Tag: 4/7/22

Categories : Diseases, Syndromes and ConditionsTags :

New Treatment for Toxoplasmosis Could Target Parasite Cysts

On By ModernMedia
Toxoplasma gondii. Source: Wikimedia CC0

Findings from a new University of Kentucky College of Medicine study published in the Journal of Biological Chemistry could lead to a new treatment for Toxoplasma gondii, the parasite that causes toxoplasmosis.

An estimated 40 million people in the US carry the parasite T. gondii, according to the Centers for Disease Control and Prevention, but most are asymptomatic because the immune system usually keeps the parasite from causing illness. However, for women newly infected during pregnancy and anyone with a compromised immune system, toxoplasmosis can cause severe illness or even death.

In individuals with severe toxoplasmosis, cyst version of the parasite may be present within brain and muscle tissue. These cysts are responsible for causing serious disease, especially in people who are immunocompromised. While there are FDA-approved drugs to treat the symptoms of toxoplasmosis, no current therapeutics target the cyst form of the parasite.

The labs of Matthew Gentry, PhD, and Craig Vander Kooi, PhD, at UKCM and Zhong-Yin Zhang, PhD, at the Purdue Institute for Drug Discovery, collaborated to develop a drug that targets the cyst form of the parasite.

In previous research, Dr Gentry identified an enzyme in T. gondii called TgLaforin, which he hypothesised was critical in allowing the parasite to access energy from a carbohydrate storage molecule. The team developed a new drug that inhibits TgLaforin with the goal of preventing enzymes from accessing and providing energy to the parasite.

The new discovery was made possible thanks to the multidisciplinary collaboration of experts from the four labs, said Dr Gentry.

Robert Murphy, PhD, a member of the Gentry and Sinai labs, conducted initial experiments that characterised TgLaforin and provided a baseline for understanding the enzyme’s function.

Tiantian Chen, a graduate student in Vander Kooi’s lab, generated models of TgLaforin using a new program called AlphaFold2, an AI algorithm that provides valuable insights into research. Chen generated models that provided a picture of the enzyme that demonstrated TgLaforin was a unique and possible drug target.

Jianping Lin, PhD, a postdoc in Dr Zhang’s lab, then used information generated by Dr Murphy and Chen in combination with novel techniques in chemistry to generate the first version of a future anti-Toxoplasma drug.

“I was excited to find that the drug was effective against TgLaforin in test tubes and that it prevented TgLaforin from performing its normal activity against a variety of substrates, including carbohydrates,” said Dr Murphy.

The labs will next test the drug on parasites, and try to increase its potency and selectivity and adapt its chemical properties to allow for animal studies.

“This study is a great example of what Provost DiPaola consistently promotes regarding transdisciplinary research,” Dr Gentry said. “This work was a true team effort and it is very exciting to see where we take it next.”

Source: University of Kentucky College of Medicine

Categories : COVIDTags :

A Nose for COVID: Sniffer Dogs Outperform Antigen Tests

On By ModernMedia
Source: Pixabay CC0

Since the start of the COVID pandemic, dogs have been found to be able to sniff out signs of the virus in infected individuals, with some countries deploying the dogs at border posts to quickly check incoming travellers. Now, a new study published in PLOS One shows that they can be faster than rapid antigen tests, and in some instances even more sensitive than PCR testing.

Applications for medical sniffer dogs have been increasingly studied in recent years, and with the arrival of the COVID pandemic, they provided a quick, efficient way to test for SARS-CoV-2 infection. A number of studies demonstrated their effectiveness, with one study reporting a 94% accuracy. Now, this new study shows that can be as accurate as antigen tests, especially in asymptomatic individuals.

The researchers conducted a prospective cohort study in two community COVID screening centres, with 143 symptomatic and 192 asymptomatic adults. Participants were tested with two nasopharyngeal swabs (NPS), one saliva and one sweat sample. The dog handlers (and the dogs…) were blinded to the individuals’ COVID status. The dogs’ sniff tests were compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing.

Overall, 109 of the 335 participants tested positive on nasopharyngeal RT-PCR, 78 symptomatic and 31 asymptomatic. The overall sensitivity of canine detection was 97% and even reached 100% in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91%, reaching 94% for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97%), but the specificity was lower (90% versus 97%).

The researchers concluded that using dogs’ sense of smell to detect SARS-CoV-2 infection could be a speedy alternative to NPS RT-PCR when rapid testing is necessary when antigenic tests are the standard for mass screening.

Categories : AddictionTags :

Teens Have Triple the Risk of Developing Cannabis Addiction

On By ModernMedia
Cannabis plants
Photo by Harrison Haines on Pexels

Adolescents have more than three times the risk of developing a cannabis addiction than adults, although they may only have the same risk of other mental health problems related to the drug, according to a new study published in the Journal of Psychopharmacology.

