Pelleting and particle size reduction of corn increase net energy and digestibility of fiber, protein, and fat in corn-soybean meal diets fed to group-housed pigs.

BACKGROUND: Reduction of the particle size of corn increases energy digestibility and concentrations of digestible and metabolizable energy. Pelleting may also reduce particle size of grain, but it is not known if there are interactions between particle size reduction and pelleting. The objective of this experiment was to test the hypothesis that particle size reduction and pelleting, separately or in combination, increase N balance, apparent total tract digestibility (ATTD) of fiber and fat, and net energy (NE) in corn-soybean meal diets fed to group-housed pigs. METHODS: Six corn-soybean meal-based diets were used in a 3 × 2 factorial design with 3 particle sizes of corn (i.e., 700, 500, or 300 µm) and 2 diet forms (i.e., meal or pelleted). Pigs were allowed ad libitum access to feed and water. Twenty-four castrated male pigs (initial weight: 29.52 kg; standard diviation: 1.40) were allotted to the 6 diets using a 6 × 6 Latin square design with 6 calorimeter chambers (i.e., 4 pigs/chamber) and 6 periods. Oxygen consumption and CO2 and CH4 productions were measured during fed and fasting states and fecal and urine samples were collected. RESULTS: Regardless of particle size of corn, the ATTD of gross energy (GE), N, and acid-hydrolyzed ether extract (AEE), and the concentration of NE were greater (P < 0.05) in pelleted diets than in meal diets. Regardless of diet form, the ATTD of GE, N, and AEE, and the concentration of NE were increased (linear; P < 0.05) by reducing the particle size of corn, but the increase was greater in meal diets than in pelleted diets (interaction; P < 0.05). CONCLUSIONS: Both pelleting and reduction of corn particle size increased nutrient digestibility and NE, but increases were greater in meal diets than in pelleted diets.

Necroptosis blockade prevents lung injury in severe influenza.

Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1-5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6-8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.

Impact of sex differences on the feasibility and safety of distal radial access for coronary procedures: a multicenter prospective observational study.

BACKGROUND: Conventional transradial access in women is associated with a lower success rate and a higher incidence of spasm compared to men. To date, the effect of sex on the performance of distal radial access (DRA) has not been fully elucidated. The aim of this study was to assess the impact of sex on catheterization success and other performance parameters of DRA procedures. METHODS: This is a prospective three-center observational study. From August 2020 to September 2022, data from all consecutive patients who underwent DRA for coronary procedures were collected. RESULTS: A total of 868 procedures were registered and stratified into two groups according to sex: women (n = 258) and men (n = 610). Female patients had less favorable baseline characteristics than male patients in terms of absent or weak pulse (29% vs. 17%; P < 0.001), distal radial diameter (2.2 ±â€…0.3 vs. 2.4 ±â€…0.4 mm; P < 0.001) and proximal radial diameter (2.5 ±â€…0.7 vs. 2.7 ±â€…0.7 mm; P = 0.001). No differences in success rates were found in women compared to men (94.2% vs. 96.6%; P = 0.135), with a higher presence of arterial spasm in women (5.8% vs. 3.0%; P = 0.044). The preprocedural ultrasound evaluation was the only predictor of DRA success [odds ratio = 20.0 (4.739-83.333); P < 0.001]. CONCLUSION: In patients undergoing coronary procedures, the success rate of DRA was high regardless of sex, with a higher incidence of arterial spasm in women.

The Septic Elbow Joint: Treatment Approaches for Improved Patient Outcomes.

Septic arthritis of the elbow is a serious problem requiring prompt, accurate diagnosis and urgent surgical intervention. Achieving successful patient outcomes depends heavily on early diagnosis and efficient streamlined surgical treatment. Essential tactics for treating the septic elbow joint include immediate joint irrigation and debridement in addition to administration of appropriate antibiotics. This comprehensive review delves into the cause of the septic elbow joint, identifies associated risk factors, and provides a comprehensive approach encompassing the diagnosis and treatment of the septic elbow. The aim of this review is to optimize patient care and outcomes.

Mitochondrial DNA competition: starving out the mutant genome.

High levels of pathogenic mitochondrial DNA (mtDNA) variants lead to severe genetic diseases, and the accumulation of such mutants may also contribute to common disorders. Thus, selecting against these mutants is a major goal in mitochondrial medicine. Although mutant mtDNA can drift randomly, mounting evidence indicates that active forces play a role in the selection for and against mtDNA variants. The underlying mechanisms are beginning to be clarified, and recent studies suggest that metabolic cues, including fuel availability, contribute to shaping mtDNA heteroplasmy. In the context of pathological mtDNAs, remodeling of nutrient metabolism supports mitochondria with deleterious mtDNAs and enables them to outcompete functional variants owing to a replicative advantage. The elevated nutrient requirement represents a mutant Achilles' heel because small molecules that restrict nutrient consumption or interfere with nutrient sensing can purge cells of deleterious mtDNAs and restore mitochondrial respiration. These advances herald the dawn of a new era of small-molecule therapies to counteract pathological mtDNAs.

Cardiorespiratory patterns of male South American sea lions (Otaria flavescens) resting on land.

