Partner-switching components PmgA and Ssr1600 regulate high-light acclimation in Synechocystis sp. PCC 6803.

Photomixotrophic growth A (PmgA) is a pleiotropic regulator essential for growth under photomixotrophic and prolonged high-light (HL) conditions in the cyanobacterium Synechocystis sp. PCC 6803. The overall similarity with the anti-sigma factor of the bacterial partner-switching system indicates that PmgA exerts a regulatory function via phosphorylation of its target proteins. In this study, we performed an in vitro phosphorylation assay and protein-protein interaction analysis and found that PmgA interacts with four anti-sigma antagonist homologs, Ssr1600, Slr1856, Slr1859, and Slr1912, but specifically phosphorylates Ssr1600. Phenotypic analyses using the set of gene disruption and overexpression strains of pmgA and ssr1600 revealed that phosphorylation by PmgA is essential for the accumulation of Ssr1600 protein in vivo. The ssr1600-disrupted mutant showed similar phenotypes as those previously reported for the pmgA-disrupted mutant, namely, no obvious phenotype just after the shift to HL, but higher chlorophyll content, 5-aminolevulinic acid synthesis activity, and psaAB transcript levels than those in the wild-type after 6 hours. These findings indicate that the phosphorylated form of Ssr1600 works as the output of the partner-switching system to coordinately repress chlorophyll biosynthesis and accumulation of photosystem I during HL acclimation.

Pathogenic Potential of Eomesodermin-Expressing T-Helper Cells in Neurodegenerative Diseases.

Eomesodermin-expressing (Eomes+) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes+ Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes+ Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes+ Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes+ Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093-1098.

Nescient helix-loop-helix 1 (Nhlh1) is a novel activating transcription factor 5 (ATF5) target gene in olfactory and vomeronasal sensory neurons in mice.

Activating transcription factor 5 (ATF5) is a transcription factor that belongs to the cAMP-response element-binding protein/ATF family and is essential for the differentiation and survival of sensory neurons in mouse olfactory organs. However, transcriptional target genes for ATF5 have yet to be identified. In the present study, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) experiments were performed to verify ATF5 target genes in the main olfactory epithelium and vomeronasal organ in the postnatal pups. ChIP-qPCR was conducted using hemagglutinin (HA)-tagged ATF5 knock-in olfactory organs. The results obtained demonstrated that ATF5-HA fusion proteins bound to the CCAAT/enhancer-binding protein-ATF response element (CARE) site in the enhancer region of nescient helix-loop-helix 1 (Nhlh1), a transcription factor expressed in differentiating olfactory and vomeronasal sensory neurons. Nhlh1 mRNA expression was downregulated in ATF5-deficient (ATF5-/-) olfactory organs. The LIM/homeobox protein transcription factor Lhx2 co-localized with ATF5 in the nuclei of olfactory and vomeronasal sensory neurons and bound to the homeodomain site proximal to the CARE site in the Nhlh1 gene. The CARE region of the Nhlh1 gene was enriched by the active enhancer marker, acetyl-histone H3 (Lys27). The present study identified Nhlh1 as a novel target gene for ATF5 in murine olfactory organs. ATF5 may upregulate Nhlh1 expression in concert with Lhx2, thereby promoting the differentiation of olfactory and vomeronasal sensory neurons.

Metabolomic responses to high-intensity interval exercise in equine skeletal muscle: effects of rest interval duration.

High-intensity interval training has attracted considerable attention as a time-efficient strategy for inducing physiological adaptations, but the underlying mechanisms have yet to be elucidated. By using metabolomics techniques, we investigated changes in the metabolic network responses in Thoroughbred horses to high-intensity interval exercise performed with two distinct (15 min or 2 min) rest intervals. The peak plasma lactate level was higher during high-intensity exercise with a 2 min rest duration than that with a 15 min rest duration (24.5±6.8 versus 13.3±2.7 mmol l-1). The arterial oxygen saturation was lower at the end of all exercise sessions with a 2 min rest duration than that with a 15 min rest duration. Metabolomic analysis of skeletal muscle revealed marked changes in metabolite concentrations in the first and third bouts of the 15 min rest interval conditions. In contrast, there were no metabolite concentrations or pathways that significantly changed during the third bout of exercise performed with a 2 min rest interval. Our findings suggest that the activity of each energy production system is not necessarily reflected by apparent changes in metabolite concentrations, potentially due in part to a better match between metabolite flux into and out of the pathway and cycle, as well as between metabolite production and disposal. This study provides evidence that changes in metabolite concentrations vary greatly depending on the number of repetitions and the length of rest periods between exercises, even if the exercises themselves are identical.