The study, led by King’s College London and University College London, found that adolescent cannabis users had the same odds for higher levels of subclinical depression or anxiety than adults cannabis users, nor were they more vulnerable than adult users to cannabis’s associations with psychotic-like symptoms.

These findings build on a separate study by the same team that found adolescents were not more vulnerable to associations between chronic cannabis use and cognitive impairment.

Lead author Dr Will Lawn said: “There is a lot of concern about how the developing teenage brain might be more vulnerable to the long-term effects of cannabis, but we did not find evidence to support this general claim.

“Cannabis addiction is a real issue that teenagers should be aware of, as they appear to be much more vulnerable to it than adults.

“On the other hand, the impact that cannabis use has during adolescence on cognitive performance or on depression and anxiety may be weaker than hypothesised.

“But we also replicated previous work that if someone becomes addicted to cannabis, that may increase the severity of subclinical mental health symptoms. Given adolescents are also at a greater risk of experiencing difficulties with mental health than adults, they should be proactively discouraged from regular cannabis use.”

The findings in both papers come from the CannTeen study, which is comparing the effects of regular cannabis use among adolescents and adults, while also comparing to age-matched controls (non-users of cannabis), a completely novel design.

The study involved 274 participants, including 76 adolescents (aged 16–17) who used cannabis one to seven days per week, alongside similar numbers of adult (aged 26–29) users, and teenage and adult control (comparison) participants, who all reported their cannabis use over the last 12 weeks and responded to mental health questionnaires. The cannabis users in the study, on average, used it four times per week. The adolescent and adult users were also carefully matched on gender, ethnicity, and type and strength of cannabis.

The researchers found that adolescent cannabis users were three and a half times as likely to develop severe ‘cannabis use disorder’ (ie addiction) than adult users, a finding which is in line with previous studies. Cannabis use disorder is defined by symptoms such as cravings; cannabis use contributing to failures in school or work; heightened tolerance; withdrawal; interpersonal problems caused by or exacerbated by cannabis use; or intending to cut back without success. Oof the teenage cannabis users studied, 50% had six or more cannabis use disorder symptoms, qualifying as severe cannabis use disorder.

Among people of any age, previous studies have found that roughly 9–22% of people who try the drug develop cannabis use disorder, and that risk is higher for people who tried it at a younger age, a finding which has now been robustly replicated.

The researchers say that adolescents might be more vulnerable to cannabis addiction because of factors such as increased disruption to relationships with parents and teachers, a hyper-plastic (malleable) brain and developing endocannabinoid system (the part of the nervous system that THC in cannabis acts upon), and an evolving sense of identity and shifting social life.

Adolescent users had greater odds than adult users or adolescent non-users of developing psychotic-like symptoms, but analysis showed that this is because all adolescents, and all cannabis users, are more likely to newly develop psychotic-like symptoms, rather than a different effect of cannabis for teenagers than adults. Thus, there was no interaction between cannabis use and being an adolescent. The researchers say this fits in with prior evidence that cannabis use may increase the likelihood of developing a psychotic disorder such as schizophrenia, but they warn their study did not investigate the risk of clinical psychosis or schizophrenia.

The researchers found that neither teenage nor adult cannabis users were more likely to develop depressive or anxiety symptoms than non-users. Only the adolescents that have severe cannabis use disorder had worse mental health symptoms, but the researchers caution that the small sample size for this group limits their confidence in this finding.

The separate study found that cannabis users were no more likely to have impaired working memory or impulsivity. Cannabis users were more likely to have poor verbal memory (remembering things said to you); this effect was the same in adults and teenagers, so again there was no adolescent vulnerability. However, the researchers caution that cannabis use could impact school performance during a key developmental stage of life.

The researchers caution that these findings were cross-sectional (only looking at one time point), and that longitudinal analyses of how their participants changed over time are ongoing.

Senior author Professor Val Curran (UCL Clinical Psychopharmacology Unit, UCL Psychology & Language Sciences) said: “Our findings suggest that schools should be teaching pupils more about the risk of addiction to cannabis, which has been neglected in drugs education. Becoming addicted to cannabis is a serious problem in itself, but it can also increase the likelihood of other mental health problems. Teenagers should therefore be informed of their greater risk of addiction.”

Source: King’s College London

Categories : AntibioticsTags :

Anti-Ligands: New Antibiotics Targeting Bacterial Adhesion

On By ModernMedia
Female scientist in laboratory
Photo by Gustavo Fring on Pexels

In a study published in Microbiology Spectrum, researchers detail how they have turned to attacking one of the critical proteins bacteria use to create an infection – adhesins, which confer the ability to adhere to cells. They also suggest that targeting adhesins with ‘anti-ligands’ could form a new class of antibiotics.

As their first decisive step in establishing a foothold in an organism, bacteria adhere to host cells. Infection pathogens use this adhesion to first colonise the host organism, and then to trigger an infection, which as a worst case scenario can end being fatal. Precise understanding of the bacteria’s adhesion to host cells is a key to finding therapeutic alternatives that block this critical interaction in the earliest possible stage of an infection.

