For over 15 years, Dr Anthony Shum, a pulmonologist at the University of California, San Francisco has been studying a rare genetic disorder called the COPA Syndrome. It stands for coatomer subunit alpha and is a rare, inherited disorder that affects the lungs, joint, and kidney. The National Organization for Rare Disorder also notes that it is a genetic autoimmune disorder that is caused by mutations in the COPA gene. This disease affects families unpredictably—some individuals with the mutation develop severe lung damage early in life, while others remain completely healthy. Now, Shum’s team has discovered a protective genetic variant that may offer new hope for treatment.

A Breakthrough

Researchers found that some relatives of COPA Syndrome patients stayed healthy despite carrying the same COPA gene mutation that causes the disease. The key difference? These unaffected individuals had a protective version of another gene called HAQ-STING.

When scientists introduced HAQ-STING into diseased lung cells from COPA patients, the cells returned to a balanced state, suggesting that this gene could be used as a therapy.

“We really think HAQ-STING could be a gene therapy tool and a step toward a cure,” said Shum, whose findings were published in the Journal of Experimental Medicine.

Families Who Solved The Mystery

Shum’s journey into COPA Syndrome research began in 2011 when he treated a young woman, Letasha, who had severe lung bleeding. Her mother, Betty Towe, mentioned that Letasha’s sister, Kristina, had suffered from similar symptoms. Over the years, Betty had taken both daughters on a four-hour trip to UCSF for treatment. After tracing their family history, Shum discovered that their distant relatives in Texas and Oakland also had lung problems and arthritis. In 2015, Shum, along with scientists from Baylor College of Medicine and Texas Children’s Hospital identified the COPA gene mutation. They realized that it was the common factor behind the illness. However, only some of the 30 individuals with the mutation actually developed symptoms, leaving a major question unanswered.

The Domino Effect

It was established that it occurs when a mutated COPA gene causes another gene STING to go overdrive. The STING that helps fight infections in COPA patients, remain permanently active, which leads to chronic inflammation that damages the lungs, kidneys, and joints. In 2020, while studying STING’s role in the disease, researchers discovered a key variation: HAQ-STING. This version of STING, present in about one-third of the population, appeared to neutralize the harmful effects of the COPA mutation.

To confirm their theory, the scientists needed both affected and unaffected family members to participate in the testing. Letasha, Kristina and Betty immediately volunteered. The researchers then analyzed DNA samples from 26 COPA patients and their healthy relatives. They also conducted CT scans and blood tests to ensure that unaffected members did not have any hidden symptoms. When the findings were all clear, it was revealed that all the healthy individuals had HAQ-STING, while none of the COPA patients did. This was the first known case of a common gene variant completely protecting against a severe genetic disease.

Encouraged by this discovery, researchers tested HAQ-STING’s effects in a lab setting. They introduced it into diseased lung cells from COPA patients, and the cells returned to normal function.

Way Ahead

Shum believes HAQ-STING could lead to game-changing treatments, including:

• Prenatal gene therapy for babies diagnosed with COPA Syndrome before birth
• Aerosol delivery of HAQ-STING for adults, directly targeting the lungs

Before publishing their findings, Shum called Betty with the news—her own HAQ-STING gene had protected her from the disease. He also informed Letasha and Kristina, who were overwhelmed with relief and joy.

“We always believed Dr. Shum would get to the bottom of it,” said Letasha. “This discovery is going to change lives.”

Non-healing mouth sores are often brushed off as minor issues, but when they persist for more than two weeks, they can signal something more serious.

Mouth ulcers are common and are often caused by stress, minor injuries, or nutritional deficiencies. Sores that do not heal may indicate underlying health concerns, particularly oral cancer.

"Early-stage oral cancers can present as painless ulcers or patches inside the mouth, making them easy to overlook. Conditions like Oral Cancer, Leukoplakia, or Lichen Planus may initially appear as harmless lesions but can progress if left unchecked," Dr. Mandeep Singh Malhotra, Director – Surgical Oncology at the CK Birla Hospital, Delhi, told HealthandMe.

Dr. Tejinder Kataria, Chairperson - Radiation Oncology, Medanta Hospital, Gurugram, added that mouth sores that don't go away after two to three weeks could be an early sign of oral cancer.

"These sores can be red or white and hurt or bleed easily. This is not the same as regular ulcers," he told HealthandMe.

