Tag: 16/8/21

Categories : Diseases, Syndromes and ConditionsTags :

Human Transmission in Antibiotic-resistant Plague Outbreak

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Scanning electron micrograph of Yersinia pestis, which causes bubonic plague, on proventricular spines of a Xenopsylla cheopis flea.
 
Credit: National Institute of Allergy and Infectious Diseases/NIH


Analysing a recent outbreak of plague in Madagascar, a team of researchers uncovered evidence of human transmission of antimicrobial-resistant plague.

While COVID dominates the global awareness of infectious diseases, others are still out there, such as Yersinia pestis, which causes plague. Even though plague has been largely eradicated in the developed world, hundreds of people globally contract it each year.

When a human is infected with bubonic plague from a flea bite and it goes untreated, the infection can progress, spread to the lungs and resulting in pneumonic plague. Pneumonic plague is usually lethal if not treated quickly, and infected patients can transmit the disease to others via respiratory droplets. A team of scientists from Northern Arizona University’s Pathogen and Microbiome Institute, led by professor Dave Wagner, recently published their findings from a remarkable study involving antimicrobial resistant (AMR) plague.

Plague is considered to be a reemerging and neglected disease, particularly in the East African island country of Madagascar, which reports the majority of annual global cases. There is no vaccine for it, so preventing mortality from plague requires rapid diagnosis followed by antibiotic treatment. In Madagascar, the antibiotic streptomycin is usually the first-line treatment for plague. The researchers isolated a streptomycin-resistant AMR strain of Y. pestis from a pneumonic plague outbreak that occurred there in 2013, involving 22 cases, including three fatalities. The study was recently published in Clinical Infectious Diseases.

“By characterising the outbreak using epidemiology, clinical diagnostics and DNA-fingerprinting approaches,” Prof Wagner said, “we determined—for the first time—that AMR strains of Y. pestis can be transmitted person-to-person. The AMR strain from this outbreak is resistant to streptomycin due to a spontaneous point mutation, but is still susceptible to many other antibiotics, including co-trimoxazole. Luckily, the 19 cases that were treated all received co-trimoxazole in addition to streptomycin, and all of them survived.

“The point mutation, which also is the source of streptomycin resistance in other bacterial species, has occurred independently in Y. pestis at least three times and appears to have no negative effect on the AMR strain, suggesting that it could potentially persist in nature via the natural rodent-flea transmission cycle. However, AMR Y. pestis strains are exceedingly rare and the mutation has not been observed again in Madagascar since this outbreak.”

Source: North Arizona University

Categories : Pain ManagementTags :

Transcranial Focused Ultrasound for Chronic Pain Relief

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Source: CC0 Creative Commons

A rodent study has demonstrated the potential for transcranial focused ultrasound (tFUS) to relieve chronic pain and other symptoms.

Neuromodulation, or therapeutic stimulation of neurons with electrical energy. chemicals or potentially with acoustic waves, can amplify or dampen neuronal impulses in the brain or body to relieve symptoms such as pain or tremor.

Ultrasound is a promising non-invasive, non-surgical type of neuromodulation. It offers a temporary modulation that can be tuned for a desired effect. In this study, researchers have shown that it can be targeted at neurons with specific functions.

A team led by Bin He, PhD, professor of biomedical engineering at Carnegie Mellon University, and funded in part by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), has demonstrated the potential of a neuromodulation approach that uses low-intensity ultrasound energy, called transcranial focused ultrasound-;or tFUS. In a paper published in Nature Communications, the authors describe the use of tFUS in rodent experiments, demonstrating the non-invasive neuromodulation alternative.

Moria Bittmann, PhD, Director of the Program in Biorobotic Systems, National Institute of Biomedical Imaging and Bioengineering, said: “Transcranial focused ultrasound is a promising approach that could be used to treat forms of chronic pain, among other applications. In conditions where symptoms include debilitating pain, externally generated impulses of ultrasound at controlled frequencies and intensity could inhibit pain signals.”

The researchers designed an assembly that included an ultrasound transducer and a multi-electrode array, which records neuronal data. During experiments with anaesthetised rodents, the researchers sent acoustic pulses into the brain cortex, targeting specific neurons, while recording change in electrophysiological signals from different neuron types.

When neurons transmit signals, whether engaging the senses or controlling movement, the firing of that signal across the synapse is termed a spike. The researchers observed two types of neurons: excitatory and inhibitory neurons.

When using tFUS to emit repeated bursts of ultrasound stimulation directly at excitatory neurons, the researchers saw an elevated impulse rate, or spike. Inhibitory neurons subjected to the same tFUS energy however did not display a significant spike rate disturbance. This showed that the ultrasound signal can be transmitted through the skull to selectively activate specific neuron sub-populations, in effect targeting neurons with different functions.

