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Can the onset and end of an epidemic be predicted? A SARS-CoV-2 modeling case study - News-Medical.Net

A recent study by researchers in France shows how differences in infection history and viral spread patterns are important factors in predicting the time course of a localized epidemic of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic is now well into its second wave worldwide. It is important to know when a national outbreak begins and when it may be expected to end, so that public health guidelines and non-pharmaceutical interventions (NPIs) – such as travel restrictions and national or regional lockdowns – are appropriately implemented to minimize their economic damage. A recent study by researchers in France shows how differences in infection history and viral spread patterns are important factors in predicting the time course of a localized epidemic of SARS-CoV-2. The team has published a preprint of their findings on the medRxiv* server. Any epidemiological prediction or inference is most reliable when buttressed by large numbers, since this compensates for or cancels out the inter-individual differences that are invariably present. Most infectious disease models rely on the deterministic approach, assuming a large initial number of infected hosts cross the ‘outbreak threshold.’ This, of course, is not true at the start and end of an epidemic. Study aims The current study examined an outbreak of COVID-19 outside China, so as to allow for the detection of some cases before the reported start, due to importation. Hidden viral spread may also occur before the larger epidemic is observed, as was seen from genome sequencing data obtained in Washington state, USA. The team also analyzed the period over which strict control measures would be needed to bring the prevalence down to below the required thresholds. This should be estimated, including superspreading events and other sources of heterogeneity, to accurately predict the end of an epidemic. The pandemic has led to several mathematical models being published, which depend on the basic reproduction number R0, and individual differences. Stochastic modeling is also important to examine what role superspreading events play, and how this affects control measures. Study models The original discrete stochastic (DS) model proposed by the current study accounts for individual differences in host transmission on the same day following infection, by using a distributed serial interval rather than a single value. Variability in transmission patterns is also accounted for. The researchers aimed to understand how exactly these factors affected the estimated start and end dates of a national outbreak, taking France as an instance. The researchers used several different models to test their parameters, in addition to the DS model. This included the non-Markovian SEIRHD model, and a classical deterministic Markovian model. Origin of the epidemic wave The researchers found that the median delay from the first imported case to the occurrence of 100 deaths a day was 67 days, indicating that in such a case, 93% of outbreaks would continue spreading until they reached this threshold. The impact of superspreading events was a small reduction in the median delay to 64 days, but about 75% of the simulated outbreaks died out before reaching a point at which 100 deaths occurred in a day. With the SEIRHD model, the median delay was 63 days, for both the deterministic and the stochastic implementation. As expected, however, this model cannot properly capture the data. A deterministic non-Markovian model also produced the same median delay. The estimates are not affected significantly by a reduction in serial interval distribution. However, the delay is reduced by eight days if the number of imported cases at the beginning is increased from one to five on the same day, but not if, more realistically, the increase is spread over some days. The researchers did not find any significant change in the period required for an epidemic to reach a point of 100 deaths per day, either with stochasticity or non-Markovian changes. Superspreading events could introduce a slight delay, as could the number of imported cases at the beginning. The end of the epidemic The researchers also found that 95% extinction probability was reached only with at least 7.6 months of lockdown, if superspreading events are ignored. When individual heterogeneity is considered, the period is slightly reduced to 6.9 months. Transmission heterogeneity is a parameter that indicates non-transmission by most infected people. Rebound risk Accounting for the period over which a newly infected individual can cause secondary cases, the researchers found that once lockdown is relaxed, the probability of new cases is sharply reduced. Here again, transmission heterogeneity reduces the rebound risk by limiting the number of possible transmissions. Changing the date of lockdown initiation The researchers found that advancing the lockdown by one month after the onset of the epidemic wave would reduce the time to extinction by 96 days and 92 days – that is, by almost 50% – without and with transmission heterogeneity, respectively. Thus, the earlier the intervention, the bigger the impact is. If this was only advanced by two weeks, the time to extinction was 95% likely to be within 188 days, without transmission heterogeneity, and 169 days with it, resulting in a reduction of 41 days of lockdown. As the restrictions relax following the first 55 days of total lockdown, the estimated periods increase. For instance, the time to extinction increases much less if the lockdown initiation date is February 17, compared to two weeks later or one month later. Since the spread of the epidemic would not be as extensive in this case, the most important period would be the first 55 days of the lockdown. What are the implications? The greatest impact of randomness in the model parameters is likely to be at the beginning and end of an epidemic, because of the low prevalence of infection and the effect of stochasticity on viral spread patterns. The study estimates that the first wave of the epidemic began on January 16, which agrees with the data obtained from genomic sequencing. The researchers point out that the latter estimate is also uncertain, and sampling incomplete, in France. The effect of superspreading was to speed up the initial phase of the epidemic, with the date of origin being January 19, because of the role played by superspreading in triggering persistent outbreaks. The study confirms that cases may be detectable far in advance of the earliest chain of transmission linked to an epidemic. The ability to estimate the period of lockdown restrictions required for the eradication of the epidemic can also help public health authorities to formulate appropriate policies, and to intervene early. Finally, it draws attention to the risk of rebound in relation to the period of lockdown. Further studies will help understand the impact of superspreading events in the spread of COVID-19. *Important Notice medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

A traditional Chinese medicine could help treat COVID‐19 symptoms - News-Medical.Net

A team of researchers in China – at Guangzhou University of Chinese Medicine and Yunnan University of Chinese Medicine – recently explored the therapeutic properties of Yinqiao powder in treating COVID-19 symptoms. Their findings were recently published in Ph…

