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Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice
2024
Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3−/−). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3−/−, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.
Journal Article
Collective memory for American leaders: Measuring recognition for the names and faces of the US presidents
by
DeSoto, K. Andrew
,
Wang, Serene Y.
,
Drake, Sarah Madison
in
American history
,
Biology and Life Sciences
,
Collective memory
2021
Collective memory studies show that Americans remember their presidents in a predictable pattern, which can be described as a serial position curve with an additional spike for Abraham Lincoln. However, all prior studies have tested Americans’ collective memory for the presidents by their names . How well do Americans know the faces of the presidents? In two experiments, we investigated presidential facial recognition and compared facial recognition to name recognition. In Experiment 1, an online sample judged whether each of the official portraits of the US presidents and similar portraits of nonpresidents depicted a US president. The facial recognition rate (around 60%) was lower than the name recognition rate in past research (88%), but the overall pattern still fit a serial position curve. Some nonpresidents, such as Alexander Hamilton, were still falsely identified as presidents at high rates. In Experiment 2, a college sample completed a recognition task composed of both faces and names to directly compare the recognition rates. As predicted, subjects recognized the names of the presidents more frequently than the faces. Some presidents were frequently identified by their names but not by their faces (e.g. John Quincy Adams), while others were the opposite (e.g. Calvin Coolidge). Together, our studies show that Americans’ memory for the faces of the presidents is somewhat worse than their memory for the names of the presidents but still follows the same pattern, indicating that collective memories contain more than just verbal information.
Journal Article
Persistent Postmastectomy Pain and Pain-Related Physical and Emotional Functioning With and Without a Continuous Paravertebral Nerve Block: A Prospective 1-Year Follow-Up Assessment of a Randomized, Triple-Masked, Placebo-Controlled Study
by
Kormylo, Nicholas J.
,
Morgan, Anya C.
,
Sandhu, NavParkash S.
in
Adult
,
Amides - administration & dosage
,
Anesthetics, Local - administration & dosage
2015
Background
In a previous randomized, triple-masked, placebo-controlled study, the authors demonstrated that extending a single-injection paravertebral nerve block with a multiple-day perineural local anesthetic infusion improves analgesia and decreases pain-related dysfunction during the 3-day infusion but not subsequent to catheter removal within 1 month after mastectomy. This report describes a prospective follow-up study of the previously published trial to investigate the possibility that extending a single-injection paravertebral block with a multiple-day infusion may decrease persistent postsurgical pain as well as pain-induced emotional and functional dysfunction 1 year after mastectomy.
Methods
Subjects undergoing uni- or bilateral mastectomy received unilateral (
n
= 24) or bilateral (
n
= 36) single-injection thoracic paravertebral block(s) with ropivacaine and perineural catheter(s). The subjects were randomized to receive either ropivacaine 0.4 % (
n
= 30) or normal saline (
n
= 30) via their catheters until the catheters were removed on postoperative day 3. Chronic pain and pain-related physical and emotional dysfunction were measured using the Brief Pain Inventory (BPI).
Results
No statistically significant difference between treatments 3 months after surgery was observed with the BPI. In contrast, after 12 months, only 4 subjects (13 %) who had received a perineural ropivacaine infusion reported pain-induced dysfunction compared with 14 (47 %) who had received saline infusion (
P
= 0.011). At 12 months, the mean BPI was 1.6 ± 4.6 for the subjects who received ropivacaine versus 5.9 ± 11.3 for the subjects who received saline (
P
= 0.007).
Conclusions
Adding a multiple-day, continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block may result in a lower incidence of pain as well as pain-related physical and emotional dysfunction 1 year after mastectomy.
Journal Article
Single-injection thoracic paravertebral block and postoperative analgesia after mastectomy: a retrospective cohort study
2015
The treatment of postoperative pain after mastectomy is an area of increasing interest, as this treatment option is now considered a standard of care for those affected by breast cancer. Thoracic paravertebral nerve block (tPVB) using local anesthetics administered before mastectomy can theoretically provide postoperative analgesia, thereby facilitating a more comfortable and shorter hospitalization.
