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COVID-19 Vaccination and Odds of Post-COVID-19 Condition Symptoms in Children Aged 5 to 17 Years

JAMA Netw Open. 2025 Feb 3;8(2):e2459672. doi: 10.1001/jamanetworkopen.2024.59672.

ABSTRACT

IMPORTANCE: An estimated 1% to 3% of children with SARS-CoV-2 infection will develop post-COVID-19 condition (PCC).

OBJECTIVE: To evaluate the odds of PCC among children with COVID-19 vaccination prior to SARS-CoV-2 infection compared with odds among unvaccinated children.

DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, children were enrolled in a multisite longitudinal pediatric cohort from July 27, 2021, to September 1, 2022, and followed up through May 2023. Analysis used a case (PCC reported)-control (no PCC reported) design and included children aged 5 to 17 years whose first real time-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection occurred during the study period, who were COVID-19 vaccine age-eligible at the time of infection, and who completed a PCC survey at least 60 days after infection. From December 1, 2022, to May 31, 2023, children had weekly SARS-CoV-2 testing and were surveyed regarding PCC (≥1 new or ongoing symptom lasting ≥1 month after infection).

EXPOSURES: COVID-19 mRNA vaccination status at time of infection was the exposure of interest; participants were categorized as vaccinated (≥2-dose series completed ≥14 days before infection) or unvaccinated. Vaccination status was verified through vaccination cards or vaccine registry and/or medical records when available.

MAIN OUTCOME AND MEASURES: Main outcomes were estimates of the odds of PCC symptoms. Multivariate logistic regression was performed to estimate the odds of PCC among vaccinated children compared with odds of PCC among unvaccinated children.

RESULTS: A total of 622 participants were included, with 28 (5%) case participants and 594 (95%) control participants. Median (IQR) age was 10.0 (7.0-11.9) years for case participants and 10.3 (7.8-12.7) years for control participants (P = .37). Approximately half of both groups reported female sex (13 case participants [46%] and 287 control participants [48%]). Overall, 57% of case participants (16 children) and 77% of control participants (458 children) were vaccinated (P = .05). After adjusting for demographic characteristics, number of acute COVID-19 symptoms, and baseline health, COVID-19 vaccination was associated with decreased odds of 1 or more PCC symptom (adjusted odds ratio [aOR], 0.43; 95% CI, 0.19-0.98) and 2 or more PCC symptoms (aOR, 0.27; 95% CI, 0.10-0.69).

CONCLUSIONS AND RELEVANCE: In this study, mRNA COVID-19 vaccination was associated with reduced odds of PCC in children. The aORs correspond to an estimated 57% and 73% reduced likelihood of 1 or more and 2 or more PCC symptoms, respectively, among vaccinated vs unvaccinated children. These findings suggest benefits of COVID-19 vaccination beyond those associated with protection against acute COVID-19 and may encourage increased pediatric uptake.

PMID:39992656 | DOI:10.1001/jamanetworkopen.2024.59672

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Availability of Mobile Crisis Services in Mental Health Facilities

JAMA Netw Open. 2025 Feb 3;8(2):e2461321. doi: 10.1001/jamanetworkopen.2024.61321.

ABSTRACT

IMPORTANCE: Rates of suicide ideation, severe depression, and acute psychosis have surged, paralleling an increase in emergency department visits for psychiatric emergencies. Mobile crisis services can play an important role in delivering timely, community-based interventions.

OBJECTIVE: To assess the national availability of mobile crisis services in mental health treatment facilities and to identify key facility, geographic, and state-level factors associated with the availability of these services.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the 2022 National Substance Use and Mental Health Services Survey, which included 9036 mental health treatment facilities in the US. Facility zip codes were linked to the Agency for Healthcare Research and Quality’s Social Determinants of Health database to assess area-level factors. The study population included facilities that reported whether they offered mobile crisis services. Data were analyzed from August to September 2024.

