Publisher Health

SharecloseShare pageCopy linkAbout sharingImage source, ReutersThe Chinese city of Shanghai, the country’s economic centre and a global trade hub, has eased Covid curbs after a two-month lockdown.At midnight local time (16:00 GMT Tuesday), restrictions were relaxed to allow most people to move freely around the city of some 25 million people.But at least 650,000 residents will remain confined to their homes.China’s overall policy of “zero Covid” remains in place and people catching Covid face quarantine or hospital.Their close contacts also face the prospect of removal to quarantine and the area immediately around where they live being locked down again.”This is a day that we dreamed of for a very long time,” Shanghai government spokeswoman Yin Xin told reporters.”Everyone has sacrificed a lot. This day has been hard-won and we need to cherish and protect it, and welcome back the Shanghai we are familiar with and missed.”E-commerce professional Chen Ying was planning to work from home after the lockdown was eased, but she told AFP news agency she might treat her two-year-old son to a long-awaited walk outside.”We should have been free to begin with, so don’t expect me to be deeply grateful now they’ve given it back to us,” she added.This video can not be playedTo play this video you need to enable JavaScript in your browser.Lockdown has seen many residents lose income, struggle to find enough food and cope mentally with prolonged isolation.Manufacturers including Western car makers Volkswagen and Tesla have been particularly impacted by the restrictions as staff were kept away from factories or had to work in “closed loop” conditions, where they lived at the plants.On Wednesday a basic service will resume on public transport and shops will open with larger ones operating at 75% capacity, but cinemas, museums and gyms will remain closed.Most children will not return to face-to-face schooling.There are new rules too:All residents will be required to show a green health code on their smartphone to leave their home compounds or buildings and access most placesAll residents wishing to move around the city on public transport and access banks, malls etc will be required to have a negative PCR test certificate valid in the last 72 hoursAnd restrictions on leaving Shanghai remain, with any resident travelling to another city facing quarantine of 7-14 days on arrival.The city has a 50-point plan aimed at revitalising its economy, which before the lockdown was worth more than $600bn (£475bn).New measures include reducing some taxes for car buyers, speeding up the issuance of local government bonds and fast-tracking approvals of building projects.Big bang for ShanghaiIt was supposed to last just nine days. A staggered lockdown to lessen the impact on the city’s economy, state media said. It lasted 65 days. It crippled Shanghai and scarred its people.The easing of restrictions is happening as quickly as they were imposed. There’s no gradual process, over several weeks. Instead there’s a big bang: one day when most of the emergency rules and regulations are simply being lifted.The relief is immense, for generations of some families who’ve lived together behind a locked front door for more than two months. For workers who’ve lived in tents inside factories where they’ve carried on working. For the shop and restaurant owners whose livelihood ground to a halt. For the thousands of people forced to leave their homes and sent to quarantine centres. For the almost 25 million people who live here.The rigidity of the lockdown caused much frustration in the city.Marketing professional Anita Xu, 32, felt “a little caught unawares”. “Even if you can go out, I don’t know what you can do,” she told AFP.But Todd Pearson, managing director of Camel Hospitality Group, which operates restaurants, bars and gyms in and around Shanghai, sounded a cautious note when he spoke to Reuters news agency.”I’m hopeful that they will rush things along to restart the economy,” he said. “I just hope it’s not at the cost of more outbreaks. I’m not sure many businesses or the people could handle much more.”China has registered at least 14,604 deaths and 2,426,568 cases of Covid during the pandemic, with nearly 90% of its population fully vaccinated.Worldwide, Covid has killed at least 6,289,241 people, according to John Hopkins University research.More on this storyShanghai to lift curbs on businessesEntire community relocated over CovidThe hard life of a homeless Shanghai deliverymanResidents ‘running out of food’

The liver has a unique ability to regenerate after damage. However, it was unknown whether this ability decreases as we age. International scientists led by Dr. Olaf Bergmann at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden used a technique known as retrospective radiocarbon birth dating to determine the age of the human liver. They showed that no matter the person’s age, the liver is always on average less than three years old. The results demonstrate that aging does not influence liver renewal, making the liver an organ that replaces its cells equally well in young and old people.
