Categories : Neurodegenerative DiseasesTags :

Protein Synthesis Fix may Reverse Cognitive Decline in Alzheimer’s

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Restoring protein synthesis in the brain may reverse the cognitive decline associated with Alzheimer’s, according to a study by researchers from New York University (NYU) and the Federal University of Rio de Janeiro (UFRJ).

Current Alzheimer’s treatment research focuses on reducing the phenomena linked to the disease, such as amyloid plaques, neurofibrillary tangles, and neuroinflammation. The study aimed to determine whether restoring protein synthesis would also be beneficial.

“The synthesis of new proteins in the brain is essential for proper neuronal function and, notably, for memory consolidation. We and others have previously shown that impairments in brain protein synthesis contribute memory deficits in Alzheimer’s disease model mice, and that the brains of Alzheimer’s patients exhibit clear signs of impaired protein synthesis. We thus asked ourselves whether rescuing brain protein synthesis might be an approach to improve memory function in Alzheimer’s disease,” said co-senior author Sergio Ferreira, a professor at UFRJ.

“Given the complex nature of Alzheimer’s disease, identifying and targeting abnormal molecular pathways that effectively improve cognition has been challenging,” added co-senior author Eric Klann, a professor at NYU. “Our findings show that jump-starting protein synthesis in the brain can revive lost cognitive functions. We hope that this work can serve as a step forward in treating this devastating disease.”

Previous research found that a cellular quality control mechanism called the integrated stress response (ISR) was found to slow down protein synthesis to weed out problems like cancerous cells, but can get stuck in the ‘on’ position. In 2013, a drug called ISRIB was developed to reverse this (ISRIB stands for ISR InhiBitor). 

Previous research with ISRIB had shown positive results in restoring memory function in mice, months after traumatic brain injury (TBI), reversing cognitive impairments in Down Syndrome , preventing noise-related hearing loss, treating certain prostate cancers, and even cognitive enhancement in healthy animals.

The researchers determined that in Alzheimer’s patients, critical components of protein synthesis are depleted in the hippocampus. The researchers hypothesised that some cognitive function could be returned if protein synthesis was restored with ISRIB.  

The researchers used mice with Alzheimer’s-like conditions as a model. Testing the mice’s memory (eg with maze runs), they found memory function and hippocampal protein synthesis restored with ISRB. Restoration of hippocampal neural plasticity and memory functions was observed even in simulated advanced Alzheimer’s. 

The results indicate that restoring protein synthesis with drugs such as ISRIB, could work together towards reversing cognitive decline from Alzheimer’s in humans. 

Source: Medical Xpress

Journal information: “Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease,” stke.sciencemag.org/lookup/doi … 26/scisignal.abc5429

Categories : Addiction PaediatricsTags :

Misuse of Psychiatric Meds Common in Teens

On By ModernMedia

A study into the use and misuse of psychoacttive drugs by US teens has found that about a fifth report misusing their prescribed medications.

Israel Agaku, PhD, of Harvard School of Dental Medicine in Boston, and colleagues used data from a survey of adolescents aged 12-17 prescribed opioids, stimulants, tranquilizers, or sedatives, and found that 20.9% reported using them not as prescribed or directed. There has been considerable concern in recent years over whether adolescents in the United States were being overprescribed psychiatric medication, although a 2018 study concluded that they are not. However, as with adults, the prospect of misuse, possibly leading to substance use disorders is a concern.
Of these youths, 3.4% reported having substance misuse disorders, and this proportion increased to nearly half when youths were taking two or more prescribed medications.

Some 25% of 12-17 year olds reported receiving a psychiatric prescription in the past year. The most common psychoactive prescription in the past year was opioids in 19% of all youth, followed by stimulants (7.2%), tranquilisers (4.3%), and sedatives (2.2%). Tranquilisers were the most commonly misused (40.1%), with substance use disorder in 7%. Stimulants were misused by 24.2%, 3% having a substance use disorder.
Among adults aged 18-25, 41% had been prescribed and had used psychoactive medication, with a third saying they had used opioids in the past year, Similarly to the 12-17 age group, stimulants and tranquilisers were most likely to be misused. 

“The largely overlapping population profiles for medical use versus misuse indicates the high abuse liability of these prescription substances,” the researchers noted. “Having serious psychological distress was consistently associated with misuse of every assessed psychoactive prescription medication.”

The researchers suggested that an open-minded, collaborative approach by healthcare providers was the best approach to dealing with the situation.

