#027 - Are We Harming Preterm Kidneys Every Time We Give Gentamicin?

Hello Friends 👋

The neonatal kidney is one of the most understudied organs in our field — and yet the drugs we use every day in the NICU may be affecting it in ways we are only beginning to understand. In this episode of At the Bench, Dr. Misty Good and Dr. Betsy Crouch sit down with Dr. Pamela Good, neonatologist and physician scientist at Columbia University, to discuss her groundbreaking research on nephron development, low nephron endowment, and acute kidney injury (AKI) in preterm infants. From building a first-of-its-kind mouse model to rethinking how we use gentamicin, this conversation will change how you think about the tiniest kidneys in your NICU.

Link to episode on youtube: https://youtu.be/zGeXFFUxxGk

----

----

The transcript of today's episode can be found below 👇

Misty Good (00:01.442) Hello and welcome back to At the Bench, the neonatal physician scientist podcast of The Incubator. I'm Misty Good, and I'm a neonatologist scientist at UNC Chapel Hill, where I also serve as the division chief. And I have the pleasure of coming up on stage today with Dr. Betsy Crouch. Betsy, would you like to introduce yourself?

Betsy Crouch (00:21.09) Yes, I'm happy to introduce myself, but I think a lot of the listeners know who I am now. I'm a vascular biologist and a neuroscientist, and I'm an assistant professor at UCSF, transitioning to associate this summer, actually. So thank you — moving along with a lot of blood, sweat, and tears. I'm excited about that.

Misty Good (00:36.63) Congrats!

Betsy Crouch (00:48.162) I'm also excited about our guest today, Dr. Pamela Good from Columbia University. Dr. Good and I first met when I was doing my sub-internship in the NICU at Columbia. There were some really special moments in that rotation — the time I thought I was going to be a pediatric neurologist, because I was a neuroscientist. I thought that in order to study the brain you had to be a neurologist.

I'm so grateful that the Columbia NICU was such a supportive and exciting place that I started to put it together and realize that I could pursue that amazing clinical practice and still be a neuroscientist. It really launched me into what I get to do today.

So thank you, Pamela, for being one of my role models at the time. Now we get to be colleagues, and we're really excited to have you. Do you want to provide a brief intro — fast forwarding about 12 years or so since then?

Pamela Good (01:45.704) Yeah, oh my goodness. That's just the nicest introduction ever. Thank you so much. My name is Pamela Good. I am also a neonatologist here at Columbia University where, as Betsy alluded to, I have done my training all the way through. I'm also a physician scientist, and I study neonatal kidneys — specifically neonatal kidney injury — as well as the long-term health effects of being born preterm and extremely preterm,

with a focus on using mouse models to study that. Thank you both so much for inviting me to chat today.

Betsy Crouch (02:26.764) We're excited to talk to you for many reasons. I think your career trajectory has been quite eventful in really good ways. We'll also touch on something right off the bat, which is that you don't have a PhD, and so you found your way into investigative science after your MD degree. I think that's a really fruitful path — and fitting for both Dr. Goods on the call.

Misty Good (02:52.872) You should probably have the disclaimer that we're not related, but I do think you're amazing. I wish you were family.

Pamela Good (02:55.941) We're not related!

Betsy Crouch (02:57.472) That's probably true. But I think it's really useful to talk about that career path too, because many people find their way into investigative science after completing their MD degree and go on to really productive careers. Maybe we'll get started and just say — can you tell us a little bit more about your science, starting all the way back at what first inspired you about the kidney?

Pamela Good (03:26.516) Yeah, absolutely. And I can talk a little bit about the MD track into becoming a physician scientist as well. When I started medical school, I was undifferentiated, other than knowing I was very much interested in pediatrics and much less interested in taking care of an aging population. So within everything I studied, I was focused a bit more on pediatric diseases.

But the one area that really pulled me toward adult medicine was actually adult nephrology. Here at Columbia, there's an amazing department of adult nephrology, and they even had a nephrocardiology rotation — really focused on taking care of patients in the cardiac or regular intensive care unit from a kidney, fluid, and electrolyte balance perspective. Fast forwarding to my

focus on pediatrics and neonatology, that really fit in with what we see in neonates in terms of understanding fluid and electrolytes and how that balances with cardiac and other disease processes. So when I started thinking about my fellowship and my fellowship research project, one thing that came back to me was that I had really loved studying kidneys in medical school here at Columbia, and that it could be something really fun to study going forward. I also felt like —

Betsy Crouch (04:49.101) Mm-hmm.