The experts noted that non-healing sores can also be associated with systemic conditions such as

• vitamin deficiencies (especially B12 and iron),
• weakened immunity,
• chronic infections.

What Is Oral Cancer?

Also read: CDC Delay In Infant Hepatitis B Shots May Surge Infections, Deaths In US: Research

Oral cancer is a wide term for cancer that affects the inside of your mouth, and it typically presents itself as white patches or sores that bleed. It can occur on the:

• Lips.
• Gums.
• Tongue.
• Inner lining of the cheeks.
• Roof of the mouth.
• Floor of the mouth

It is estimated that about 60,000 new cases of oral cancer are reported annually in India, and five people die from the condition every hour. It is the most common cancer in Indian men and the third most common in women, with roughly 20 in 100,000 people affected.

Signs To Watch For

Oral cancer grows slowly, and the first signs usually don't hurt, so a lot of people don't notice them. However, it's important to look out for

• a change in voice,
• a lump in the mouth,
• trouble chewing
• A lip or mouth sore that won't heal.
• A white or reddish patch on the inside of the mouth.
• Loose teeth
• Mouth pain
• Ear pain
• Difficult or painful swallowing.

• Not brushing teeth,
• Tobacco use,
• Alcohol consumption,
• Ill-fitting dental appliances

How To Prevent

Early diagnosis plays a crucial role in effective treatment. If a mouth sore persists, grows, or is accompanied by pain, bleeding, or difficulty swallowing, it is important to consult a healthcare professional promptly. Paying attention to such small signs can make a significant difference in long-term health outcomes.

• Avoid smoking,
• drinking alcohol,
• Eat a lot of fruits and vegetables
• Keep your mouth clean.
• Going to the dentist regularly can help spot changes early.

Knee replacement surgery has witnessed remarkable advancements over the past few years. Traditionally, total knee replacement was performed as a uniform procedure ("one procedure fits all"), where the entire knee joint was replaced regardless of the extent or location of damage.

However, with the evolution of modern orthopedics, the focus has shifted towards precision and personalized treatment. In this direction, an A La Carte or Modular approach towards patients who need knee Replacement has emerged, which customizes or personalizes the surgery according to the patient’s specific condition.

Understanding The “à la carte” Concept

The term “à la carte” refers to selecting individual items from a menu. In knee replacement surgery, it means replacing only the damaged portion of the joint instead of the entire knee.

The knee is anatomically divided into three compartments:

• Medial compartment (inner side)
• Lateral compartment (outer side)
• Patellofemoral compartment (front portion involving the kneecap)

In many patients suffering from osteoarthritis, the disease affects only one or two of these compartments—most commonly the medial compartment. In such cases, replacing the entire knee may not be necessary. Modular implants allow surgeons to selectively treat the affected area while preserving healthy bone and ligaments.

The à la carte technique helps preserve the natural structure of the knee while effectively treating only the damaged portion, resulting in better and more natural functional outcomes for patients.

However, this approach is not suitable for all patients. It is generally not recommended in inflammatory conditions such as rheumatoid arthritis.

How It Differs From Total Knee Replacement

In Total Knee Replacement (TKR), all three compartments of the knee are replaced, making it an effective solution for advanced and widespread arthritis.

In contrast, Modular Knee Replacement offers a more targeted approach:

• Replacement of a single compartment (Partial Knee Replacement)
• Replacement of two compartments (e.g., medial + patellofemoral)

This selective treatment helps maintain the knee’s natural structure and function.

Advantages Of The Modular Approach

For carefully selected patients, this technique offers several important benefits:

• More natural knee function: Preservation of ligaments and bone provides a more natural feel.
• Faster recovery: Less invasive surgery leads to quicker rehabilitation.
• Reduced pain and blood loss: Minimal surgical trauma results in less discomfort.
• Improved mobility: Patients often achieve a better range of motion.
• Enhanced lifestyle comfort: Activities like sitting cross-legged or squatting may be easier and can be done unrestricted compared to total knee replacement.

Who Is the Ideal Candidate?

Not every patient is suitable for this procedure. Proper patient selection is one of the most critical factors in ensuring the success of this procedure. Ideal candidates typically include people:

• Having arthritis limited to one or two compartments
• Having stable knee ligaments
• Who do not have a severe deformity in the knee

Long-Term Outcomes

When performed in the right patient, modular knee replacement delivers excellent long-term outcomes (90 to 95 per cent survivorship for 15 years). Its success largely depends on accurate patient selection and flawless surgical expertise.

