Researchers from Boston University Chobanian & Avedisian School of Medicine now suggest studying persons after they sustain knee trauma such as anterior cruciate ligament tears (ACL).

“Given the repeated, expensive and discouraging past failures in the development of effective treatments for OA, a new approach is needed that focuses research into effective treatment on those with early disease,” said corresponding author David T. Felson, MD, MPH, professor of medicine and epidemiology at the School of Medicine and Boston University School of Public Health.

While most patients recover after sustaining a major joint injury like an ACL tear, a few experience persistent pain and develop OA. Felson suggests that sufficient numbers of such patients exist and could be identified in advance to form a high-risk group in which treatments to prevent disease could be tested.

Current options for treatments that reduce joint pain such as nonsteroidal anti-inflammatory drugs (NSAIDs) are successful in some patients but their use is limited by their toxicity . Exercise or weight loss are effective but long-term adherence is poor. Rates of total knee replacement surgeries are rising rapidly suggesting that nonsurgical treatments have not successfully alleviated patients’ pain and disability.

BU and Cleveland Clinic researchers reviewed the data from the MOON (Multicenter Orthopaedic Outcomes Network) cohort, a group of 2,340 persons undergoing ACL reconstructions (ACLR) after traumatic tears. The MOON investigators reported that 26% of the ACL reconstruction patients who responded had at least moderate knee pain on daily activities, especially stair climbing and walking. They also found that 16.6% had Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scores of less than80 (0-100 scale where 100 is no pain) suggesting that mild to moderate pain is not rare after ACLR.

By using the MOON risk factors — incorporating pain and structural changes in all joint tissues, especially cartilage loss — to select persons at high risk of later pain, they could assemble a cohort at high risk of substantial post ACLR pain. “This approach offers the opportunity to prevent disease and is especially valuable in targeting young adults who, after a knee injury, may have significant joint pain and disability for many years before they become eligible for joint replacement,” he adds.

These findings appear online in the Annals of the Rheumatic Diseases.

Funding for this study was provided by the Arthritis Foundation and by the national Institutes of Health (NIH P30 AR072571).

One of the greatest strengths of NASA’s James Webb Space Telescope is its ability to give astronomers detailed views of areas where new stars are being born. The latest example, showcased here in a new image from Webb’s Mid-Infrared Instrument (MIRI), is NGC 346 — the brightest and largest star-forming region in the Small Magellanic Cloud.

The Small Magellanic Cloud (SMC) is a satellite galaxy of the Milky Way, visible to the unaided eye in the southern constellation Tucana. This small companion galaxy is more primeval than the Milky Way in that it possesses fewer heavy elements, which are forged in stars through nuclear fusion and supernova explosions, compared to our own galaxy.

Since cosmic dust is formed from heavy elements like silicon and oxygen, scientists expected the SMC to lack significant amounts of dust. However the new MIRI image, as well as a previous image of NGC 346 from Webb’s Near-Infrared Camera released in January, show ample dust within this region.

In this representative-color image, blue tendrils trace emission from material that includes dusty silicates and sooty chemical molecules known as polycyclic aromatic hydrocarbons, or PAHs. More diffuse red emission shines from warm dust heated by the brightest and most massive stars in the heart of the region. An arc at the center left may be a reflection of light from the star near the arc’s center. (Similar, fainter arcs appear associated with stars at lower left and upper right.) Lastly, bright patches and filaments mark areas with abundant numbers of protostars. The research team looked for the reddest stars, and found 1,001 pinpoint sources of light, most of them young stars still embedded in their dusty cocoons.

By combining Webb data in both the near-infrared and mid-infrared, astronomers are able to take a fuller census of the stars and protostars within this dynamic region. The results have implications for our understanding of galaxies that existed billions of years ago, during an era in the universe known as “cosmic noon,” when star formation was at its peak and heavy element concentrations were lower, as seen in the SMC.The James Webb Space Telescope is the world’s premier space science observatory.

Scientists from Bristol and the University of Occupational and Environmental Health in Japan, sought to understand how ‘circadian misalignment’ — a phenomenon commonly associated with ‘jet-lag’ whereby the body’s biological clock is disrupted — affects the hormones responsible for regulating appetite.

Prevalent in night shift workers, in this new study, the international team reveal how circadian misalignment can profoundly alter the brain’s regulation of hormones controlling hunger to the detriment of metabolic health.

