UCSF

Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.

INTRODUCTION: Treatment indications for oligometastatic/oligoprogressive lung tumors are growing. Safety and lack of detrimental effect on patients' quality of life are critical for novel local therapies. METHODS: We tested that the additive effect of pulsed electric field (PEF) ablation with lower-dose stereotactic body radiation therapy (SBRT) on health-related quality of life (HRQoL) as a secondary endpoint in a prospective clinical trial. FACT-Lung Cancer Subscale (FACT-LCS) and FACT-General domain surveys were collected at screening, 3 months, and 12 months. Functional clinical data included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS: Six patients with eight tumors were enrolled. Baseline well-being domain scores were: Physical 25.9 (Std Dev 2.3), Social 21.0 (Std Dev 6.9), Emotional 17.3 (Std Dev 4.7), Functional 21.2 (Std Dev 5.8), and LCS 19.4 (Std Dev 5.3). There were no significant changes following combined modality treatment in HRQoL domain scores or pulmonary function metrics after treatment. Lower EWB and SWB were associated with worse FVC and FEV1. CONCLUSION: In this small pilot study, no clinically meaningful declines in pulmonary function or patient-reported quality of life were observed at 3 months following combination therapy.

Background: Zinc is widely used in oral care products due to its antimicrobial and anti-biofilm properties; however, the molecular mechanisms by which zinc influences Streptococcus mutans (S. mutans) physiology remain incompletely understood. The AdcABC system is the primary high-affinity zinc transporter in S. mutans. We investigated whether loss of adcBC is associated with altered physiological responses in S. mutans. Material and methods: Wild-type (WT), ΔadcBC mutant, and complemented S. mutans UA159 strains were evaluated under zinc-replete and zinc-limited conditions using zinc sulphate (ZnSO₄) at defined concentrations. Growth, carbohydrate utilization, acidogenicity, acid tolerance, aggregation, biofilm formation, and expression of stress response and regulatory genes were assessed. Results: Loss of adcBC impaired growth and reduced utilization of multiple carbohydrates, including key glycolytic substrates, indicating altered metabolism. Zinc supplementation restored growth but did not consistently recover redox-based metabolic activity. Expression of pflA, associated with fermentative metabolism, was reduced in the mutant. Acid tolerance was unaffected by AdcBC. Zinc enhanced aggregation and surface attachment independently of AdcBC, whereas biofilm biomass showed partial dependence on AdcBC-mediated zinc uptake. The ΔadcBC mutant also exhibited altered expression of genes involved in oxidative stress, metal homeostasis, and regulatory pathways. Conclusion: Loss of adcBC is associated with altered physiological responses in S. mutans. Zinc influences bacterial physiology through both uptake-dependent and uptake-independent mechanisms, highlighting its context-dependent role in oral environments.

Purpose of ReviewTailoring treatment strategies to the biological features of invasive disease and the individual needs and preference of each patient has transformed the way we manage breast cancer. This article calls for a similar shift in the management paradigm of ductal carcinoma in situ (DCIS) from a uniform treatment model toward a risk-stratified stepwise approach that aligns with the heterogeneous nature of the disease to avoid overtreatment.Recent FindingsMost DCIS lesions are hormone receptor positive, and only a subset have a risk for progression to invasive cancer. Early results from observational and clinical studies indicate that active surveillance is a safe and feasible alternative to upfront surgical treatment for low-risk DCIS. Ongoing clinical trials like RECAST will further inform and refine strategies for optimal management of this condition.SummaryThe integration of risk-adapted management strategies, endocrine risk-reducing interventions, and advanced imaging modalities into active surveillance protocols hold significant potential to reduce overtreatment and personalize care for patients with DCIS. Early data from clinical trials support the notion that providing a period of active surveillance is safe and offers a critical assessment window during which DCIS treatment can be individualized. Strengthening the evidence base to support the adoption of active surveillance as an initial approach in the management of DCIS is an important clinical priority.

BACKGROUND: Intersectionality, xenophobia, and health behavior theories suggest that sexual and gender minority (SGM) status, race/ethnicity, and nativity jointly shape healthcare access, yet these dimensions are often examined separately. This study identifies intersectional differences within foreign-born groups that may have previously been obscured. METHODS: Using six waves (2015-2020) of restricted California Health Interview Survey data, we estimated multinomial logistic models of insurance coverage and usual source of care among foreign-born adults, comparing by sexual orientation and gender identity, adjusting for predisposing, enabling, and need factors. To capture racialized differences, we stratified models by ethnoracial identity, for Black, Indigenous, Person of Color (BIPOC) vs. non-BIPOC. RESULTS: Insurance patterns varied by sexual orientation. Compared with heterosexuals, gay/lesbian foreign-born adults had lower probability of being uninsured; respondents reporting sexual orientation as "none" had higher Medicaid/other and lower employer/private coverage. For usual source of care, gay/lesbian adults were less likely to lack a source, whereas bisexual, "none," and "other" groups had higher probabilities of no usual source and lower physician-based care. Transgender identity showed no consistent differences. Hispanic and Black foreign-born adults were more likely to use community/other sites and less likely to use physician care. In BIPOC-stratified models, bisexual/"none"/"other" groups had higher probability of lacking a usual source of care. Among non-BIPOC adults, gay/lesbian adults had lower probabilities of lacking insurance or usual source of care. CONCLUSIONS: Heterogeneity exists within foreign-born SGM populations, with policy-relevant disparities concentrated among BIPOC subgroups. Findings highlight the need for targeted, culturally responsive coverage and care interventions.