“Rather than asking only about cigarette smoking, pediatric practitioners should screen for different commonly used substances, including ‘social use.’ Specifically asking youth and young adults if they have used certain substances, including occasional use, is important as those who use such substances infrequently or only occasionally may not self-identify as users if asked in generic terms,” the researchers explained.

Source: MedPage Today

Journal information: Agaku I, et al “Medical use and misuse of psychoactive prescription medications among US youth and young adults” Fam Med Com Health 2021; DOI: 10.1136/ fmch-2020-000374.

Categories : HIVTags :

Revolutionary HIV Prophylaxis Pill Rollout in SA

On By ModernMedia

Amidst the COVID pandemic and concerns about vaccines, the South African government is rolling out a gaming-changing pill that protects against contracting HIV.

Due to delays including COVID-19, the revolutionary HIV pre-exposure prophylaxis (PrEP) pill is currently only available at 36% of public healthcare facilities – but the impact as it is rolled it will be significant.

Yogan Pillay, Deputy Director for Communicable and Non-Communicable  Diseases, Prevention, Treatment and Rehabilitation at the National Department of Health, says the PrEP pill will be available at all public healthcare providers by the end of September this year.

The pill combines two antiretrovirals, tenofovir disoproxil fumarate and emtricitabine (TDF/FTC), and gives nearly complete protection against contracting HIV. Over the past 4 years, over 50 000 people received the pill during trials. Young women and adolescent girls aged 15 to 24 are at four times higher risk of contracting HIV than males the same age, and since they may not be in a position to negotiate condom use, PrEP allows them to reduce the risk of contracting HIV through sexual activity. The TDF/FTC pill takes seven days to achieve full protection, and should be continued to be taken 28 days after the last HIV exposure. Periodic HIV and kidney function tests will be administered after the first month.

“The PrEP targets in the National Strategic Plan (NSP) for HIV, TB and STIs 2017-2022 is 85 000,” said Pillay. “We do however estimate based on the uptake trend at the current PrEP sites that approximately 10.5% of HIV negative persons offered PrEP will take up PrEP.”

The TDF/FTC pill can be taken at any point of the day, with alcohol, and is compatible with the use of birth control pills and other contraceptives. The pill will be made available through the public sector to any HIV negative person with healthy kidneys willing to take it daily. The TDF/FTC pill can only be prescribed by NIMART (Nurse Initiated Management of Antiretroviral Therapy) trained nurses, not other nurses or clinical associates at this time.

Source: Spotlight

Categories : Cancer Cardiovascular DiseaseTags :

Simvastatin Treatment Hope for Subtype of Ovarian Cancer

On By ModernMedia

Researchers have found that simvastatin has anti-proliferative potential against ovarian clear cell carcinoma, a highly lethal gynaecological cancer.

Dr Ingrid Hedenfalk from The Lund University explained: “Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) accounting for 5–10% of cases diagnosed in Europe and America, while the incidence in Asia is reported to be higher (10–20%).”

GTPases are a range of enzymes that hydrolyse guanosine triphosphate (GTP) to guanosine diphosphate (GDP). They are also involved in cells as switches and timers. Rho GTPases have been studied for their role in cancers. However, it is difficult to target Rho GTPases directly, so research has involved indirect strategies.

The researchers tested three cell lines of OCCC and one line of high-grade serous ovarian carcinoma (HGSOC) with simvastatin, which is a Rho GTPase interfering drug, and another GTPase interfering drug, CID-1067700, as a control. CID-1067700 is a pan-GTPase, which makes it useful as a comparator.

The research was motivated by a study which found deregulated expression of both Rho GTPases and cytoskeletal pathways in primary human OCCC tumours. The OCCC cell lines treated with simvastatin showed reduced c-Myc protein expression and signs of cell death, as well as curbing proliferation and migration.

Simvastatin could act through Rho GTPase interference as simvastatin affects the cytoskeletal integrity of OCCC cells at clinically relevant levels. However, the mechanism involved is different from Rho GTPase inhibition by CID-1067700.

However, caution is warranted with simvastatin as combination with chemotherapy may yield an antagonistic response. Further research is warranted to develop simvastatin as a potential drug candidate for the treatment of OCCC. 

Source: Oncotarget

Journal information: Arildsen N, Hedenfalk I. Simvastatin is a potential candidate drug in ovarian clear cell carcinomas. Oncotarget. 2020;11(40):3660-3674. doi:10.18632/oncotarget.27747

Categories : Diet and Nutrition GastrointestinalTags :

Eating Saturated Fats can Cut Symptoms of Pancreatitis

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A study has found that symptoms of pancreatitis are less severe when foods with saturated fats are eaten.

