Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response.

BACKGROUND: The myocardium adapts to ischemia/reperfusion (I/R) by changes in gene expression, determining the cardiac response to reperfusion. mRNA translation is a key component of gene expression. It is largely unknown how regulation of mRNA translation contributes to cardiac gene expression and inflammation in response to reperfusion and whether it can be targeted to mitigate I/R injury. METHODS: To examine translation and its impact on gene expression in response to I/R, we measured protein synthesis after reperfusion in vitro and in vivo. Underlying mechanisms of translational control were examined by pharmacological and genetic targeting of translation initiation in mice. Cell type-specific ribosome profiling was performed in mice that had been subjected to I/R to determine the impact of mRNA translation on the regulation of gene expression in cardiomyocytes. Translational regulation of inflammation was studied by quantification of immune cell infiltration, inflammatory gene expression, and cardiac function after short-term inhibition of translation initiation. RESULTS: Reperfusion induced a rapid recovery of translational activity that exceeds baseline levels in the infarct and border zone and is mediated by translation initiation through the mTORC1 (mechanistic target of rapamycin complex 1)-4EBP1 (eIF4E-binding protein 1)-eIF (eukaryotic initiation factor) 4F axis. Cardiomyocyte-specific ribosome profiling identified that I/R increased translation of mRNA networks associated with cardiac inflammation and cell infiltration. Short-term inhibition of the mTORC1-4EBP1-eIF4F axis decreased the expression of proinflammatory cytokines such as Ccl2 (C-C motif chemokine ligand 2) of border zone cardiomyocytes, thereby attenuating Ly6Chi monocyte infiltration and myocardial inflammation. In addition, we identified a systemic immunosuppressive effect of eIF4F translation inhibitors on circulating monocytes, directly inhibiting monocyte infiltration. Short-term pharmacological inhibition of eIF4F complex formation by 4EGI-1 or rapamycin attenuated translation, reduced infarct size, and improved cardiac function after myocardial infarction. CONCLUSIONS: Global protein synthesis is inhibited during ischemia and shortly after reperfusion, followed by a recovery of protein synthesis that exceeds baseline levels in the border and infarct zones. Activation of mRNA translation after reperfusion is driven by mTORC1/eIF4F-mediated regulation of initiation and mediates an mRNA network that controls inflammation and monocyte infiltration to the myocardium. Transient inhibition of the mTORC1-/eIF4F axis inhibits translation and attenuates Ly6Chi monocyte infiltration by inhibiting a proinflammatory response at the site of injury and of circulating monocytes.

Mechanism of action and synergistic effect of Eugenia uniflora extract in Candida spp.

The limited arsenal of antifungal drugs have prompted the search for novel molecules with biological activity. This study aimed to characterize the antifungal mechanism of action of Eugenia uniflora extract and its synergistic activity with commercially available antifungal drugs on the following Candida species: C. albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. dubliniensis. In silico analysis was performed to predict antifungal activity of the major compounds present in the extract. Minimal inhibitory concentrations (MICs) were determined in the presence of exogenous ergosterol and sorbitol. Yeast cells were grown in the presence of stressors. The loss of membrane integrity was assessed using propidium iodide staining (fluorescence emission). Synergism between the extract and antifungal compounds (in addition to time kill-curves) was determined. Molecular docking revealed possible interactions between myricitrin and acid gallic and enzymes involved in ergosterol and cell wall biosynthesis. Candida cells grown in the presence of the extract with addition of exogenous ergosterol and sorbitol showed 2 to 8-fold increased MICs. Strains treated with the extract revealed greater loss of membrane integrity when compared to their Fluconazole counterparts, but this effect was less pronounced than the membrane damage caused by Amphotericin B. The extract also made the strains more susceptible to Congo red and Calcofluor white. A synergistic action of the extract with Fluconazole and Micafungin was observed. The E. uniflora extract may be a viable option for the treatment of Candida infections.

Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis.