MAIN OUTCOMES AND MEASURES: The primary outcome was the availability of mobile crisis services at mental health treatment facilities, as reported by facility directors. Key independent variables included facility characteristics, local area factors, and state Medicaid policies. Logistic regression models were used to examine the associations between these factors and the availability of mobile crisis services.

RESULTS: Of 9036 facilities, 1882 (20.8%) reported offering mobile crisis services. Facilities providing integrated dual diagnosis services (marginal effect, 3.44 [95% CI, 1.41-5.53] percentage points), suicide prevention services (marginal effect, 6.74 [95% CI, 4.29-9.20] percentage points), and assertive community treatment (marginal effect, 11.26 [95% CI, 9.02-13.51] percentage points) were significantly more likely to offer mobile health crisis services. Facilities in areas with lower percentages of residents with only a high school education were also more likely to offer mobile crisis services (marginal effect, 1.33 [95% CI, 0.15-2.51] percentage points).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US mental health facilities, facilities with integrated services and located in areas with certain geographic characteristics were more likely to offer mobile crisis services. Addressing gaps in service availability is essential to improving access to crisis care.

PMID:39992654 | DOI:10.1001/jamanetworkopen.2024.61321

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Neighborhood Environment, DNA Methylation, and Presence of Crown-Like Structures of the Breast

JAMA Netw Open. 2025 Feb 3;8(2):e2461334. doi: 10.1001/jamanetworkopen.2024.61334.

ABSTRACT

IMPORTANCE: Inflammation impacts cancer risk and tumor biological processes, yet studies linking it to social and environmental risk factors are lacking.

OBJECTIVE: To investigate the association of neighborhood deprivation and air pollution with breast adipose inflammation as well as the association between crown-like structures of the breast (CLS-B) and DNA methylation in Black and White women.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed women with and without breast cancer participating in the National Cancer Institute-Maryland Breast Cancer Study, most of whom were recruited between January 1, 1993, and December 1, 2003, from the University of Maryland Medical Center and surrounding hospitals in the Baltimore, Maryland, area. A small subset of the sample was recruited between March 27, 2012, and November 27, 2017. Noncancerous breast tissue was collected from women who underwent reduction mammoplasty or breast cancer surgery. Statistical analyses were conducted between May and August 2024.

EXPOSURES: Two socioenvironmental exposures were examined: air pollution (specifically, fine particulate matter less than 2.5 μm in diameter [PM2.5]) and neighborhood deprivation (measured with Neighborhood Deprivation Index [NDI]). Participant geocodes were linked to 2000 US Census data to calculate PM2.5 concentrations (total mass [μg/m3]) and NDI.

MAIN OUTCOMES AND MEASURES: Breast tissues underwent immunohistochemical staining for pan-macrophage marker CD68 to detect 2 outcomes: CLS-B and adipose-associated macrophages. CLS-B and adipose-related macrophages were assessed by pathologists using artificial intelligence-assisted and manual approaches. Covariate-adjusted logistic regression models were used to ascertain associations between PM2.5 and NDI (exposures) and presence or absence of CLS-B (outcome); CD68-positive adipose macrophages were modeled as a dichotomous high or low variable. Covariate-adjusted linear regression was used to identify associations between CLS-B (exposure) and DNA methylation (outcome).

RESULTS: The cohort included 205 participants (127 Black [62.0%], 78 White [38.0%] women; mean [SD] age, 48.7 [13.3] years). Women with vs without CLS-B had higher median (IQR) body mass index (calculated as weight in kilograms divided by height in meters squared; 35.5 [30.5-40.9] vs 31.8 [26.6-36.4]; P = .02). Higher levels of PM2.5 (odds ratio [OR], 2.32; 95% CI, 1.12-4.78; P = .02) and NDI (OR, 1.21; 95% CI, 1.02-1.43; P = .03) were associated with presence of CLS-B overall; findings were still significant among Black women (PM2.5: OR, 2.64 [95% CI, 1.10-6.33], P = .03; NDI: OR, 1.22 [95% CI, 1.01-1.48], P = .04) but were not statistically significant among White women (PM2.5: OR, 1.65 [95% CI, 0.45-5.99], P = .45; NDI: OR, 1.19 [95% CI, 0.83-1.70], P = .35). Higher PM2.5 concentration was associated with increased macrophage infiltration (OR, 2.11; 95% CI, 1.24-3.60; P = .006), with similar outcomes by race. The top 2 significant differentially methylated CpG sites by CLS-B status were SAR1B (β = 0.01; 95% CI, 0.01-0.02; P < .001) and IL2RB (β = -0.04; 95% CI, -0.05 to -0.02; P < .001). Significant interaction was observed between CLS-B status and race for IL2RB methylation levels (β = -0.03; 95% CI, -0.04 to -0.01; P for interaction <.001).

