatite.

Fair warning, this article is going to be a deep dive that provides a lot of details about hydroxyapatite.

So if you're new here and you'd like a more high-level introduction to remineralization or hydroxyapatite's role in helping to stop and/or protect against tooth decay, these articles may be an easier read:

In 2016, we launched our Shine Remineralizing Tooth Whitening Powder, which contains naturally sourced hydroxyapatite (it's actually the #1 ingredient in Shine 🙂 ). Since then, many other companies have developed oral hygiene products using various forms of hydroxyapatite.

It makes sense that hydroxyapatite's popularity is on the rise. After all, the research clearly shows that hydroxyapatite protects against tooth decay just as well as (and sometimes even better than) fluoride.

However, like so many things in life, not all hydroxyapatites are created equal. The quality, quantity, and particle size of a product's hydroxyapatite can all make a big difference.

Speaking of particle size, the blogosphere has recently been abuzz with debates about the risks vs. benefits of nano-sized hydroxyapatite. So, we decided to provide more information so you can make up your own mind on this developing subject.

What is hydroxyapatite?

To start, let's make sure we're all on the same page.

Hydroxyapatite (high-drox-ee-appetite), is the chemical name for a molecule made up of calcium, phosphorus, oxygen, and hydrogen. For you scientists (or armchair scientific types, like me), the chemical composition is Ca5(PO4)3OH. However, since it shows up as a pair in nature, it's commonly notated as Ca10(PO4)6(OH)2. The word 'hydroxyapatite' is commonly abbreviated as HA.

The HA molecule is very important for oral care.

It's the primary building block that our teeth are made of.

But for decades, instead of focusing on hydroxyapatite, we've been taught that we need to use fluoride to prevent tooth decay. Leaning on our high school chemistry class, we might recall that fluoride is a halide, which means it's a super 'attractive' element.

When we introduce fluoride into the mouth, it binds with the calcium and phosphorus components of our teeth, which creates fluorapatite (note, not hydroxyapatite). However, our teeth do not naturally contain fluoride, and tooth decay is not the result of a fluoride deficiency. 

So, for the purposes of this article, we'll set aside fluoride. Instead, we'll anchor on the fact that our teeth are made of hydroxyapatite, which is why HA is such a supportive compound for tooth health.

Quick primer on particle size…

Particle sizes can be expressed using different units of measurement. For the size we'll be dealing with here, the metric system is generally used. We'll be talking in micrometers (also called microns) and nanometers. And for perspective, let's zoom out and start with millimeters.

Millimeters are the tiniest marks on a standard US/metric ruler. 10 millimeters = 1 centimeter, which is about ⅓ of an inch. 

(As a side note, if you've had a periodontal depth test, you probably know that the numbers the dentist calls out to the assistant are in millimeters. Any gum pocket that's deeper than 4 millimeters is problematic. Once gum pockets get deeper than that, it's difficult to effectively maintain healthy bacterial populations. Thankfully, there's a product solution that can help if you have deeper gum pockets. Now let's get back to measurements…)

There are 1000 micrometers in a millimeter. 

Stepping down another rung into the hard-to-imagine range, there are 1000 nanometers in 1 micrometer.

So, that means that there are one million nanometers in one millimeter. 

Here's the takeaway that will help simplify this: 'nano' is one thousand times smaller than 'micro'. 


So for example, something that's 5 micrometers in diameter could also be measured as 5000 nanometers. In other words, nanoparticles are WAY smaller than microparticles.

To look at it another way, if a golf ball were one nanometer in diameter, a micrometer would be nearly half a football field in diameter, and one millimeter would be just over 23 miles. So, nanometers are 1000 times smaller than micrometers, which are 1000 times smaller than millimeters.

Particle size matters…

Hydroxyapatite can come in many different particle sizes. For medical, dental, and oral supplement applications, particle sizes range from about 800 micrometers all the way down to 10 nanometers (80,000 times smaller).

To assist with optimal uptake in the mouth, we want the particle size to be pretty tiny. That way, it can go into suspension with our saliva and be available to deposit more minerals into and onto our teeth. (For more info on how this works with Shine, please take a look at this video.)

The naturally sourced hydroxyapatite we use in Shine is pharmaceutical-grade bone powder from grass-fed New Zealand cattle. 

(Incidentally, the same hydroxyapatite that we use is also used in the supplement field as a bioavailable source of calcium. In fact, there's substantial evidence that suggests that the body uptakes HA better than other forms of calcium.) 