In this retrospective cohort study, we aimed to determine the duration and degree to which tPVB provides postoperative analgesia in patients who underwent either unilateral or bilateral mastectomy (n = 182). We retrospectively examined the numeric rating scale (NRS) for pain scores recorded by nursing staff throughout individual patient hospitalizations, looking specifically at the following time points: arrival from the postanesthesia care unit to the surgical wards, noon on postoperative day 1 (POD1), and discharge. We also examined the number of days until patients were discharged from the hospital.
Our results revealed a statistically significant decrease in NRS in pain scores for patients who had received a tPVB (n = 92) on arrival from the postanesthesia care unit to the surgical wards (mean NRS decrease of 1.9 points; 99% confidence interval [CI], −3.0 to −0.8; P < .001) but did not show statistically significant decreases in NRS for pain scores for patients at noon on POD1 (mean NRS decrease of 0.3 points at noon on POD1, P = .43) or at discharge (mean NRS decrease of 0.1 point at discharge, P = .65). Moreover, use of tPVB did not have an impact on time until discharge (average decrease of 0.5 hours; 95% CI, −6 to +5 hours, P = .87).
Single-injection tPVB appears to provide meaningful postoperative analgesia in the immediate postoperative period after mastectomy but not after the first day of surgery.
•We examined patients who underwent either unilateral or bilateral mastectomy.•We determined the duration and degree that thoracic paravertebral nerve block provides postoperative analgesia.•We examined the numeric rating scale for pain scores from 182 individual patient hospitalizations.•Thoracic paravertebral nerve block provides postoperative analgesia in the immediate postoperative period after mastectomy.•Thoracic paravertebral nerve block does not provide postoperative analgesia after the first day of surgery.
Journal Article
FGFR4 Is Required for Concentric Growth of Cardiac Myocytes during Physiologic Cardiac Hypertrophy
2024
Fibroblast growth factor (FGF) 23 is a bone-derived hormone that promotes renal phosphate excretion. Serum FGF23 is increased in chronic kidney disease (CKD) and contributes to pathologic cardiac hypertrophy by activating FGF receptor (FGFR) 4 on cardiac myocytes, which might lead to the high cardiovascular mortality in CKD patients. Increases in serum FGF23 levels have also been observed following endurance exercise and in pregnancy, which are scenarios of physiologic cardiac hypertrophy as an adaptive response of the heart to increased demand. To determine whether FGF23/FGFR4 contributes to physiologic cardiac hypertrophy, we studied FGFR4 knockout mice (FGFR4−/−) during late pregnancy. In comparison to virgin littermates, pregnant wild-type and FGFR4−/− mice showed increases in serum FGF23 levels and heart weight; however, the elevation in myocyte area observed in pregnant wild-type mice was abrogated in pregnant FGFR4−/− mice. This outcome was supported by treatments of cultured cardiac myocytes with serum from fed Burmese pythons, another model of physiologic hypertrophy, where the co-treatment with an FGFR4-specific inhibitor abrogated the serum-induced increase in cell area. Interestingly, we found that in pregnant mice, the heart, and not the bone, shows elevated FGF23 expression, and that increases in serum FGF23 are not accompanied by changes in phosphate metabolism. Our study suggests that in physiologic cardiac hypertrophy, the heart produces FGF23 that contributes to hypertrophic growth of cardiac myocytes in a paracrine and FGFR4-dependent manner, and that the kidney does not respond to heart-derived FGF23.