Pamela Good (04:54.86) back around 2015, 2016, we were just starting to get some of the really interesting studies about the effects of prematurity on kidney health, both in the short and long term. It felt like such an exciting area to dive into. So during my fellowship search, I started looking for research projects and collaborators and really landed with some amazing mentors and great prospects here at Columbia. That's sort of how I launched into this area. And one of the other stories I really like to tell about why I love the kidneys is that in medical school, when we did the histology studies and got to look at them under the microscope, they are just so, so beautiful and cool looking. I remember seeing some of those pictures in that old amphitheater we used to sit in and just thinking this would be a great thing to look at all day every day. I still look at kidneys a lot under the microscope, and I still

Betsy Crouch (05:43.875) Mm-hmm.

Pamela Good (05:51.158) think that they're absolutely stunning. So that has been really fun. And another thing that really pulled me into this area —

Misty Good (05:58.925) Can I ask — if you love the kidney so much and were inspired to study it early on, how did you decide on neonatology versus nephrology?

Pamela Good (06:08.396) Good question. I think I loved the transitional physiology that all of us neonatologists love. I loved being in deliveries — the clinical experience was so fantastic. I loved OB as well. This is the one area within pediatrics where we collaborate so well with obstetricians. And I loved the acute care inpatient nature of it. One of the other things I've loved about neonatology is that we take care of the whole baby. And so in research, of course, we're able to focus in on one organ system — but the kidneys regulate so much that in some ways it still feels like I'm a generalist.

Misty Good (06:50.178) I love that.

Betsy Crouch (06:53.678) Yeah, a lot of that resonates with me too, thinking about the brain. I will say I'm a little dissatisfied with the therapeutic toolbox we have for — to give one example — AKI (acute kidney injury). Are you thinking yet about a different future for that? Because we'll get into some of your papers, but I really appreciate that they're thinking about the long-term consequences of prematurity on nephron development and nephrogenesis. But what about the acute picture as well?

Pamela Good (07:43.468) Yeah, absolutely. My R01 that I just submitted is much more focused on acute kidney injury. In the area of neonatal AKI, we need better diagnostic tools, we need better treatment strategies. But in order to get there, you first have to have a better understanding of the pathophysiology. The working hypothesis all along has been that premature kidneys are not going to respond the same way as a term infant's or an adult's kidneys to all of the insults they encounter in the neonatal period.

That's why during my fellowship, we generated a mouse model that we think does a pretty good job of simulating preterm kidneys in order to start to work in that space.

Betsy Crouch (08:44.054) I love that model. Yeah.

Betsy Crouch (08:51.48) But it didn't exist before, right? And that's the whole amazing thing about being a neonatal physician scientist — you can generate these models for conditions that are incredibly important, but where other scientists have limited insight into exactly how to build the model. Sorry, Misty, I cut you off.

Misty Good (09:09.918) No, I was just going to say — while we know your model well, please share with our listeners how it came about: the forethought involved in developing it, the reproducibility, all the things we love to see in mouse models.

Pamela Good (09:26.86) Yeah, so it was a collaborative effort with some amazing mentorship here. Myself, my primary mentor Fangming Lin, and Frank Constantini — who is a developmental biologist here — sat down together and looked at what had been done and what could be done. We also had a colleague in our shared lab space, in that team science approach, who had a mouse she thought could contribute. That's Meenakshi Rao over at Harvard.

Together, we thought about how to generate a mouse with low nephron number that simulates the low nephron number we see in humans born preterm. We were able to use a triple transgenic mouse and use both genetic and chemical approaches. What we ultimately did was inhibit the end of kidney development. Kidneys develop through branching morphogenesis, and we were able to take advantage of some of the signaling pathways involved in that process —

breed mice, know exactly when they were pregnant, and then at the end of their gestation — through either chemical or genetic approaches — stop the branching of the developing kidney. That gives us mice with roughly a 40 to 60% nephron reduction, which we think is a good

simulation of what we see in our preterm infants, although all of that data is based on human autopsy studies, which are imperfect in and of themselves. But it was a huge collaborative effort with a lot of help from incredibly smart people who knew how one might go about doing this. We've been using both the chemical and the genetic approaches within that model for years —

Pamela Good (11:16.172) really since 2017 and 2018. And they're going strong.

