Pulmonary fibrosis (PF) and acute lung injury (ALI) are severe and often fatal pulmonary conditions with high morbidity and limited treatment options, characterized by progressive interstitial scarring or acute diffuse alveolar damage, respectively. Mitochondrial dysfunction is increasingly implicated in their pathogenesis, and LACTB (Lactamase beta), a mitochondrial serine protease, is a potential regulator of these. However, current diagnostics cannot capture early molecular or organelle-level changes. This gap highlights the need for a noninvasive, mitochondria-targeted imaging approach to monitor disease-related biochemical alterations in vivo.

HD-LACTB is a hemicyanine-based Near-Infrared (NIR) fluorescent probe, whose activation is triggered by enzymatic bond cleavage. LACTB recognizes the peptide sequence within the probe and catalyzes hydrolysis at the cleavage site, releasing a free hemicyanine fluorophore and the corresponding peptide fragment. It features emission in the NIR spectrum (725 nm) for enhanced tissue penetration, along with high selectivity for LACTB and low cytotoxicity, outperforming previous fluorescent probes. The cationic hemicyanine moiety drives selective mitochondrial accumulation, ensuring that the fluorescence signal specifically reports mitochondrial LACTB activity in cells. In murine models of PF and ALI (bleomycin- and LPS-induced, respectively), systemic administration of HD-LACTB enabled noninvasive lung imaging with robust, organ-specific NIR signals. The probe readily distinguished fibrotic or acutely injured lungs from normal controls by visualizing LACTB-mediated metabolic alterations, with fluorescence intensities correlating with disease severity, thereby improving diagnostic precision over prior non-targeted imaging approaches.

The development of HD-LACTB showcases a conceptual advance in probe design: a mitochondria-targeted, enzyme-responsive NIR fluorophore that bridges a critical gap in lung disease imaging. This strategy illustrates how rationally engineered chemical probes can provide unprecedented molecular specificity in vivo, heralding a new class of materials-based diagnostics for respiratory diseases. By enabling precise, noninvasive visualization of pathological processes at the organelle level, HD-LACTB paves the way for innovative diagnostic approaches in pulmonary medicine.

This study aimed to investigate the impact of preconception maternal inactivated COVID-19 vaccination on fetal metabolic recovery following maternal SARS-CoV-2 infection during pregnancy. Umbilical cord blood samples were collected from neonates born to mothers with SARS-CoV-2 infection during pregnancy. Mothers were stratified into two groups: those fully vaccinated (inactivated COVID-19 vaccines) before conception (n = 81) and unvaccinated (n = 56). Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for metabolomic profiling. The vaccinated group exhibited markedly reduced amino acid/purine metabolism dysregulation and oxidative stress compared to unvaccinated counterparts. Crucially, within the critical IRT window of 5-6 months, vaccination effectively suppressed mTOR signaling-driven pathological metabolic remodeling. In contrast, the unvaccinated group demonstrated sustained metabolic disturbances (> 6 months from infection). In conclusion, preconception maternal inactivated COVID-19 vaccination reprograms fetal metabolism and accelerates intrauterine recovery from maternal SARS-CoV-2 infection, which may confer a beneficial impact on early-life growth. It prevents the establishment of a detrimental "metabolic memory" effect posing potential developmental risks. These findings reveal a novel non-immune, metabolome-mediated protective mechanism of maternal vaccination, which thus supports COVID-19 vaccination for women of childbearing age.

Between July and October 2025, among the total 117 influenza A(H1N1)pdm09 strains characterised in Catalonia, 20% to 100% per week were carrying the NA:S247N substitution. The mutation, conferring reduced susceptibility to oseltamivir, was phenotypically confirmed (IC₅₀ between 0.82 and 1.63 nM, compared to median IC₅₀ of 0.3 nM for susceptible strains). An increased proportion of S247N variants was also observed in sequence data (10,944 sequences) from other parts of Spain and five of 35 submitting countries across Europe.

Aspergillus is a life-threatening opportunistic pathogen in lung transplant recipients (LuTRs). Isavuconazole (ISA) is a broad-spectrum triazole with favorable pharmacokinetics and safety profile. The clinical experience with ISA in LuTRs, however, is still limited.

We performed an ambispective observational study from June 2019 to June 2024 in 5 Spanish centers. Adult LuTRs with isolation of Aspergillus spp. in respiratory tract specimens and indication of ISA therapy (either for the treatment of invasive pulmonary aspergillosis [IPA] or tracheobronchial aspergillosis [TBA] or for preemptive therapy) were eligible. The safety outcome comprised the occurrence of treatment-emergent adverse events (trAEs) and the need for modification of tacrolimus dose. Effectiveness outcomes included clinical, mycological, and radiological response at the end of treatment (EoT).

