Nine years after losing three of her limbs to a life-threatening bout of sepsis, Ottawa’s Christine Caron is devoted to helping others cope with the often painful aftermath of the same condition.
Nine years after losing three of her limbs to a life-threatening bout of sepsis, Ottawa’s Christine Caron is devoted to helping others cope with the often painful aftermath of the same condition.
Caron leads two support groups for people suffering from post-sepsis syndrome and another for those struggling to deal with their amputations.
Sepsis can be a life changing medical event and many survivors deal with post-traumatic stress, chronic pain, fatigue and reduced organ function.
“There are many people suffering with brain fog and pain from vascular damage after surviving sepsis,” said Caron, 58, a mother of four and a new grandmother.
“It’s strange to say, but I’m one of the lucky ones: I don’t have the same joint and vascular pain that a lot of these people have.”
Sepsis is a life-threatening condition resulting from the body’s runaway response to a serious infection. It can be triggered by a bacterial, fungal or viral infection, including COVID-19, and, if not identified and treated promptly, can led to septic shock, organ failure and death.
Caron’s life-and-death struggle with sepsis began in May 2013 after one of her four dogs, Buster, a three-year-old Shih Tzu, accidentally bit her left hand during a game of tug-of-war.
The bacteria commonly found in dog and cat saliva, Capnocytophaga, can infect people. In rare cases, it can lead to serious illness, including sepsis.
“It wasn’t a deep bite, just a break of the skin,” Caron remembered. “There was no redness around it, no pain.”
She washed and disinfected the wound, but some of her other dogs also licked her hand.
It was a Saturday. She was a single-parent of four children who worked full-time while also looking after four dogs. “I was used to going 100 miles an hour all the time,” she said. “My feet hit the ground in the morning and I just started going.”
Two days after the bite, she noticed she hadn’t gone to the bathroom all day and thought it strange. She would later recognize it as a sign that her kidneys were shutting down.
On Tuesday, during her daily half-hour run, she didn’t make it more than a block. She went to work, but felt so ill that she returned home and slept. Later that evening, she asked a friend to take her to an after-hours clinic in Orléans, but they arrived to find the clinic closed, so Caron decided to go to hospital in the morning.
She spent most of the night in the bathroom with nausea. She thought she had a terrible flu or pneumonia.
“I should have called an ambulance, but my brain wasn’t working properly,” she said.
Caron made it to the Montfort Hospital the next morning and passed out in the waiting room.
She woke from a coma more than one month later only to be told she needed to have three limbs amputated because the blood-clotting associated with sepsis had stemmed the blood flow to her extremities and destroyed much of their tissue.
It was only then, she said, that she learned for the first time about sepsis.
She went through rehabilitation to learn to walk and live with prosthetic limbs, but it was another five years before she fully recovered from post-sepsis brain fog and speech problems.
“That’s one of the other reasons I started these support groups: because you go from having all of this support to being left on your own,” she said. “There’s no support for survivors.”
Caron wants more research into post-sepsis syndrome and more help for those who suffer from it. She also wants more information made available to people so they can recognize when sepsis has taken hold.
“If you recognize those signs and bring them to the attention of a doctor in the emergency room, you can walk out of the ER, rather than be wheeled out,” said Caron, who told her story this past week to mark sepsis awareness month.
One reason sepsis kills so many people — more than 9,000 each year in Canada — is that it’s often hard to recognize as a medical emergency.
Most sepsis cases start at home, and a campaign has been launched by the Sepsis Alliance, a U.S.-based charity, to help people recognize its symptoms. Warning signs include chills or fever, a high heart rate and shortness of breath. People with sepsis can also have extreme pain or discomfort, clammy or sweaty skin and can exhibit signs of confusion or disorientation.
The Sepsis Alliance recommends: “Watch for a combination of these symptoms. If you suspect sepsis, call 911 or go to a hospital with an advocate and ask, ‘Could it be sepsis?’”
Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic–pituitary–adrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription co-activators (CRTCs). We hypothesised that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioural tests, virus-mediated gene transfer, enzyme-linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunofluorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced significant changes in SIK1-CRTC1 signalling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naive mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN. In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced beneficial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of fluoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.
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The authors declare that all data supporting the findings of this study are available within the paper and its Supplementary information files.
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This work was supported by four grants from the National Natural Science Foundation of China (Nos. 82071519, 81873795, 81900551, and 82001606).
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Wang, Y., Liu, L., Gu, JH. et al. Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis.
Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01881-4
Received: 05 August 2022
Revised: 30 October 2022
Accepted: 09 November 2022
Published: 25 November 2022
An ongoing outbreak of a deadly strain of bird flu has now killed more birds than any past flare-up in U.S. history.
The virus, known as highly pathogenic avian influenza, has led to the deaths of 50.54 million domestic birds in the country this year, according to Agriculture Department data reported by Reuters on Thursday. That figure represents birds like chickens, ducks and turkeys from commercial poultry farms, backyard flocks and facilities such as petting zoos.