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in Wuhan, China, in December 2019, causing the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is a highly transmissible disease that has spread to over 191 countries and territories around the world. To date, 97.61 million cases have been confirmed and over 2 million people have lost their lives. Whole-genome sequencing and phylogenetic analysis indicate that SARS-CoV-2 is related to the SARS bat virus. However, the main and intermediate routes SARS-CoV-2’s jump to humans remains unclear; researchers have continued to explore what, when and how this zoonosis occurred. Meanwhile, clinical trials are ongoing to find effective antiviral drugs or prophylactic vaccines for COVID-19. A team of researchers in China – at Guangzhou University of Chinese Medicine and Yunnan University of Chinese Medicine – recently explored the therapeutic properties of Yinqiao powder in treating COVID-19 symptoms. Their findings were recently published in Phytotherapy Research. Can traditional Chinese medicine help treat COVID-19 symptoms? Traditional Chinese medicine (TCM) has a comprehensive system that plays a key role in the prevention and treatment of infectious diseases. Several provinces in China have been following TCM-based prevention and treatment plans for COVID-19, with remarkable results. After more than 2,000 years of development, traditional Chinese medicine (TCM) has formed a comprehensive and unique system from disease diagnosis to prognosis, which plays an important role in the prevention and treatment of human infectious diseases.” Based on big data analysis, it was found that Yinqiao powder is the basic formulation used to treat the early stages of COVID-19. According to pharmacological studies, Yinqiao powder has an antitussive and expectorant effect, alleviates acute lung injury, improves lung function, relieves pulmonary fibrosis, improves immune response to viruses, and eases the adverse reactions of modern drugs. Active ingredients in Yinqiao powder and their key functions The active ingredients in Yinqiao powder were identified using high-performance liquid chromatography analysis are rutin and hesperidin. Rutin binds to the main protease (3CLpro) of SARS-CoV-2 with more affinity than drugs such as remdesivir, chloroquine, and hydroxychloroquine. Studies show that rutin may inhibit SARS-CoV-2 by downregulating interleukin-6 (IL-6). Hesperidin, on the other hand, has been found to have an inhibitory effect on human angiotensin-converting enzyme 2 (ACE2), GRP78, TMPRSS2, and AT1R receptors and hence may be effective in the treatment of COVID-19. Although some bio-active substances are being investigated for their ability to treat COVID-19, in-depth studies of the ability of Yinqiao powder to treat COVID-19 are sparse. Exploring the active ingredients and potential mechanisms of Yinqiao powder in COVID-19 treatment The researchers recently used several techniques to analyze the active ingredients, targets, and possible mechanisms of Yinqiao powder in COVID-19 treatment. They used techniques such as target selection and DisGeNET scoring, protein–protein interaction network construction, drug–ingredient–gene network construction, molecular docking, and surface plasmon resonance (SPR) analysis, gene tissue analysis, geneontology (GO) functional analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. The researchers also predicted the therapeutic impact of Yinqiao powder with the help of TCManti-COVID-19 (TCMATCOV). Yinqiao powder has an intervention score of 20.16. In our study, 30 ingredients of Yinqiao powder were screened from the TCMSP database based on the OB and DL, and five ingredients, namely hesperetin, eriodictyol, luteolin, quercetin, and naringenin, were verified by LC‐MS analysis.” Luteolin, eriodictyol, quercetin, and naringenin were the other effective active ingredients present in Yinqiao powder that act against COVID-19. The hub-proteins in Yinqiao powder were IL-6, tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), and tumor protein P53 (TP53). Drug–ingredient–gene target network analysis revealed that drugs such as Jinyinhua, Jingjiesui, Lianqiao, Bohe, Jiegeng, and Gancao have the ability to improve the symptoms of COVID-19 patients. Drug–ingredient–gene target network analysis revealed that Jinyinhua, Lianqiao, Jingjiesui, Jiegeng, Bohe, and Gancao have potential anti-COVID-19 effects. Some of these drugs have been confirmed to have obvious advantages in improving the clinical symptoms of COVID-19 patients According to the authors, the potential mechanisms by which Yinqiao powder can help treat COVID-19 are the TNF signaling pathway, Toll-like receptor signaling pathway, T-cell receptor signaling pathway, and MAPK signaling pathway. They believe that this study offers a new perspective for finding potential drugs for treating COVID-19. Although these signaling pathways were related to the occurrence and development of COVID‐19, there is currently no experiment to further verify the specific role of Yinqiao powder against COVID‐19 in these signaling pathways.”

• Lin, Haixiong, Xiaotong Wang,  Minyi Liu, Minling Huang, Zhen Shen, Junjie Feng, Huijun Yang, Zige Li  Junyan Gao and Xiaopeng Ye. (2021) Exploring the treatment of COVID‐19 with Yinqiao powder based on network pharmacology. Phytotherapy Research. https://doi.org/10.1002/ptr.7012, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7012.

Pfizer-BioNTech vaccine shows reduced neutralization potential against SARS-CoV-2 B.1.1.7 spike variant - News-Medical.Net

Researchers in the UK have conducted a study assessing the efficacy of the Pfizer-BioNTech COVID-19 vaccine BNT162b2 against the new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COV…