Overall, 50 LuTRs were included. ISA was administered for a median duration of 101 days (interquartile range: 27-161) for the treatment of IPA (18 [36.0%]) or TBA (27 [54.0%]) and as preemptive therapy (5 [10.0%]). The incidence rates of any trAE and trAE requiring premature ISA discontinuation were 24.0% and 10.0%, respectively. Most patients (35 [70.0%]) completed the planned course of therapy. Tacrolimus daily dose was reduced by a median of one-third in half of the patients (26/48 [54.2%]). Clinical, mycological, and radiological responses at EoT among were achieved in 66.7%, 84.2%, and 64.3% of evaluable patients, respectively. Aspergillosis-attributable mortality at the end of follow-up was 12.0%.

ISA was well tolerated in LuTRs and proved to be effective for the treatment of invasive Aspergillus syndromes.

To compare maternal and perinatal outcomes in pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection among admissions in public and private maternity hospitals before COVID-19 vaccination.

We performed a secondary analysis of the REBRACO (in Portuguese, the Brazilian Network of COVID-19 During Pregnancy) initiative, a national multicenter cohort study in Brazil, considering pregnant and postpartum women with suspected or confirmed SARS-CoV-2 infections (from February 2020 to February 2021) in 15 maternity centers (2 private and 13 public facilities). Sociodemographic and obstetric characteristics were compared according to the type of hospital care. The clinical and laboratory findings and maternal and perinatal outcomes were compared between the two groups. The prevalence ratio and its 95% confidence interval for each predictor and outcome were calculated.

Of the 559 symptomatic cases tested, 289 confirmed COVID-19 cases were included, with 213 (72.7%) and 76 (27.3%) women in public and private hospitals, respectively. The frequency of SARS-CoV-2 infection did not differ significantly between the groups. Women treated at public hospitals had lower education levels (p<0.001), and 50% declared that their pregnancy was unplanned. We recorded 13 maternal deaths among women treated at public hospitals and no maternal deaths among pregnant women treated at private hospitals (p=0.024). Pregnant women in public hospitals had higher rates of fever (p=0.041), tachypnea (p=0.003), abnormal laboratory findings of liver enzymes (p=0.005), and severe acute respiratory syndrome (SARS) (p=0.014), and their neonates presented with more neonatal respiratory distress (p=0.020).

Adverse maternal and perinatal outcomes were worse in the public hospital group, with increased rates of SARS and neonatal respiratory distress. The alarming difference in the number of deaths between patients treated in the public and private sectors highlights the urgency of better understanding the social determinants of health and calls the attention of leaders and policymakers to take action in mitigating their impact.

We present a case of endonasal leishmaniasis diagnosed on a frozen section biopsy specimen obtained from a 47-year-old woman treated with corticosteroids and anti-TNF^α for rheumatoid arthritis. Similar cases of isolated mucosal leishmaniasis have not yet been reported in Croatia. Microscopic analysis of the biopsy specimen sent for frozen sections revealed Leishmania amastigotes in macrophages infiltrating nasal mucosa. Subsequent communication with the referring clinician revealed that the patient had been diagnosed with visceral leishmaniasis 13 years prior to current biopsy. Thus, the present nasal lesion was interpreted as a solitary lesion related to reactivation of the previous infection. She received liposomal amphotericin B which led to prompt amelioration of the lesion. As shown in the present case, clinical presentation of leishmaniasis is unspecific and can mimic many other conditions, especially in the setting of concomitant immunosuppressive and anti-inflammatory treatment. It is important to be aware of this entity in order to treat such patients properly.

Night-time parasympathetic activation, diminished effect of long-acting muscarinic antagonists (LAMA) closer to end of the dosing period, and frequent exacerbations in chronic obstructive pulmonary disease (COPD) during night suggests greater benefits of evening administration of once-daily LAMA.

We electronically invited 172,852 Danish COPD patients who used once-daily LAMA (including dual/triple therapy) to participate in a randomized controlled, digital platform, pragmatic trial comparing evening with morning LAMA administration. Of these, 10,011 patients consented and were randomized. National health registries were the main source for follow-up data. The primary endpoint was a composite of COPD exacerbations requiring hospitalization or all-cause death within one year. Secondary endpoints were moderate COPD exacerbations, all-cause hospitalization, intensive-care admission, non-invasive ventilation, all-cause mortality, and consumption of short-acting beta-2-agonists.

A total of 10,011 COPD patients were randomized to evening (n=4,983) or morning (n=5,028) LAMA administration. We had complete (100%) follow-up on the primary and secondary outcomes. In the evening-LAMA group, 245 persons (5%) met the primary outcome compared with 249 persons (5%) in the morning-LAMA group (P=0.93). There were 61 (1%) intensive-care admissions in the evening-LAMA group versus 95 (2%) in the morning-LAMA group (P=0.046). Other secondary outcomes were neutral. Administration-time adherence was low in the evening-LAMA group being 73% at 6 months and 66% at 12 months among survey responders (65% and 63%, respectively).

Evening administration of LAMA did not reduce the incidence of COPD exacerbations requiring hospitalization or all-cause death. Poor adherence may have contributed to the negative study outcome. The trial serves as a proof-of-concept for decentralized digital trials.