OBJECTIVE: Potential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac disease in patients with PCD remain uncertain. In this systematic review and meta-analysis, we aimed to evaluate the clinical outcomes of patients with PCD. DESIGN: We searched Medline, Embase, Scopus and Cochrane Library from 1991 through May 2024 to identify studies evaluating the clinical outcomes of patients with PCD. The progression rates to villous atrophy, seroconversion and response to a gluten-free diet (GFD) were analysed. A random-effect meta-analysis was performed, and the results were reported as pooled proportions with 95% CIs. RESULTS: Seventeen studies comprising 1010 patients with PCD were included in the final analyses. The pooled prevalence of PCD among patients with suspected coeliac disease was 16% (95% CI 10% to 22%). The duration of follow-up in most of the studies was at least 1 year, with follow-up periods within individual studies ranging from 5 months to 13 years. During follow-up, 33% (95% CI 18% to 48%; I2=96.4%) of patients with PCD on a gluten-containing diet developed villous atrophy, and 33% (95% CI 17% to 48%; I2=93.0%) had normalisation of serology. Among those who adhered to a GFD, 88% (95% CI 79% to 97%; I2=93.2%) reported symptomatic improvement. CONCLUSION: Almost a third of patients with PCD develop villous atrophy over time, whereas a similar proportion experience normalisation of serology despite a gluten-containing diet. Most symptomatic patients benefit from a GFD. These findings highlight the importance of structured follow-up and individualised management for patients with PCD.

Deciphering the Hearts: Geometric Morphometrics Reveals Shape Variation in Abatus Sea Urchins across Subantarctic and Antarctic Seas.

Abatus is a genus of irregular brooding sea urchins to the Southern Ocean. Among the 11 described species, three shared morphological traits and present an infaunal lifestyle in the infralittoral from the Subantarctic province; A. cavernosus in Patagonia, A. cordatus in Kerguelen, and A. agassizii in Tierra del Fuego and South Shetlands. The systematic of Abatus, based on morphological characters and incomplete phylogenies, is complex and largely unresolved. This study evaluates the shape variation among these species using geometric morphometrics analysis (GM). For this, 72 individuals from four locations; South Shetlands, Kerguelen, Patagonia, and Falklands/Malvinas were photographed, and 37 landmarks were digitized. To evaluate the shape differences among species, a principal component analysis and a Procrustes ANOVA were performed. Our results showed a marked difference between the Falklands/Malvinas and the other localities, characterized by a narrower and more elongated shape and a significant influence of location in shape but not sex. Additionally, the effect of allometry was evaluated using a permutation test and a regression between shape and size, showing significant shape changes during growth in all groups. The possibility that the Falklands/Malvinas group shows phenotypic plasticity or represents a distinct evolutionary unit is discussed. Finally, GM proved to be a powerful tool to differentiate these species, highlighting its utility in systematic studies.

Patient preferences for the diagnosis of coeliac disease: A discrete choice experiment.

BACKGROUND: There is potential for a paradigm shift from a biopsy-to a serology-based diagnosis of coeliac disease in selected adult patients. However, it remains unknown if this approach would be acceptable to patients. We aimed to explore patients' preferences regarding the no-biopsy approach for coeliac disease diagnosis. METHODS: We developed a discrete choice experiment survey containing 12 different scenarios with two possible alternatives (endoscopy & biopsy or serology) to estimate patient preferences. The scenarios were based on 5 attributes: risk of false positive results, risk of missed diagnosis, waiting time to start treatment, risk of complications, discomfort, or pain. Patient preferences and the relative importance of the attributes were estimated using a mixed logit model. RESULTS: In total, 385 people (70.6% female, 98.2% white) across the four nations of the United Kingdom completed the survey. Respondents preferred a serology-based diagnosis over endoscopy and duodenal biopsies (59% vs. 41%, ß coefficient 1.54, p < 0.001). Diagnostic test accuracy (p < 0.001), shorter waiting time to start treatment (p < 0.001), and discomfort levels during the procedure (p < 0.001) were the most important attributes to respondents. The risk of complications, including perforation and bleeding, did not significantly influence respondents' choices. Respondents with previous endoscopy experience were more willing to undergo endoscopy compared with those who never had one. CONCLUSION: The no-biopsy approach to diagnosing coeliac disease is acceptable and preferred by patients over endoscopy and biopsy. Our findings highlight the importance of patient-centred care and shared decision-making in guiding diagnostic strategies for optimal patient outcomes.

