Kristin Kirkby Shaw, DVM, PhD, MS, DACVS-SA, DACVSMR, discusses 2 nutritional modifications that can help manage arthritis in feline patients.

Nutritional strategies for managing arthritis in cats

According to Kristin Kirkby Shaw, DVM, PhD, MS, DACVS-SA, DACVSMR, founder of Canine Arthritis Resources and Education—an organization offering free educational materials for veterinarians and dog owners on osteoarthritis in dogs—one multimodal management approach veterinarians can adopt to help manage arthritis in feline patients is implementing modifications to the patient’s diet. As Kirkby Shaw explains in this short video, key nutritional strategies include maintaining a healthy weight through calorie reduction or a weight loss diet and using fish oil or joint-specific diets that contain omega-3 fatty acids.

Below is the interview transcript, which has been lightly edited for improved clarity.

Kristin Kirkby Shaw, DVM, PhD, MS, DACVS-SA, DACVSMR: 

One of the ways that we want to provide a multimodal management for arthritis for cats is [by] including nutritional modifications. And the 2 primary ways we're going to modify nutrition, or approach from a nutritional standpoint, are:

making sure that the cat's not overweight. And that is usually going to be a matter of reducing the calories or using a weight loss diet—so making sure the cat's not overweight using an appropriate diet that they will eat that is appropriate for any other comorbidities that they may have. So something like k/d [kidney care] plus j/d [joint care] [is] a diet that I've used for cats.

And speaking of that, the j/d portion of that is the omega-3 content. So omega-3 fatty acids are really the only joint supplement that has been shown to be effective for OA [(osteoarthritis)] pain in cats or dogs. So, adding fish oil to the diet or using a joint-specific diet that would be a good recommendation for them.

To hear more from Kirkby Shaw on osteoarthritis in cats, check out:

4 steps to diagnosing feline osteoarthritis

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The American Veterinary Medical Association (AVMA) has named Michael Blackwell, DVM, MPH, the recipient of the AVMA Frederick Douglass Patterson Lifetime Achievement Award.

 The award recognizes a veterinary member of the AVMA who has made significant contributions to the veterinary profession through transformative leadership in promoting diversity, equity, and inclusion (DEI), and whose efforts have brought distinction to the field.

Blackwell, who earned his doctor of veterinary medicine degree from Tuskegee University in Alabama, is recognized for his leadership and commitment to DEI, which he combines with One Health objectives.

“I am deeply honored to receive this award, especially one named for Frederick Douglass Patterson, [DVM, PhD], a man whose visionary leadership opened doors for people like my father and me,” Blackwell said during the opening of his award acceptance speech at the AVMA House of Delegates’ regular annual session on July 18, 2025, which was held together with the AVMA Convention in Washington, DC, this year.

 “As a Tuskegee graduate, I carry his legacy with me every day.”

Michael Blackwell, DVM, MPH (left) receiving his award from Sandra Faeh, DVM, AVMA president. (Photo courtesy of R. Scott Nolen and American Veterinary Medical Association)

Currently, Blackwell is the director of the Program for Pet Health Equity in the Center for Behavioral Health Research at the University of Tennessee. In this role, he ensures veterinary care is accessible to all pets, including those from families with limited resources.

Blackwell, along with his team, created AlignCare, a nationwide initiative that uses a community-funded, One Health approach to help care for pets and their families. He also leads the Access to Veterinary Care Coalition, an organization focused on bringing attention to the lack of access to veterinary care.

During his tenure as dean of the University of Tennessee College of Veterinary Medicine from 2000 to 2008, Blackwell worked to advance DEI by appointing a DEI director, offering mentorship programs, expanding support services for underrepresented students, and working with organizations committed to DEI in veterinary medicine.

“Progress happens, problems are solved, [and] justice is realized when leaders lead. Leadership in our profession demands more than clinical excellence; it requires us to see the whole family, to understand the barriers they face, and to act with courage and compassion. It means listening to those we serve and to each other with humility and purpose,” Blackwell said during his acceptance speech.

Prior to serving as the University of Tennessee College of Veterinary Medicine’s dean, Blackwell served in the Commissioned Corps of the United States Public Health Services for 23 years, during which he was the organization’s chief veterinary officer. In addition, he served as deputy director of the FDA Center for Veterinary Medicine. More than 2 decades later, Blackwell retired as assistant surgeon general with the rank of rear admiral and chief of staff in the Office of the US Surgeon General.

