Tag: 15/6/22

Categories : AddictionTags :

Fentanyl Induces Autism-like Behaviours in Young Mice

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Mouse
Photo by Kanasi on Unsplash

Fentanyl is one of the most commonly used analgesics in the hospital and, in rodents, may have lasting sensorimotor and behavioural impacts. A study published in the British Journal of Anaesthesia has shown that fentanyl can induce changes similar to autism-like behaviours in young mice.

Fentanyl, a mu-opioid receptor agonist, is a potent synthetic opioid, which, similar to morphine, produces analgesia but is 50 to 100 times more potent. A dose of only 100 micrograms can produce equivalent analgesia to approximately 10mg of morphine. However, fentanyl exhibits vastly different properties and pharmacokinetics. Clinically, its most common use is as a sedative in intubated patients and severe cases of pain in patients with renal failure due to its primarily hepatic elimination. Fentanyl’s side effects are similar to those of heroin.

However, whether the use of fentanyl is associated with the development of autism is not known. An animal study led by investigators at Massachusetts General Hospital (MGH), Shanghai 10th People’s Hospital, and the University of Pennsylvania e. The findings are

Research by other groups has shown that N-methyl-D-aspartate receptor dysfunction contributes to autism. Variations in Grin2a and Grin2b, the genes encoding GluN2A and GluN2B subunits of N-methyl-D-aspartate receptor, are associated with autism. In addition, the anterior cingulate cortex of the brain is affected in autism.

In this current study, the research team reported that fentanyl induces autism-like behaviors in young male and female mice via activating the mu-opioid receptor in the anterior cingulate cortex. Further, these fentanyl-induced autism-like behaviors appear partially due to the hypermethylation-mediated reduction of Grin2b expression in the anterior cingulate cortex of mice.

“Because the anterior cingulate cortex is a hub for mediating social information, we focused on the expression of Grin2b in that area,” says Yuan Shen, MD, PhD, the paper’s senior author and a professor of Psychiatry at Shanghai 10th People’s Hospital. “We found fentanyl decreased expression of Grin2b in the anterior cingulate cortex. The overexpression of Grin2b prevents fentanyl-induced autism-like behavior in the mice. These findings suggest a potential mechanism to prevent or treat the autism-like behavior,” says Shen.

The group used an open field test (in which a mouse can walk inside a box) and an elevated plus-maze (in which a mouse can walk on an elevated platform) to observe the anxiety and stereotyped behaviours of mice. Using a three-chamber social preference test (where a mouse can interact with another mouse), they also assessed potential social deficits. “We used these tests because impaired social interaction, stereotyped behaviours, and anxiety are the key feature of autism-like behaviours in mice,” said Zhihao Sheng, co-first author of the paper. Sheng is a graduate student at Shanghai 10th People’s Hospital.

“However, the changes of mice in these behavioral tests do not equal autism in humans. These behavioral tests are only used to study the autism-like behaviors in mice because they can demonstrate certain features of behavior changes similar to the manifestation of autism,” said co-first author Qidong Liu, PhD, assistant professor at Shanghai 10th People’s Hospital.

Co-senior author Zhongcong Xie, MD, PhD, added: “There is no current evidence that fentanyl is associated with a similar effect in humans and the outcome of the animal study is not an indication to avoid fentanyl in clinical anesthesia. However, the outcome will promote further research, including clinical investigations, to determine the potential neurobehavioral influence of opioids on brain development.” 

Categories : Surgeries & ProceduresTags :

AI-enabled Kidney Surgery Makes it Easier for Novice Surgeons

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Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Percutaneous nephrolithotomy (PCNL) is an efficient surgical intervention for removing large kidney stones. However, it is a challenging procedure that requires years of training to perform. To address this, a group of scientists from the Nagoya City University, developed and trialled an artificial intelligence (AI)-enabled robotic device for assisting surgeons in PCNL.

Creating a renal access from the skin on the back to the kidney is a crucial yet challenging step in PCNL. A poorly performed renal access can lead to severe complications including massive bleeding, thoracis and bowel injuries, renal pelvis perforation, or even sepsis. This procedure takes years of training to master. The two main renal access methods for PCNL – X-ray guidance and ultrasound (US) guidance deliver similar postoperative outcomes but require experience-based expertise.

