Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Preexposure Prophylaxis Uptake Among Spanish-Speaking Transgender Women: A Randomized Controlled Trial in North and South Carolina, 2019-2022.

Objectives. To evaluate Chicas Creando Acceso a la Salud (Girls Creating Access to Health; ChiCAS), a Spanish-language, small-group intervention designed to increase preexposure prophylaxis (PrEP) use, consistent condom use, and medically supervised gender-affirming hormone therapy use among Spanish-speaking transgender Latinas who have sex with men. Methods. Participants were 144 HIV-negative Spanish-speaking transgender Latinas, aged 18 to 59 years, living in North and South Carolina. From July 2019 to July 2021, we screened, recruited, and randomized them to the 2-session ChiCAS intervention or the delayed-intervention waitlist control. Participants completed assessments at baseline and 6-month follow-up. Follow-up retention was 94.4%. Results. At follow-up, relative to control participants, ChiCAS participants reported increased PrEP use (adjusted odds ratio [AOR] = 4.64; 95% confidence interval [CI] = 1.57, 13.7; P < .006). However, ChiCAS participants did not report increased use of condoms or medically supervised gender-affirming hormone therapy. ChiCAS participants reported increases in knowledge of HIV (P < .001), sexually transmitted infections (P < .001), and gender-affirming hormone therapy (P = .01); PrEP awareness (P < .001), knowledge (P < .001), and readiness (P < .001); condom use skills (P < .001); and community attachment (P < .001). Conclusions. The ChiCAS intervention was efficacious in increasing PrEP use among Spanish-speaking, transgender Latinas in this trial. (Am J Public Health. 2024;114(1):68-78. https://doi.org/10.2105/AJPH.2023.307444).

Kelp forests collapse reduces understorey seaweed ß-diversity.

BACKGROUND AND AIMS: Kelps are the primary foundation species in temperate subtidal rocky shores worldwide. However, global change is causing their decline with consequences for the organisms that rely on them. An accurate assessment of these consequences may depend on which attributes of the associated community are considered. This study shows that conventional α-diversity approaches may overlook some of these consequences compared to spatially explicit approaches such as with ß-diversity. METHODS: A 1-year seasonal study was conducted to compare the macroalgal understorey between healthy reefs with a Laminaria ochroleuca canopy and degraded reefs where the canopy collapsed years ago due to excessive fish herbivory. At each reef, the understorey seaweed assemblage was recorded in five replicate quadrats to estimate α-diversity (total richness, species density, Shannon index) and ß-diversity (intra- and inter-reef scale). KEY RESULTS: The understorey assemblage exhibited a distinct seasonal dynamic in both healthy and degraded reefs. α-Diversity attributes increased in spring and summer; turf-forming algae were particularly dominant in degraded reefs during summer. ß-Diversity also showed seasonal variability, but mostly due to the changes in degraded reefs. None of the α-diversity estimates differed significantly between healthy and degraded reefs. In contrast, spatial ß-diversity was significantly lower in degraded reefs. CONCLUSIONS: Although the loss of the kelp canopy affected the composition of the macroalgal understorey, none of the conventional indicators of α-diversity detected significant differences between healthy and degraded reefs. In contrast, small-scale spatial ß-diversity decreased significantly as a result of deforestation, suggesting that the loss of kelp canopy may not significantly affect the number of species but still have an effect on their spatial arrangement. Our results suggest that small-scale ß-diversity may be a good proxy for a more comprehensive assessment of the consequences of kelp forest decline.

Discriminative capacity of the Spanish version of the Inventory of Depression and Anxiety Symptoms-II (IDAS-II) for detecting DMS-5 specific disorders and poor quality of life in a clinical sample.