He has also been a practice owner in Oklahoma and Maryland, was the Humane Society of the United States’ (now named Humane World for Animals) chief veterinary officer, and assumed the role of president and CEO of Blackwell Consulting, which offered services related to FDA regulations, public health, veterinary medicine, and organizational and human resources management.

At the end of his acceptance speech at the AVMA House of Delegates, Blackwell directly addressed the audience. “You’re not only stewards of veterinary medicine; you’re architects of its future,” he said. “Let us lead in a way that reflects the diversity of the communities we serve. Let us lead in a way that ensures no family is left behind when it comes to the care of their beloved pet.”

Michael Blackwell honored with AVMA Frederick Douglass Patterson Lifetime Achievement Award. News release. American Veterinary Medical Association. July 30, 2025. Accessed July 31, 2025. https://www.avma.org/news/michael-blackwell-honored-avma-frederick-douglass-patterson-lifetime-achievement-award

AVMA Frederick Douglass Patterson Lifetime Achievement Award. American Veterinary Medical Association. Accessed July 31, 2025. https://www.avma.org/about/awards/avma-frederick-douglass-patterson-lifetime-achievement-award

Articles

“Leadership...requires us to see the whole family, to understand the barriers they face, and to act with courage and compassion," Blackwell said during his acceptance speech.

AVMA honors Michael Blackwell, DVM, MPH, for lifetime contributions to DEI

Accurate blood analysis is essential for early disease detection, but traditional methods can be time-consuming and complex. Zoetis Vetscan OptiCell™ introduces new opportunities to improve efficiency and precision for in-clinic hematology applications. Powered by advanced artificial intelligence (AI), Vetscan OptiCell can help veterinary professionals to identify blood cell abnormalities within minutes, with greater confidence, supporting clinical decision-making and contributing towards improved patient care.

Expert Insights: How AI Is Shaping Veterinary Hematology

Veterinary diagnostics are evolving rapidly, and nowhere is this more evident than in the field of hematology. As clinics face increasing demands for speed, accuracy, and efficiency, the integration of artificial intelligence (AI) into diagnostic tools is transforming how veterinarians approach blood analysis.

Clinical pathologist Austin Viall, DVM, DACVP, has observed significant advancements in in-clinic CBC analyzers over the past 15 years. Recent developments have brought microscopy and dye-based methods, once exclusive to reference laboratories, into the hands of in-clinic practitioners, enhancing diagnostic capabilities at the point of care.

One of the most promising innovations in this space is Zoetis’ Vetscan OptiCell™, a next-generation hematology analyzer powered by AI. Designed to deliver rapid, reliable Complete Blood Count (CBC) results, Vetscan OptiCell enables veterinary professionals to identify blood cell abnormalities within minutes, supporting faster clinical decision-making and helping to improve patient care.

AI in tools such as Vetscan OptiCell functions as a powerful assistant to veterinary healthcare teams, generating reliable results that will help complete the clinical status of the patient and with seamless integration to practice management software

This supportive technology does not replace veterinary expertise but – importantly – amplifies it. When used correctly, AI enhances diagnostic capabilities, treatment planning, and medication prescription while allowing the clinician to make the final decision on patient care. As AI continues to evolve, the need for continuous training and education about its potential uses and limitations is vital.

Staffing shortages and burnout could also be relieved with AI’s ability to pick up more of the repetitive tasks, allowing veterinary teams to focus more on patient interaction and complex case management. This efficiency is especially valuable in busy practices where time and resources are limited.

Expanding the Zoetis Diagnostics Portfolio

In addition to the Vetscan OptiCell analyzer, Zoetis is pushing the boundaries of veterinary diagnostics with its Vetscan Imagyst® platform. The promise of Vetscan Imagyst was continuous innovation, and the company has delivered, with the most recent introduction of AI Masses. The latest indication enhances Zoetis’ cytology offering by enabling fast, accurate

AI analysis of lymph node and skin/subcutaneous masses, delivering results in minutes. Now with a total of seven unique testing applications, this makes Vetscan Imagyst the world’s most capable veterinary artificial intelligence (AI) analyzer.