CONCLUSIONS AND RELEVANCE: This cross-sectional study uncovered an association between neighborhood-level social and environmental risk factors and breast tissue inflammation. The findings help inform efforts to reduce racial and socioeconomic disparities in breast cancer and improve health equity for socially vulnerable populations.

PMID:39992653 | DOI:10.1001/jamanetworkopen.2024.61334

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Acute Alcohol Use and Suicide

JAMA Netw Open. 2025 Feb 3;8(2):e2461409. doi: 10.1001/jamanetworkopen.2024.61409.

ABSTRACT

IMPORTANCE: While acute alcohol use (AAU) is known to increase the risk of suicide significantly, the underlying mechanisms of this association are still understudied.

OBJECTIVE: To examine the association between AAU and the risk factors for suicide, focusing on the association between AAU and choice of suicide methods.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included data from the Korean National Investigations of Suicide Victims Study (KNIGHTS). The KNIGHTS dataset comprises nationally representative data encompassing nearly all suicide deaths in South Korea from January 1, 2013, to December 31, 2020. The study was analyzed from November 2 to 10, 2023.

MAIN OUTCOMES AND MEASURES: The main outcome was whether decedents who died by suicide had consumed alcohol before their death. Trained investigators conducted psychological autopsies by reviewing police reports of suicide deaths. Whether the decedent who died by suicide had consumed alcohol before death was determined from 3 sources: (1) confirmation by informants, (2) autopsy reports indicating a positive blood alcohol concentration, and (3) observations from police officers. Demographic characteristics, premortem psychiatric symptoms, and suicide characteristics, including method of suicide and presumed reasons for suicide, were examined. Hierarchical logistic regression models were used to examine the association between the contributing factors and AAU.

RESULTS: This study included 55 226 decedents who died by suicide (65.5% male), of whom 21 998 (39.8%) were under the influence of alcohol at the time of death. AAU was associated with being male (odds ratio [OR], 1.37 [95% CI, 1.31-1.44]); being middle aged (eg, from age 30 to 39 years: OR, 1.20 [95% CI, 1.06-1.35]); and having alcohol use disorder symptoms (OR, 13.28 [95% CI, 12.38-14.24]). Among suicide methods, gas, drug, and pesticide poisoning showed a positive association with AAU, with gas poisoning showing the highest OR (OR, 1.88 [95% CI, 1.61-2.20]). An interaction was found between age and suicide method, with older adults (eg, aged 80 years or older) having higher odds of AAU when using methods such as drug (OR, 6.28 [95% CI, 3.53-11.17]), pesticide (OR, 6.56 [95% CI, 3.86-11.13]), and gas (OR, 2.48 [95% CI, 1.52-4.04]) poisoning.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that AAU was associated with gas poisoning, as indicated by the ORs. Given that charcoal burning involves substantial preparation time, alcohol may have been deliberately used to facilitate planned suicide attempts. Furthermore, the deaths of older adults who consumed alcohol prior to suicide, even when using less lethal methods, highlight the critical need for monitoring and effectively managing alcohol use within this population.

PMID:39992652 | DOI:10.1001/jamanetworkopen.2024.61409

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Knowledge of and Preferences for Medical Aid in Dying

JAMA Netw Open. 2025 Feb 3;8(2):e2461495. doi: 10.1001/jamanetworkopen.2024.61495.