The liver is an essential organ that takes care of clearing toxins in our bodies. Because it constantly deals with toxic substances, it is likely to be regularly injured. To overcome this, the liver has a unique capacity among organs to regenerate itself after damage. Because a lot of the body’s ability to heal itself and regenerate decreases as we age, scientists were wondering if the liver’s capacity to renew also diminishes with age.
The nature of liver renewal in humans also remained a mystery. The animal models provided contradictory answers. “Some studies pointed to the possibility that liver cells are long-lived while others showed a constant turnover. It was clear to us that if we want to know what happens in humans, we need to find a way to directly assess the age of human liver cells,” says Dr. Olaf Bergmann, research group leader at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden.
The Human Liver Remains a Young Organ
The interdisciplinary team of biologists, physicists, mathematicians, and clinicians led by Dr. Bergmann analyzed the livers of multiple individuals who died at ages between 20 and 84 years old. Surprisingly, the team showed that the liver cells of all subjects were more or less the same age.
“No matter if you are 20 or 84, your liver stays on average just under three years old,” explains Dr. Bergmann. The results show that the adjustment of liver mass to the needs of the body is tightly regulated through the constant replacement of liver cells and that this process is maintained even in older people. This ongoing liver cell replacement is important for various aspects of liver regeneration and cancer formation.

The multidisciplinary Zurich research team Liver4Life has succeeded in doing something during a treatment attempt that had never been achieved in the history of medicine until now: it treated an originally damaged human liver in a machine for three days outside of a body and then implanted the recovered organ into a cancer patient. One year later, the patient is doing well.
The Liver4Life research team owes its perfusion machine, which was developed in house, to the fact that it became possible to implant a human organ into a patient after a storage period of three days outside a body. The machine mimics the human body as accurately as possible, in order to provide ideal conditions for the human livers. A pump serves as a replacement heart, an oxygenator replaces the lungs and a dialysis unit performs the functions of the kidneys. In addition, numerous hormone and nutrient infusions perform the functions of the intestine and pancreas. Like the diaphragm in the human body, the machine also moves the liver to the rhythm of human breathing. In January 2020, the multidisciplinary Zurich research team — involving the collaboration of University Hospital Zurich (USZ), ETH Zurich and the University of Zurich (UZH) — demonstrated for the first time that perfusion technology makes it possible to store a liver outside the body for several days.*
From poor to good in three days
The team prepared the liver in the machine with various drugs. In this way, it was possible to transform the liver into a good human organ, even though it was originally not approved for transplantation due to its poor quality. The multi-day perfusion, i.e. the mechanical circulation of the organ, enables antibiotic or hormonal therapies or the optimization of liver metabolism, for example. In addition, lengthy laboratory or tissue tests can be carried out without time pressure. Under normal circumstances, this is not possible because organs can only be stored for 12 hours if they are stored conventionally on ice and in commercially available perfusion machines.
Treatment attempt successful
As part of an approved individual treatment attempt, the doctors gave a cancer patient on the Swisstransplant waiting list the choice of using the treated human liver. Following his consent, the organ was transplanted in May 2021. The patient was able to leave hospital a few days after the transplantation and is now doing well: “I am very grateful for the life-saving organ. Due to my rapidly progressing tumor, I had little chance of getting a liver from the waiting list within a reasonable period of time.”
Saving more lives
The article on the first transplantation of a liver prepared in a perfusion machine was published in Nature Biotechnology, on May 31, 2022. “Our therapy shows that by treating livers in the perfusion machine, it is possible to alleviate the lack of functioning human organs and save lives,” explains Prof. Pierre-Alain Clavien, Director of the Department of Visceral Surgery and Transplantation at the University Hospital Zurich (USZ). Prof. Mark Tibbitt, Professor of Macromolecular Engineering at ETH Zurich, adds: “The interdisciplinary approach to solving complex biomedical challenges embodied in this project is the future of medicine. This will allow us to use new findings even more quickly for treating patients.”
