We’ve long thought that the need for sleep begins and ends in the brain. But a new study by scientists at the University of Oxford flips this notion on its head, or rather, down to a cellular level. According to research published in Nature, the mitochondria within specific sleep-regulating neurons may be the ones quietly counting the minutes we stay awake and deciding when it’s time to shut down.

The study, led by neuroscientist Gero Miesenböck, used Drosophila melanogaster (fruit flies) as the model species to explore this phenomenon. The team’s data suggests that after prolonged periods of wakefulness, mitochondria in certain neurons accumulate oxidative stress, and that stress appears to be the trigger for sleep.

Mitochondria as Sleep Sensors

Mitochondria are often described as the powerhouses of the cell, responsible for producing ATP, the molecule that stores and transports energy. But the Oxford team discovered that these tiny structures do more than keep the lights on. In the sleep-regulating neurons of the fly’s dorsal fan-shaped body, a known sleep center, mitochondria remained active even when the neurons themselves were idle.

This constant mitochondrial activity causes a slow leak of electrons from the respiratory chain, leading to the production of reactive oxygen species (ROS). These unstable molecules can damage cell membranes if they build up unchecked.

According to Miesenböck, the sleep-inducing neurons appear to use this oxidative stress as a kind of internal clock. Once the ROS level passes a certain threshold, the brain flips the switch for sleep, triggering a period of rest and recovery.

Sleep Is for Repair, Not Just Rest

Crucially, the researchers observed that when the flies were allowed to sleep, their mitochondrial shape and function quickly returned to normal, a strong indication that the primary purpose of sleep, at least on a cellular level, may be repair rather than simply energy conservation.

“When these unstable molecules pile up, the only fix is to shut the system down,” Miesenböck said. “The sleep homeostat is actually looking at its own mitochondria to estimate the need for sleep.”

Shaking Flies, Testing Theories

To test whether wakefulness alone, rather than stress or injury, triggered this mitochondrial activity, the researchers kept one group of flies awake using non-harmful methods like gentle shaking or activating arousal neurons. Both methods led to the same signature of mitochondrial stress, strengthening the argument that sleep need is directly linked to time spent awake.

Further experiments showed that flies with fragmented (damaged) mitochondria in their sleep neurons slept less and were unable to recover lost sleep. However, when the researchers forced mitochondrial fusion, essentially improving the cells’ repair tools, the flies slept longer and bounced back better after deprivation.

An especially clever twist involved optogenetics. By installing a light-sensitive proton pump into the mitochondria, the researchers were able to trigger sleep with just an hour of green light exposure, increasing rest time by 25 percent.

Not Just a Fly Problem

While the study was conducted in fruit flies, its implications could extend to humans. Mitochondrial proteins are highly conserved across species, and fatigue is a hallmark symptom of many mitochondrial disorders. Ryan Mailloux of McGill University, who wasn’t involved in the research, noted the potential of targeting mitochondrial stress pathways to treat human sleep issues, as reported by Earth.com.

Previous rodent studies have shown similar patterns, forced wakefulness raises ROS levels, which can lead to cell damage and even death if the stress isn’t alleviated with sleep. A 2023 review also identified mitochondrial redox shifts as a possible master regulator of sleep homeostasis.

Implications for Human Sleep Disorders

The findings could pave the way for novel sleep therapies. If mitochondria truly act as internal sleep meters, then tweaking electron flow within sleep neurons might help manage insomnia or shift-work fatigue.

That said, targeting mitochondria must be done with precision. Drugs that broadly affect electron transport could generate excess heat and deplete energy, not an ideal outcome for patients. More targeted approaches, like modulating lipid repair enzymes or focusing only on specific brain regions, may offer a safer route.

Wearable diagnostics could also emerge from this research. If circulating markers of mitochondrial ROS correlate with sleep need, a blood or breath test might one day tell people when their bodies are approaching critical rest thresholds, a potential game-changer for shift workers or pilots.

Is Sleep A Strategic Shutdown?

Ultimately, the study challenges the idea of sleep as passive downtime. Instead, it presents a view of sleep as a metabolically driven maintenance window, one commanded not from the whole brain, but from microscopic sentinels inside individual neurons.