“Our research addresses an unmet need to develop non-toxic, non-addictive, non-pharmacologic therapies for human use,” said Prof He. “We hope to further develop the tFUS approach with variation in ultrasound frequencies and to pursue insights into neuronal activity so that this technology has the optimal chance for benefiting brain health.”

There are many broad applications for this research. Prof He believes non-invasive tFUS neuromodulation could be used to facilitate treatment for many people suffering from pain, depression and addiction. “If we can localise and target areas of the brain using acoustic, ultrasound energy, I believe we can potentially treat a myriad of neurological and psychiatric diseases and conditions,” Prof He said.

Source: National Institute of Biomedical Imaging and Bioengineering

Categories : Medical Research & TechnologyTags :

Improvement of Cell Culture Reporting Needed

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Photo by CDC on Unsplash
Photo by CDC on Unsplash

There is an urgent need for more standardised and detailed reporting of research on mammalian cells, and for greater control over and measurement of the environmental conditions of cell cultures, according to a recent study. This will improve the precision of human physiology models and contribute to the reproducibility of research.

Researchers analysed 810 randomly selected papers on mammalian cell lines. Fewer than 700 of those, involving 1749 individual cell culture experiments, included relevant data on the environmental conditions of the media in which the cells were cultured. The analysis suggests that the relevance and reproducibility of this type of research needs significant improvement.

“Mammalian cell cultures are fundamental to manufacturing viral vaccines and other biotechnologies,” explained marine scientist, Shannon Klein. “They are used to study basic cell biology, replicate disease mechanisms and investigate the toxicity of novel drug compounds before they are tested on animals and humans.”

Though cells are cultured in controlled incubators in line with standard protocols, cells grow and ‘breathe’ over time and exchange gases with their surrounding environment. This impacts their immediate environment, and even these small changes can affect parameters like culture acidity and dissolved oxygen and carbon dioxide. These changes in turn can affect cell function, causing different conditions to that found in a living human body.

The researchers found that around half of the papers analysed failed to report the temperature and carbon dioxide settings of their cell cultures. Less than 10 percent reported the atmospheric oxygen levels in the incubator and less than 0.01 percent reported the medium’s acidity. No papers reported the dissolved oxygen or carbon dioxide in their media.

“We were very surprised that researchers largely overlooked the maintenance of environmental factors, like culture acidity, at levels relevant to the physiological body over the full course of the cell cultures, despite it being well known that this is important for cell function,” said Ph.D. student Samhan Alsolami.

The team, led by KAUST’s marine ecologist Carlos Duarte and stem cell biologist Mo Li in collaboration with developmental biologist Juan Carlos Izpisua Belmonte from the Salk Institute, who is currently a visiting professor at KAUST, recommends that biomedical scientists develop standard reporting and control and measuring procedures, in addition to employing specialised instruments for controlling the culture environments of different cell types. Additionally, scientific journals should establish reporting standards and require adequate monitoring and control of culture medium acidity and dissolved oxygen and carbon dioxide.

“Better reporting, measurement and control of the environmental conditions of cell cultures should improve how well scientists can repeat and reproduce experimental results,” said Alsolami. “More careful attention could drive new discoveries and increase the relevance of preclinical research to the human body.”

The study is published in Nature Biomedical Engineering.

Source: Medical Xpress

Categories : Cardiovascular DiseaseTags :

Lung Fibrosis Drug Pirfenidone Shines in Heart Failure Trial

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Source: Mat Napo on Unsplash

Pirfenidone, a drug to treat lung fibrosis, has shown in early trial phases that it could also help patients who suffer from a common form of heart failure.

Trialed by University of Manchester and Manchester University NHS Foundation Trust doctors and scientists, in conjunction with Liverpool Clinical Trials Centre, pirfenidone could offer a much-needed viable treatment for heart failure with preserved ejection fraction (HFpEF). The study was published in Nature Medicine.

Just under a third of 55-year-olds will develop heart failure, and 2 to 3 of every 10 people diagnosed die within a year. In about half of patients with heart failure, the forward pumping function of the heart is normal, referred to as heart failure with preserved ejection fraction (HFpEF).

While a number of processes lead to heart failure, fibrosis of the heart muscle is thought to be an important mechanism in around half to two-thirds of patients with HFpEF and is associated with adverse outcomes.

Study leader Dr Chris Miller, National Institute for Health Research Clinician Scientist at The University of Manchester, said: “Heart failure is as devastating an illness as some of the most common cancers, however its profile is much lower and treatment options for HFpEF are very limited.

“Using cardiac MRI, we were able to select patients in whom heart scarring is important. Pirfenidone then reduced that scarring.”

Pirfenidone inhibits the biological processes involved in scar formation.

The study enrolled 94 patients with heart failure, normal forward pumping function of the heart and evidence of fluid retention, randomising half to a pirfenidone treatment group and half to placebo.

Eligible patients had cardiac MRI scanning, and those who had evidence of heart scarring, as indicated by a measurement called ‘extracellular volume’. 