The next step in the Liver4Life project is to review the procedure on other patients and to demonstrate its efficacy and safety in the form of a multicenter study. Its success would mean that in the future, a liver transplantation, which usually constitutes an emergency procedure, would be transformed into a plannable elective procedure. At the same time, a next generation of machines is being developed. In addition, those involved in basic research continue to look for ways of treating other liver diseases outside the body with drugs, molecules or hormones.
Liver4Life: a Wyss Zurich project
The Liver4Life project was launched in 2015 under the umbrella of the Wyss Zurich Translational Center (Wyss Zurich). It brings together the highly specialized technical know-how and biomedical knowledge of around ten medical professionals, biologists and engineers. The project is being financed with donations from the initiator of Wyss Zurich, Dr. h.c. mult. Hansjörg Wyss.
* https://www.sciencedaily.com/releases/2020/01/200113111147.htm
Story Source:
Materials provided by University of Zurich. Note: Content may be edited for style and length.

One powerful way cancer cells defend against tumor-killing immune cells is to load up their cell surface with a protein known as PD-L1. Now a team of UCLA Jonsson Comprehensive Cancer Center researchers led by Roger S. Lo, MD, PhD, has identified a method to degrade tumor cell-surface PD-L1, thereby making tumors susceptible to immune attack. This approach, in combination with existing therapies, could improve treatment responses of metastatic melanoma and other cancers by suppressing resistance to current therapies.
Lo and his co-authors published their findings Tuesday in the journal Cancer Discovery.
Lo, a professor of medicine (dermatology) and molecular and medical pharmacology at UCLA’s David Geffen School of Medicine, and the team at his lab first found that tumor cell-surface PD-L1 is destabilized or degraded by a protein named ITCH. By searching a trove of small molecules at a National Institutes of Health library, they found and deployed a small molecule, which they characterized to be an ITCH activator. By activating ITCH, the small molecule degrades tumor cell-surface PD-L1. This small molecule, when used together with an existing therapy, suppresses relapses of melanoma in animal models.
Reducing the accumulation of PD-L1 clears the path for tumor-killing T-cells to do their work. “Once ITCH is activated, it’s now able to degrade or destabilize tumor surface PD-L1,” Lo said. “And once PD-L1 is degraded, then there are more T cells active to help therapies work better.”
Lo and his lab have been focusing on developing mutation-targeted therapy, as common cancer mutations drive disease progression by hyper-activating the so-called MAPK pathway. Therapy targeting the MAPK pathway for patients with metastatic cutaneous melanoma is associated with a high rate of response. However, the disease often comes back in a process called acquired resistance, causing clinical relapses.
According to Zhentao Yang, PhD, a postdoctoral fellow in Lo’s lab, “In prior work from our group, we found that melanoma cells treated with MAPK-targeted therapy accumulate PD-L1 on their cell surface. So we hypothesized that, if we find the protein whose normal job is to degrade cell-surface PD-L1, then we have the first clue as to how to reduce PD-L1 protein levels in cancers treated with MAPK-targeted therapy.”
In collaboration with another UCLA team led by James Wohlschlegel, PhD, professor of biological chemistry at the David Geffen School of Medicine, Yang identified ITCH as the protein that binds to surface PD-L1 and tags it biochemically for degradation by the tumor cell. In follow-up work, “We were excited to go further to find a potential path for this knowledge to help patients with cancers. Identification of a small molecule that can activate ITCH became a priority,” said Yan Wang, a first-year PhD student who joined the Lo Lab from the department of molecular and medical pharmacology.
PD-L1 “is regarded as a universal tumor-evasive mechanism,” Lo says, and therefore a therapy that degrades it could potentially have wide applications in the immuno-oncology space. He points out that the MAPK pathway is one of the most dysregulated cancer pathways, especially in aggressive cancers like melanoma and pancreatic cancer. “This study advances our knowledge of how to combine mutation- and immune-targeted therapies for patients with cancers.”
Story Source:
Materials provided by University of California – Los Angeles Health Sciences. Note: Content may be edited for style and length.

Natural selection has produced mammals that age at dramatically different rates. Take, for example, naked mole rats and mice; the former can live up to 41 years, nearly ten times as long as similar-size rodents such as mice.