The platform’s cloud-based architecture also enables remote consultations and second opinions, fostering collaboration between general practitioners and specialists. This connectivity ensures that even smaller or rural clinics can access advanced diagnostic insights without needing to send samples off-site.

While AI-driven diagnostics are still evolving, the potential for the technology is immense. As adoption grows, these innovations will not only improve operational efficiency but also elevate the standard of care, making advanced diagnostics more accessible to veterinary practices of all sizes.

The future of veterinary medicine lies in leveraging technology to support veterinarians in their mission to provide high-quality care, helping them navigate today’s challenges while preparing for tomorrow’s demands. With AI-driven diagnostics at the forefront, the future of veterinary medicine is brighter than ever.

Vetscan Imagyst is the only commercially available analyzer on the market offering seven testing capabilities.

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How AI is Shaping Veterinary Hematology

When most veterinarians hear the term "stem cell therapy," their minds often go to autologous procedures – tissue harvested from the patient, processed by a company, and then injected back into the same patient days later. That was the old way of regenerative medicine. Now the field has advanced.

We are entering a new era defined by allogeneic therapies–stem cells derived from healthy donor tissue, manufactured in FDA-regulated facilities, and stored for use across multiple patients. Unlike autologous products, which have minimal regulatory oversight or published standards, allogeneic stem cell therapies are classified as drugs and must meet FDA requirements for safety, effectiveness, and manufacturing quality. These therapies are scalable, quality-controlled, and ready-to-use, representing a fundamentally new category in veterinary medicine.

This progress is exciting, and recent data shows that nearly half of veterinarians report high intent to adopt regenerative therapies in their practice.

 Yet despite growing interest, misconceptions remain. Many of the concerns I hear day-to-day stem from outdated models or an incomplete understanding of how stem cells function in clinical care.

This article will walk through the most common misconceptions I encounter, alongside what the current science, regulation, and clinical data actually support.

: Autologous and allogeneic stem cells are similar

The quality and function of stem cells vary significantly depending on their source, consistency, and biological characteristics. Here’s how those differences play out in practice:

Stem cell yield, identity, viability, quality, and potency can vary widely depending on harvest site, processing methods, and patient health. This variability makes treatments from various sources inequivalent. Allogeneic or “ready-to-use” stem cells are pre-dosed and quality-controlled under stringent GMP-compliant manufacturing conditions, allowing for consistent and predictable administration.

Multiple studies have shown that aging negatively affects MSC functionality.

 Stem cells from older animals show reduced proliferation, impaired ability to form bone and cartilage, increased senescence, and decreased migratory capacity. This matters, as regenerative therapies can greatly impact how we treat age-related diseases, such as arthritis and chronic kidney disease, and using autologous cells from older patients may be less effective in these cases.

MSCs harvested from sick or inflamed animals tend to have reduced potency. Research in humans with inflammatory conditions shows these cells can have impaired immunomodulatory effects compared to MSCs from healthy donors.

 This limits the therapeutic potential of autologous options in diseased animals.

Most autologous therapies are sourced from adipose tissue, which contains a large volume of other cells. This total volume of cells is referred to as the stromal vascular fraction (SVF), and it is the SVF that is typically administered to the patient. Within the SVF, a small portion (~10%) are actually stem cells. Cells from SVF have different immunogenic potential compared to a pure MSC product, therefore, they cannot be viewed as equivalent stem cell therapies.

Allogeneic stem cells are ready-to-use and will be available on demand once FDA-approved. Harvested from FDA-qualified, healthy donors and manufactured in GMP-compliant labs, they are shipped frozen and can be thawed and administered as needed. These cells remain stable for 18+ months if stored under appropriate conditions.

: Stem cell therapy is the “wild west” with no oversight

While this may have been true for earlier, loosely regulated options, today’s legitimate allogeneic stem cell therapies are progressing through formal FDA pathways. Just like any other veterinary drug, they are regulated by the FDA’s Center for Veterinary Medicine (CVM).