BACKGROUND: Emotional problems can be evaluated using categorical approaches to guide treatment choices focused on targeting specific disorders, or dimensional approaches to reduce symptom severity. Moreover, recent evidence points out the need to intervene in patients' quality of life (QoL), which often remains low even after the remission of emotional problems. Thus, assessment instruments are needed to provide information on diagnosis, symptom severity, and QoL. The present study aimed to provide diagnostic and QoL cutoffs for the Inventory of Depression and Anxiety Symptoms-II (IDAS-II). METHODS: 273 patients recruited from mental health services in Huelva (Spain) completed the IDAS-II, Mini International Neuropsychiatric Interview, and Short Form-36 Health Survey. Receiver operating characteristic curve analyses were used to establish cutoff values. Diagnostic, balanced, and screening cutoffs were provided for each IDAS-II scale to detect corresponding diagnoses and poor QoL. RESULTS: The specific IDAS-II scales Suicidality, Panic, Social Anxiety, Claustrophobia, and Traumatic Intrusions showed adequate discrimination values for their corresponding diagnoses (suicidal behavior disorder, panic disorder, social anxiety disorder, agoraphobia, and post-traumatic stress disorder, respectively). Both the General Depression and Dysphoria scales showed adequate ability to detect major depressive disorder. The IDAS-II scales showed a higher discrimination ability for Mental Health-related QoL, than for General Health-related QoL. CONCLUSIONS: The diagnostic and QoL cutoffs expand the clinical utility of the IDAS-II in clinical practice and research, making it a comprehensive, detailed, and versatile self-report tool. The IDAS-II allows for the assessment of emotional problems consistent with the dimensional, categorical, transdiagnostic, and QoL approaches.

NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

Sexual dysfunction and self-perceived sexual health in patients with rheumatoid arthritis and systemic lupus erythematosus: results from a cross-sectional survey.

Sexual dysfunction (SD) has been associated with worse quality of life and higher disease activity in patients with rheumatic diseases, yet it is still not regularly addressed during routine rheumatologic evaluations. This study aimed to determine the prevalence of sexual dysfunction in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and evaluate their perception of their sexual health. We performed a retrospective study in an outpatient rheumatology clinic to evaluate patients over 18 years old with a diagnosis of RA or SLE through the Spanish version of the Arizona Sexual Experiences Scale (ASEX) and the Sexual Health Perception Survey (SHEPS), a questionnaire of 6 items designed in our clinic. Additionally, we applied the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F version 4) and the Hospital Anxiety and Depression Scale (HADS). A total of 567 patients were evaluated with SHEPS, most of whom were women with a median age of 50 years (IQR: 34) and a median disease duration of 5 years (IQR: 9). Through the ASEX, we found that 67% of the patients with RA and 60% of the patients with SLE experienced SD. Patients reported the level of sex drive, arousal, and the ability to achieve orgasms as the areas with the most difficulties. Most patients did not know their disease could affect their sexuality and had never addressed these issues with their rheumatologists, but almost all of them were willing to. Our findings highlight the importance of addressing sexual health issues regularly during rheumatologic evaluations.

Short-term high-fat feeding exacerbates degeneration in retinitis pigmentosa by promoting retinal oxidative stress and inflammation.

A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystrophic retinal degeneration 10 (rd10) mice, a model of retinitis pigmentosa, fed an HFD for 2 to 3 wk. Short-term HFD feeding impaired retinal responsiveness and visual acuity and enhanced photoreceptor degeneration, microglial cell activation, and Müller cell gliosis. HFD consumption also triggered the expression of inflammatory and oxidative markers in rd10 retinas. Finally, an HFD caused gut microbiome dysbiosis, increasing the abundance of potentially proinflammatory bacteria. Thus, HFD feeding drives the pathological processes of retinal degeneration by promoting oxidative stress and activating inflammatory-related pathways. Our findings suggest that consumption of an HFD could accelerate the progression of the disease in patients with retinal degenerative disorders.

Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis.

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure and cancer predisposition syndrome caused by mutations in telomerase or telomeric proteins. Here, we report that zebrafish telomerase RNA (terc) binds to specific DNA sequences of master myeloid genes and controls their expression by recruiting RNA Polymerase II (Pol II). Zebrafish terc harboring the CR4-CR5 domain mutation found in DC patients hardly interacted with Pol II and failed to regulate myeloid gene expression in vivo and to increase their transcription rates in vitro. Similarly, TERC regulated myeloid gene expression and Pol II promoter occupancy in human myeloid progenitor cells. Strikingly, induced pluripotent stem cells derived from DC patients with a TERC mutation in the CR4-CR5 domain showed impaired myelopoiesis, while those with mutated telomerase catalytic subunit differentiated normally. Our findings show that TERC acts as a transcription factor, revealing a target for therapeutic intervention in DC patients.

Examining Profiles and Treatment Outcomes in Dual Diagnosis: Comparison of Coordinated Treatment With Mental Health Services Versus Addiction Center Alone. A Real-World Data Analysis.

OBJECTIVE: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. METHODS: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. RESULTS: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. CONCLUSIONS: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.