We use the finest particle size our team can mechanically produce, which is right around 70 micrometers. To differentiate it from nano-HA, we refer to our hydroxyapatite as MCHA (microcrystalline hydroxyapatite) with the 'micro' distinguishing the particle size of the HA.

But if a tiny size is better, why not use the smallest possible particle size?

As we go from micrometers to nanometers, we have to think about what might happen in the body if we use an ingredient with such a tiny particle size.

Nano or no-no?

If you've been reading our material for a while, you already know that OraWellness is hardwired to a holistic paradigm. This affects many of our decisions, especially when it comes to product development.

When we were doing the R&D for Shine, we saw that the research literature supported using nano-HA for helping to restore demineralized areas in teeth. But we also saw some bad PR about nano-sized particles indiscriminately traveling throughout the body (due to their extremely tiny particle size).

In our opinion, nano-HA had two things going against it:

  1. The particle size was so tiny that the molecule was able to easily migrate throughout the body (for example, across the blood-brain barrier and even into the cellular structure), and literature was emerging that suggested that this wasn't safe.
  2. Nanoparticles are synthetically produced (not naturally derived).

So, with our holistic paradigm guiding us, we chose to apply the 'precautionary principle' and avoid nano-HA until we knew for certain that it was safe to use long-term.

(For more info on our thought process in these situations, check out our simple, two-step exercise that you can apply to any hygiene product to determine if it's holistic or not.)

What are the risks with nano-HA?

In the EU, there's a General Product Safety Directive that says, "Businesses must only place products which are safe on the market…" But, nano-HA hasn't been proven to be safe.

In fact, earlier this year, the European Union announced that it plans to ban several nano-sized materials (including nano-HA) for use in cosmetic and oral hygiene applications. Here's a link to the full report on nano-HA from the EU's Scientific Committee on Consumer Safety (SCCS).

The SCCS is especially concerned about the potential for nano-HA to damage cell DNA. The term they reference is 'genotoxic potential', which means the possibility for something (in this case, nano-HA) to damage the genetic information within a cell, causing mutations that may lead to cancer. 

In their report, the SCCS states, "Having considered the data provided, and other relevant information available in scientific literature, the SCCS cannot conclude on the safety of the hydroxyapatite composed of rod-shaped nanoparticles for use in oral-care cosmetic products at the maximum concentrations and specifications given in this Opinion. This is because the available data/information is not sufficient to exclude concerns over the genotoxic potential of HAP-nano."

And their hesitancy seems warranted for other reasons, too. Other studies point to issues like the risk that nano-HA may cause cellular breakdown in kidney cells and that it may even have a negative impact on human blood cells.

All of this provides plenty of reasons for us to continue to apply the precautionary principle and steer clear of nano-HA. 

But what does the SCCS think about NON-nano-HA?

In section 3.3.4 Assessment of the systemic toxicity of the non nanoform of HAP, the report says, "Calcium phosphate is a common mineral on earth and the most common calcium phosphate mineral is hydroxyapatite. Calcium phosphates have been generally recognized as safe (GRAS) in food by the FDA in 1975. Calcium phosphate is highly biocompatible in contact with hard tissue because the body is well accustomed to this mineral."

Thank goodness we can still benefit from using hydroxyapatite without the risks of using nanoparticles.

Is microcrystalline HA as effective as nano-HA?

There are two ways science seeks to prove or disprove any hypothesis: via clinical trials or via empirical evidence (any patterns or behaviors found during personal observation or experimentation).

Let's start with what the research currently says about the efficacy of micro-HA.

To our knowledge, there are no research studies comparing different sizes of HA against one another. Here's a study that mentions both micro- and nano-HA, but we haven't yet found data that compares the efficacy of various particle sizes of HA.

However, here's a well-done study that compares micro-HA to the gold standard of conventional dentistry: 1400 ppm (particles per million) fluoride. The researchers chose to study individuals with braces (which is a group that's at high risk for decay). Here's the takeaway:

"In highly caries-active patients, the impact of the regular use of a microcrystalline HAP dentifrice [toothpaste] on caries [cavities] progression is not significantly different from the use of a 1400 ppm fluoride toothpaste."

At first blush, that might not sound very noteworthy. But, the data in that study actually shows that the participants who used a micro-HA toothpaste had less decay than those who used a fluoride-based toothpaste.

And, this one-year, double-blinded, randomized controlled trial tested whether micro-HA protects children against early cavities as effectively as fluoride-based toothpaste. It found, "This RCT [randomized controlled trial] showed for the first time, that in children, the impact of the daily use of a toothpaste with microcrystalline hydroxyapatite on enamel caries progression in the primary dentition is not inferior to a fluoride control toothpaste."