What accounts for longer lifespan? According to new research from biologists at the University of Rochester, a key piece of the puzzle lies in the mechanisms that regulate gene expression.
In a paper published in Cell Metabolism, the researchers, including Vera Gorbunova, the Doris Johns Cherry professor of biology and medicine; Andrei Seluanov, professor of biology and medicine; and Jinlong Lu, a postdoctoral research associate in Gorbunova’s lab and the first author of the paper, investigated genes connected to lifespan. Their research uncovered specific characteristics of these genes and revealed that two regulatory systems controlling gene expression — circadian and pluripotency networks — are critical to longevity. The findings have implications both in understanding how longevity evolves and in providing new targets to combat aging and age-related diseases.
Comparing longevity genes
The researchers compared the gene expression patterns of 26 mammalian species with diverse maximum lifespans, from two years (shrews) to 41 years (naked mole rats). They identified thousands of genes related to a species’ maximum lifespan that were either positively or negatively correlated with longevity.
They found that long-lived species tend to have low expression of genes involved in energy metabolism and inflammation; and high expression of genes involved in DNA repair, RNA transport, and organization of cellular skeleton (or microtubules). Previous research by Gorbunova and Seluanov has shown that features such as more efficient DNA repair and a weaker inflammatory response are characteristic of mammals with long lifespans.

Breathing difficulties are the main cause of death following opioid use. In the UK, the number of adults entering treatment for opioid use was 140,863 in 2020/21* and opioid use remains a significant cause of premature death, contributing to 3,726 drug-related deaths last year1. Opioid misuse causes death by supressing respiratory activity.
New research, published in The Journal of Physiology, points to a novel treatment for respiratory depression associated with opioid use that administers electrical pulses to the back of the neck, helping patients regain respiratory control following high dosage opioid use. This could offer an alternative to pharmacological treatments, which can cause withdrawal symptoms, heart problems and can negatively affect the central nervous system.
Breathing problems can occur after opioid use or post-operative complications from anaesthesia because opioids desensitise the brain stem to rises in carbon dioxide. This can cause respiratory failure, which can be fatal. Current treatments, such as manual lung inflation and medication, can work in the short term to combat breathing problems following opioid use, but getting patients to breathe independently remains a challenge. Therefore, this new research, which administers epidural electrical stimulation (EES) offers an alternative, non-pharmacological treatment.
EES administered at the cervical spinal cord, which is located at the back of the neck, activates a network of neurons in the brainstem that stimulates and coordinates respiratory muscles and improves the rate and depth of breathing.
Researchers from the David Geffen School of Medicine at the University of California (UCLA), Los Angeles, US, targeted sensory-motor circuits in the cervical spinal cord of 18 patients with degenerative spine diseases who were anesthetised for surgical treatment. They delivered 30 Hertz of EES to the cervical spinal cord continuously for no longer than 90 seconds.
They found that short periods of continuous low-intensity EES not only increased the volume of breath but also actively controlled the frequency and rhythm during opioid-induced breathing problems. The rhythmic breathing pattern was sustained briefly after the EES stopped in the presence of high-dose opioids.
Dr. Daniel Lu, senior author and UCLA professor and vice chair of neurosurgery, said:
“Our results provide proof of principle that cervical EES could improve respiration following opioid use. We can compare the human body to a car, our goal is to jump start the body so it can run by itself without periodic pushes. We hope to use EES to provide novel approaches to restore breathing for healthcare providers as we are now using defibrillation devices for restoring cardiac activities.”
Future trials in humans with larger cohorts will be conducted to further assess the practical application and impact of EES to determine whether EES can alleviate or reduce the need for ventilator support in acute pathological conditions such as OIRD, stroke, and traumatic brain, brain stem or spinal cord injury. Experimental studies in mice will be carried out to further investigate the role specific neurons play in response to EES.
* Adult substance misuse treatment statistics 2020 to 2021: report (November 2021)
Story Source:
Materials provided by The Physiological Society. Note: Content may be edited for style and length.