The team focused on glucocorticoid hormones in the adrenal gland which regulate many physiological functions including metabolism and appetite. Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some increasing appetite (orexigenic) and some decreasing appetite (anorexigenic).

In an experiment using animal models, comprising a control group and a out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated, driving an increased desire to eat significantly more during the inactive phase of the day.

Strikingly, the team discovered that rats in the control group ate 88.4% of their daily intake during their active phase, and only 11.6% during their inactive phase. In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase (without an increase in activity during this time). This equated to nearly five-times more (460% more) than what the control group consumed during the inactive phase. These results show that it is timing of consumption that has been affected.

This new discovery revealed how completely, and significantly, disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues. However, the authors suggest the neuropeptides identified in this study may be promising targets for drug treatments adapted to treat eating disorders and obesity.

Dr Becky Conway-Campbell, Research Fellow in Bristol Medical School: Translational Health Sciences (THS) and the study’s senior author, said: “For people working throughout the night, a reversed body clock can play havoc with their health.

“For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours. However, internal brain messages to drive increased appetite are difficult to override with ‘discipline’ or ‘routine’ so we are currently designing studies to assess rescue strategies and pharmacological intervention drugs. We hope our findings also provide new insight into how chronic stress and sleep disruption leads to caloric overconsumption.”

Stafford Lightman, Professor of Medicine at Bristol Medical School: THS and co-senior author on the study, added: “The adrenal hormone corticosterone, which is normally secreted in a circadian manner, is a major factor in the daily control of brain peptides that regulate appetite. Furthermore when we disturb the normal relationship of corticosterone with the day to night light cycle it results in abnormal gene regulation and appetite during the period of time that the animals normally sleep.

“Our study shows that when we disturb our normal bodily rhythms this in turn disrupts normal appetite regulation in a way that is at least in part a result of desynchrony between adrenal steroid hormone production and the timing of the light and dark cycle.”

Dr Benjamin Flynn, one of the study’s co-authors who conducted the study while at Bristol but is now based at the University of Bath, added: “This is further evidence of how phase shift ‘jet-lag’ affects feeding behaviours and neuronal gene expression — data important for shift work co-morbidity research.”

This research was funded by the Medical Research Council.

As the largest member of the dolphin family, killer whales, also known as orcas, are found worldwide. Marine vessel traffic can disturb the hunting and communication of these black-and-white marine mammals. But they face another type of human threat — legacy and emerging persistent organic pollutants (POPs) in their environments. POPs include chlorinated hydrocarbons and flame retardants, and can accumulate in animals’ fat stores as the contaminants move up the food chain though a process called biomagnification.

Previous studies have shown that some Pacific orca populations can carry POP loads in their blubber that pose potential health risks, including reduced immunity, hormonal imbalances and reproductive issues. But information on orcas living in the North Atlantic are lacking. So, Anaïs Remili, Melissa McKinney and colleagues wanted to assess the contaminants present in animals spanning from Eastern Canada to Norway.

The researchers collected skin and blubber biopsies from over a hundred free-ranging killer whales, across the North Atlantic Ocean from Canada, Greenland, Iceland to Norway. They analyzed half of each tissue sample for five classes of POPs, including polychlorinated biphenyls (PCBs). The other portion was used to evaluate the animals’ diets. Multiple features stood out in the data:

• Specimens from orcas in the western North Atlantic contained substantially higher contaminant loads than ones from orcas on the eastern side — a pattern that contrasts with previously reported POP levels in other Arctic marine organisms.
• The pattern could be attributed to individuals’ diet rather than location. Specifically, killer whales foraging on fish had the lowest POP levels, and animals consuming marine mammals, such as seals or other whales, had the highest.
• PCB-associated health risks were highest for killer whales that ate primarily marine mammals, with most animals’ levels exceeding the threshold for a higher risk of female reproductive failure.
• The levels of one POP, known as α-HBCDD, were the highest reported for any marine mammal to date, despite the fact that this brominated flame retardant was banned a decade ago.

The researchers say the findings support the need for proper waste disposal to prevent contaminants from entering the oceans’ food chains and reaching the top predators. They explain that the findings of their study underscore the need for action to protect North Atlantic killer whales and their ecosystems.