ABSTRACT

IMPORTANCE: Medical aid in dying (MAID) is legal in jurisdictions covering more than one-fifth of the US population and has been used by a largely White, educated population. The extent to which knowledge of MAID and preferences for personal use align with patterns of use is unknown.

OBJECTIVE: To evaluate knowledge among US adults of the legal status of MAID as well as interest in using MAID.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, self-report online survey study used a national Prime Panels-based sample of US adults recruited between July 16 and August 10, 2024. A total of 3227 respondents aged 18 years or older from all US states and Washington, DC, were included. Individuals from states with legal MAID, aged 60 years or older, and members of racial and ethnic minority groups were oversampled.

MAIN OUTCOMES AND MEASURES: Knowledge of the legality of MAID in the US and in respondents’ state of residence as well as potential interest in future use of MAID. Descriptive statistics and χ2 tests were used to examine associations by demographic characteristics and place of residence.

RESULTS: Of 3227 respondents (mean [SD] age, 55.7 [17.4] years; 1839 women [57.0%]), 1654 (51.3%) did not know if MAID was legal the US, and 1638 (50.8%) did not know if MAID was legal in their state. Respondents in states where MAID is legal were more likely to know that MAID is legal in the US compared with those in states where MAID is not legal (728 of 2164 [33.6%] vs 216 of 1063 [20.3%]; P < .001). Across all respondents, 1420 (44.0%), including 96 of 222 Asian respondents (43.2%), 206 of 605 Black respondents (34.0%), and 129 of 308 Hispanic respondents (41.9%), reported they would definitely or probably consider MAID if they received a diagnosis of a terminal illness.

CONCLUSIONS AND RELEVANCE: In this online survey study of US adults, substantial interest in using MAID as well as significant knowledge gaps regarding the legality of MAID were reported. These findings highlight the need for public education, policy initiatives, and patient-clinician discussions to ensure equitable access to patient-centered end-of-life options and informed decision-making.

PMID:39992651 | DOI:10.1001/jamanetworkopen.2024.61495

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Detection of Epileptogenic Focal Cortical Dysplasia Using Graph Neural Networks: A MELD Study

JAMA Neurol. 2025 Feb 24. doi: 10.1001/jamaneurol.2024.5406. Online ahead of print.

ABSTRACT

IMPORTANCE: A leading cause of surgically remediable, drug-resistant focal epilepsy is focal cortical dysplasia (FCD). FCD is challenging to visualize and often considered magnetic resonance imaging (MRI) negative. Existing automated methods for FCD detection are limited by high numbers of false-positive predictions, hampering their clinical utility.

OBJECTIVE: To evaluate the efficacy and interpretability of graph neural networks in automatically detecting FCD lesions on MRI scans.

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter diagnostic study, retrospective MRI data were collated from 23 epilepsy centers worldwide between 2018 and 2022, as part of the Multicenter Epilepsy Lesion Detection (MELD) Project, and analyzed in 2023. Data from 20 centers were split equally into training and testing cohorts, with data from 3 centers withheld for site-independent testing. A graph neural network (MELD Graph) was trained to identify FCD on surface-based features. Network performance was compared with an existing algorithm. Feature analysis, saliencies, and confidence scores were used to interpret network predictions. In total, 34 surface-based MRI features and manual lesion masks were collated from participants, 703 patients with FCD-related epilepsy and 482 controls, and 57 participants were excluded during MRI quality control.

MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and positive predictive value (PPV) of automatically identified lesions.

RESULTS: In the test dataset, the MELD Graph had a sensitivity of 81.6% in histopathologically confirmed patients seizure-free 1 year after surgery and 63.7% in MRI-negative patients with FCD. The PPV of putative lesions from the 260 patients in the test dataset (125 female [48%] and 135 male [52%]; mean age, 18.0 [IQR, 11.0-29.0] years) was 67% (70% sensitivity; 60% specificity), compared with 39% (67% sensitivity; 54% specificity) using an existing baseline algorithm. In the independent test cohort (116 patients; 62 female [53%] and 54 male [47%]; mean age, 22.5 [IQR, 13.5-27.5] years), the PPV was 76% (72% sensitivity; 56% specificity), compared with 46% (77% sensitivity; 47% specificity) using the baseline algorithm. Interpretable reports characterize lesion location, size, confidence, and salient features.