The study, by researchers from Mayo Clinic, the Saint Louis University School of Medicine and the Washington University School of Medicine, examines the obesity paradox in which obese patients had better results when being treated for certain conditions, compared to non-obese patients.

Pancreatitis is the leading cause of hospitalisation from gastrointestinal disorders in the United States. It can have a variety of causes, such as gallstones, having abdominal surgery or overconsumption of alcohol.
Saturated fats are found in meat and dairy, while unsaturated fats are found in plants and fish, and in general consumption of unsaturated fats over saturated fats is encouraged as it is associated with reduced risk of heart disease and other conditions. However, exceptions such as the obesity paradox exist.

To delve into this question, the researchers examined 20 clinical reports from 11 countries, where fat intake in obese patients was monitored. They found that among obese patients who developed pancreatitis, those who ate a diet heavy in saturated fats had less severe symptoms than those who did not. 

To determine the cause of this protective effect, the researchers fed mice a diet rich in either saturated or unsaturated fats, and then induced pancreatitis in them. Those fed saturated fats developed less severe symptoms. On closer examination, they found that saturated fat did not interact well with pancreatic triglyceride lipase, reducing production of long-chain non-esterified fatty acids, which reduced the symptoms of pancreatitis.  

Source: Medical Xpress

Journal information: Biswajit Khatua et al. Adipose saturation reduces lipotoxic systemic inflammation and explains the obesity paradox, Science Advances (2021). DOI: 10.1126/sciadv.abd6449

Categories : Exercise Injury & Trauma PaediatricsTags :

Young Athletes’ Recovery Helped by New Concussion Guidelines

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A study has found that the adoption of new concussion guidelines, which emphasises a more active form of rest, reduced the duration of symptoms among athletes aged 11 to 18.

Concussions are the most common form of traumatic brain injury, often occurring either as a direct result of a blow to the head, or from forces experienced by the body that impart an acceleration to the head. Symptoms include mood changes, cognitive changes, sensory phenomena such as headaches or dizziness, and changes in sleep pattern.

The researchers compared medical records from 2016-18, which used the newer guidelines, to a set from 2011-13, which used the older guidelines.

Lead researcher John Neidecker, DO, and Sports Concussion Specialist, explained: “The most significant change in care involved a shift from strict rest or cocoon therapy to a return to low-intensity physical or cognitive activity after 24 to 48 hours. Our results show active rest dramatically improved recovery times among young athletes with first-time concussions.”

Active rest involves light activity that steadily increases under supervision, with minimal head movement.

“If diagnosis of a pre-existing condition has never been given, patients cannot be expected to report one during our concussion assessment,” said Dr. Neidecker. “This is especially true in the adolescent age group, as some may have a condition that they are not aware of yet. This makes screening for preexisting conditions more complex, yet even more essential for this age group.”

For example, intolerance to 3D movies could indicate an unrelated pre-existing condition. Information from parents about preinjury personality and behaviour could uncover anxiety.

“This more individualised, osteopathic approach in screening the athletes’ past medical history helped us identify health issues that may have been overlooked in the past,” said Dr Neidecker. This allows treatment to be more effectively tailored, he explained.

Knowledge about concussions has improved; in the 2011-13 dataset, the counselling given was more cautious and ominous, Dr Neidecker noted. Adequate communication and a positive outlook may have helped reduce reported symptoms, and may be essential for patients with anxiety. 

Source: News-Medical.Net


Journal information: Neidecker, J. M., et al. (2021) First-time sports-related concussion recovery revisited: management changes and impact on recovery. Journal of Osteopathic Medicine. doi.org/10.1515/jom-2020-0106.

Categories : Allergies Respiratory DiseasesTags :

Smoking Risks for Allergic and Asthmatic Cannabis Users

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A survey in the US has shown that cannabis users are often asthmatic, and some have allergies from cannabis smoking or its second-hand smoke.

Cannabis allergies can potentially cause respiratory symptoms, contact urticaria, angioedema, and uncommonly anaphylaxis. Inhalation of cannabis may also manifest in allergic rhinitis, conjunctivitis, wheezing, and throat oedema. Given the widespread legal use of cannabis, more information is needed on the effects of cannabis use, particularly smoking, on individuals with asthma and allergies.