And what about empirical evidence?

Well, we have plenty of that from the thousands of testimonials we've received from you, our community, through the years since we launched Shine, our remineralizing tooth whitening powder with MCHA.

We love all of the testimonials we regularly receive. Some of them are jaw-droppers, like this one:


"I just found out one of the reasons I struggled with cavities for years: I have an autoimmune disease which causes dry mouth, and was depleted by stress and further health issues. I ended up with 11 cavities a few years ago despite great oral hygiene. I finally ordered many of your products at that time, including several containers of Shine.

Within 3 months, 10 of the cavities were gone and only the oldest deepest one needed a filling. The hygienist thought I must have had those cavities filled elsewhere as they were gone.

I have continued to use your products, and in the 3 years since then, have no new cavities, continued great gum health, and very little plaque at my dental visits. I love the smooth feel of the oil blend on my teeth, and it feels good to know that I can prevent cavities despite this autoimmune condition. Thank you!"

– Tara B. from Canada< /h2>

This is empirical evidence, plain and simple. And we're honored that so many of you have used our product solutions to create greater oral health for yourself. That's dental self-empowerment.

Wrapping up…

Thanks for joining us for this fascinating deep dive on hydroxyapatite and particle sizes. For more information on hydroxyapatite as well as other in-the-mouth and whole-body strategies for helping teeth remineralize, feel free to download our free eBook, How to Stop Tooth Decay and Remineralize Your Teeth.

What about you, what are your thoughts on nano- vs. microparticles? Are the benefits of using nano-HA greater than the risks? Ultimately, it becomes a personal value judgment. We hope this information helps you to make educated decisions on what ingredients to use in your oral hygiene strategy. Please share your thoughts and experiences in the comments below so we can all learn from each other.

Helpful, related resources:

Other resources:

The post Nano or No-No? Hydroxyapatite Particle Size Matters… appeared first on OraWellness.

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Experimental borosilicate bioactive glasses: pulp cells cytocompatibility and mechanical characterisation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Aim

To assess in vitro the effect of two novel phase separated borosilicate glasses (PSBS) in the system SiO2-B2O3-K2O-CaO-Al2O3 on dental pulp cells; and to compare their bioactivity and mechanical properties to a conventional fluoroaluminosilicate glass namely FUJI IX.

Methodology

The cytocompatibility assessment of the two novel borosilicate glasses, one without alumina (PSBS8) and one containing alumina (PSBS16), was performed on cultured primary human pulp cells (hDPCs). Alamar blue assay was used to assess cell metabolic activity and cell morphology was evaluated by confocal imaging. The bioactivity in Stimulated Body Fluid was also evaluated after 1 and 3 weeks of immersion using SEM-EDX analysis. Vickers microhardness and flexural strength were assessed after incorporating the glass particles into a commercial glass ionomer cement liquid containing both polyacrylic and polybasic carboxylic acid.

Results

The data revealed that the two borosilicate glasses enhanced cell viability ratios at all-time points in both direct and indirect contact assays. After 3 days of contact, PSBS8 without alumina showed higher viability rate (152%) compared to the PSBS16 containing alumina (145%) and the conventional glass ionomer particles (117%). EDX analysis confirmed an initial Ca/P ratio of 2.1 for 45S5K and 2.08 for PSBS8 without alumina after 3 weeks of immersion. The cement prepared using PSBS8 showed significantly higher Vickers hardness values (p=0.001) than that prepared using PSBS16 (46.6 vs 36.7 MPa). After 24 hours of maturation, PSBS8 (without alumina) exhibited a flexural strength of 12.9 MPa compared to a value of 16.4 MPa for the commercial control. PSBS8 without alumina had a higher strength than PSBS16 with alumina, after 1 and 7 days of maturation (p=0.001).

Conclusions

The present in vitro results demonstrated that the borosilicate bioactive glass without alumina enhanced pulp cell viability, spreading and acellular bioactivity better than the conventional glass ionomer cement and the experimental borosilicate glass containing alumina.