Scientists have identified a new role for a protein complex at the center of a human genetic disorder called Bardet-Biedl syndrome, or BBS, for which there is currently no cure.
Bardet-Biedl syndrome arises when the BBSome protein complex malfunctions. Because the BBSome regulates the form and function of cilia, the hair-like structures on the surface of cells, BBS has been classified as a disease of the cilia.
But the wide spectrum of symptoms associated with BBS — the most common of which is vision loss, as well as obesity, extra fingers or toes and kidney malfunction — have led to hypotheses that the cause of the syndrome may not lie solely within the cilia.
In a new study published in Developmental Cell, a team from the University of Michigan Life Sciences Institute now offers the first known direct evidence for these hypotheses. Their findings demonstrate that the BBSome operates outside of cilia to support sight, at least in one common model species.
The discovery began when scientists in the lab of LSI faculty member Shawn Xu were investigating how tiny roundworms called Caenorhabditis elegans can sense light despite having no eye-like organs. Because C. elegans have a simple and well-mapped nervous system, the Xu lab uses them as a model to understand the fundamental biology behind various forms of sensation.
The team performed a genetic screen, a process of introducing random mutations to identify which genes are required for a given biological process, to find the genes involved in the worms’ ability to respond to light. Most of the mutations that caused worms to stop sensing light turned out to be in the BBSome. And, like the progressive vision loss that BBS patients experience, the worms with BBSome mutations progressively lost the ability to sense light as they aged.

Getting diagnosed with Alzheimer’s disease or another kind of dementia is never pleasant — but a new study shows that when and how someone’s cognitive issues come to light can also make a big difference in their health care costs.
The study, from a University of Michigan team, uses long-term data from thousands of older adults who either got diagnosed formally, or started to show clear signs of memory and thinking problems on a screening questionnaire they took as part of a long-term study they’re in.
Those costs rose sharply — by 150% — from the months just before a formal diagnosis to the months just after it. But for those whose cognitive impairment was identified through screening, there was no jump in costs.
Diving deeper, the researchers show that a health crisis leading to a hospital stay and perhaps a nursing home stay accounted for the sharp spike in costs to the Medicare system at the time of a dementia diagnosis.
In fact, the researchers say, the undiagnosed dementia may have played a role in that health crisis — for instance, by getting in the way of managing conditions or recognizing symptoms.
The study, led by U-M School of Nursing researcher Geoffrey Hoffman, Ph.D. and published in the Journal of the American Geriatrics Society, used data from the Health and Retirement Study, which tracks the health of thousands of older adults over time. He and his colleagues received permission to study anonymous data that connects the results of the participants’ questionnaires to their Medicare billing records.
In all, they looked at data from 2,779 older adults who received a formal diagnosis of Alzheimer’s disease or another dementia, and 2,318 HRS participants whose screening test results strongly suggested they had developed dementia since the last time they took the same screening. All took part in the HRS for multiple years during the time period of 2000 to 2018.
The analysis shows that overall Medicare costs jumped from about $5,400 in the three months before a dementia diagnosis to nearly $13,800 in the three-month period that included the diagnosis, with the dementia diagnosis occurring at the same time patients were treated for strokes, sepsis, heart failure, urinary tract infections and more. For those whose impairment was noted on a screening test but not formally diagnosed, costs stayed steady at about $2,900 for the three-month periods before and after they were screened.
“This fits a broader pattern, in terms of spending after incident diagnoses of chronic disease or injury — there are often sharp, immediate upticks in spending for treatment. But uniquely, spikes in spending after a dementia diagnosis may reflect costs associated with a health care crisis in which the dementia is a contributing factor, rather than the primary factor,” says Hoffman, an assistant professor and member of the U-M Institute for Healthcare Policy and Innovation. “More attention to and support for patients with cognitive decline earlier on may have health benefits and spending implications.”
The U.S. Preventive Services Task Force does not formally recommend screening older adults for dementia because the evidence about the impact of screening on patient outcomes is inconclusive. But many tests are available for people to take themselves or for health providers to give.
In addition to Hoffman, the study’s authors are Donovan T. Maust, M.D., M.S., Melissa Harris, R.N., Ph.D., Jinkyung Ha, Ph.D., and Matthew A. Davis, Ph.D.