Clinicaltrials.gov: NCT05563675, registered 28/09/2022 https://clinicaltrials.gov/study/NCT0556367 .

The COVID-19 pandemic, caused by the emergence of the SARS-CoV-2 virus in 2019, has led to a global state of emergency declared by the World Health Organization (WHO). The search for effective therapies against the virus is ongoing, and traditional medicine is emerging as a promising alternative, as many plants with known antiviral potential have been utilized during the pandemic. In this study, we investigated the inhibition of cysteine proteases (Mpro, PLpro, and papain) by bioactive compounds from Moringa oleifera leaves, with the ultimate goal of developing a novel treatment. We conducted a virtual screening based on the structure of the Mpro and PLpro enzymatic targets of SARS-CoV-2, for the selection of compounds with higher inhibitory potential. We then identified 14 bioactive compounds with high binding energy against Mpro and PLpro using AutoDock. Gamma-sitosterol was particularly promising since it showed higher interaction energy with Mpro (-8.6Kcal/mol) and PLpro (-7.4Kcal/mol). Phytochemicals in Moringa oleifera leaves were extracted using aqueous and hydromethanolic solvent system. It was found that polyphenols (4.20-5.01 mg GAE/g DM) and flavonoids (95.86-135.41 mg QE/ g DM) were the major constituents in the extracts. Antioxidant activity in the extracts, particularly DPPH scavenging activity (63.46-123.58 mg TE/g DM) and FRAP activity (48.14-49.66 mg TE/g DM), was high suggesting a potential for the prevention of oxidation and inflammation. Global and multiple alignment were conducted between Mpro, PLpro and papain, and results showed high conservation of the amino acid residues in the active site of the enzymes, suggesting a similar molecular catalysis mechanism. The extracts showed inhibitory activity against papain with the IC50 of 7.5 mg/mL for the hydromethanolic extract and 12.5 mg/mL for the aqueous extract. It was found in kinetic studies that hydromethanolic extract was a competitive inhibitor of papain, while aqueous extract was a hyperbolic non-competitive inhibitor, suggesting the presence of compounds with different interaction profiles to the enzymes. This study demonstrates that Moringa oleifera leaf extracts have substantial antioxidant activity and inhibit the model cysteine protease papain in vitro. These data, together with in silico docking against Mpro and PLpro, identify candidate phytochemicals that merit further evaluation; however, papain inhibition is a preliminary biochemical filter and does not by itself establish antiviral activity against SARS-CoV-2.

Inflammatory bowel disease (IBD) treatments and pregnancy can independently modulate immune responses, but the combined impacts on SARS-CoV-2 vaccine-induced immunity are poorly understood. This study explores the efficacy of SARS-CoV-2 vaccination and placental antibody transfer among pregnant women with IBD on biologic therapies. This observational study included pregnant women with and without IBD from the PIANO and PREVENT-COVID studies and their neonates. We assessed anti-SARS-CoV-2 neutralizing antibody titers (NT50) in maternal and cord blood post-vaccination using a pseudotype neutralization assay and calculated placental transfer ratios. A total of 32 pregnant women participated, and 27 were exposed to a biologic medication during pregnancy. Neutralizing antibody titers were similar between biologic-treated and non-treated groups, and biologic-exposed women demonstrated robust placental transfer of neutralizing antibodies. Corticosteroid use during pregnancy was significantly associated with reduced placental transfer efficiency, although this effect was not significant in a sensitivity analysis excluding patients treated with immunomodulators. Vaccination timing and SARS-CoV-2 infection impacted maternal and cord antibody levels, with higher titers observed in those vaccinated before pregnancy or infected during pregnancy. Overall, our findings suggest that upon vaccination, pregnant women with IBD on biologic therapies mount effective SARS-CoV-2 neutralizing antibody responses similar to their non-biologic-exposed counterparts, with efficient placental transfer. These findings support the efficacy of SARS-CoV-2 vaccination in this population, though further research with larger cohorts is needed for validation and to explore the long-term protective effects of transferred antibodies in neonates. Furthermore, corticosteroid use, immunomodulator use, and vaccination timing may influence antibody dynamics, underscoring the need for tailored clinical management in this vulnerable population.

The purpose of this study is to describe the experiences of women with symptoms of perinatal mental health disorders who recently gave birth and participated in a virtual peer support specialist program for maternal mental health during the COVID-19 pandemic.

A qualitative descriptive design was used to describe the experiences of six women with symptoms of perinatal mental health disorders who participated in a peer support specialist program. Participants were recruited from online Indiana-based Facebook parenting groups targeted to women with young children. Semi-structured interviews were conducted, and data were analyzed using a basic inductive content analysis.

We identified three main themes: 1) Seeking help for mental health symptoms, 2) Receiving unbiased peer support, and 3) Improving mental health symptoms.

Implications for nursing practice include developing strategies to increase peer networks for women in the perinatal period, increasing the screening of women for symptoms of perinatal mental health disorders, and conducting more research on the efficacy of a peer support specialist programs for improving maternal mental health.