Researchers in the UK have conducted a study assessing the efficacy of the  Pfizer-BioNTech COVID-19 vaccine BNT162b2 against the new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19). The new B.1.1.7 variant, which has higher transmission potential than previous SARS-CoV-2 strains, recently emerged in the UK, South Africa and Brazil and has now been identified in 50 countries. The emergence of B.1.1.7 has triggered concerns over whether the vaccines that are currently being rolled out in an effort to control the COVID-19 pandemic will still be effective against SARS-CoV-2. Now, Ravindra Gupta from the University of Cambridge and colleagues have demonstrated evidence of a reduced antibody response against the B.1.1.7 mutant among individuals (aged between 64 and 85) three weeks after they received the first dose of the Pfizer BioNTech vaccine BNT162b. However, the researchers say the reductions were expected, that vaccines should still retain good activity and that vaccination is still a priority. Nevertheless, “further work is needed to establish the impact of these observations on real-life vaccine efficacy,” adds the team. A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review. Vaccines have quickly emerged, but so have variants Since the COVID-19 outbreak first began in Wuhan, China, in late 2019, the rapid spread of SARS-CoV-2 has culminated in a global pandemic that has had scientists racing to develop vaccines against the causative agent SARS-CoV-2. The unprecedented scientific response to this global challenge has led to three vaccines now being licensed for use, namely the Pfizer BioNTech BNT162b2 vaccine, the Moderna mRNA-1273 vaccine, and the Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine. These vaccines all target a protein expressed on the surface of SARS-CoV-2 called spike, which is the main structure the virus uses to bind to and infect the cell. However, these vaccines were designed against the Wuhan strain isolated in 2019. Since then, the virus has evolved to optimize its infectivity and evade being targeted by drugs and the immune system. Now, SARS-CoV-2 transmission has been confounded in many areas of the world by the recently emerged B1.1.7 variant, which has now been identified in 50 countries. Concerns are growing as to whether the Pfizer BioNTech, Moderna, and Oxford-AstraZeneca vaccines will be effective against this new variant. Furthermore, vaccine supply is limited, and many governments have had to extend the interval time between first and second doses in order to expand vaccine coverage. “Information on vaccine-elicited responses in real-world settings outside of highly selective clinical trials is important,” says Gupta and colleagues. “It is unclear whether real-world neutralizing antibody titers will follow those in clinical trials, particularly in elderly persons, and how this will be impacted by mutations in strains such as B1.1.7.” What did the researchers do? Gupta and colleagues assessed immune responses induced three weeks following one dose of the Pfizer BioNTech vaccine BNT162b2 vaccine among 23 individuals who have received the first dose as part of vaccine rollout in the UK. The team also tested neutralizing antibody responses against pseudoviruses engineered to express wild-type spike protein or the three key mutations present in B.1.1.7 (deletion 69/70, N501Y, A570D). In addition, the team tested a panel of sera from eleven individuals who had recovered from SARS-CoV-2 infection. The study cohort had a median age of over 80 (82 years), in line with the targeting of this age group in the initial UK vaccine rollout. What did the study find? The team reports that titers of anti-spike immunoglobulin G (IgG) correlated well with neutralization responses. The data showed that ant-spike IgG antibody titers were much higher among vaccinated individuals than among healthy controls and were similar to those seen among recovered individuals. However, there was an almost 100-fold variation in IgG responses among the vaccinated participants. Those older than 80 years exhibited significantly reduced IgG responses and lower neutralization potency than those younger than 80. “This may or may not be compensated for by the second dose and it will be important to follow all participants over the following months for measurement of neutralization activity as well as data on re-infection,” say the researchers. How did the three B.1.1.7 mutations affect immune responses? The three B.1.1.7 mutations in spike did not significantly impact neutralization titers among recovered individuals or people who had been vaccinated. Next, the team engineered a pseudovirus to express spike protein that included the full set of mutations present in the B.1.1.7 variant (del69/70, del 144/145, N501Y, A570D, P681H, T716I, S982A, D1118H). When sera were tested against this full set of B.1.1.7 spike mutations, neutralization titers were reduced among the vaccinated individuals. Among 15 individuals who had exhibited neutralization activity three weeks following vaccination, 10 showed evidence of a reduced antibody response against the B.1.1.7 mutant. Overall, the reduction in efficacy was less than 3-fold, while the most significant reduction was around 6-fold, and the median reduction was 3.85-fold. Vaccination remains a priority, but further research is needed “These modest changes are what we expected to see given the mutational profiles. Vaccines should still retain good activity and vaccine coverage is a priority,” write the researchers. However, further research is needed to investigate the impact of these observations on real-life vaccine efficacy, says Gupta and colleagues “Other variants also need to be tested against vaccine sera, some with more concerning mutations such as E484K and K417N that have been shown to impact neutralization by monoclonal antibodies or convalescent sera,” concludes the team. *Important Notice medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Study: Vast majority of U.S. infants may be suffering from gut microbiome deficiency - News-Medical.Net

A new peer-reviewed study reveals that the vast majority of U.S. infants may be suffering from a substantial deficiency in an important bacterium key to breast milk utilization and immune system development, as well as protection against gut pathogens linked …