For serious conditions with limited alternatives, like refractory feline chronic gingivostomatitis (FCGS), the CVM offers a conditional approval pathway for minor conditions in a major species (MUMS). The conditional approval pathway allows therapies to reach patients quickly after meeting FDA requirements for safety, efficacy, and manufacturing standards. There are not yet any FDA-approved, ready-to-use allogeneic stem cell therapies in veterinary medicine.

: Intravenous stem cells just get trapped in the lungs

: The lungs help promote anti-inflammatory activity of IV stem cells AND MSCs still reach their target

This myth misrepresents the biodistribution and function of MSCs. Yes, many MSCs do initially localize in the lungs after IV administration. While there, they influence the pulmonary macrophages to shift toward an anti-inflammatory (M2) phenotype. These macrophages can then leave the lungs and exert anti-inflammatory effects elsewhere. After passing through the lungs, many viable MSCs migrate to peripheral organs, including the liver, spleen, heart, and even brain, guided by inflammatory signals.

 Immediately after injection, MSCs exert paracrine effects – secreting cytokines and growth factors that influence immune cells in the bloodstream and tissues, allowing MSCs to modulate immune responses and promote restoration, even without long-term tissue engraftment.

: Allogeneic stem cells are rejected by the immune system

: Immune reactions are rare and short-lived

Allogeneic stem cells are generally well-tolerated, with a low risk of immune response or rejection.

 MSCs are considered “immune-evasive” or “immune-privileged” because they lack MHC class II expression and display only low levels of MHC class I molecules. This limited expression helps them avoid detection by both the innate and adaptive immune systems.

When delivered intravenously, MSCs primarily act through paracrine signaling, influencing nearby cells rather than integrating long-term. Since they typically remain in the body for only a short time, the likelihood of delayed or lasting immune reactions is minimal.

: There is no evidence to date that MSCs cause tumors

This concern often comes from confusion around the different types of stem cells. They are classified into four main categories, based on their range of differentiation – from the most versatile to the most specialized:

 Can form all body and extraembryonic tissues (e.g., placenta); found only in the earliest embryonic stages.

 Can become any cell in the body but not extraembryonic tissue; includes embryonic stem cells and induced pluripotent stem cells (iPSCs).

 Found in adult tissues; can become several cell types within a specific lineage. This includes MSCs, the type most commonly used in therapy.

 Found in adult tissues; can form only one cell type but can self-renew.

Totipotent and pluripotent stem cells (those with the ability to form all tissue types) do carry a low tumorigenic risk. However, the MSCs used in veterinary medicine are multipotent, meaning they can only differentiate into a few specific cell types (like bone, cartilage, or fat). Their role is to support repair, not regenerate entire organ systems, making tumor formation highly unlikely.

: Stem cells should only be used when other treatments fail

: Their ability to target disease at its root makes them a strong early option

MSCs work by reducing inflammation, modulating immune responses, and supporting tissue repair. They don’t just mask symptoms; they target underlying pathology.

That makes them ideal for early intervention, especially in conditions like osteoarthritis, chronic kidney disease, and several immune-mediated diseases. In human medicine, stem cells are increasingly used as part of a multimodal approach, not a last-ditch effort. Waiting until all else fails may actually limit the potential benefits of regenerative therapy.

: All stem cell therapies come from embryos

: Stem cells are sourced from adult tissues like fat and uterus in veterinary medicine

Stem cells used in clinical trials in support of FDA approval are derived from adult tissues, such as fat or uterus, and are collected from healthy donors. No embryonic tissue is used in these preparations.

For example, Gallant uses uterine-derived stem cells from FDA-qualified, pathogen-free donors. Uterine tissue offers several advantages as a stem cell source: it is abundantly available, collected non-invasively during routine procedures, and provides a consistent supply for manufacturing. By using tissue that would otherwise be discarded, this approach also aligns with principles of ethical sourcing and sustainability.

: Stem cell therapy will be too expensive for most clients

: Stem cell therapy is more affordable than it may seem

While regenerative medicine may sound high-cost at first mention, when you compare it to the long-term costs of chronic disease management, the picture shifts.

Take NSAIDs, which are often a first-line treatment for osteoarthritis and chronic inflammation. At a typical dose and weight range, they can cost $60 to $90 per month, not including the recommended bloodwork and regular check-ins needed to monitor for side effects.

Monoclonal antibodies offer a newer approach but require monthly injections and can cost $120 to $200 per dose, depending on the size of the animal.