In aging studies, preserving mitochondrial health has already been shown to protect cognitive function. This new research ties those dots even closer together, showing that sleep, aging, energy balance, and cellular repair may all be chapters in the same story.

As science digs deeper, it appears that sleep may not be a simple “off switch”, but rather, a strategic and necessary pause, dictated by the fiery engines within us all.

Sneezing? Have a cold? Wheezing because of pollen? Take a cetirizine! This is what we do and have continued to do since so long, but, it may be now the time that we stop.

Diphenhydramine, a first-generation antihistamine approved in 1946, has long held a place in medicine cabinets worldwide. Commonly used to treat everything from seasonal allergies to bug bites, it also appears in nighttime cold medications and over-the-counter sleep aids. However, according to a recent review by allergy experts from Johns Hopkins University and the University of California, San Diego, it’s time to move on.

The study, published earlier this year, emphasized that while diphenhydramine does offer symptom relief, it comes with a host of potentially dangerous side effects, especially when safer, second-generation antihistamines like cetirizine, loratadine, and fexofenadine are readily available.

Dr. Anna Wolfson, an allergist at Massachusetts General Hospital, said she sees the medication misused in clinical settings far too often. “If someone has an allergic reaction to food, people will say, ‘Don’t worry, I have diphenhydramine in my purse,’ but really, epinephrine is the first-line treatment,” she noted. The sedative effect of the drug can actually mask worsening symptoms, putting patients in more danger. So if you thought sleeping it off helps, maybe not?

The Hidden Dangers: Sedation, Cognitive Impairment and Misuse

The review also highlighted how diphenhydramine interacts with the brain, often causing drowsiness, confusion, cognitive impairment, and even cardiac complications. These effects are more pronounced in older adults, where the drug’s effects can linger for up to 18 hours, leading to falls and disorientation.

In children, misuse has resulted in hospitalizations, paradoxical hyperactivity, and even fatalities, some tied to the viral and deadly “Benadryl Challenge” on TikTok.

The medication was also found to have no substantial clinical advantage over newer antihistamines in randomized trials. While it may reduce sneezing and itching, it offers minimal benefit for nasal congestion and often comes with more side effects.

Expert Insights on Tighter Oversight

Dr. Siri Kamath, a consultant in internal medicine at Gleneagles BGS Hospital in Bengaluru, agrees with the growing global consensus. “Diphenhydramine is an older antihistamine, and while it works, the safety cushion is thinner now, especially when anyone can buy it over the counter,” she said.

Dr. Kamath explains that while the drug can still be useful in emergencies, such as anaphylactic reactions when paired with epinephrine or in managing motion sickness and certain neurological conditions, its use in routine allergy management is unnecessary and potentially harmful.

She adds that regulatory bodies in India, such as the Central Drugs Standard Control Organization (CDSCO) and the Indian Pharmacopoeia Commission (IPC), monitor drug safety through real-world data. “When a drug begins doing more damage than healing, especially with safer choices available, it sparks a fresh look from regulators,” she notes.

Misuse Is a Key Part of the Problem

Diphenhydramine’s accessibility without prescription has made it susceptible to misuse. Dr. Kamath says it’s not just the drug’s inherent properties, but also the lack of awareness among the public and the way it’s marketed. “Clearer labels, more thoughtful dispensing by pharmacists, and public awareness can go a long way in preventing misuse,” she said. “We can’t overlook troubling trends online. This medicine does its job when used right, but without proper checks, its easy access can turn into a silent danger.”

This sentiment is echoed by American pharmacists and pediatricians who report that the medication is often misused in children for sleep and cold symptoms, despite its limited efficacy and serious risks. Saline drops, suctioning, or second-generation antihistamines like cetirizine are now preferred options for children above six months.

The Case for Moving Diphenhydramine Behind the Counter

Globally, experts are now calling for diphenhydramine to be either removed from the over-the-counter market or moved behind the counter to ensure pharmacist oversight.