Evaluation of Unsaponifiable Fraction of Avocado Oil on Liver and Kidney Mitochondrial Function in Rats Fed a High-Fat and High-Carbohydrate Diet.

High-fat and high-carbohydrate (HF-HC) diets induce metabolic syndrome via mitochondrial dysfunction and oxidative stress. We have previously shown that this may be prevented by avocado oil, a source of bioactive molecules with antioxidant properties. However, it is unknown if these effects are mediated by the unsaponifiable fraction of avocado oil (UFAO). Thus, we tested if this fraction improves glucose metabolism, bioenergetics and oxidative stress in mitochondria from the kidney and liver of rats fed an HF-HC diet. We found that 12 weeks of an HF-HC diet impaired glucose utilization and increased insulin resistance, which was prevented by UFAO administration. The HF-HC diet decreased respiration, membrane potential and electron transport chain (ETC) function in liver and kidney mitochondria. These mitochondrial dysfunctions were prevented by UFAO intake. Unexpectedly, UFAO increased ROS levels in the mitochondria of control animals and did not decrease them in rats with an HF-HC diet; however, UFAO protects liver and kidney mitochondria from iron-induced oxidative stress. These findings suggest that impairments in glucose metabolism and mitochondrial function by an HF-HC diet may be prevented by UFAO, without decreasing ROS generation but protecting mitochondria from oxidative damage.

Medication Adherence to Direct Oral Anticoagulants: Extent and Impact of Side Effects.

Purpose: Arterial and venous thromboembolism are a leading cause of mortality. Direct oral anticoagulants (DOACs) are highly effective in both stroke prevention and prevention of venous thrombotic events. Medication adherence is a prerequisite for optimal protection against thromboembolic complications. Recent studies have shown that good adherence cannot be taken for granted by DOACs. In this cross-sectional study adherence among DOAC users was investigated and associations between beliefs about medication, perceived side effects and adherence were explored. Patients and Methods: We included 100 randomly selected adult DOAC users visiting one of the two participating Dutch community pharmacies in the summer of 2020. The self-reported adherence (primary outcome) was assessed with the Medication Adherence Rating Scale-5 (MARS-5) using three different cut-off scores. Beliefs about DOACs were assessed with the Beliefs about Medicine Questionnaire Specific (BMQ-S), while side effects and side effect burden were assessed with a self-developed questionnaire based on the Lareb Intensive Monitoring (LIM) system. Results: Of the participants, 9% reported non-adherence on the primary MARS-5 cut-off score <24. For the MARS-5 scores <23 and <25 non-adherence percentages of, respectively, 3 and 33% were calculated. Associations were found between adherence and both side effects and side effect burden, regardless of the MARS-5 cut-off score. Bruising and minor bleeds were the most reported side effects (both 20%). For all patients, the necessity beliefs outweighed the concern beliefs. No associations were found between adherence and either gender, indication, DOAC or dosage. Conclusion: This study confirms that adherence in patients on DOACs cannot be taken for granted. High necessity beliefs do not guarantee good adherence, as side effects impair adherence even in patients having high necessity beliefs. Therefore, we recommend that both physicians and pharmacists evaluate both adherence and side effects with these patients on a regular base.