The international collaborative effort has now explained the exact bacterial adhesion mechanism using the human-pathogenic bacterium Bartonella henselae. This pathogen causes ‘cat-scratch disease‘, which affects the lymph nodes draining the area where a cat scratch or bite occurs, causing regional lymphadenopathy. The bacterial adhesion mechanism was deciphered with the help of a combination of in-vitro adhesion tests and high-throughput proteomics. Proteomics is the study of all the proteins present in a cell or a complex organism.

The research group, led by University Hospital Frankfurt and Goethe University Frankfurt, shed light on a key mechanism: the bacterial adhesion to the host cells can be traced back to the interaction of a certain class of adhesins, trimeric autotransporter adhesins, with fibronectin, a common protein in human tissue. Adhesins are components on the surface of bacteria which enable the pathogen to adhere to the host’s biological structures. Homologues of the adhesin identified here as critical are also present in many other human-pathogenic bacteria, such as the multi-resistant Acinetobacter baumannii, which the World Health Organization (WHO) has classified as the top priority for research into new antibiotics.

The researchers visualised the exact points of interaction between the proteins using cutting-edge protein analytics. They also demonstrated that experimental blocking of these processes almost entirely prevents bacterial adhesion. Therapeutic approaches that aim to prevent bacterial adhesion in this way could represent a promising treatment alternative as a new class of antibiotics (known as ‘anti-ligands’) to treat the constantly growing array of multi-resistant bacteria.

Source: Goethe University Frankfurt

Categories : Ethics and LawTags :

Understanding the Basic Steps to Obtaining Informed Consent

On By ModernMedia

Taking the time to obtain proper informed consent is one of the most effective ways to avoid medico-legal challenges. Other than building the doctor-patient relationship, it ensures that patients do not encounter unpleasant surprises on their care journey which may result in unnecessary anger and blame. 

Informed consent is a process where you provide information sufficient to enable the patient to make an informed decision relating to their healthcare. Although the signature of a consent form often constitutes completion of the consent process, a signature on a consent form without a balanced discussion does not constitute informed consent.

Informed consent is both a legal and ethical requirement. The National Health Act gives patients the right to be informed of the various treatment options available, and the benefits, risks and costs of each treatment option. It also gives patients the right to participate in decisions regarding their treatment and the right to consent before any treatment is given unless it is an emergency and they aren’t able to consent. From an ethical perspective, informed consent has two main objectives, firstly to respect and promote patients’ autonomy and secondly, to protect patients from potential harm. Medical intervention with a patient’s body is potentially an infringement of the constitutional right to bodily integrity and is legally wrongful unless there is a ground of justification. One such ground of justification is patient consent.

  • Knowing your patient will help focus the discussion during the informed consent process. Enquire about your patient’s personal circumstances, expectations and fears, and assess their understanding of medical concepts and ability to make decisions.  
  • Use simple language and avoid technical terminology when discussing medical facts.
  • Ensure your patient understands their medical condition and its natural history before discussing treatment options. This lets them know what to expect without treatment.
  • List the range of diagnostic procedures and treatment options generally available.  For each, highlight potential benefits and risks, including recognised complications and any potential follow-up treatment.
  • Explain the possible need for emergency management of unforeseen conditions that may emerge.
  • Discuss cost implications and payment responsibility. This considers medical aid coverage, any out-of-pocket costs, the cost of the different procedures, as well as any complications.
  • Allow an opportunity for questions and answers.  Encourage your patient to ask questions. Test your patient’s understanding. Let patients contact you prior to the planned procedure, if they have more questions or concerns.

If a patient has specified that they would rather a procedure didn’t go ahead in the event of certain clinical findings, the patient’s decision must be recorded and respected.

If the patient decides to consent to an intervention, obtain their signed written consent. The patient’s details, health status, the treatment options discussed and the procedure to be performed must be entered into your consent form.

Document complications that have a reasonable likelihood of occurring and/or which are likely to be of importance to your patient, considering personal circumstances.

For example, an abnormal sense of touch after carpal tunnel syndrome surgery may affect a practising dentist more significantly than a retired librarian. 

  • Ensure that your consent form documents that no guarantees or promises have been made regarding the outcomes of the procedure and the patient has a right to refuse the procedure.
  • Your consent form must include any discussions relating to financial consent, the use of anaesthesia and blood products and the need for emergency management in the event of unforeseen complications.
  • Check that the patient initials the document and signs with the correct date. Countersign and date the consent form. Attach any relevant patient information sheet to the informed consent form and allow the patient to take a copy and keep one for the practice.

Consent remains valid until it is withdrawn by the patient or until their circumstances change in a meaningful way. However, if significant time has passed since the original consent was obtained, you may need to update and document your discussion with the patient. Additions or corrections to the consent form must be dated, timed and signed by both parties.

Trust EthiQal to provide you with local legal advice and professional support when you need it most.

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