Journal Article
Treatment of Postmastectomy Pain With Ambulatory Continuous Paravertebral Nerve Blocks: A Randomized, Triple-Masked, Placebo-Controlled Study
2014
BackgroundWe aimed to determine with this randomized, triple-masked, placebo-controlled study if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine paravertebral nerve block to a single-injection ropivacaine paravertebral block after mastectomy.MethodsPreoperatively, 60 subjects undergoing unilateral (n = 24) or bilateral (n = 36) mastectomy received either unilateral or bilateral paravertebral perineural catheter(s), respectively, inserted between the third and fourth thoracic transverse process(es). All subjects received an initial bolus of ropivacaine 0.5% (15 mL) via the catheter(s). Subjects were randomized to receive either perineural ropivacaine 0.4% or normal saline using portable infusion pump(s) [5 mL/h basal; 300 mL reservoir(s)]. Subjects remained hospitalized for at least 1 night and were subsequently discharged home where the catheter(s) were removed on postoperative day (POD) 3. Subjects were contacted by telephone on PODs 1, 4, 8, and 28. The primary end point was average pain (scale, 0–10) queried on POD 1.ResultsAverage pain queried on POD 1 for subjects receiving perineural ropivacaine (n = 30) was a median (interquartile) of 2 (0–3), compared with 4 (1–5) for subjects receiving saline (n = 30; 95% confidence interval difference in medians, −4.0 to −0.3; P = 0.021]. During this same period, subjects receiving ropivacaine experienced a lower severity of breakthrough pain (5 [3–6] vs 7 [5–8]; P = 0.046) as well. As a result, subjects receiving perineural ropivacaine experienced less pain-induced physical and emotional dysfunction, as measured with the Brief Pain Inventory (lower score = less dysfunction): 14 (4–37) versus 57 (8–67) for subjects receiving perineural saline (P = 0.012). For the subscale that measures the degree of interference of pain on 7 domains, such as general activity and relationships, subjects receiving perineural saline reported a median score 10 times higher (more dysfunction) than those receiving ropivacaine (3 [0–24] vs 33 [0–44]; P = 0.035). In contrast, after infusion discontinuation, there were no statistically significant differences detected between treatment groups.ConclusionsAfter mastectomy, adding a multiple-day, ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block results in improved analgesia and less functional deficit during the infusion. However, no benefits were identified after infusion discontinuation.
Journal Article
Continuous Adductor Canal Versus Continuous Femoral Nerve Blocks: Relative Effects on Discharge Readiness Following Unicompartment Knee Arthroplasty
by
Sztain, Jacklynn F
,
Khatibi, Bahareh
,
You, Jing
in
Catheters
,
Joint replacement surgery
,
Joint surgery
2015
BackgroundWe tested the hypothesis that, following unicompartment knee arthroplasty, a continuous adductor canal block decreases the time to reach 4 discharge criteria compared with a continuous femoral nerve block.MethodsSubjects were randomized to either an adductor canal or femoral perineural catheter (2-day ropivacaine 0.2% infusion) in an unmasked fashion. The primary outcome was the time to attain 4 discharge criteria: (1) adequate analgesia; (2) intravenous opioid independence; (3) ability to independently stand, walk 3 m, return, and sit down; and (4) ambulate 30 m.ResultsSubjects with an adductor canal catheter (n = 15) reached all 4 criteria in a median of 35 hours (interquartile range, 24–43 hours), compared with 40 hours (interquartile range, 27–69 hours) for those with a femoral catheter (n = 15; Wilcoxon rank sum test: P = 0.46; log-rank test: P = 0.16). However, the percentages of subjects (adductor canal: femoral) who reached the 2 mobilization criteria were 27%:0% on postoperative day (POD) 0, 93%:53% on POD 1, and 100%:73% on POD 2. Of adductor canal subjects, 100% were discharge ready by POD 2, compared with only 73% of femoral subjects (P < 0.001).ConclusionsCompared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the median number of hours to overall discharge readiness, yet did decrease the number of discrete days until discharge readiness. These results are applicable to only unicompartment knee arthroplasty and must be considered preliminary because of the limited sample size of this pilot study.
Journal Article