A second cardiac MRI was conducted a year later to measure change in heart scarring, and researchers found that extracellular volume fell by 1.21% on average in patients who took pirfenidone compared with those receiving placebo.

“Based on data from previous studies, this amount of reduction in heart scarring could translate into a substantial reduction in rates of death and admission to hospital for heart failure, however larger trials are needed to determine this,” said Dr Miller.

Additionally, fluid retention also improved in patients taking pirfenidone compared to those receiving placebo, measured using a blood test called NT-proBNP.

Dr Miller added: “Though further investigation is required, the associated improvement in fluid retention provides support for heart scarring having a causal role in heart failure and being an effective treatment target”.

The most common side effects were nausea, insomnia and rash, which are similar to that which lung patients can experience taking the drug. The results are “exciting”, Dr Miller said, but added that further trials are needed.

Source: University of Manchester

Categories : Cancer Mental HealthTags :

How do Patients Who Exit Clinical Trials Early Feel?

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Source: JD Mason on Unsplash

A new study has helped researchers understand the experiences of people who withdraw from clinical cancer trials.

Cancer clinical trials (CCTs) provide patients with an opportunity to receive experimental drugs, tests, and/or procedures that may lead to remissions. Such opportunities can be a great benefit for those who took part, but there is little known of the experiences of participants who withdraw from CCTs.

To address this, a first-of-its-kind study from the University of Pennsylvania School of Nursing (Penn Nursing) was conducted to better understand the post-trial needs of these patients and define responsible transitions when patients exit CCTs.

“Understanding the post-trial needs of patients with cancer and their families represents a measure of ethical respect of the many contributions that patients with cancer make to advancing our scientific knowledge and finding treatments that save lives,” said the study’s lead researcher, Connie M Ulrich, the Lillian S Brunner Chair in Medical and Surgical Nursing, professor of nursing, professor of medical ethics and health policy.

The study revealed three important areas:

  • Patients exiting CCTs feel intense symptoms, emotions, and awareness that their life spans are short and options seem limited.
  • The limited discussions with patients who are exiting on their immediate post-trial care needs can result in many feeling that there is no clear path forward.
  • Good communication that deliberately includes attention to post-trial needs throughout the CCT is needed to help scared and disappointed patients navigate their next steps.

The study is set for publication on the JAMA Network.

Source: University of Pennsylvania

Categories : COVIDTags :

WHO Urges Support for New COVID Origin Investigation

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Photo by Asad Photo Maldives from Pexels

The World Health Organization (WHO) has urged all countries “to put differences aside” in order to speed up investigations into the origins of the SARS-CoV-2 virus – including the unproven suggestion that it was accidentally released from laboratory.

This announcement follows a joint report into the origins of the coronavirus issued in March by the WHO and China. The UN agency, noting “insufficient scientific evidence to rule any of the hypotheses out” about the origins of the new coronavirus, insisted that to address the ‘lab hypothesis’, it needed access “to all data” in order to prevent global health threats in future.
“WHO calls for all governments to depoliticise the situation and cooperate to accelerate the origins studies, and importantly to work together to develop a common framework for future emerging pathogens of pandemic potential,” it said.

“We call on all governments to put differences aside and work together to provide all data and access required so that the next series of studies can be commenced as soon as possible.”

In a detailed statement, WHO explained the need for additional studies into “all hypotheses” about how SARS-CoV-2 made the jump from animals to humans.

Transparency call
A new independent advisory group of experts, the International Scientific Advisory Group for Origins of Novel Pathogens (SAGO), will support the project by coordinating the studies recommended in the March report, it said.

Nominations for the panel would be welcomed from all countries, WHO said, whose task would be similar to previous COVID missions to China and those launched to investigate the origins of avian influenza, Lassa virus and Ebola virus.

“This open call aims to ensure that a broad range of scientific skills and expertise are identified to advise WHO on the studies needed to identify the origins of any future emerging or re-emerging pathogen of pandemic potential,” the UN agency said.

Scientific endeavour
Noting how hard it is to identify the origin of any novel pathogen, the agency insisted that the mission “is not and should not be an exercise in attributing blame, finger-pointing or political point-scoring. It is vitally important to know how the COVID pandemic began, to set an example for establishing the origins of all future animal-human spill-over events.”

Access to sensitive information was needed for the success of the operation with “a further examination of the raw data from the earliest cases”, along with blood serum from potentially infected people in 2019, before the pandemic.

Data sharing
Data from “a number of countries” that reported finding the virus in blood samples taken in 2019 has already been shared with WHO, it noted. This included Italy, where WHO coordinated retesting of pre-pandemic blood samples outside the country.

“Sharing raw data and giving permission for the retesting of samples in labs outside of Italy reflects scientific solidarity at its best and is no different from what we encourage all countries, including China, to support so that we can advance the studies of the origins quickly and effectively,” WHO said, and restated that access to data was “critically important for evolving our understanding of science and should not be politicised in any way”.

Source: UN News