Cyclosporine, used for a variety of immune-mediated diseases, can run between $80 to $150 per month, often indefinitely, especially when paired with additional supportive therapies.

Allogeneic stem cell therapy will be no higher in cost than these commonly used treatments, and in many cases, may cost less. It typically involves just 2 injections, spaced 2 weeks apart. That simplicity can lead to fewer follow-ups, reduced reliance on long-term medications, and lower overall expenses – not to mention greater peace of mind and a better quality of life for the pets we care for.

: Administering stem cells requires complex tools or facilities

: No special equipment required – it’s as easy as an IV injection

In truth, allogeneic stem cell therapies are delivered just like any slow IV injection. No specialized training or infusion pumps are needed.

At Gallant, for example, therapies arrive frozen, are thawed in-clinic, diluted in saline, and administered via a peripheral IV catheter. The process takes just a few minutes, with post-treatment monitoring for 1-2 hours.

This makes regenerative therapy far more practical and scalable than earlier autologous protocols, which often required anesthesia, tissue collection, and lab harvesting.

Stem cell therapy is not futuristic or experimental anymore. It’s here – and it’s being held to the same standards as any other veterinary drug. With continued research and FDA-reviewed pathways, regenerative medicine is moving from promise to practice. As a profession, this opens the door to something deeper than symptom management. It’s a chance to address the underlying disease process – to help pets not just feel better, but get better.

Gallant Staff. Veterinarians Agree: Current Treatments Manage Symptoms; Anticipate Regenerative Options – Gallant Study. Gallant. Published June 30, 2025. Accessed July 30, 2025. https://www.gallant.com/blog/veterinarians-agree-current-treatments-manage-symptoms-anticipate-regenerative-options-gallant-study/

Durand N, Zubair AC. Autologous versus allogeneic mesenchymal stem cell therapy: The pros and cons. 

. 2022;171(5):1440-1442. doi:10.1016/j.surg.2021.10.057

Taguchi T, Borjesson DL, Osmond C, Griffon DJ. Influence of Donor’s Age on Immunomodulatory Properties of Canine Adipose Tissue-Derived Mesenchymal Stem Cells. 

. 2019;28(23):1562-1571. doi:10.1089/scd.2019.0118

Tran TDX, Pham VQ, Tran NN, et al. Stromal Vascular Fraction and Mesenchymal Stem Cells from Human Adipose Tissue: A Comparison of Immune Modulation and Angiogenic Potential. 

. Published online April 8, 2022. doi:10.1007/5584_2022_708

Maslennikov, Serhii & Golovakha, Maksym. (2023). The most commonly used cell surface markers for determining mesenchymal stromal cells in stromal vascular fraction and bone marrow autologous concentrate: a systematic review. Journal of Biotech Research. 14. 85-94

Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The Dynamic in vivo Distribution of Bone Marrow-Derived Mesenchymal Stem Cells after Infusion. 

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Barbash IM, Chouraqui P, Baron J, et al. Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium: Feasibility, Cell Migration, and Body Distribution. 

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Fukumura S, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous infusion of mesenchymal stem cells reduces epileptogenesis in a rat model of status epilepticus. 

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Kahts M, Mellet J, Durandt C, et al. A proof-of-concept study to investigate the radiolabelling of human mesenchymal and hematopoietic stem cells with [89Zr]Zr-Df-Bz-NCS. 

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Lu D, Jiao X, Jiang W, et al. Mesenchymal stem cells influence monocyte/macrophage phenotype: Regulatory mode and potential clinical applications. 

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Abumaree MH, Al Jumah MA, Kalionis B, et al. Human Placental Mesenchymal Stem Cells (pMSCs) Play a Role as Immune Suppressive Cells by Shifting Macrophage Differentiation from Inflammatory M1 to Anti-inflammatory M2 Macrophages. 

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Williams ZJ, Pezzanite LM, Chow L, Rockow M, Dow SW. Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023). Stem Cells. 2024;42(8):677-705. doi:10.1093/stmcls/sxae034

Baranovskii DS, Klabukov ID, Arguchinskaya NV, et al. Adverse events, side effects and complications in mesenchymal stromal cell-based therapies. Stem Cell Investig. 2022;9:7-7. doi:10.21037/sci-2022-025

Thompson M, Mei SHJ, Wolfe D, et al. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. EClinicalMedicine. 2020;19:100249. doi:10.1016/j.eclinm.2019.100249

What today’s science really says about safety, regulation, and clinical use of stem cell therapies.