Misty Good (11:22.626) Do you have a preference between the two, or how do you select which one to use?

Pamela Good (11:29.192) Yeah, the chemical approach has effects outside of the kidney, whereas our genetic approach is really specific to the developing kidney. So I prefer the genetic approach. You always worry about having extra-renal effects that you're not even looking for. We did screen for the known possible side effects of the inhibitor we were using and found it was pretty clean. And it's great if you're going to pair it with another genetic model. But overall I prefer our genetic model, and most of what we're doing now is focused on that one specifically.

Misty Good (12:12.674) That's great. Thanks.

Betsy Crouch (12:15.406) So maybe to jump in here — I was so pleased when I was reviewing your materials for this podcast and remembered that you did your K award looking specifically at the effects of gentamicin on the model of the preterm kidney. For those of our listeners who haven't had a chance to read your papers, could you provide a brief overview of your findings and what you're thinking of for next steps?

Pamela Good (12:46.602) Yeah, of course. So we are primarily interested in neonatal acute kidney injury. As mentioned earlier, we're also looking at some of the long-term effects of low nephron number at birth. But for neonates specifically, we had to come up with a neonatal AKI model. There are a few out there. We extrapolated from those and from some adult studies and ultimately landed on using aminoglycoside toxicity — so using gentamicin to induce AKI. We are able to do that in mice at about one to two days of life, really trying to target that newborn period when we're giving gentamicin to our patients. And what we found was —

Betsy Crouch (13:29.708) That's interesting, because I figured you were using gentamicin because it's a drug we commonly use in the NICU. It's really important to understand the pharmacology and pharmacokinetics. I still remember when I learned about the dosing — that you give this once-daily dosing based on GFR. I didn't realize you were actually looking for an AKI model first and then chose gentamicin.

Pamela Good (13:58.43) Yeah, that was an AKI model originally — that's how we landed on it. I'm so glad it worked out on both sides, because of course we also want to understand how the interventions we're doing in the NICU are affecting our patients more broadly. But yes, we specifically chose it as an AKI model.

So we were able to extrapolate from older rodent studies to determine dosing and have the pups survive the insult. And ultimately what we found was that there was much more severe injury in mice with low nephron number — simulating our preterm humans — compared to littermate controls, specifically using the genetic model. So we were able to look, based on what we presume is purely related to nephron endowment at birth,

at the effect of this commonly used medication. There's more inflammation, there is impaired proliferation after injury, and ultimately there's accelerated development of a chronic kidney disease (CKD) phenotype. When I thought about gentamicin use in clinical practice during fellowship and beyond, I really thought, okay, maybe you might get an acute kidney injury from it, but you'll likely recover and there'll be no permanent damage. So I was really interested to find that in those with normal nephron number, they did indeed recover and their kidneys looked pretty much normal at adolescent and adult age — but those with low nephron number had really impaired structure by that time.

Misty Good (15:46.103) That's awesome. Could you share a little more? I know you're on a K award. And I'm also curious about the gentamicin model — in the NICU, we do all these rule-out sepsis courses, amp and gent, amp and gent. I'm curious whether repeated exposures impact nephron number, and if you've looked at that, or whether

Pamela Good (16:04.096) Yeah, yeah.

Misty Good (16:14.37) culture-negative sepsis courses — like seven days versus the 48-hour —

Betsy Crouch (16:18.338) Yikes.

Pamela Good (16:26.166) Yeah, so for my K, I had proposed just doing seven days of the standard rodent AKI dose. But since then, we've done quite a bit of dose titration to determine how soon you start to see an effect, really still focusing on that neonatal period. And we start to see effects by two doses —

so two days of gentamicin. I do have to state that these doses are much, much higher than what we use in humans — 100 mcg compared to far less in humans — but these pups are otherwise healthy. They're not preterm, they don't have hemodynamic instability or other medications on board or anything like that. So while it is a much larger dose, there is still clinical relevance in this model. We've scaled back the doses and we're in the process of cutting it back further to see at what point injury begins. But certainly by two days of administration, you start to see evidence of proximal tubular damage.

Misty Good (17:48.994) Wow, that's so interesting.