In India, Dr. Kamath suggests tighter regulation rather than a blanket ban. “Instead of a full ban, we need better communication and tighter dispensing rules,” she said.

The Consumer Healthcare Products Association, which represents manufacturers like Benadryl's maker Kenvue, maintains that the medication is safe when used as directed and already includes clear warning labels. However, with over 1.5 million prescriptions still written annually in the U.S. alone, and countless untracked OTC purchases worldwide, some experts believe more than warning labels may be needed.

Balancing Familiarity with Evidence

For many patients and families, diphenhydramine is a go-to remedy that evokes familiarity and trust. But Dr. Kamath cautions against letting that history cloud present risks. “So many patients hold on to older medicines not out of defiance, but because they’ve leaned on them for years. But familiarity should never come at the cost of safety.”

Organ donation is a selfless way to give back to one’s community and a great way to look out for those who are in need, even after you pass on. This has been growing sentiment all over the world and India has shown massive growth in the sector. The Ministry of Health and Family Welfare announced the milestone achievement of India completing more than 18,900 organ transplants, the most ever in a single year. This is a big jump from fewer than 5,000 transplants in 2013.

Because of this effort, India is now third in the world for organ transplants, just behind the United States and China. Union Health Minister Shri Jagat Prakash Nadda spoke at the 15th Indian Organ Donation Day ceremony, he also noted that India is a world leader in hand transplants, showing the high skill of its surgeons.

What Helped The Rise In Numbers of Donations?

The government is working hard to make organ donation easier for everyone. Since a new online pledge website was launched in 2023, over 3.30 lakh people have signed up to donate their organs. This shows that more and more citizens are willing to help.

To support this, the government is improving hospitals and training more staff to make sure organs can be moved quickly and safely. They also provide financial help of up to ₹15 lakh for poor patients needing a transplant and cover kidney transplants under the Ayushman Bharat PM-JAY health plan.

What To Expect When You Pledge To Donate Organs

Organ donation can save lives, and there are two main ways to do it. According to All India Institute of Medical Science (AIIMS) you can choose to be a donor while you are alive, or your family can give their permission after you pass away. The Organ Retrieval Banking Organization (ORBO) helps coordinate this entire process. If you want to donate your organs after you die, you can pledge to be a donor now. Here’s how it works:

Fill out a form: You can get a free donor form from ORBO's website or by contacting them directly.

Get it signed: You need to fill out the form and have it signed by two witnesses, one of whom should be a close family member.

Send it in: Mail the completed form back to ORBO.

Receive your card: ORBO will send you a donor card with a registration number.

Tell your family: It’s important to keep your donor card with you and tell your family about your decision. This helps make sure your wishes are known.

Can Anyone Donate Organs?

The Kerala State Organ and Tissue Transplant Organization (K-SOTTO) explains that generally, anyone can donate organs or tissues, regardless of age. People with conditions like cancer or HIV are typically not able to donate, but even these rules can be flexible in certain situations. Before any organs are used, doctors will run tests to make sure they are healthy and won't pass on any diseases. The final decision on whether an organ is suitable for donation is made by doctors at the time of death.

Informing Your Family Is Important

K-SOTTO states that in India, the most important step for an organ donor is to talk with their family. Your donor card is not a legal document; it only shows your wish. By law, organ donation can only happen if your family gives written permission. That's why it's crucial to tell your family about your decision. Explain why it matters to you so they will be more likely to honor your wishes if the time comes.

Organ Donation After Death

AIIMS adds to the previous point and explains that even if a person did not register as an organ donor, their family can still choose to donate their organs after their death. The family simply needs to sign a consent form, and the organs are then quickly and respectfully removed within a few hours. The Organ Retrieval Banking Organization (ORBO) team manages this entire process, ensuring that the body is returned to the family in a dignified manner with no disfigurement. This allows funeral arrangements to proceed as normal.

Pledging your organs is simply the first step towards the donation process, having open conversations and necessary dialogues with your family, health care professionals will ensure the process happens smoothly.