The issue Thrombosis affects many people. Complications like stroke and lung embolism are a major cause of health damage, disability and even death. Direct oral anticoagulants (DOACs) are highly effective drugs at preventing these complications. However, patients need to take their medication properly to get the best protection. Recent studies showed that not all patients consistently take their DOACs. What's new? In this study, we discovered that patients experiencing bothersome side effect were less likely to stick to their medication schedule. The most common side effects reported were bruising and minor bleeding, by 20% each. There were no differences in how well patients took their medication based on gender, medical condition, type of DOAC or prescribed dosage. Most patients believed their medication was necessary for their health. Why is this important? This study shows that side effects hinder patients taking their medication correctly even when they believe their medication is necessary for their health. This means that patients on DOAC therapy who experience side effects may be less protected against stroke and lung embolism. Therefore, we recommend that doctors and pharmacists regularly check in with patients about any side effects they experience and how consistently they take their DOACs. What's next? This study highlights the importance of developing, testing, and implementing practical tools to find and help patients who do not take their DOACs correctly, to ensure they are better protected against blood clots.

Role of capsule endoscopy and double-balloon enteroscopy in the management of adult patients with coeliac disease and persisting symptoms.

BACKGROUND: Small bowel capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are recommended for the management of patients with nonresponsive or refractory coeliac disease (CD). However, there is a paucity of data regarding the clinical profiles and outcomes of patients undergoing these investigations. METHODS: We conducted a retrospective analysis of two databases of adult patients with CD who underwent CE and/or DBE between 2017 and 2022 at the National Centre for Refractory CD in England. Patient demographic, clinical and endoscopic data were collected, and clinically relevant outcomes were reported. RESULTS: A total of 132 patients (median age 53 years, 64.4 % female) underwent 146 CEs and 25 DBEs. The most common symptoms were diarrhoea (51.5 %), abdominal pain (37.8 %), bloating (34.8 %), and weight loss (29.5 %). The overall detection rate of CE and DBE was 87.6 % and 92 %, respectively. Following CE and DBE, 14 patients (10.6 %) were diagnosed with CD-related complications such as ulcerative jejunitis, strictures and malignancy. Seven patients (5.3 %) died during follow-up, with five of these deaths directly attributed to CD. Older age, weight loss and anaemia were associated with poor outcomes. CONCLUSIONS: The sequential approach of CE and DBE identified CD-related complications in almost 1 in 10 patients with nonresponsive or refractory CD. Older patients with persistent villous atrophy, weight loss and anaemia require close monitoring to help with the early diagnosis and management of complications.

Tlx3 mediates neuronal differentiation and proper condensation of the developing trigeminal ganglion.

The trigeminal ganglion, the largest of the vertebrate cranial ganglia, is comprised of sensory neurons that relay sensations of pain, touch, and temperature to the brain. These neurons are derived from two embryonic cell types, the neural crest and ectodermal placodes, whose interactions are critical for proper ganglion formation. While the T-cell leukemia homeobox 3 (Tlx3) gene is known to be expressed in placodally-derived sensory neurons and necessary for their differentiation, little was known about Tlx3 expression and/or function in the neural crest-derived component of the developing trigeminal ganglion. By combining lineage labeling with in situ hybridization in the chick embryo, we show that neural crest-derived cells that contribute to the cranial trigeminal ganglion express Tlx3 at a time point that coincides with the onset of ganglion condensation. Importantly, loss of Tlx3 function in vivo diminishes the overall size and abundance of neurons within the trigeminal ganglion. Conversely, ectopic expression of Tlx3 in migrating cranial neural crest results in their premature neuronal differentiation. Taken together, our results demonstrate a critical role for Tlx3 in neural crest-derived cells during chick trigeminal gangliogenesis.

Unlocking opioid neuropeptide dynamics with genetically encoded biosensors.

Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

The History of Agrobacterium Rhizogenes: From Pathogen to a Multitasking Platform for Biotechnology.