The study was funded by the Center to Accelerate Population Research in Alzheimers, which is supported byt he National Institute on Aging (AG066582)

In recent years Alzheimer’s disease has been on the rise throughout the world and is rarely diagnosed at an early stage when it can still be effectively controlled. Using artificial intelligence, KTU researchers conducted a study to identify whether human-computer interfaces could be adapted for people with memory impairments to recognise a visible object in front of them.
Rytis Maskeliūnas, a researcher at the Department of Multimedia Engineering at Kaunas University of Technology (KTU), considers that the classification of information visible on the face is a daily human function: “While communicating, the face “tells” us the context of the conversation, especially from an emotional point of view, but can we identify visual stimuli based on brain signals?”
The visual processing of the human face is complex. Information such as a person’s identity or emotional state can be perceived by us, analysing the faces. The aim of the study was to analyse a person’s ability to process contextual information from the face and detect how a person responds to it.
Face can indicate the first symptoms of the disease
According to Maskeliūnas, many studies demonstrate that brain diseases can potentially be analysed by examining facial muscle and eye movements since degenerative brain disorders affect not only memory and cognitive functions, but also the cranial nervous system associated with the above facial (especially eye) movements.
Dovilė Komolovaitė, a graduate of KTU Faculty of Mathematics and Natural Sciences, who co-authored the study, shared that the research has clarified whether a patient with Alzheimer’s disease visually processes visible faces in the brain in the same way as individuals without the disease.

Cells rely on a process known as RNA interference (RNAi) to control protein production. The centerpiece of that process is the protein Argonaute, which seeks out and destroys mRNA molecules. Cold Spring Harbor Laboratory scientists discovered how Argonaute efficiently jumps from one target to the next. Their work may help improve current RNAi-based therapies and develop better ones in the future.
Cells produce proteins like little factories. But if they make too much at the wrong times it can lead to diseases like cancer, so they control production with a process called RNA interference (RNAi). As of July 2021, several drugs already take advantage of RNAi to treat painful kidney and liver diseases — with another seven in clinical trials. There is a lot of potential for RNAi therapeutics, and Cold Spring Harbor Laboratory (CSHL) researchers are working hard to paint a complete picture of the process, to improve therapies today and make better ones tomorrow.
CSHL Professor & HHMI Investigator Leemor Joshua-Tor and recent CSHL School of Biological Sciences graduate Brianna Bibel are filling in some of the blanks. They recently discovered how RNAi’s workhorse protein Argonaute (Ago) leverages limited resources to keep protein production on track.
It’s important to understand exactly how RNAi works because it’s such a basic and heavily used process, Joshua-Tor said. It also offers a kind of safety net for therapeutics because it doesn’t make permanent changes to cells and can be reversed. Joshua-Tor says:
“For therapeutics, you’d kinda maybe not wanna mess around with the genome so much. In all these kinds of things, you wanna know exactly what’s happening, and if something isn’t working, then you know what to do and where to look. The more information you have, the better it is — you get a complete picture of what’s happening.”
Ago helps cut off protein production by finding, binding, and destroying molecules called mRNA — which tell cells to make proteins. But the amount of Ago in the body pales in comparison to the amount of mRNA it must target. After destroying one, the protein is still capable of finding another but it can’t move on without help. Bibel discovered how cells use a process called phosphorylation to break Ago’s grip on a mRNA target, allowing it to commute to the next. Bibel explains:
“Our theory is that having phosphorylation promote release is a way that you could free up Argonaute because when the target gets released, the guide’s still there and it’s super duper stable. So our thinking is that by phosphorylating it, you’re going to free it to go repress other targets — because it’s still totally capable of doing that work.”
Bibel hopes her discovery will come in handy as research into RNAi continues. “A lot of great advances in science come from just doing basic research,” she said. “And this is one of those basic research questions, trying to figure out how this is working.”
Story Source:
Materials provided by Cold Spring Harbor Laboratory. Original written by Nick Wurm. Note: Content may be edited for style and length.