Pamela Good (17:51.42) And coming back to the clinical piece — two days is a rule-out sepsis course at birth because you were born premature. So when we started to see those findings, that was worrisome. And in terms of the effect on nephron number — when the mice are this small

Betsy Crouch (18:03.822) Ugh.

Pamela Good (18:15.444) and we're doing the AKI studies, we aren't also counting nephron number. We're extrapolating from the larger population data we generated early on, which showed roughly a 40 to 60% nephron reduction based on the model we used. So we're doing it less to look at nephrons generated in the post-nephrogenesis period and more as a pure AKI study, if that makes sense.

Misty Good (18:39.584) Yeah, that's great. I see Betsy thinking.

Betsy Crouch (18:43.79) Yeah, I'm running to catch up because it's really good stuff. I was telling Misty before you got on the call today that the kidneys are really understudied — I think everything in neonatology is deserving compared to the correlate adult organ systems and the attention they receive. But the kidney especially is challenging, as evidenced by the fact that you had to create a model to study it. So my mind is running to catch up. Why is it that if you have fewer nephrons — just because you have fewer of them doesn't necessarily mean they're weaker or more sensitive —

Pamela Good (20:31.98) Okay, regarding why there's more severe injury in the setting of low nephron endowment, that's actually one of the big questions I submitted for my K. What is the mechanism?

Betsy Crouch (21:30.173) Mm-hmm.

Pamela Good (21:30.188) in the setting of low nephron endowment that causes more severe injury? One of our hypotheses is that with low nephron number, you may have increased uptake of gentamicin per cell. What we did was use a fluorescent-labeled gentamicin — we injected what ended up being the human-equivalent dose into pups — and were then able to look under a microscope to see how much gentamicin is being taken up. By counting the number of cells, you can see how much is taken up per cell. And it's about 30 to 40% increased gentamicin uptake per cell in the setting of low nephron number. So while clinically we look at things like the gentamicin trough level, that same gentamicin is being seen by each cell in the kidney — and we're not measuring how much is being taken up in each proximal tubular cell.

I think that increased exposure per cell is causing increased toxicity per cell. And that's why we're seeing more severe AKI in these mice, impaired repair processes, and accelerated development of a CKD phenotype.

Betsy Crouch (22:45.304) So how would you measure that non-invasively?

Pamela Good (22:49.012) In a human, I think it would be really hard to measure non-invasively. And even measuring kidney function in preterm infants is challenging — you're measuring serum creatinine, which is a poor way to assess it. So I think it's really difficult. A lot of people ask when I give talks about my research how this has affected my practice. And I think one thing that's really changed for me is to

actually think about each patient and whether their nephron number might be lower than average — knowing that some of that is genetically programmed, that adult humans have a very wide range of nephron number, but some of it relates to things like whether they were growth restricted and how preterm they were. For those who are extremely preterm or growth restricted, I do think extra hard about using gentamicin.

Betsy Crouch (23:31.138) Mm-hmm.

Pamela Good (23:43.178) And we just don't have the clinical data to be able to do that in an evidence-based way, because again, this is all preclinical and mice are not humans. But they're a great model.

Betsy Crouch (23:54.062) I mean, they're the best model that exists for prematurity-related low nephron number.

Pamela Good (24:13.364) Yeah. I mean, you can say low nephron number. Sometimes I say "underdeveloped kidneys" when I'm talking to patients and families.

Misty Good (24:25.086) Is there anything that can be done to enhance nephron number or development?

Pamela Good (24:32.158) Yeah, it's a great question. There are studies showing that things like prenatal steroids encourage development, but we don't really have anything that will increase nephron number, which is ultimately what many

people interested in neonatal nephrology are concerned about in preterm infants — particularly in the extremely preterm population. Over 50% of nephrons are formed in the third trimester. So under 28 weeks, you're looking at pretty significant deficits. And when you push down to 22 or 23 weeks, extreme nephron deficits would be expected. We don't have a great way to address that right now. If we did, that would be amazing and something we'd want to share with the world — but not that I'm aware of currently.

Betsy Crouch (25:39.032) What about our dosing of gentamicin — is there any room to decrease the dose while maintaining effectiveness against gram-negatives?

Pamela Good (25:51.314) Yeah, a lot of the dosing is based on the pharmacology and on expected changes in kidney function and GFR (glomerular filtration rate) over time. In my first K submission, we really wanted to look at gentamicin levels in these mice, which I think would be outstanding. I struggled to do that and recently got a lead on trying to outsource it.