Agrobacterium's journey has been a roller coaster, from being a pathogen to becoming a powerful biotechnological tool. While A. tumefaciens has provided the scientific community with a versatile tool for plant transformation, Agrobacterium rhizogenes has given researchers a Swiss army knife for developing many applications. These applications range from a methodology to regenerate plants, often recalcitrant, to establish bioremediation protocols to a valuable system to produce secondary metabolites. This chapter reviews its discovery, biology, controversies over its nomenclature, and some of the multiple applications developed using A. rhizogenes as a platform.

Chronic Kidney Disease Study in Diabetic Patients: Insights From Primary Care Units in Northern Portugal.

Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb amputations. Early detection of kidney damage, indicated by microalbuminuria (MA), is crucial for managing DM. Given the impact of these conditions, evaluating the prevalence of chronic kidney disease (CKD) in diabetic populations within primary healthcare is essential. Methodology This was a cross-sectional and observational study. Adults diagnosed with DM type 1 or 2, from five primary care units (PCUs) located in the North of Portugal, were included in this study. Descriptive and correlational statistics were performed using IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY). Statistical significance was set to P < 0,05. Logistic regression models were created to identify the factors associated with CKD and DM. Results A sample of 357 diabetic patients was obtained, with 166 (46.5%) females. Of the sample, 250 (70.1%) were aged 65 or older, and the median known duration of DM was 9.36 years. Excess weight or obesity accounted for 79.8%, with a median body mass index of 28.73 kg/m2 and hypertension in 284 (79.6%). An estimated glomerular filtration rate (eGFR) less than 60 mL/min was present in 89 (24.9%) and an MA of 30 mg/dL or higher was present in 68 (19.0%). In total, 130 (36.4%) individuals exhibited eGFR and MA consistent with CKD. Among these, 25 (78.1%) had other identifiable causes of CKD besides DM, hypertension, overweight, or obesity. Binary logistic regression models were constructed to find a relationship between CKD with eGFR < 60 mL/min and MA. A statistically significant association was found between CKD with eGFR < 60 mL/minute and age (odds ratio [OR] = 1.150; P < 0.001), kidney stones (OR = 5.112; P = 0.003), absence of excess weight or obesity (OR = 0.267; P < 0.001). The use of GLP1 agonists showed statistical significance as a predictor (OR = 4.653; P = 0.042) of the presence of MA. Discussion The study investigates the impact of DM and its complications in the surveyed population. While most patients had controlled DM (284, 76.2%), prolonged disease duration correlated with poorer glycemic control, underscoring the need for more effective management strategies in advanced disease stages. Notably, a third of individuals with DM had CKD, with significant implications for therapeutic interventions and heightened risks of renal failure and cardiovascular morbidity. MA was a crucial marker for endothelial injury, with prevalence influenced by DM duration and medication type. However, in many cases, correct identification of CKD was lacking, suggesting under-recognition of renal deterioration in DM. While the study offers valuable insights, its limited sample size and geographic scope warrant cautious interpretation, emphasizing the need for broader, context-specific research to inform comprehensive healthcare strategies. Conclusions In conclusion, this study highlights the significant burden of CKD among diabetic patients, emphasizing the need for proactive screening, personalized management, and accurate diagnosis. Despite limitations, it underscores the importance of early detection and tailored interventions, advocating for improved diabetes care to mitigate renal complications on a broader scale.

Plant Micropropagation and Temporary Immersion Systems.

Temporary immersion systems (TIS) have been widely recognized as a promising technology for micropropagation of various plant species. The TIS provides a suitable environment for culture and allows intermittent contact of the explant with the culture medium at different immersion frequencies and aeration of the culture in each cycle. The frequency or immersion is one of the most critical parameters for the efficiency of these systems. The design, media volume, and container capacity substantially improve cultivation efficiency. Different TIS have been developed and successfully applied to micropropagation in various in vitro systems, such as sprout proliferation, microcuttings, and somatic embryos. TIS increases multiplication and conversion rates to plants and a better response during the ex vitro acclimatization phase. This article covers the use of different immersion systems and their applications in plant biotechnology, particularly in plant tissue culture, as well as its use in the massive propagation of plants of agroeconomic interest.