Many technologies are being developed to bridge this skill gap. This inspired a Nagoya University research team to question if artificial intelligence (AI)-powered robotic devices could be used for improved guidance compared with conventional US guidance. Specifically, they wanted to see if the AI-powered device called the Automated Needle Targeting with X-ray (ANT-X), which was developed by the Singaporean medical start-up, NDR Medical Technology, offers better precision in percutaneous renal access along with automated needle trajectory.

The team performed a randomised, single-blind, controlled trial comparing their robotic-assisted fluoroscopic-guided (RAF) method with US-guided PCNL. The results of this trial were detailed in the The Journal of Urology. “This was the first human study comparing RAF with conventional ultrasound guidance for renal access during PCNL, and the first clinical application of the ANT-X ,” said Dr Kazumi Taguchi, Assistant Professor at NCU.

The trial was conducted with 71 patients—36 in the RAF group and 35 in the US group. The primary outcome of the study was single puncture success, with stone-free rate (SFR), complication rate, parameters measured during renal access, and fluoroscopy time as secondary outcomes.

The single puncture success rate was ~34 and 50% in the US and RAF groups, respectively. Fewer needle punctures were needed in the RAF group (1.82 times) as opposed to the US group (2.51 times). In 14.3% of US-guided cases, the resident was unable to obtain renal access due to procedural difficulty, prompting a surgeon change. However, none of the RAF cases faced this issue. The median needle puncture duration was also significantly shorter in the RAF group (5.5 minutes vs 8.0 minutes). No significant differences in the other secondary outcomes was found.

Multiple renal accesses during PCNL are directly linked to postoperative complications including, decreased renal function. Therefore, the low needle puncture frequency and shorter puncture duration, as demonstrated by the ANT-X, may provide better long-term outcome for patients. While the actual PCNL was performed by residents in both RAF and US groups, the renal access was created by a single, novice surgeon in the RAF group, using ANT-X. This demonstrates the safety and convenience of the novel robotic device, which could possibly reduce surgeons’ training load and allow more hospitals to offer PCNL procedures.

Dr Taguchi commented, “The ANT-X simplifies a complex procedure, like PCNL, making it easier for more doctors to perform it and help more number of patients in the process. Being an AI-powered robotic technology, this technique may pave the way for automating similar interventional surgeries that could shorten the procedure time, relieve the burden off of senior doctors, and perhaps reduce the occurrence of complications.”

Source: Nagoya City University

Categories : Diet and NutritionTags :

Humans Naturally Moderate their Intake of Energy-rich Meals

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A hamburger
Photo by Ilya Mashkov on Unsplash

A new study has shown that, instead of overeating, humans moderate the size of energy-rich meals they consume, suggesting people are smarter eaters than previously thought.

The findings, published in The American Journal of Clinical Nutrition, revisit the long-held belief that humans don’t notice the energy content of the foods they consume, making them prone to eating the same quantity of food by weight, regardless of it being energy-rich or energy-poor.

The study, led by the University of Bristol, challenges a common view among researchers that people tend to overconsume high-energy foods.

Previous studies manipulated the energy content of foods or meals to create low- and high-energy versions. In those studies, people were not informed of which version they ate, and findings showed they tended to eat meals of the same weight, resulting in greater calorie intake with the high-energy version.

“For years we’ve believed that humans mindlessly overeat energy-rich meals. Remarkably, this study indicates a degree of nutritional intelligence whereby humans manage to adjust the amount they consume of high-energy density options,” said lead author Annika Flynn, Doctoral Researcher in Nutrition and Behaviour at the University of Bristol.

Rather than artificially manipulating the calories in single foods, this study looked at data from a trial using a normal, everyday meals with different energy densities, such as a chicken salad sandwich with fig roll biscuits or porridge with blueberries and almonds. The trial involved 20 healthy adults who temporarily lived in a hospital ward where they were served a variety of meals for four weeks.

The international team of researchers calculated the calories, grams, and energy density (calories per gram) for every meal each participant consumed. They found that meal calorie intake increased with energy density in energy-poor meals as previous observations with artificially manipulated foods also found. Surprisingly, with greater energy density a turning point was observed whereby people start to respond to increases in calories by reducing the size of the meals they consume. This suggests a previously unrecognised sensitivity to the energy content of the meals people were eating.

As this finding was based on data from a small, highly-controlled trial, the researchers next investigated whether the general population followed this pattern eating freely. Using data from the UK National Diet and Nutrition Survey, researchers again found meal calorie intake increased with energy density in meals which were energy-poor and then decreased in energy-rich meals. Importantly, for this turning point pattern to occur, participants would have needed to consume smaller meals, by weight, of the more energy-rich meals.