As we grow old, it is said that our balance and stability decreases, and the chances of us falling and injuring ourselves is much more prevalent. It was just another day in the emergency room when a 71-year-old was admitted after cranial and thoracic trauma from a fall. He was a bit confused and struggling to catch his breath, but the team was optimistic. They began the standard workup, expecting to stabilize him for further evaluation.

However, the treatment was derailed when he suddenly experienced a cardiorespiratory arrest. The emergency room staff-initiated CPR, following the strict protocols of Advanced Life Support. They checked for cardiac tamponade, a potential cause, but the bedside ultrasound showed nothing. Despite receiving CPR for 20 minutes, his heart didn't respond. He was declared dead. About one minute later, however, his heart began beating on its own, and he ‘rose from the dead’. He still couldn't breathe on his own and was moved to the ICU.

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Although he was stabilized, the man eventually died. His injuries included bleeding in the brain, fractures to his skull, neck, and ribs. This report was published in the International Journal of Innovative Research in Medical Science, detailing a case of Lazarus phenomenon that happened in February of 2025.

Rising From the Dead – Not A Miracle But Medical Phenomenon

When an emergency situation arises and we must rush to the doctors, they try their level best to ensure that the person receiving the care survives and has the best possible quality of life. However, it is not always possible. So, it is nothing short of a miracle when a person comes back to life, after some period of being declared dead. This is called the Lazarus Syndrome. It is a rare event where a person's heart spontaneously starts beating again after they've been pronounced dead following a failed CPR attempt, it was named after the biblical figure Lazarus.

The International Journal of Community Medicine and Public Health 2024 review explains that even though it has been documented in medical literature, doctors don't fully understand why the Lazarus syndrome happens. Several theories have been proposed. Sometimes, the drugs given during CPR might not work right away. The heart could restart when the medication finally takes effect. Some possible theories suggested by the:

Delayed Medication Effect

Sometimes, drugs given during CPR might not work right away. The heart could restart when the medication finally takes effect.

Hyperkalemia

An excess of potassium in the bloodstream may play a role.

Myocardial Stunning

This refers to a temporary loss of heart function that can improve on its own.

Reperfusion Injury

When blood flow returns to the heart after a period of being stopped, it can sometimes cause further damage.

Is It Medical Negligence Or An Unavoidable Phenomenon?

To understand this, a 2012 survey published in the Critical Care Medicine, asked doctors what methods they used to declare a patient dead. Out of 501 intensive care doctors in Canada, 49% responded to a survey about how they determine death after a patient's heart stops. The doctors had an average of 10 years of experience and typically worked in large, university-affiliated hospitals.

The survey revealed a lot of variation in how doctors declare a patient dead. The most common methods were listening for heart and breath sounds and checking for a pulse, but no single method was used by everyone. Despite the variations, many doctors agreed on a few key points:

Lazarus Phenomenon

65% of the doctors believe that autoresuscitation, or the Lazarus phenomenon, is real, with 37% saying they have personally seen a possible case during their career.

Need for Guidelines

A large majority of doctors (69%) believe there needs to be a standardized process for declaring death after a cardiac arrest. This number was even higher (91%) when it came to cases involving organ donation.

How Does The Lazarus Phenomenon Change Medical Care?

The 2024 review of Lazarus syndrome details how the syndrome forces us to rethink what it means to be alive or dead. It raises difficult questions, such as:

• When is someone really dead? It makes doctors re-examine the rules for declaring death.
• What about organ donation? If a patient could potentially come back to life, it complicates the process of organ donation.
• What if they survive with brain damage? Doctors and families must consider the patient's potential quality of life if they recover but have suffered brain injury.

How Do the Doctors Deal With Lazarus Syndrome?

To understand the effects of Lazarus syndrome, the medical team’s main goal is to figure out what caused it and to give the appropriate treatment. They might use advanced cardiac life support, which means giving the highest level of care possible.

Doctors might also use a special machine called extracorporeal membrane oxygenation (ECMO) to help the heart and lungs work.

Another treatment option is therapeutic hypothermia, where the patient's body is cooled down to help protect their brain from damage.

Ultimately, we still have a lot to learn about this rare event, and more research is needed to better understand how to manage it.