The anonymous survey, conducted in concert with the Allergy & Asthma Network, consisted of 489 participants, 18% of whom reported cannabis use. A surprising 60% were asthmatic, and 40% had uncontrolled asthma. 

Inhalation routes were the most popular way of taking cannabis. About half of users smoked cannabis, while a third vaped it. Only 40% reported being asked by their physician about cannabis use, and about the same proportion of participants were willing to talk to a physician about their cannabis use, said study co-author and cannabis allergy expert, William Silvers, MD.

“In order to more completely manage their allergy/asthma patients, allergists should increase their knowledge about cannabis and inquire about cannabis use including types of cannabinoid, route of use, reasons for use, and adverse effects,” said Dr Silvers. “As with cigarette smoking, efforts should be made to reduce smoking of cannabis, and recommend other potentially safer routes such as edibles and sublingual tinctures.”

Reported positive effects of cannabis use (eg, reduced pain, calm, improved sleep) were more frequent than adverse effects (eg, cough, increased appetite, anxiety). Approximately 20% of survey respondents reported coughing from cannabis, which was associated with smoking cannabis; this was cause for concern as it may indicate smoking risks for cannabis users.

“It surprised me that over half of the cannabis users in this study who have asthma were smoking it,” said principal investigator Joanna Zeiger, PhD. “And further, of those with uncontrolled asthma, half reported smoking cannabis. We also found that people with asthma are not routinely being asked or advised by their physician about cannabis and how they are consuming it.”

The researchers commented that further research into the relationship of cannabis and allergies is warranted.
“We look forward to future studies of larger, more diverse cohorts to better explore more deeply the effect of cannabis use on asthma and other allergic disorders,” said Dr Zeiger.

Source: News-Medical.Net

Journal information: Zeiger, J. S., et al. (2021) Cannabis attitudes and patterns of use among followers of the Allergy & Asthma Network. Annals of Allergy, Asthma & Immunology.doi.org/10.1016/j.anai.2021.01.014.

Categories : Ageing HIVTags :

Anti-HIV Drugs may Combat Macular Degeneration

On By ModernMedia

New research has shown that anti-HIV drugs may fight macular degeneration – overturning a preconception about DNA in the process.

Macular degeneration is the leading cause of blindness in developed countries. Even though HIV does not cause dry macular degeneration, the drugs prevented the loss of vision.

“We are extremely excited that the reduced risk was reproduced in all the databases, each with millions of patients,” said Jayakrishna Ambati, MD, a leading macular degeneration researcher at the University of Virginia School of Medicine. “This finding provides real hope in developing the first treatment for this blinding disease.”

A Big Data Archeology review of four health insurance databases showed that Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a commonly used HIV treatment, reduced the incidence of dry macular degeneration by 40%. The records spanned two decades and covered over 100 million patients. The drugs had also previously been shown to possibly prevent diabetes.

The finding also comes with the discovery that DNA can be produced inside the cytoplasm. Alu DNA (found exclusively in primates), which makes up 10% of the human genome, is transposable and can insert itself into other places on the genome. It was long considered “junk” DNA, but are now believed to have important functions, such as allowing for multiple expressions of proteins from a single Alu element. Since it cannot replicate itself, Alu DNA requires a transposon called L1 to accomplish this, which was now reported to allow the production of Alu DNA outside the chromosome. The buildup of Alu DNA in cells contributes to macular degeneration, by killing off cells that support the retina.
The researchers are urging further investigation into NRTIs or safer derivatives known as Kamuvudines, both of which block a key inflammatory pathway, can be useful in preventing vision loss from dry macular degeneration.

“A clinical trial of these inflammasome-inhibiting drugs is now warranted,” said Ambati. “It’s also fascinating how uncovering the intricate biology of genetics and combining it with big data archeology can propel insights into new medicines.”

Source: Medical Xpress

Journal Information: Shinichi Fukuda el al., “Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.202275111

Categories : CancerTags :

Pre-op Immune Checkpoint Inhibition in Lung Cancer

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According to a prospective multicenter trial, one fifth of patients with operable early-stage non-small cell lung cancer (NSCLC) had major pathologic responses (MPR) and over 40% had pathologic downstaging after neoadjuvant atezolizumab.

Out of 144 patients, 30 achieved MPR (defined as ≤10% viable tumour cells), 10 of whom had pathologic complete response (pCR), while 66 experienced downstaging and upstaging occurred in 29. 