Similarities between frontotemporal lobar degeneration with transactive response DNA‐binding protein of 43 kDa (TDP‐43) (FTLD‐TDP) and limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) raise questions about whether they represent distinct entities or a single disease spectrum. The literature mostly examined series with disproportionate numbers of LATE‐NC over FTLD‐TDP. Leveraging a clinicopathological collection of FTLD‐TDP (N = 148) from the University of California, San Francisco, we compared demographic, clinical, genetic, and neuropathological features of FTLD‐TDP, particularly FTLD‐TDP type A (N = 39), and LATE‐NC (N = 42). FTLD‐TDP type A cases were younger at onset and death, had shorter disease duration, and frequent genetic causes (GRN, C9ORF72) compared to LATE‐NC, which were mostly sporadic and older. Blinded evaluation of middle frontal gyrus (MFG) TDP‐43 immunostaining alone proved insufficient to reliably differentiate FTLD‐TDP type A from LATE‐NC stage 3. However, factoring in all neuropathologic features, FTLD type A and LATE‐NC could be differentiated with >95% confidence. These overall findings support distinct diagnostic entities for FTLD‐TDP and LATE‐NC. FTLD‐TDP and LATE‐NC can overlap clinically and pathologically, but key features help distinguish them in practice. Using brain bank data enriched for FTLD‐TDP, we provide an original side‐by‐side comparison of FTLD‐TDP and LATE‐NC cases. Age at death and regional vulnerability patterns differ between FTLD‐TDP and LATE‐NC in our cohort. Assessing TDP‐43 pathology in the MFG alone is not sufficient to differentiate FTLD‐TDP from LATE‐NC. We offer a perspective on the literature comparing FTLD‐TDP and LATE‐NC, highlighting points of convergence/divergence and implications for classification and interpretation across studies.

Ischemic injury to the somatosensory ventrobasal (VB) thalamus is strongly associated with central post-stroke pain (CPSP), yet preclinical models of selective focal ischemic VB injury remain limited. Here, we developed a mouse model of ischemic VB stroke using photothrombotic occlusion. Stroke-affected mice exhibited persistent spontaneous facial grimace throughout the four-week observation period, consistent with a sustained affective behavioral state. Hindpaw mechanical hyposensitivity and postural abnormalities were transient, emerging early after stroke and resolving within two weeks. These evoked and postural measures were not correlated with facial grimace behavior across time points, indicating dissociation between persistent grimace behavior and transient sensory or motor phenotypes. Immunohistochemistry showed increased thalamic glial activation, and VPL microgliosis was positively associated with four-week facial grimace severity. Together, these findings establish a reproducible model of focal ischemic somatosensory thalamic stroke characterized by persistent spontaneous facial grimace behavior alongside dissociated transient evoked and postural changes. This model provides a framework for investigating mechanisms associated with CPSP following ischemic thalamic injury.

ABSTRACT: Objective: The Veterans Health Administration (VA) uses e-screening surveys to request information from Veterans before appointments, and VA Video Connect (VVC) readiness calls to ensure that Veterans can attend appointments virtually. Providers and staff face challenges in working with Veterans to complete e-screenings and VVC readiness calls. For example, in 2023, VA’s Sleep Clinical Resource Hub completed 20% of e-screenings. Team leaders therefore asked UCSF’s Patient Support Corps (PSC) to deploy student interns who could help with e-screenings and VVC readiness calls. PSC is a four-year co-op internship where pre-health college students earn academic credit while gaining experience and serving patients. Eighty percent of PSC students are from underrepresented populations, thereby extending the cultural and linguistic competency of the workforce. Study Design: In March 2024, PSC signed a Trainee Qualifications and Credentials Verification Letter with VA, designating three undergraduate student interns as Health Professions Trainees (HPTs). As HPTs, students gained access to VA clinical systems including the electronic health record and VVC telehealth system. Nurses tasked interns with administering e-screenings by email or by telephone, as well as conducting VVC readiness calls, for veterans undergoing sleep apnea evaluations. We audited program records between 7/23/24 and 2/13/25, to evaluate the reach of intern VVC readiness calls; and also evaluated the reach of intern e-screenings between 1/2/25 and 2/13/25. Principal Findings: Between 7/23/24 and 2/13/25, VA nurses assigned 90 VVC readiness calls to interns, who reached 66 (73%) of these Veterans. Between 1/2/25 and 2/13/25, interns initiated 313 e-screenings, and Veterans completed 168 (54%), representing an increase in completion rate when compared to 20% in 2023. Implications: PSC is successfully deploying students to extend the TeleSleep workforce at VA. Student support for Veterans frees up providers and staff to “practice at the top of their training.” This implementation serves as a potential proof of concept for other clinical resource hubs or virtual care teams at VA.