It would be done using mass spectrometry, for example. But we have to make sure we have a machine that can measure gentamicin levels from mouse samples. And as you both know when working with small mice, it's always a volume issue too. But that's something we definitely need to do, because it would be really helpful to then be able to translate back to humans.

Misty Good (26:43.916) When our mice with NEC (necrotizing enterocolitis) are euthanized, they often have these big bladders. So if you ever want me to save any urine for you — or kidneys — I used to just deflate the bladders because they were in the way.

Pamela Good (26:55.616) Save me some urine! Yeah, for sure.

Pamela Good (27:07.692) Yeah, because you probably couldn't get around the intestinal contents otherwise, right?

Misty Good (27:11.169) Yes.

Pamela Good (27:13.278) Yeah, we can get urine from the pups, but it's always an issue of whether you need to pool it, how much you can get per mouse, and how many times you can coax them to pee for you.

Betsy Crouch (27:27.598) Yeah. And I think another thing you do really well is distinguish male and female effects. That opens up even more groups — you've got control, your genetic model, and then male and female. So there's already quite a bit of complexity there. So for listeners, we were talking a little bit about the fact that you're in your K award now,

Pamela Good (27:43.434) Yeah, exactly.

Betsy Crouch (27:56.78) and you just submitted your R01, which is excellent — about the right timing. And Misty was sharing a tip about other grant mechanisms available to you.

Misty Good (28:11.298) Yeah, I'm happy to talk about that for our listeners. Something I was really grateful for when I was on a K award through the NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) at the NIH was the R03 that is specific for K awardees. I was just asking Pamela before the show whether she had applied for that and what her thoughts were. But it's an

amazing mechanism — it's $50,000 per year, so certainly not the equivalent of an R01, but I think it's really important for listeners who are on K awards through institutes that have that option to consider applying. It's additional funding that can go toward reagents, and while you don't need salary support when you're on a K, you can put it toward a technician

or mouse cross-breeding, et cetera.

Pamela Good (29:14.668) Totally. Yeah, and as we talked about a bit before, it's definitely on the list. We made a big push for this past submission cycle, but it will likely go in in the spring or summer. And as you know, there's always a lot on the K. It was such an amazing opportunity to get the protected time to do these studies —

but sometimes when I go back and look, I think, my goodness, look at all these other things I proposed that I haven't quite gotten to yet. So it would be a great opportunity to look at the pieces that are still outstanding, expand on them, and get some support for that. Every dollar helps.

Misty Good (29:58.965) Especially in this funding climate. And I remember going through the process of writing the first R01 — props to you, because it is hard. And I think going for it is very admirable. I remember having a lot of pressure on me to apply

for the R01, and I was very resistant. So it all worked out in the end.

Misty Good (30:28.15) I applaud you for going for it.

Pamela Good (30:30.668) It was definitely daunting, but it helps to have collaborators, mentors, and people who are willing to read drafts and give feedback. And a shout out to our grants administrators here, who did an amazing job walking me through everything that needed to get done so I could focus on the science. That made a huge difference for this submission — it did feel incredibly overwhelming

originally, but I'm sure the next time around when I revise it, it'll be less so.

Misty Good (31:08.54) I think it is less overwhelming the second time. And yes — shout out to the grants administrators.

Betsy Crouch (31:12.962) I was actually going to say we should have a session dedicated entirely to the grants administrators for this segment of At the Bench.

Pamela Good (31:13.356) Yes! Oh my goodness. If I look at my sent email, within any given day there are so many messages to them. And they were right there — they've submitted so many grants, our staff here knew exactly what they were doing, and they were so kind throughout the process. I really, really appreciated that.

Misty Good (31:40.247) They're experts at that. I always make a point of getting them something after we submit — it's usually down to the wire, because I'm not one of those people who submits early. So I'll get them a Starbucks gift card to say thank you, which also primes them for the next stressful cycle.

Pamela Good (32:04.012) That's a great tip.

Betsy Crouch (32:06.434) I have an amazing story about my grants administrator, Beth Bartlemez. This past fall, there were some layoffs at UCSF in the pre-awards division — including the staff who had been submitting for graduate students, since things were now centralized rather than department-specific.