A new peer-reviewed study reveals that the vast majority of U.S. infants may be suffering from a substantial deficiency in an important bacterium key to breast milk utilization and immune system development, as well as protection against gut pathogens linked to common newborn conditions such as colic and diaper rash. According to the study published today in Scientific Reports, approximately nine out of ten infants are missing Bifidobacterium longum subsp. infantis (B. infantis) in their gut microbiome, a type of bacteria that plays a critical role in infant health and development. This specific type of gut bacteria has been widely documented as providing the most beneficial impact to infant gut health and possessing the ability to fully unlock the nutritional benefits of breast milk. The study is the largest to date to benchmark the widespread deficiency in gut bacteria among U.S. infants, and the resulting diminished function of their gut microbiomes. The vast majority of infants are deficient in this key gut bacterium from the earliest weeks of life, and this is completely off the radar for most parents and pediatricians, alike. This study provides the clearest picture to date of just how widespread this issue is and highlights the need to address B. infantis deficiency in the infant gut right from the start." Karl Sylvester, MD, Study Co-Author, Professor of Surgery and Pediatrics and Associate Dean of Maternal Child Health Research, Stanford University B. infantis had been widely considered one of the most prevalent bacteria in the GI tracts of infants, accordingly its absence from such a wide swath of outwardly healthy infants is surprising. When present, B. infantis breaks down carbohydrates in human breast milk called human milk oligosaccharides (HMOs) which are otherwise inaccessible to the infant. In fact, B. infantis differs from other Bifidobacteria species in its unique adaptation to human breastmilk and specifically in its ability to break down HMOs into usable nutrients. Perhaps more importantly, B. infantis is increasingly linked to the development of the infant immune system, protecting the infant intestinal tract from potentially dangerous bacteria as well as lower incidence of common childhood conditions like colic and diaper rash. Researchers also discovered that potentially dangerous bacteria comprised, on average, 93 percent of all bacteria in the infant gut microbiome, with the most prevalent bacteria being Escherichia coli (E. coli), Klebsiella pneumoniae, Salmonella, Streptococcus, Staphylococcus and Clostridium difficile (C. diff). Many of these bacteria are known to harbor genes related to antibiotic resistance. In fact, a total of 325 antibiotic resistant genes were found in the gut bacteria, with more than half (54 percent) of those genes being those that confer bacterial resistance to multiple antibiotics. "The infant gut is essentially a blank slate at birth, and rapidly acquires bacteria from mom and the environment. We were surprised not only by the extensive lack of good bacteria, but the incredibly high presence of potentially pathogenic bacteria and an environment of antibiotic resistance that appears to be so widespread," said Dr. Sylvester. "The infant gut microbiome in the U.S. is clearly dysfunctional, and we believe this is a critical factor underpinning many of the infant and childhood ailments we see today across the country." Study methodology Researchers collected fecal samples from 227 infants under 6 months of age during pediatrician office visits in five different states (CA, GA, OR, PA, SC). The samples were analyzed for bacterial type and amount present, which represents the bacterial composition in the infants' guts. The fecal samples were assessed for bacterial ability to fully use human breast milk -- a hallmark of the presence of health-promoting bacteria, as well as for the presence of antibiotic-resistant genes in the bacteria. The researchers did not include samples from infants with jaundice, those who were actively undergoing antibiotic treatment, or those diagnosed with problems with absorbing carbohydrates in their intestine, due to the impact such conditions may have on the ability of the infant gut to carry out normal processes. Newborn gut and the impact on newborn health The infant gut requires the presence of thousands of different bacteria to perform different functions - from biological processes to the development of biological structures and systems. Infant gut dysbiosis is marked by a substantial imbalance between beneficial and potentially pathogenic bacteria in the GI tracts of newborn babies. There has been a strong evidence characterizing a substantial loss of Bifidobacteria in the infant gut over the past 100 years, with research pointing to numerous factors including increased C section delivery, increased use of antibiotics and increased use of infant formula. As a result of the loss of B. infantis, the infant gut is at greater risk for negative consequences including suboptimal access to the full value of human breast milk, compromised immune system development, an increase in harmful gut pathogens due to increased gut pH, and negative impact on the infant's intestinal wall. Evolve BioSystems, Inc. Casaburi, G., et al. (2021) Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States. Scientific Reports.doi.org/10.1038/s41598-020-80583-9.

Study examines association between gut mycobiome and Parkinson’s disease - News-Medical.Net

The bacterial gut microbiome is strongly associated with Parkinson's disease (PD), but no studies had previously investigated he role of fungi in the gut.

The bacterial gut microbiome is strongly associated with Parkinson's disease (PD), but no studies had previously investigated he role of fungi in the gut. In this novel study published in the Journal of Parkinson's Disease, a team of investigators at the University of British Columbia examined whether the fungal constituents of the gut microbiome are associated with PD. Their research indicated that gut fungi are not a contributing factor, thereby refuting the need for any potential anti-fungal treatments of the gut in PD patients. Several studies conducted since 2014 have characterized changes in the gut microbiome. Most existing studies, however, employ bacterial-specific sequencing. To date, a potential role for the fungal constituents of the gut microbiome, also known as the "mycobiome," has remained unexplored." Silke Appel-Cresswell, MD, Lead Investigator, Pacific Parkinson's Research Centre and Djavad Mowafaghian Centre for Brain Health and Division of Neurology, Faculty of Medicine, University of British Columbia In order to investigate whether the fungal constituents of the gut microbiome are associated with PD researchers enrolled 95 PD patients and 57 controls from the Pacific Parkinson's Research Centre (PPRC) at the University of British Columbia. Participants provided a single fecal sample and completed a two-hour study visit during which their PD symptoms were assessed. Analysis determined that the fungal microbiome in PD did not essentially differ from that of matched controls, and there were no strong associations between gut fungi and PD symptoms. Fungi were very sparse among participants' fecal microbiomes. After filtering, 106 of the 152 participants (64/95 PD and 42/57 control) remained for downstream compositional analysis; the remainder had virtually no detectable fungal genomic content. Most of the genera identified were environmental or dietary in origin. Saccharomyces was by far the most dominant fungal genus detected. Although these investigations did not reveal any significant role for gut fungi in PD, interestingly, lower overall fungal abundance (relative to bacteria) in the PD gut were observed, which might reflect a less hospitable environment of the gut in PD. This paper plays an important role by answering the call by the PD research community and funding organizations to publish negative results, crucial to avoid investing precious research funding into likely futile endeavors and providing a more balanced reflection of data in the field. "The data are an important piece in the puzzle of understanding the overall role of the gut microbiome in PD," continued Dr. Appel-Cresswell. "PD patients can rest assured that gut fungal overgrowth, or dysbiosis, is likely not a contributing factor to any of their PD symptoms, both motor and non-motor." "The gut microbiome in PD continues to be an exciting field of research where we are just at the beginning of unraveling potential mechanisms. It will be important to publish negative results as well as positive findings along with detailed methods to have a realistic reflection of the data in the literature to accelerate discovery," she concluded. PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age. In recent years, more attention has been given to the gut as a key player in the initiation and progression of PD. IOS Press Cirstea, M.S., et al. (2020) The Gut Mycobiome in Parkinson’s Disease. Journal of Parkinson's Disease.doi.org/10.3233/JPD-202237.