Jay M Lee, MD, of the David Geffen School of Medicine at the University of California Los Angeles, explained: “The LCMC (Lung Cancer Mutation Consortium)3 study successfully met its primary endpoint of achieving major pathologic response in 21% of patients, and a pathologic complete response rate of 7%. Neoadjuvant atezolizumab monotherapy was well tolerated, with no new safety signals, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window, with a short time frame from completion of atezolizumab and with a corresponding high R0, or complete resection rate.”

Some 90% of patients were still alive at 18 months, and 80% were disease-free and alive. The findings indicate that neoadjuvant therapy with an immune checkpoint inhibitor (ICI) is possible thought it does make surgery harder, said invited discussant Shinichi Toyooka, MD, of Okayama University Hospital. Similar outcomes were seen in patients with stage I-II versus stage III disease, although survival data is currently lacking, requiring follow-up to find out if single-agent ICI is sufficient for all patients with operable NSCLC.

“I think single ICI can be used for early-stage disease and poor performance status,” said Toyooka. “On the other hand, a combination of ICI and chemotherapy is suitable for advanced-but-resectable cases.”

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy. Lee said 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

The trial included 181 patients with newly diagnosed, resectable stage Ib-IIIa and selected IIIb (T4 because of mediastinal invasion) NSCLC and no targetable mutations, of which 159 underwent surgery. 15 patients were later found to have EGFR/ALK-positive disease and excluded from analysis. Patients had radiographic staging before and after two cycles of atezolizumab and then underwent surgery within 30 to 50 days after finishing neoadjuvant therapy.

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy; 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

Source:MedPage Today

Presentation reference: Lee JM, et al “Surgical and clinical outcomes with neoadjuvant atezolizumab in resectable stage Ib-IIIb NSCLC: LCMC3 trial primary analysis” WCLC 2020; Abstract PS01-05.

Categories : Cardiovascular Disease GenderTags :

Women are Less Likely to Undergo Critical Heart Surgery

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A scientific presentation at the 57th Annual Meeting of The Society of Thoracic Surgeons revealed that women are less likely to have a coronary artery bypass grafting (CABG) using guideline-recommended approaches, possibly resulting in worse post-surgery outcomes.

CABG is a major surgical operation involves bypassing atheromatous blockages in a patient’s coronary arteries with venous or arterial conduits harvested from elsewhere in the patient’s body.

Dr Oliver Jawitz and colleagues from Duke and The Johns Hopkins University School of Medicine used the STS Adult Cardiac Surgery Database (containing records of nearly all CABG procedures done in the US), and identified adult patients from 2011 to 2019 who underwent first-time isolated CABG, along with detailed demographic, clinical and procedural data.

The association between female sex and three different CABG surgical techniques from US and European guidelines was investigated. Grafting of the left internal mammary artery to the left anterior descending artery, complete revascularisation, and multiarterial grafting have been linked to better short and/or long-term outcomes. Despite this, the results indicated that women were 14%-22% less likely than men to undergo CABG procedures with these revascularisation strategies.

“With these findings, we did in fact see less aggressive treatment strategies with women,” said Dr Jawitz. “It is clear that sex disparities exist in all aspects of care for patients with coronary artery disease (CAD), including diagnosis, referral for treatment, and now, in surgical approaches to CABG. We must ensure that female patients undergoing CABG are receiving evidence-based, guideline-concordant techniques.”

The results are in accordance with an overall neglect of heart disease treatment in women. Women are much more likely than men to have non-typical symptoms of heart disease which are also subtler, such as abdominal pain and fatigue, as well as having their own particular set of risk of factors. This is compounded by women being underrepresented in cardiac disease study cohorts.

Women’s health historically focused on mother and child, and breast cancer. As such, the period from symptom onset to diagnosis and treatment is longer, allowing the disease to progress and worsen outcomes. This is also reflected by fewer women being referred for beneficial treatments such as CABG. 


“Delayed diagnosis of CAD in women leads to late initiation of key behavioral and pharmacologic interventions for minimizing heart disease risk, as well as delayed referral for invasive diagnostic and therapeutic procedures, including surgical revascularisation with CABG,” said Dr Jawitz. “This often means that by the time female patients undergo these procedures, they have more severe disease than males, as well as a greater number of comorbidities, which leads to worse outcomes.

“Now that we have identified specific differences in surgical approaches to CABG between females and males, we must further elucidate how these differences result in disparate outcomes such as increased mortality, readmissions, and complications,” he concluded. “These findings will help inform the development of sex-specific guidelines for the diagnosis and management of cardiovascular disease.”

Source: News-Medical.Net