CONCLUSIONS AND RELEVANCE: In this study, the MELD Graph represented a state-of-the-art, openly available, and interpretable tool for FCD detection on MRI scans with significant improvements in PPV. Its clinical implementation holds promise for early diagnosis and improved management of focal epilepsy, potentially leading to better patient outcomes.

PMID:39992650 | DOI:10.1001/jamaneurol.2024.5406

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Melt electrowriting of bioglass-laden poly(ε-caprolactone) scaffolds for bone regeneration

J Mater Chem B. 2025 Feb 24. doi: 10.1039/d4tb02835j. Online ahead of print.

ABSTRACT

Novel and promising biomaterials for bone tissue engineering have been investigated over the years. Aiming to contribute to this progress, this study developed and evaluated polycaprolactone (PCL) scaffolds with 5% (w/w) 58S-bioactive glass (58S-BG) fabricated via melt electrowriting (MEW). Morphological and chemical characterization of the scaffolds was conducted. The biological potential was assessed in vitro with alveolar bone-derived mesenchymal stem cells through cytotoxicity, adhesion, protein production, alkaline phosphatase activity, and mineral nodule formation assays. In vivo, scaffolds implanted in rats were analyzed for biocompatibility, inflammation, and degradation using H&E staining and immunohistochemical markers for angiogenesis and macrophage polarization. Statistical analysis was performed at a 5% significance level. Appropriate fiber alignment but a higher fiber diameter was found for PCL + BG5% compared to PCL scaffolds (p = 0.002). EDS spectra confirmed the presence of BG’s chemical components for BG-laden scaffolds, attesting to BG particle incorporation into the filaments. Raman spectroscopy evidenced the chemical nature of the BG powder, and FTIR spectra revealed -OH stretching for PCL + BG5%, evidencing its hydrophilic potential. None of the scaffolds were cytotoxic, and BG-laden formulation increased cell viability after 7 days (p = 0.0006), also showing greater cell adhesion/spreading over time compared to pristine PCL scaffolds. BG’s presence also increased the mineral matrix formation (p ≤ 0.0021) over 21 days and retained ALP activity after 14 days (p = 0.705) compared to PCL. In vivo, PCL scaffolds retained fiber alignment and preserved their volume throughout the evaluation, showing minimal structural alteration. In contrast, PCL + BG5% scaffolds showed more visible structural changes at 28 days. Despite this, the PCL + BG5% formulation remained biocompatible and significantly promoted angiogenesis compared to pristine PCL scaffolds. In sum, BG-laden scaffolds were successfully melt electrowritten, retaining the scaffolds’ porous architecture, showing appropriate properties, including cell viability, adhesion, mineralized nodule deposition, biocompatibility, and angiogenesis, indicating that these materials are a promising alternative for enhancing bone tissue regeneration.

PMID:39992649 | DOI:10.1039/d4tb02835j

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Emulating a Target Trial Using Observational Data

JAMA Intern Med. 2025 Feb 24. doi: 10.1001/jamainternmed.2024.8129. Online ahead of print.

NO ABSTRACT

PMID:39992643 | DOI:10.1001/jamainternmed.2024.8129

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Mortality Among US Physicians and Other Health Care Workers

JAMA Intern Med. 2025 Feb 24. doi: 10.1001/jamainternmed.2024.8432. Online ahead of print.

ABSTRACT

IMPORTANCE: National estimates of mortality among physicians and other health care workers are lacking. It is also unknown if distinct patterns exist across sex, race, and ethnicity.

OBJECTIVE: To compare all-cause and cause-specific mortality rates among physicians, health care workers, and non-health care workers by sex, race, and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: The National Vital Statistics System, a population-based registry of US death certificates, was used to obtain data on deaths among adults aged 25 to 74 years from January 2020 to December 2022 by usual occupation. Data were analyzed from January 2024 to December 2024.