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A soluble DR5‐Fc chimeric protein (sDR5‐Fc) attenuates inflammatory responses induced by coronavirus MHV‐A59 and SARS‐CoV‐2

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Mortality in COVID-19 patients has been linked to the presence of "cytokine storm" induced by SARS-CoV-2 infection, which involves elevated levels of circulating cytokines and immune-cell hyperactivation. Targeting cytokines during the management of COVID-19 patients has the potential to improve survival rates and reduce mortality. Although cytokine blockers and immune-host modulators are currently being tested in severely ill COVID-19 patients to cope with the overwhelming systemic inflammation, no significant efficacy has been observed yet, thus finding new cytokine blockers to attenuate the cytokine storm syndrome is meaningful. In this paper, we significantly attenuated the inflammatory responses induced by mouse hepatitis viruses A59 (MHV-A59) and SARS-CoV-2 through a soluble DR5-Fc (sDR5-Fc) chimeric protein that blocking the TRAIL-DR5 interaction. Our finding indicates that blocking TRAIL-DR5 pathway through sDR5-Fc chimeric protein is a promising strategy to treat with COVID-19 severe patients requiring ICU admission or with chronic metabolic diseases.

This article is protected by copyright. All rights reserved.

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Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia‐Pacific

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction:

Liver disease is a growing burden among PLHIV in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD).

Methods:

Patients on cART with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels >5 times its upper limit of normal) were analysed using repeated measure logistic regression over a ten-year follow-up period. Liver cirrhosis was defined as having an APRI score >1.5, FIB-4 score >3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyse factors associated with cirrhosis among those in follow-up after 2015.

Results:

Of 5182 patients, 101 patients (1.9%) had high ALT levels with HCV-antibody positive (OR 4.98, 95%CI 2.82-8.77, p <0.001) an d ever high alcohol consumption (OR 2.33, 95% CI 1.00-5.46, p=0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate= 0.82 per 100 person-years). Those HCV-antibody positive (HR 5.54, 95% CI 3.75-8.18, p<0.001) and had high alcohol consumption (HR 2.06, 95%CI 1.23-3.45, p=0.006) were associated with liver cirrhosis.

Conclusion:

HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reduce the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

This article is protected by copyright. All rights reserved.

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Incidence and clearance of anal human papillomavirus infection in 16 164 individuals, according to HIV status, gender, and male sexuality: an international pooled analysis of 34 longitudinal studies

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programmes but has not been systematically characterised.
Methods
We reanalysed data from 34 studies with 16 164 individuals in six risk groups defined by HIV status, gender, and male sexuality: men who have sex with men (MSM) living with HIV (LWH) [MSMLWH], HIV-negative MSM, women LWH (WLWH), HIV-negative women, men who have sex with women (MSW) LWH (MSWLWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants.
Results
HPV16 had the highest incidence:clearance ratio of the hrHPV types. MSMLWH had highest hrHPV incidence (e.g. 15.5% newly HPV16-infected within two years), followed by HIV-negative MSM (7.5%), WLWH (6.6%), HIV-negative women (2.9%), MSWLWH (1.7%), and HIV-negative MSW (0.7%). Determinants of H PV16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behaviour for MSM only. HPV16 clearance was lower for people LWH (PLWH), and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV16 infection.
Conclusions
This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programmes on anal cancer prevention, particularly in MSM and PLWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.
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Interferon‐gamma inducible protein 16 and type I interferon receptors expression in experimental apical periodontitis induced in wild type mice

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Aim

The aim of this study was to evaluate the IFI16 and IFN-α/β receptors expression during the genesis and development of experimental apical periodontitis (AP) in mice teeth.

Methodology

AP was induced in the lower first molars of 40 C57BL/6 mice. They were divided according to the experimental periods 2, 7, 14, 21 and 42 days (n=8 per group). Five animals were used as a control group (without AP). Specimens were submitted to histological processing for description of the inflammatory process, immunostaining for the presence/absence and localization of IFI16 and IFN-α/β receptors (qualitative and semi-quantitative analysis), and tartrate-resistant acid phosphatase (TRAP) histoenzimology.

Results

The results showed a gradual development of AP over the experimental times. The expression of IFI16 was noticeably more exacerbated in the experimental early period (day 2) while the lowest expression was observed in the control group (p=0.02). For IFN-α/β receptors, a higher intensity staining was observed 42 days after AP induction, that was statistically different from the control group (p=0.02). Also, the number of TRAP positive cells was higher on the later periods (days 21 and 42) (p<0.001).

Conclusion

IFI16 protein expression was highest during the early periods after apical periodontitis induction in mice teeth, whilst IFN-α/β receptors expression was highest after apical periodontitis became established.

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Protective Effects of Cannabis sativa on chemotherapy‐induced nausea

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa (C. sativa) and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (8 animals per group): Group 1: Normal control (saline i.p). Group 2: rats received cyclophosphamide (200 mg/kg i.p) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg ip) across days 1 – 7 and C. sativa (20 and 40 mg/kg sc) was administered on cyclophosphamide days 4 – 7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestina l homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5HT, dopamine and noradrenaline, as well as, decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa, also, improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.

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