Scale-Up of Coffea canephora Somatic Embryogenesis in Temporary Immersion System.

Somatic embryogenesis (SE) is a clear example of cellular totipotency. The SE of the genus Coffea has become a model for in vitro propagation for woody species and for the large-scale production of disease-free plants that provide an advantage for modern agriculture. Temporary immersion systems (TIS) are in high demand for the propagation of plants. The success of this type of bioreactor is based on the alternating cycles of immersion of the plant material in the culture medium, usually a few minutes, and the permanence outside the medium of the tissues for several hours. Some bioreactors are very efficient for propagating one species but not another. The efficiency of bioreactors depends on the species, the tissue used to propagate, the species' nutritional needs, the amount of ethylene produced by the tissue, and many more. In this protocol, we show how we produce C. canephora plants that are being taken to the field.

CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice.

Cardiac signaling pathways functionally important in the heart's response to exercise often protect the heart against pathological stress, potentially providing novel therapeutic targets. However, it is important to determine which of these pathways can be feasibly targeted in vivo. Transgenic overexpression of exercise-induced CITED4 has been shown to protect against adverse remodeling after ischemia/reperfusion injury (IRI). Here we investigated whether somatic gene transfer of CITED4 in a clinically relevant time frame could promote recovery after IRI. Cardiac CITED4 gene delivery via intravenous AAV9 injections in wild type mice led to an approximately 3-fold increase in cardiac CITED4 expression. After 4 weeks, CITED4-treated animals developed physiological cardiac hypertrophy without adverse remodeling. In IRI, delivery of AAV9-CITED4 after reperfusion resulted in a 6-fold increase in CITED4 expression 1 week after surgery, as well as decreased apoptosis, fibrosis, and inflammatory markers, culminating in a smaller scar and improved cardiac function 8 weeks after IRI, compared with control mice receiving AAV9-GFP. Somatic gene transfer of CITED4 induced a phenotype suggestive of physiological cardiac growth and mitigated adverse remodeling after ischemic injury. These studies support the feasibility of CITED4 gene therapy delivered in a clinically relevant time frame to mitigate adverse ventricular remodeling after ischemic injury.

Findings and Challenges in Replacing Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in Private Gynecological Practice in Mexico.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.

Use of a gas-operated ventilator as a noninvasive bridging respiratory therapy in critically Ill COVID-19 patients in a middle-income country.

During the COVID-19 pandemic, there was a notable undersupply of respiratory support devices, especially in low- and middle-income countries. As a result, many hospitals turned to alternative respiratory therapies, including the use of gas-operated ventilators (GOV). The aim of this study was to describe the use of GOV as a noninvasive bridging respiratory therapy in critically ill COVID-19 patients and to compare clinical outcomes achieved with this device to conventional respiratory therapies. Retrospective cohort analysis of critically ill COVID-19 patients during the first local wave of the pandemic. The final analysis included 204 patients grouped according to the type of respiratory therapy received in the first 24 h, as follows: conventional oxygen therapy (COT), n = 28 (14%); GOV, n = 72 (35%); noninvasive ventilation (NIV), n = 49 (24%); invasive mechanical ventilation (IMV), n = 55 (27%). In 72, GOV served as noninvasive bridging respiratory therapy in 42 (58%) of these patients. In the other 30 patients (42%), 20 (28%) presented clinical improvement and were discharged; 10 (14%) died. In the COT and GOV groups, 68% and 39%, respectively, progressed to intubation (P ≤ 0.001). Clinical outcomes in the GOV and NIV groups were similar (no statistically significant differences). GOV was successfully used as a noninvasive bridging respiratory therapy in more than half of patients. Clinical outcomes in the GOV group were comparable to those of the NIV group. These findings support the use of GOV as an emergency, noninvasive bridging respiratory therapy in medical crises when alternative approaches to the standard of care may be justifiable.