In some cases, if arthritis progresses in the remaining compartments over time, conversion to total knee replacement can still be done. However, this is relatively uncommon when proper indications are followed.

Role Of Robotic Technology

Robotic-assisted surgery has further enhanced the precision of this technique. It enables:

• Millimeter-level accuracy
• Precise implant positioning
• Restoration of patient-specific knee alignment

Conclusion

Ala Carte or Modular Knee Replacement represents a significant shift toward personalized orthopaedic care. Instead of a "one-size-fits-all " approach, surgeons can now tailor treatment based on the patient’s anatomy and disease pattern.

For many patients, this means less invasive surgery, faster recovery, improved function, and a more natural-feeling knee. Individuals experiencing persistent knee pain are advised to consult an orthopaedic specialist early to determine the most appropriate treatment option.

Beyond lung cancers, air pollution fine particulate matter (PM2.5) is increasing mortality for breast as well as liver cancers, according to a global study led by the Union for International Cancer Control (UICC), including researchers from the Indian Council of Medical Research (ICMR).

The important study showed that long-term exposure to PM2.5 increases the overall risk of developing cancer and the chances of dying from it compared with those living in cleaner environments.

For every 10 micrograms per cubic meter (µg/m³) increase in PM2.5 exposure, the overall risk of cancers increases by more than 11 per cent. At the same time, the risk of death also increases by more than 12 per cent for every 10 µg/m³ increase in PM2.5 exposure.

The researchers argued that while other common risk factors like tobacco and alcohol are being targeted with notable progress, air pollution is silently eroding the gains being made.

“We have made huge strides in reducing deaths from cancer, but polluted air is silently undermining that progress. It is a risk people cannot opt out of, and one that disproportionately affects women, children, and people living in poverty,” Cary Adams, CEO, UICC.

“The cancer community continues to make progress in addressing other major risk factors, including tobacco use, alcohol consumption, and viral, bacterial, or parasitic infections such as HPV and HBV that cause cervical and liver cancers. It is increasingly clear that air pollution must also be recognized as a major and preventable factor that increases the risk of developing cancer and of dying from the disease,” added Dr Elisabete Weiderpass, Director, IARC.

Risks of PM2.5: Beyond Lung Cancer

The study, based on data from 42 meta-analyses and systematic reviews published between 2019 and 2024, showed significantly strong associations for liver, colorectal, and breast cancers.

As per recent data from the International Agency for Research on Cancer (IARC), PM₂.₅ exposure contributes to 434,000 lung cancers per year, accounting for more than a quarter of preventable lung cancers in women and nearly one in six in men.

In addition to lung cancer risk, the study noted that the rising levels of PM2.5 are associated with

• a 32 per cent higher incidence of liver cancer
• an 18 per cent increase in the odds of developing colorectal cancer.

• a 12 per cent higher overall risk of dying from cancer,
• a 20 per cent higher risk of death from breast cancer,
• a 14 per cent from liver cancer,
• a 12 per cent from lung cancer.

Who Is At A Higher Risk

According to the researchers, people living in low- and middle-income countries bear the greatest overall burden. These countries frequently lack the resources to reduce pollution at source or to provide timely access to cancer prevention, diagnosis, and treatment.

The challenge is compounded by the projected rise in global cancer cases, expected to increase from 20 million in 2022 to 35 million by 2050. People at risk include:

• Women and children, particularly in settings where solid fuels are used for cooking and heating.
• Women exposed to household air pollution face a 69 per cent higher risk of lung cancer, alongside increased risks of cervical cancer.
• Outdoor workers and communities living near industrial facilities are also at heightened risk, with exposure often concentrated in economically deprived areas.

What Actions Are Required?

The researchers underscored that the evidence presented in the report is already sufficient to justify decisive action to reduce exposure to polluted air. They called upon policymakers to make required changes across energy, transport, industry, and urban planning to reduce the risk of cancer from air pollution.

The study urged the need for properly implementing effective interventions that are well-established. These include:

• Stronger emissions standards and enforcing the WHO air quality Standards
• A transition to clean energy and clean cooking
• Improved urban design by investing more in green infrastructure
• Expanded air-quality monitoring in High-Risk Areas
• Update cancer control plans.