The goal of this study was to characterize the cardiorespiratory patterns of male South American sea lions (SASLs, Otaria flavescens) resting on land. We recorded respiratory and heart rate (n = 360 individuals studied) by observing the nostrils, chest movements and the impact of the heart on the thoracic wall. The sea lions breathe apneustically with a pause on inspiration, representing 74% of the respiratory cycle. The mean breathing frequency was 3.2 ± 1.0 breaths min-1, with a breathing cycle presenting periods of bradypneas, tachypneas, and long-term post-inspiratory pauses. The normal heart rate (nHR) was 73.4 ± 14.5 beats min-1 and no significant differences were observed between age classes. All animals showed variability in HR in relation to respiratory phases (Inspiration: 101.2 ± 18.4 beats min-1; post-inspiratory pause: 73.4 ± 14.5 beats min-1; expiration: 64.6 ± 17.7 beats min-1), consistent with respiratory sinus arrhythmia (RSA). The mean HR (measured during all respiratory phases) was 79.9 ± 22.7 beats min-1, and was significantly different between age classes. The total duration of respiratory cycle, and duration of both inspiration and expiration, decreased with an increment in ambient temperature, with no variation in the pause duration. Heart rate during pause and expiration was significantly higher during high temperatures. Similar changes in cardiorespiratory patterns have been reported in other pinnipeds. Our results showed ontogenetic differences in development and typical variations with environmental and behavioral variables.

Management of the Septic Wrist: A Systematic Review of Etiology and Therapeutic Strategies.

Septic arthritis of the wrist can have severe deleterious effects on cartilage and bone if not promptly addressed. Expedient diagnosis and early medical intervention are important. The most effective strategy involves immediate arthrocentesis of the infected joint, enabling precise antibiotic selection based on joint fluid analysis. Diagnostic imaging is important in excluding fractures and identifying abscesses. This review explores the etiologic factors underlying septic wrist joint, identifying risk factors, and delineating optimal diagnosis and treatment approaches. The overarching goal is to impart valuable insights and guidance in the management of septic wrist joint, ensuring the highest quality patient care and optimal clinical outcomes.

Decrease in Mortality after the Implementation of a Hospital Model to Improve Performance in Sepsis Care: Princess Sepsis Code.

Sepsis is a time-dependent disease whose prognosis is influenced by early diagnosis and therapeutic measures. Mortality from sepsis remains high, and for this reason, the guidelines of the Surviving Sepsis Campaign recommend establishing specific care programs aimed at patients with sepsis. We present the results of the application of a hospital model to improve performance in sepsis care, called Princess Sepsis Code, with the aim of reducing mortality. A retrospective study was conducted using clinical, epidemiological, and outcome variables in patients diagnosed with sepsis from 2015 to 2022. A total of 2676 patients were included, 32% of whom required admission to the intensive care unit, with the most frequent focus of the sepsis being abdominal. Mortality in 2015, at the beginning of the sepsis code program, was 24%, with a declining rate noted over the study period, with mortality reaching 17% in 2022. In the multivariate analysis, age > 70 years, respiratory rate > 22 rpm, deterioration in the level of consciousness, serum lactate > 2 mmol/L, creatinine > 1.6 mg/dL, and the focus of the sepsis were identified as variables independently related to mortality. The implementation of the Princess Sepsis Code care model reduces the mortality of patients exhibiting sepsis and septic shock.

XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells.

Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene expression. XRN1 deletion causes PKR pathway activation and consequent cancer cell lethality. Disruption of interferon signaling with the JAK1/2 inhibitor ruxolitinib can decrease cellular PKR levels and rescue sensitivity to XRN1 deletion. Conversely, interferon-ß stimulation can increase PKR levels and induce sensitivity to XRN1 inactivation. Lastly, XRN1 deletion causes accumulation of endogenous complementary sense/anti-sense RNAs, which may represent candidate PKR ligands. Our data demonstrate how XRN1 regulates PKR and how this interaction creates a vulnerability in cancer cells with an activated interferon cell state.

Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation.

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, nor were the effects on cell membranes or the wider cell known. Using patient-derived cells we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases. Lysosomes are also more numerous in Drosophila neural progenitor cells expressing mutant Atad3, which exhibit abundant membrane-bound cholesterol aggregates, many of which co-localize with lysosomes. Using nutrient restriction and cholesterol supplementation, we show that the Drosophila Atad3 mutant displays heightened cholesterol dependence. Collectively, these findings suggest elevated cholesterol enhances tolerance to pathological ATAD3 variants, at a cost of inducing cholesterol aggregation in membranes, which lysosomal clearance only partly mitigates.

Intra- and inter-rater reliability in ultrasonographic measurements of coracohumeral distance.