So they laid off the person who was supposed to submit my graduate students' fellowship awards. There was a supervisor who was supposedly available but didn't respond to any emails. Half an hour before the deadline, we'd been emailing someone who had an out-of-office message for the day the grant was due.

Pamela Good (32:57.964) Hm.

Betsy Crouch (33:04.984) We were just thinking, how do we submit this grant? So I called my person half an hour before it was due and said, "Beth, I'm in a pickle. It's not your pickle, but I'm wondering if you could help me with my pickle." And she said, "I was aware this could be a problem. Just assign me as the institutional person and I'll make sure it gets done." And she did. And one of my students got the award.

Misty Good (33:29.132) That's great.

Pamela Good (33:29.462) Wow, congrats!

Betsy Crouch (33:34.702) That's my most extraordinary grants administrator story.

Misty Good (33:37.25) That deserves a reward.

Betsy Crouch (33:41.942) Yes, I did. I also nominated her for a UCSF-wide award for that example of excellence. It was literally saving the day. But it's also nice to honor her formally. Anyway — this has been a blast. We always like to end on something fun about our

Pamela Good (33:54.763) Yeah.

Betsy Crouch (34:10.104) guests and their research teams. Pamela, do you want to tell us something you do to relax, or something you do to build camaraderie with your colleagues?

Pamela Good (34:20.204) Absolutely. And actually before we wrap up — earlier when you mentioned that the kidney is understudied in neonatology, I want to give a shout out to the Neonatal Kidney Collaborative, and encourage our trainees who are listening today to look into this organization. It's a group of pediatric nephrologists and neonatologists working together to address exactly that problem —

Betsy Crouch (34:33.422) Cool, yeah.

Pamela Good (34:46.922) in the realms of education, patient advocacy, and research. It's an outstanding group, and there's excellent educational content on their website. So I can direct you there if this conversation was inspiring and you want to jump into the world of neonatal nephrology. There are also some really great recent

Betsy Crouch (35:08.288) Or just to brush up, you know.

Pamela Good (35:15.628) papers within the field as well. But to get back to your question — our lab does do some fun lab lunches. One of the things I started this year was asking each person in the lab what their favorite dessert is. That sent me on an exploration of amazing dessert places in Manhattan, of which there are so, so many.

Pamela Good (35:43.372) I've tried some really fun new things — including a miso carrot cake last time, which ended up coming from the bakery down the street from my apartment. I think it's really fun to have dedicated time with your team that has nothing to do with science. This year we've been making a real effort to do that, and we've really enjoyed it.

And I have two small kids — as Betsy knows — and they've also been able to come and meet people in the lab. I'm hoping to inspire some future female scientists. I have two girls, so.

Misty Good (36:27.394) That's awesome. Speaking of inspiring — what would you share with our listeners who might be going through a tough stretch? What have you told yourself to keep going when times get rough?

Pamela Good (36:41.394) Yeah, that's such an important question. I think one thing I've found personally is that when I get unexpected or disappointing results, or have failed experiments, it's pretty easy to get really fixated on that one failure and feel really down — because we're so invested. We've put so much into these models and these projects. So what I like to do in those moments is to

take a step back and look at the bigger picture, because there are always other things we're working on. There's usually multiple projects, and there's also the clinical side and the education side as a physician scientist. So when I've had the tenth failed staining and I'm really discouraged that I can't get an antibody to work, I like to step back and look at the past two weeks of lab meeting agendas and find something that was successful.

Pamela Good (37:39.564) Or even if there's nothing there, go back and think about the last time I was on call and find an opportunity that went well on the clinical side. I think that's one of the great things about being a physician scientist — you have the opportunity to exist in all of those worlds. When things aren't going well in one area, you can always draw from another, or even just think back to the patients you're taking care of and remember why you're

studying NEC (necrotizing enterocolitis), or the brain, or the kidney.

Misty Good (38:12.938) I love that. It's important to know your why, and circle back to it when you're slogging through and things aren't working.

Pamela Good (38:21.43) Totally. And remember that if you could do it in one experiment, this would be easy and everyone would do it and things would move super quickly. So you have to dig back into that resilience that we all worked so hard to build through training, and keep trying.

Misty Good (38:42.046) Absolutely. Well, that's terrific. I love that advice.

Betsy Crouch (38:45.09) Yeah. Thank you, Pamela, for your time and for that really fantastic ending. To our listeners, thanks for joining us, and we look forward to catching you at the next At the Bench.