Busting myths around stem cell therapy 

Dômes Pharma, a global leader in veterinary ophthalmology solutions, is proud to announce its strategic alliance with Fear Free®, joining the Fear Free Preferred Product Program. This collaboration recognizes Dômes Pharma’s dedication to reducing stress in pets during eye care visits and highlights three of the company’s flagship products:

Oculenis – A preservative-free ocular barrier gel specifically designed for pets with corneal ulcers. Its BioHAnce™ technology enhances contact time and comfort, aiding healing while minimizing application frequency.

Ocunovis– A daily-use, preservative-free gel eye drop formulated to provide long-lasting hydration and relief for pets with dry eye or ocular surface disease, using the same advanced BioHAnce™ technology.

Fluodrop – A sterile, single-use fluorescein ophthalmic solution used in diagnostic procedures to detect corneal defects and assess tear film breakup, offered in a convenient, stress-minimizing solution.

“At Dômes Pharma, we believe that true innovation in veterinary medicine must consider not only clinical outcomes but also the emotional experience of the animal,” said Anne Moulin, President of Dômes Pharma, Inc. “Collaborating with Fear Free allows us to further our mission of being a leader in ophthalmology by aligning with an organization that shares our commitment to compassionate, forward-thinking care. We’re proud that Oculenis, Ocunovis, and Fluodrop have been recognized as tools that support stress-free, effective treatment for pets, their families, and the veterinary teams who care for them.”

“Fear Free is grounded in education that empowers veterinary professionals to deliver care that prioritizes both physical and emotional wellbeing. Dômes Pharma’s dedication to developing ophthalmic solutions that enhance patient comfort and treatment compliance aligns seamlessly with our mission. We’re proud to highlight their innovative contribution to advancing more effective, emotionally considerate eye care for pets and the teams who care for them. ” — Dr. Jennifer Merlo, Vice President of Veterinary Affairs, Fear Free.

Dômes Pharma Teams Up with Fear Free to  Make Eye Care Less Stressful for Pets

A small animal internist answers the question in an interview with dvm360

Why does PU/PD improve in cats on SGLT2 inhibitors?

Polyuria and polydipsia (PU/PD)—excessive urination and thirst/drinking—are common concerns in cats with diabetes. Approximately 80% to 90% of cats on sodium-glucose cotransporter 2 (SGLT2) inhibitors will show an improvement in PU/PD symptoms. In this video, Ellen Behrend, VMD, PhD, MS, DACVIM (SAIM), consultant at Veterinary Information Network and Joezy Griffin Endowed professor and alumni professor Emeritus at Auburn University College of Veterinary Medicine, explains how SGLT2 inhibitors impact PU/PD in feline patients with diabetes and why many of these patients experience a significant improvement in this condition.

Listen to Behrend answer these other SGLT2 inhibitor-related questions in the following short clips:

Can cats on an SGLT2 inhibitor go into remission?

Should cats on an SGLT2 inhibitor go on a special diet?

Below is the interview transcript, which has been lightly edited for improved clarity:

Ellen Behrend, VMD, PhD, MS, DACVIM (SAIM): 

 You would think with all that glucose in the urine it would not get better, but it does in about 80% to 90% of cats.

I'm not sure that it completely resolves but it's hugely better and the owners are happy. We're not exactly sure why that is. Remember, though, that the SGLT2 inhibitors are sodium glucose cotransporter inhibitors, so you're messing around with the reabsorption of sodium, and that is also going to affect PU/PD, get the renin angiotensin aldosterone system involved.

The more likely explanation is that we're controlling the blood sugar so well, that there's a lot less glucose in the urine than when [the patients are] first diagnosed. They come in, their blood glucose is 400, 500 [mg/dL], they have huge amounts of glucose in their urine. We bring that down with an SGLT2 inhibitor. There's less glucose in the urine and then the PU/PD gets much better.

A small animal internist answers the question in an interview with dvm360.