The count surpasses the previous record of 50.5 million dead birds from a 2015 outbreak, according to Reuters.
Turkeys in a barn on a poultry farm.
On farms, some birds die from the flu directly, while in other cases, farmers kill their entire flocks to prevent the virus from spreading after one bird tests positive. Such farmers have occasionally drawn condemnation from animal welfare advocates for using a culling method known as “ventilation shutdown plus,” which involves sealing off the airways to a barn and pumping in heat to kill the animals.
The virus has raged through Europe and North America since 2021. A variety of wild birds have been affected worldwide, including bald eagles, vultures and seabirds. This month, Peru reported its first apparent outbreak of highly pathogenic avian influenza after 200 dead pelicans were found on a beach.
Pelicans suspected to have died from highly pathogenic avian influenza are seen on a beach in Lima, Peru, on Nov. 24.
The migration of infected wild birds has been a major cause of the spread. Health and wildlife officials urge anyone who keeps domestic birds to prevent contact with their wild counterparts.
While health experts do not generally consider highly pathogenic avian influenza to be a major risk to mammals, a black bear cub in Alaska was euthanized earlier this month after contracting the virus. Wildlife veterinarian Dr. Kimberlee Beckmen told the Juneau Empire newspaper that the young cub had a weak immune system.
Over the summer, avian flu also spread among seals in Maine, which the National Oceanic and Atmospheric Administration believed contributed to an unusually high number of seal deaths.
The Centers for Disease Control and Prevention states that the risk “to the general public” from the bird flu outbreak is low. However, the agency recommends precautions like wearing personal protective equipment and thoroughly washing hands for people who have prolonged contact with birds that may be infected.
In April, a Colorado prisoner working at a commercial farm became the first person in the U.S. to test positive for the new strain, though he was largely asymptomatic.
An experimental mRNA-based vaccine against all 20 known subtypes of influenza virus provided broad protection from otherwise lethal flu strains in initial tests, according to a study.
This could serve one day as a general preventative measure against future flu pandemics, the researchers from University of Pennsylvania, US, said.
According to the study, tests in animal models showed that the vaccine dramatically reduced signs of illness and protected from death, even when the animals were exposed to flu strains different from those used in making the vaccine.
The “multivalent” vaccine, which the researchers described in a paper published in the journal Science, used the same messenger ribonucleic acid (mRNA) technology employed in the Pfizer and Moderna SARS-CoV-2 vaccines, the study said.
This mRNA technology that enabled those Covid-19 vaccines was pioneered at Penn, the study said.
“The idea here is to have a vaccine that will give people a baseline level of immune memory to diverse flu strains, so that there will be far less disease and death when the next flu pandemic occurs,” said study senior author Scott Hensley.
Influenza viruses periodically cause pandemics with enormous death tolls. The best known of these was the 1918-19 “Spanish flu” pandemic, which killed at least tens of millions of people worldwide.
Flu viruses can circulate in birds, pigs, and other animals, and pandemics can start when one of these strains jumps to humans and acquires mutations that adapt it better for spreading among humans.
Current flu vaccines are merely “seasonal” vaccines that protect against recently circulating strains, but would not be expected to protect against new, pandemic strains. The strategy employed by the Penn researchers is to vaccinate using immunogens – a type of antigen that stimulates immune responses – from all known influenza subtypes in order to elicit broad protection, the study said.
The vaccine is not expected to provide “sterilizing” immunity that completely prevents viral infections. Instead, the new study showed that the vaccine elicited a memory immune response that can be quickly recalled and adapted to new pandemic viral strains, significantly reducing severe illness and death from infections.
“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines, which were targeted to the original Wuhan strain of the coronavirus.
“Against later variants such as Omicron, these original vaccines did not fully block viral infections, but they continue to provide durable protection against severe disease and death,” said Hensley.
The experimental vaccine, when injected and taken up by the cells of recipients, started producing copies of a key flu virus protein, the hemagglutinin protein, for all twenty influenza hemagglutinin subtypes—H1 through H18 for influenza A viruses, and two more for influenza B viruses.
“For a conventional vaccine, immunizing against all these subtypes would be a major challenge, but with mRNA technology it’s relatively easy,” Hensley said.
In mice, the mRNA vaccine elicited high levels of antibodies, which stayed elevated for at least four months, and reacted strongly to all 20 flu subtypes. Moreover, the vaccine seemed relatively unaffected by prior influenza virus exposures, which can skew immune responses to conventional influenza vaccines.
The researchers observed that the antibody response in the mice was strong and broad, whether or not the animals had been exposed to flu virus before.
Hensley and his colleagues currently are designing human clinical trials, he said. The researchers envision that, if those trials are successful, the vaccine may be useful for eliciting long-term immune memory against all influenza subtypes in people of all age groups, including young children.
“We think this vaccine could significantly reduce the chances of ever getting a severe flu infection,” Hensley said.
In principle, he added, the same multivalent mRNA strategy can be used for other viruses with pandemic potential, including coronaviruses.
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