EXPOSURES: Usual occupation, sex, race, and ethnicity.

MAIN OUTCOMES AND MEASURES: Overall and cause-specific mortality rates were calculated for each occupation, as well as sex, race, and ethnicity subgroups, and compared using mortality rate ratios. Mortality estimates were age-adjusted and sex-adjusted, and health care occupations were compared with non-health care occupations with similar income levels (categorized as low income, medium income, and high income based on US Census income terciles).

RESULTS: Most health care workers had lower age-adjusted and sex-adjusted annual mortality rates per 100 000 population than non-health care workers (eg, physicians [269.3], high-income non-health care workers [499.2], and non-health care workers overall [730.6]). While female individuals had lower mortality than male individuals in non-health care occupations overall (female to male ratio, 0.55; 95% CI, 0.55-0.55) and high-income non-health care occupations specifically (0.60; 95% CI, 0.60-0.60), this advantage was absent for several health care occupations, including physicians (0.97; 95% CI, 0.93-1.01). In particular, female physicians experienced higher mortality than male physicians of neoplasms and chronic lower respiratory diseases, despite lower mortality of these causes among female individuals in high-income non-health care occupations. Black workers had higher mortality than White workers across all occupations, although the Black to White mortality ratio was largest for physicians (2.13; 95% CI, 1.99-2.29), with the largest differences due to neoplasms, heart disease, and COVID-19. Black female physicians had higher mortality rates than all other physician subgroups and White female individuals in non-health care occupations. While Hispanic workers had lower mortality than White workers in non-health care occupations overall (Hispanic to White ratio, 0.83; 95% CI, 0.83-0.83) and high-income non-health care occupations specifically (0.90; 95% CI, 0.90-0.91), this pattern was reversed for several health care occupations, including physicians (1.18; 95% CI, 1.09-1.27).

CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that although physicians and most health care workers experienced lower mortality rates compared with the general population, this benefit did not fully extend to female individuals or racial and ethnic minority groups. Renewed efforts are needed to address health inequities within the health care workforce.

PMID:39992637 | DOI:10.1001/jamainternmed.2024.8432

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Postbiotic Supplementation Increases Amino Acid Absorption from Plant-Based Meal: A Placebo-Controlled, Randomized, Double-Blind, Crossover Study

Probiotics Antimicrob Proteins. 2025 Feb 24. doi: 10.1007/s12602-025-10480-y. Online ahead of print.

ABSTRACT

Supplementation of probiotic strains can enhance the absorption of amino acids from protein in the gut. The purpose of this study was to assess if supplementation of a multi-strain probiotic or a postbiotic, consisting of the same strains, would alter the absorption of individual and total amino acids following ingestion of a plant-based meal. Sixteen male participants consumed either probiotic (PRO) or postbiotic (cells inactivated by γ-irradiation; POST), both consisting of L. paracasei LP-DG® (CNCM I-1572) plus L. paracasei LPC-S01 (DSM 26760), or a placebo (PLA) for 2 weeks in a randomized, double-blind, crossover design study separated by a 4-week washout period. During the testing session, blood samples were taken at baseline, 30-, 60-, 120-, and 180-min post-ingestion of a plant-based vegan burger patty. Plasma amino acid levels were analyzed, and percent changes from baseline were assessed using linear mixed-effects models, with the PLA condition as the reference group. There was statistically significant POST condition-by-time interactions for percent changes in alanine, asparagine, citrulline, cystine, glycine, methionine, proline, and total amino acids (p < 0.05, for all). Additionally, there was a statistically significant condition (PRO) by time interactions for cystine (p = 0.02). Two weeks of POST supplementation resulted in significant improvements in amino acid absorption profiles for various individual amino acids and total amino acids compared to PLA. This is the first study to report improved amino acid absorption from a mixed macronutrient meal following a period of postbiotic supplementation.

PMID:39992622 | DOI:10.1007/s12602-025-10480-y