Researchers discover Important Cause Of Preeclampsia - News-Medical.Net

Despite being the subject of increasing interest for a whole century, how preeclampsia develops has been unclear - until now.

Despite being the subject of increasing interest for a whole century, how preeclampsia develops has been unclear - until now. Researchers believe that they have now found a primary cause of preeclampsia. We've found a missing piece to the puzzle. Cholesterol crystals are the key and we're the first to bring this to light." Gabriela Silva, Researcher Silva works at the Norwegian University of Science and Technology (NTNU) Centre of Molecular Inflammation Research (CEMIR), a Centre of Excellence, where she is part of a research group for inflammation in pregnancy led by Professor Ann-Charlotte Iversen. More effective treatment possible The findings are good news for the approximately three per cent of pregnant women in Norway who get this disease. Worldwide, preeclampsia is a leading cause of illness and death in both mother and fetus. In a preeclamptic pregnancy, the placenta does not develop properly, and the baby sometimes also receives too little nutrition. The symptoms of preeclampsia are often mild, but in some cases the condition becomes so severe that the baby needs to be delivered prematurely. Preeclampsia does not disappear until the baby is born. Since no one has understood why the condition occurs, the current treatment is to monitor and alleviate the symptoms. Silva believes that future treatment will now become more effective. Cholesterol checked in uterine wall and placenta "A pregnancy is actually a kind of natural inflammatory condition, and in the case of preeclampsia, the inflammation has become too strong and leads to disease," Silva says. Women who have had preeclampsia have an increased risk of developing cardiovascular disease later in life. It was precisely this connection that led the researchers to choose to examine cholesterol in pregnant women with preeclampsia. Cholesterol is a major cause of cardiovascular disease. Cholesterol crystals are found in plaque that clogs blood vessels. The crystals are formed when bad cholesterol accumulates in the blood vessel walls. Studies have shown that cholesterol crystals are a particularly powerful initiator of inflammation in the body and can cause the blood to clot. When the immune response runs wild Cholesterol crystals are identified as harmful substances in the body that need to be cleared out. But the defense cells that come in to do the job aren't able to break them down. They call for reinforcements, and more immune cells come in, to no avail. The immune response runs wild, and the inflammatory process escalates. Silva found that the inflammation was at its highest in the region called the maternal-fetal interface, where the mother's cells come into direct contact with fetal cells. This happens in the placenta and uterine wall. "This direct contact means that the inflammation directly affects the communication between mother and fetus and contributes to even greater inflammation in the mother," says Silva. All pregnant women have high cholesterol levels Cholesterol levels are high in all pregnant women, because both the foetus and the placenta need cholesterol. But levels were even higher in women with preeclampsia. They also had much more of the bad cholesterol, which is the type of cholesterol found in people who are at high risk for cardiovascular disease. Silva went to great lengths to solve the riddle. She used tissue samples from a biobank that the research group at CEMIR has built up, and included placenta samples from 90 women with preeclampsia obtained immediately after birth. The researchers therefore had tissue samples from both the uterine wall and the placenta. The samples were examined using advanced microscopes. It has taken years of research to arrive at the result. Women at risk should have their cholesterol checked Future treatment for preeclampsia may simply include cholesterol-lowering medications, such as statins, but further research is needed to clarify their effects. "Some women have an increased risk of preeclampsia right from the start. They should be followed up with a cholesterol check. This isn't done regularly today, but it should be done regularly in the future. The use of statins during pregnancy is not recommended now, but several clinical studies are looking more closely at this and are showing that pravastatin, for example, can be safe to use during pregnancy," says Silva. Norwegian University of Science and Technology (NTNU) Silva, G.B., et al. (2020) Cholesterol Crystals and NLRP3 Mediated Inflammation in the Uterine Wall Decidua in Normal and Preeclamptic Pregnancies. Frontiers of Immunology.doi.org/10.3389/fimmu.2020.564712.

ACE2 and furin levels linked to higher levels of inflammation in smokers with COVID-19 - News-Medical.Net

A new study reports the level of ACE2 and furin, two enzymes that are intimately linked to infection with SARS-CoV-2, the causative agent of COVID-19.