Annika said: “For instance, people ate smaller portions of a creamy cheese pasta dish, which is an energy-rich meal, than a salad with lots of different vegetables which is relatively energy-poor.”

This research sheds new light on human eating behaviour, specifically an apparent subtle sensitivity to calories in energy-rich meals.

Co-author Jeff Brunstrom, Professor of Experimental Psychology, said: “This research gives added weight to the idea humans aren’t passive overeaters after all, but show the discerning ability to moderate how much of an energy-rich meal they consume.

“This work is particularly exciting as it reveals a hidden complexity to how humans interact with modern energy-rich foods, something we’ve been referring to as ‘nutritional intelligence’. What this tells us is we don’t seem to passively overconsume these foods and so the reason why they are associated with obesity is more nuanced than previously thought. For now, at least this offers a new perspective on a longstanding issue and it opens the door to a range of important new questions and avenues for future research.”

Source: University of Bristol

Categories : COVIDTags :

Few Patients get ‘Rebound COVID’ after Paxlovid Treatment

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Mayo Clinic researchers studied the outcomes of 483 high-risk patients  treated for COVID with a five-day oral regimen of Paxlovid, a combination of nirmatrelvir and ritonavir. Only a handful developed COVID rebound symptoms, something which the researchers say needs further investigation. Their findings appear in the journal Clinical Infectious Diseases.

All of the patients benefited from Paxlovid and recovered, including the patients who developed rebound symptoms, which were generally mild.

“We found that rebound phenomenon was uncommon in this group of patients,” says senior author Aditya Shah, MBBS, an infectious diseases physician and researcher at Mayo Clinic. “The four individuals who experienced rebound [symptoms] represent only 0.8% of the group, and all of them recovered quickly without additional COVID-directed therapy.”

Most of the patients had been vaccinated, and many had received booster vaccinations. The median age was 63. While these patients were high-risk for COVID, none was immunocompromised. Only two patients were admitted to the hospital, and it was for reasons other than COVID.

The study focussed on four patients with rebound symptoms:

  • A 75-year-old man with coronary artery disease who had increased cough and muscle aches 19 days after treatment.
  • A 40-year-old woman with obesity, hypertension and kidney disease who developed fatigue and sore throat six days after treatment.
  • A 69-year-old man with hypertension and obesity who exhibited nasal discharge and cough 10 days following therapy.
  • A 70-year-old man with a history of prostate cancer, obesity, hypertension and high cholesterol, who developed significant sinus congestion 10 days after treatment.

Why did some rebound?

Researchers think one explanation could be that a replication of SARS-CoV-2 could have triggered a secondary immune response, which showed up as mild COVID symptoms. This question could be answered by prospective studies could answer the question. They also note that all four patients with rebound symptoms had many serious health problems known as comorbidities — a factor shown to complicate recoveries. And all four patients had been vaccinated more than 90 days before becoming infected with COVI.

Source: Mayo Clinic

Categories : Obstetrics & GynaecologyTags :

Comorbidities are Common in Polycystic Ovary Syndrome

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Photo by Andrea Piacquadio on Pexels

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in reproductive-age women. In a study published in Acta Obstetricia et Gynecologica Scandinavica, women with PCOS were more likely to also have migraine, hypertension, tendinitis, osteoarthritis, and endometriosis.  Affected women were also using medications more often and reported their own health to be poorer than women without PCOS.  

Few studies have systematically assessed the overall comorbidity in women with PCOS, which should be of greater importance given the high costs of PCOS-related comorbidity. For example, PCOS-related type 2 diabetes alone has been estimated to carry an annual cost of $310 million in the UK and $1.77 billion in the USA. The syndrome often remains underdiagnosed despite being so common, and therefore is less represented in national databases, making it harder to assess comorbidities.

The present study included 246 women with PCOS symptoms or diagnoses and 1573 controls who were surveyed during their late reproductive years at age 46.  

“PCOS is often labelled as a reproductive concern; however, in most cases this is well managed with fertility treatments. Our study underscores the need for health professionals to acknowledge the risk for several comorbidities and increased health burden related to this common syndrome,” said senior author professor Terhi T. Piltonen, MD, PhD, of the University of Oulu, in Finland. “Women should also be aware of this risk, and they should be supported by early diagnosis and treatment.”  

Source: Wiley