BACKGROUND: Ultrasonography (US) is a widely used diagnostic tool in physical therapy. One of the US variables often utilized to quantify the dimensions of the subacromial space and its association with shoulder pathology is the coracohumeral distance (CHD), however, this measurement presents diverse evidence in terms of reliability. OBJECTIVES: To assess the intra- and inter-rater reliability of both expert and non-expert raters when measuring CHD through US in asymptomatic subjects. Additionally, we determined the effect of rater experience and measurement conditions on the recording of CHD. METHODS: CHD of 15 individuals were recorded from US images of the glenohumeral joint of both upper extremities in three different positions. An expert and a non-expert rater in US usage recorded three CHD measurements, after a randomization procedure. To determine intra- and inter-rater reliability, the interclass correlation coefficient (ICC) and a multivariate variance model for the effects of rater experience, joint position and time of measure were used. Standard Error of Measurement and Minimal Detectable Change was also estimated for CHD measurements. RESULTS: Intra-rater reliability ranged 0.970 to 0.998) and Inter-rater reliability ranged 0.48 to 0.876). Joint position (F2;55 = 38.308; p < 0.001; ηp2 = 0.582) and measurement time (F2;55 = 6.019; p = 0.004; ηp2 = 0.180) effect was observed on CHD. CONCLUSION: Excellent intra- and poor to moderate inter-rater reliability between expert and non-expert clinicians was determined, the latter being influenced by the position of the glenohumeral joint position at the time of US recording and the time of recording the measurement.

Differences in efficacy and safety between intrathecal infusion devices in cancer pain.

BACKGROUND: Intrathecal infusion therapy is widely accepted for cancer pain patients when conventional analgesic treatments are not sufficient. There are different types of devices for carrying out this therapy: partially externalized devices (PED), used when life expectancy is under 3 months, and totally implanted devices (TID), when it is larger. Our objective is to compare the efficacy, functionality, and complication rate in both types. METHODS: We included 132 patients with mild-severe cancer pain, treated with intrathecal infusion therapy by fixed flow devices, PED, or TID, during the study time. Demographic, physical oncologic, and pain control data of the patients were recorded prior to starting therapy and at months 1, 3, and 6. Functionality status and complications were also collected from the patient's medical records and clinical files. RESULTS: Pain control improved after starting therapy, with an overall reduction of 4.75 points in VAS score at 1 month in the both groups, without significant differences between them, keeping it at 3 months and 6. 33.3% of the patients developed complications and were more frequent in the PED group, being catheter dislocation the most common. Patients with TID required more often hospital admission to solve the complication. CONCLUSIONS: Intrathecal infusion therapy has been shown to be a very effective and safe therapy for the treatment of moderate to severe oncologic pain. There are no significant differences between PED and TID in terms of degree of pain control, therapeutic success, efficacy on episodic or nocturnal pain, or the presence of serious complications.

Predictive factors for efficacy and safety of intrathecal infusion devices for oncological pain.

Introduction: In an important percentage of intrathecal infusion therapy, the pain after implantation of a spinal device does not improve. Our objective is to identify factors that can predict therapeutic success and complications, developing a predictive model based on univariate and multivariate analyses. Methods: Retrospective observational study, including 132 patients with oncological pain who were implanted with a fixed-flow device for intrathecal infusion. Four time points were established for data collection and, in addition to demographic and anthropometric data, variables related to oncologic pain pathology, initiation of therapy, pain control and complications were collected. Based on univariate and multivariate analyses, we performed predictive models on efficacy and complications. Results: The mean baseline pain intensity was VAS 7.78, and when comparing the values before implantation with those at month 1, we observed an overall decrease of 4.75 points, maintained at months 3 and 6. Nocturnal pain progressively decreased in incidence from 50.0% before implantation to 21.8%, 9.1% and 4.3% at 1, 3 and 6 months. Episodic pain was present in 90.1% of the patients before implantation (7.79 episodes/day), and at 6 months the incidence remained at 53.8%. Most of the patients (66.6%) had no complications related to therapy. We constructed a highly significant multivariate model for the efficacy of the therapy with a predictive capacity of 30.2% and composed of factors: absence of nocturnal pain before implantation and clinical improvement on day 2 after implant. Regarding the prediction of complications, it was not possible to achieve a significantly multivariate effective model. Conclusion: We identify two factors that predict therapeutic success in a multivariate model: the absence of nocturnal pain before implantation and the improvement of pain on the second day after implantation.

Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans.

In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but their role in longevity is unclear. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we uncovered an important role for lipid droplets in proteostasis and longevity. Using genome-wide RNAi screening, we identified several SQST-1 modulators, including lipid droplets-associated and aggregation-prone proteins. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan. Notably, a substantial amount of ubiquitinated proteins were found on lipid droplets. Reducing lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised, and significantly reduced the lifespan of long-lived daf-2 animals. Altogether, our study uncovered a key role for lipid droplets in C. elegans as a proteostatic mediator that modulates ubiquitinated protein accumulation, facilitates autophagy, and promotes longevity.

Metacarpal fractures.

Metacarpal fractures are common and can be functionally disabling. The majority are managed non-operatively. When surgical intervention is indicated, various methods of fixation are available with the utility of each being based on injury pattern, patient function and surgeon preference. Early mobilization, especially in case of open reduction and internal fixation, is a critical component of treatment to prevent stiffness and restore function. When possible, a fixation construct that can withstand the applied forces of early postoperative motion is chosen. We provide an updated description for diagnosis, treatment options and operative fixation for metacarpal fractures.