Many risk factors for adverse outcomes in coronavirus disease 2019 (COVID-19) have been identified, including obesity, heart disease and diabetes mellitus. Smoking is involved in aggravating or contributing to the disease process in several conditions, including infections. A new preprint on the medRxiv* server reports the level of angiotensin-converting enzyme 2 (ACE2) and furin, two enzymes that are intimately linked to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. The ACE2 receptor COVID-19 is a primarily pneumonic condition, with most terminally ill patients displaying signs of acute respiratory failure. Often, however, this is linked to multi-organ dysfunction with underlying vascular damage and thrombosis. The virus is thought to enter through the host membrane receptor, ACE2, which is found at high levels in lung epithelium. Among the various types of respiratory cells, the type II pneumocytes, goblet cells, epithelial and ciliated cells of the nose, and the cells of the oral mucosa, are found to have the highest expression of this receptor. ACE2 also has physiological activity, since it converts the vasoactive hormone angiotensin 2 to vasodilatory metabolites, thus preventing the harmful effects of the former molecule. Despite the intense focus on this receptor with the pandemic's onset, it is still unclear as to the change induced in ACE2 by the virus. There are two possibilities: either its activity is modulated, or its expression is modified. Smoking and COVID-19 risk Several early reports have suggested that smokers face a lower risk from COVID-19, but this conclusion is now suspect, because of more recent data. For instance, a meta-analysis of 15 studies, including over 2,400 people, showed that COVID-19 was likely to be more severe and deadly in patients who currently smoke. Another study showed that the rate of progression of COVID-19 is almost double in smokers compared to that in non-smokers. The researchers aimed to identify a possible association between smoking and systemic inflammatory markers, and between the sex of the individual and the expression of ACE2 and furin. ACE2 levels have been suggested to be higher in the lungs of smokers, but this has not been studied with respect to the risk of development and severity of COVID-19. The researchers obtained serum samples from patients with COVID-19 and those who had recovered from the infection, with and without a history of smoking. Smokers with COVID-19 have higher levels of inflammatory cytokines Acute COVID-19 is known to be characterized by high levels of inflammatory mediators. The current study therefore looked at 27 cytokines and chemokines. They found that inflammatory cytokines such as IL-1α, IL-8, IL-2, VEGF and IL-10, were expressed at higher levels in patients with COVID-19 relative to controls without the infection. Among COVID-19 patients with a history of smoking, there was a marked increase in the production of certain specific cytokines, such as IFN-γ, 43 Eotaxin, MCP-1 and IL-9, compared to those who did not smoke. Interestingly, the latter subset of cytokines is associated with hyperactive inflammation, suggesting that smoking worsens the severity of COVID-19. Smoking increases ACE2 levels in COVID-19 patients SARS-CoV-2 entry into host cells is mediated by ACE2, which was increased in the serum of COVID-19 patients compared to the controls. However, the researchers also found higher levels in the serum of COVID-19 patients with a past or current history of smoking, relative to controls (non-smokers). Males had higher ACE2 levels than females. “Our results show that age and smoking status play a crucial role in governing the COVID-19 related enzyme activity in human subjects.” Smoking increases furin levels in COVID-19 patients who smoke Furin levels in serum were also higher in COVID-19 patients with a history of smoking, as above, compared to non-smokers with COVID-19. Males showed a trend towards increased furin levels. Furin is a proprotein convertase that is crucial to the mechanism of SARS-CoV-2 infection. COVID-19 associated with changes in lipid profile Lipid mediators such as prostaglandins are often altered during infections, and may decrease or exaggerate the associated inflammation. The researchers showed the presence of a discriminatory lipid profile among COVID-19 patients vs. those who had recovered from the infection. The affected lipid markers include PGF2α, HETEs, LXA4 and LTB4 – from prostaglandin, hydroxyeicosatetraenoic acid, lipoxin and leukotriene pathways, respectively. However, smoking did not appear to be linked to changes in these lipid pathways. What are the implications? Overall, the study shows that inflammatory molecules are markedly higher in smokers with COVID-19 relative to controls. The researchers also demonstrated increased levels of cytokines and furin in patients with active COVID-19 relative to recovered patients. These findings suggest the feasibility of developing these molecules as biomarkers to stratify COVID-19 patients by disease severity, to optimize their management. As hospitals and healthcare systems worldwide are increasingly stretched, these sorts of biomarkers can help them prioritize care and resources through more accurate disease outcome predictions. The study suggests that COVID-19 is associated with a distinctive profile of systemic inflammatory markers and molecules that facilitate or mediate viral-host interactions. These are adversely impacted by smoking, indicating a higher risk of poor outcomes among COVID-19 patients who have a history of smoking. Further research could tease out the effects of vaping and the perceived persistence of high ACE2 levels in recovered patients, which may underlie the ‘long-haul’ symptoms being reported in many COVID-19 convalescents. *Important Notice medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

SPT Labtech announces acquisition of Apricot Designs - News-Medical.net

SPT Labtech announces the acquisition of Apricot Designs Inc., headquartered in Covina, California.

SPT Labtech, a global leader in the design and development of automated instrumentation and consumables for life science applications, announces the acquisition of Apricot Designs Inc., headquartered in Covina, California. Apricot Designs has established a 30-year track record supporting increasingly complex and evolving laboratory research requirements with the design and manufacture of multichannel micro-volume pipettors and sample preparation devices. The acquisition allows SPT Labtech to strategically expand its range of liquid handling technologies as part of its broader portfolio of innovative automation solutions for drug discovery, structural biology, genomics, cryo-EM, sample management, and biobanking. We are delighted to welcome Apricot Designs to the SPT Labtech group. The company's liquid handling technology products seamlessly complement our existing portfolio of high-performance positive displacement instruments. The addition reflects our continued commitment to accelerating scientific research by maximizing our customers' productivity. The powerful combination of technologies and application know-how will enable us to streamline end-to-end workflows and serve a wider range of research applications." Patrick Bennett, Group CEO at SPT Labtech The deal further strengthens SPT Labtech's global footprint through Apricot Designs' significant hubs in California, USA, and Asia. Felix H. Yiu, CEO of Apricot Designs, added, "We are delighted to join SPT Labtech, a company with an impressive reputation for creating innovative, automated solutions for life sciences. We are confident that customers will benefit from the partnership's combined product capabilities, industry-leading applications and technical support, and enhanced infrastructure." SPT Labtech continues to strengthen its position as a global leader in the life sciences market with automated solutions that empower scientists and increase productivity. About SPT Labtech SPT Labtech makes products that transform the way scientists work. For nearly two decades, our expert scientists, engineers, and business innovators have created innovative solutions for liquid handling, sample preparation, and management that help accelerate research and make a real difference to human health. We work collaboratively with our customers, building trusted relationships that enable us to deliver exceptional, personalized experiences designed for real-world challenges in the lab. For more information, please visit www.sptlabtech.com. About Apricot Designs Apricot Designs creates and manufactures multichannel micro-volume pipettors, disposable pipette tips, and solid-phase extraction and sample preparation devices for markets worldwide. For 30 years, the company has provided accurate, precise, and affordable liquid handling technology and laboratory automation solutions to life sciences customers around the world.

Pharmacists play key role in managing medication-based therapies for older patients - News-Medical.Net

Pharmacists play an important role in managing medication-based therapies for older community-dwelling patients, according to a study published in the British Journal of Clinical Pharmacology.

Pharmacists play an important role in managing medication-based therapies for older community-dwelling patients, according to a study published in the British Journal of Clinical Pharmacology. In the study of patients aged 65 years and older who came to a pharmacist-led outpatient clinic at a general hospital in Beijing, China between 2016 and 2018, pharmacists were helpful not only for identifying and solving drug-related problems, but also for improving measures such as blood pressure and cholesterol, and for reducing the cost of medications for patients. To the best of our knowledge, this study was the first to evaluate the outcomes of pharmacist-led medication therapy management services in ambulatory elderly patients in mainland China." Study Authors Wiley Wang, X., et al. (2021) Impact of pharmacist‐led medication therapy management in ambulatory elderly patients with chronic diseases. British Journal of Clinical Pharmacology. doi.org/10.1111/bcp.14709.

Arthritis drug is no better than standard care in improving severe COVID-19 outcomes, shows new trial - News-Medical.Net

Adding the arthritis drug tocilizumab to standard care for patients in hospital with severe or critical covid-19 is no better than standard care alone in improving clinical outcomes at 15 days, finds a new trial published by The BMJ today.

Adding the arthritis drug tocilizumab to standard care for patients in hospital with severe or critical covid-19 is no better than standard care alone in improving clinical outcomes at 15 days, finds a new trial published by The BMJ today. There was an increased number of deaths at 15 days in patients receiving tocilizumab, resulting in the trial being stopped early. Today's results contradict earlier observational studies suggesting a benefit of tocilizumab. However, observational effects are limited by a high risk that they may be due to other unknown (confounding) factors - and some studies have not yet been peer-reviewed or published in a medical journal. A randomized trial assessing tocilizumab in critically ill patients with covid-19 (REMAP-CAP) published as a preprint earlier this month, found a beneficial effect of the drug on days free from organ support within 21 days and mortality. Reasons for these apparently contradictory effects, for example, differences between patients' characteristics, need to be assessed in future analysis, say the researchers. Tocilizumab blocks a specific part of the immune system (interleukin 6) that can go into overdrive in some patients with covid-19. Doctors think this might help lessen the body's inflammatory response to the virus and avert some of the more dire consequences of the disease, but its effects are not well defined. To test this theory, researchers based in Brazil conducted a randomized controlled trial comparing tocilizumab plus standard care with standard care alone in patients admitted to hospital with severe or critical covid-19. Their findings are based on 129 relatively young adults (average age 57 years) with confirmed covid-19 at nine hospitals in Brazil between 8 May and 17 July 2020. Patients were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two chemicals linked to inflammation in their blood. Patients were randomly divided into two groups: 65 received tocilizumab plus standard care and 64 received standard care alone. Other potentially important factors, such as underlying conditions and use of other medication, were taken into account and all patients were monitored for 15 days. By day 15, 18 (28%) patients in the tocilizumab group and 13 (20%) in the standard care group were receiving mechanical ventilation or died. Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group. The increased number of deaths in the tocilizumab group raised safety concerns and the trial was stopped early. In both groups, deaths were attributed to covid-19 related acute respiratory failure or multiple organ dysfunction. The researchers point to some limitations including the small sample size, which affects the chances of detecting a true effect. However, results were consistent after adjusting for levels of respiratory support needed by patients at the start of the trial, suggesting that the findings withstand scrutiny. As such, the researchers conclude that in patients with severe or critical covid-19, "tocilizumab plus standard care was not superior to standard care alone in improving clinical status at 15 days and might increase mortality." And they say these results "raise questions about an anti-inflammatory approach in the treatment of covid-19 beyond corticosteroids." BMJ Veiga, V. C., et al. (2021) Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. The BMJ. doi.org/10.1136/bmj.n84.

Having plants at home had a positive influence on emotional well-being during lockdown - News-Medical.Net

An international study coordinated by the Research Group for Urban Nature and Biosystems Engineering (NATURIB) from the University of Seville's Escuela Técnica Superior of Agricultural Engineering emphasizes that having plants at home had a positive influence…

An international study coordinated by the Research Group for Urban Nature and Biosystems Engineering (NATURIB) from the University of Seville's Escuela Técnica Superior of Agricultural Engineering emphasizes that having plants at home had a positive influence on the psychological well-being of the dwelling's inhabitants during COVID-19 lockdown. Researchers from the Hellenic Mediterranean University (Greece), the Federal Rural University of Pernambuco (Brazil) and the University of Genoa (Italy) participated in the study along with representatives from the University of Seville. This study, published in the scientific journal Urban Forestry and Urban Greening, evaluated the role played by plants at home during the first COVID-19 lockdown. The situation between the months of March and June deprived the public of the chance to enjoy open spaces and nature, and forced them to spend extended periods of time indoors. Its results have confirmed that having plants at home had a positive influence on emotional well-being during lockdown. This was agreed by 74% of the more than 4,200 respondents in 46 countries. In fact, more than half of them (55.8%) stated that they would have preferred to have more plants in their house during that difficult period. The frequency with which study participants experienced negative emotions was higher in those who stated they had no indoor plants. Those living in small or poorly lit dwellings and those who did not visit green spaces frequently before lockdown also experienced more negative emotions. Moreover, just over half of respondents (52%) reported spending more time on plant care at home during lockdown and almost two thirds (62.5%) expressed a desire to do so once normality was restored. As a result, 40% of the participants indicated that they were motivated to have more plants at home in future. University of Seville Pérez-Urrestarazu, L., et al. (2020) Particularities of having plants at home during the confinement due to the COVID-19 pandemic. Urban Forestry & Urban Greening.doi.org/10.1016/j.ufug.2020.126919.

How does SARS-CoV-2 infect brain cells? - News-Medical.Net

Researchers from the University of California San Francisco, Gladstone Institutes in the USA, and The Aga Khan University in Pakistan investigated if human neural cells can be infected by SARS-CoV-2.

Using primary human cortical tissue and cortical organoids derived from stem cells to test if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect brain cells, researchers found significant infection of the astrocytes and not much in other cell types. Some typical symptoms of coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, are fever, runny or stuffy nose, and sore throat. Although the virus infects the respiratory system and impairs respiratory functions, there have been reports of the virus infecting other organs. Many COVID-19 patients have shown neurological symptoms like headache, dizziness, short-term memory loss, seizures, and strokes. However, it is not known if these are because of direct infection of the neural tissue or a secondary consequence of the infection. Studies have shown that the virus can infect brain cells. Viral RNA and antibodies have been detected in the cerebrospinal fluid of some patients. SARS-CoV-2 can also infect the nasal epithelial cells and thus enter the central nervous system (CNS). How the virus affects developing brains is yet unknown. Infants have a greater risk for infection and adverse complications. Some studies have reported children born to positive mothers become infected within a few days of birth. However, the transmission route to newborns is still unknown. There have been a few reports of placental infection of newborns, although the impact of the virus on long-term development needs to be determined. The effect of the virus on a developing brain and impacts on brain function and health require more studies. SARS-CoV-2 infects astrocytes Researchers from the University of California San Francisco and Gladstone Institutes in the USA, and The Aga Khan University in Pakistan, investigated if human neural cells can be infected by SARS-CoV-2. They published their results in a paper in the bioRxiv* preprint server. SARS-CoV-2 Infects Astrocytes in Developing Human Cortex. A) Experimental paradigm for viral infection of human cortical tissue. Primary cortical tissue was acutely sectioned and cultured at the air-liquid interface. The next day tissue was infected with SARS-CoV-2 at MOI 0.5 and cultured for 72 hours before being collected and processed. B) SARS-CoV-2 infects GFAP+AQP4+ astrocyte cells in the developing human cortex, which are predominantly located in the subventricular zone (SVZ), where >81% of cells assayed expressed markers of astrocytes. 100% of infected cells expressed both SARS-CoV-2+ nucleocapsid (N) antibody and double-stranded (ds)RNA antibody. White arrowheads indicate dsRNA+GFAP+ infected astrocytes (dsRNA+SARS-CoV-2 N+ n=31 cells, GFAP+AQP4+ n=74 cells across two biological samples and four technical replicates). C) Few other neural types were infected, as indicated by co-labeling of SARS-CoV-2 N or dsRNA, where <8% of cells assayed expressed NEUN, a marker of cortical neurons, and <17% expressed KI67, a marker of dividing cells (NEUN n=613 cells, KI67 n=186 cells across two biological samples and four technical replicates). D) Vascular cell types can also be infected where 7% of LAMININ+ blood vessels, 13% of CD31+ endothelial cells and 18% of PDGFR-ß+ mural cells have infection. White arrowheads indicate infected vascular cells (Laminin n=269 cells, CD31 n=247 cells, PDGFRB=225 cells across two biological samples and four technical replicates). They exposed tissue slice cultures of developing human cortical samples to SARS-CoV-2 for two hours. After allowing the cells to grow for 72 hours, they tested them for the virus. They found significant infection of the astrocytes, but minimal infection on the other cell types in the neural tissue. This suggests glial cell types are more susceptible to infection compared to neuronal cell types or neuronal progenitors. The team found that blood cells were also infected, although at a lower level than astrocytes. Blood cells are present adjacent to astrocytes, suggesting this may be a route for infection of astrocytes, which are important in blood-brain barrier formation. They also explored which stages of cell development are more vulnerable to infection using cortical organoids infected with SARS-CoV-2 at early neurogenesis (week 5), peak neurogenesis at (week 10), early gliogenesis (week 16) and peak gliogenesis (week 22). They found significant infection of the astrocytes at week 22, but almost no infection occurred earlier, indicating the virus can infect astrocytes in the developing human cortex. Co-factors for brain cell infection The human angiotensin-converting enzyme 2 (ACE2) receptor is a key entry target of SARS-CoV-2 during infection. However, ACE2 is not expressed much in the human cortex, developing or adult, nor in neural tissue. Recent studies have reported other factors, such as restriction enzymes and proteases, are also involved in SARS-CoV-2 infection. The team found expression of extracellular glycoproteins, coronavirus restriction factors, and proteases like TMPRSS5 in different cortical cells among the various tissues, which may help with virus infection. In infected astrocytes, they found the presence of coronavirus receptors DPP4 and CD147. DPP4 is abundant in astrocytes before virus infection, suggesting it may be a key receptor in astrocyte reception. The ability of SARS-CoV-2 to use other extracellular glycoproteins suggests the virus can infect a variety of cell types using different receptors in many organ systems, causing severe damage. In astrocytes, although the results suggest DPP4 is a key infection-mediating receptor, if not the sole receptor. DPP4 inhibition does not eliminate infection. Other proteases expressed, like TMPRSS5, FURIN, and CTSB could be alternate modes of viral entry into the brain. Thus, the results suggest SARS-CoV-2 has the ability to infect astrocytes. Astrocytes regulate many functions in the developing and adult brain. They regulate neurotransmitter concentration and re-uptake, mediate blood-barrier function, and control neural metabolism and inflammation. Disruptions in their functioning can severely impact the brain, resulting in seizures, inability to control motor function, and even death. Although the results of the study suggest developing astrocytes, in particular, are susceptible to SARS-CoV-2 infection, even adult astrocytes are vulnerable. Further post-mortem studies of neural tissues of patients will help understand this in more detail, including furthering our knowledge of the receptors that help viral infection. *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.