Field-training in young two-year-old thoroughbreds: investigating cardiorespiratory adaptations and the presence of exercise induced pulmonary hemorrhage.

BACKGROUND: Comparatively little is known regarding the initial cardiorespiratory response of young racehorses to training. The objectives were to compare physiological parameters before and after introductory training and determine whether young Thoroughbreds show endoscopic signs of exercise-induced pulmonary hemorrhage (EIPH). Ten Thoroughbreds (20-23 months) underwent 12-weeks of introductory training, including weekly speed sessions. Two 600 m high-speed exercise tests (HSET) were performed following weeks 4 and 12 while wearing a validated ergospirometry facemask. Peak oxygen consumption (V̇O2pk) and ventilatory parameters (tidal volume, VT; peak inspiratory and expiratory flow, PkV̇I, PkV̇E; respiratory frequency, Rf; minute ventilation, V̇E) were measured. The ventilatory equivalent of oxygen (V̇E/V̇O2) and the aerobic and anaerobic contributions to energy production were calculated. Maximal heart rate (HRmax) and HR at maximal speed (HRVmax) were determined. Post-exercise hematocrit, plasma ammonia and blood lactate were measured. Evidence of EIPH was investigated via tracheobronchoscopy post-exercise. Results were compared (paired t-test, P < 0.05). RESULTS: Horses were faster following training (P < 0.001) and V̇O2pk increased 28 ml/(kg total mass.min) (28 ± 16%; P < 0.001). Ventilatory (V̇E, P = 0.0015; Rf, P < 0.001; PkV̇I, P < 0.001; PkV̇E, P < 0.001) and cardiovascular parameters (HRmax, P = 0.03; HRVmax, P = 0.04) increased. The increase in V̇E was due to greater Rf, but not VT. V̇E/V̇O2 was lower (26 ± 3.6 vs 23 ± 3.7; P = 0.02), indicating improved ventilatory efficiency. Anaerobic contribution to total energy production increased from 15.6 ± 6.1% to 18.5 ± 6.3% (P = 0.02). Post-exercise hematocrit (P < 0.001), plasma ammonia (P = 0.03) and blood lactate (P = 0.001) increased following training. Horses showed no signs of EIPH. CONCLUSIONS: Young two-year-old Thoroughbreds responded well to introductory training without developing tracheobronchoscopic evidence of EIPH.

Structural Validity of the Mini-Balance Evaluation Systems Test in Individuals With Spinocerebellar Ataxia: A Rasch Analysis Study.

OBJECTIVE: To examine the structural validity of the Mini-Balance Evaluation Systems Test (Mini-BESTest) in individuals with spinocerebellar ataxia (SCA). DESIGN: Methodological research on data gathered in a cross-sectional study. A Rasch analysis was conducted (partial credit model). SETTING: Inpatients in a hospital rehabilitation setting. PARTICIPANTS: A pooled sample of patients with SCA (N=65 [total 110 data]; 23 women, 42 men; mean±SD age 63.1±9.9y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We evaluated the Mini-BESTest's category structure, unidimensionality, and measurement accuracy (0: unable to perform or requiring help to 2: normal performance). RESULTS: The Mini-BESTest rating scale fulfilled the category functioning criteria. The analysis of the standardized Rasch residuals showed the scale's unidimensionality, but there were 7 item pairs indicating local dependence. All of the items fit the underlying scale construct (dynamic balance), with the exception of item #1, "Sit to stand," which was an underfit. The Mini-BESTest demonstrated adequate reliability (person separation reliability=.87) and separated the patients into 5 strata. The item-difficulty measures ranged from -4.49 to 2.02 logits, and the person ability-item difficulty matching was very good (the mean of person ability=-.07 logits and the mean of item difficulty=.00). No floor or ceiling effects were detected. The keyform identified items with small (#11, "Walk with head turns, horizontal") and large (#3, "Stand on 1 leg") item thresholds. CONCLUSIONS: The Mini-BESTest has a unidimensional balance assessment scale with good category structure and reliability even for individuals with SCA. However, it also has some inherent shortcomings such as fit statistics, local item dependencies, and item thresholds. The results obtained when the Mini-BESTest is administered to patients with cerebellar ataxia should, thus, be interpreted cautiously.

Inhibition of Heat Shock Protein 90 Lowered Intraocular Pressure without Affecting the Production of Aqueous Humor in Rabbits.

INTRODUCTION: Heat shock protein (Hsp) 90 is one of the most abundant proteins in unstressed cells and regulates stability and functional maintenance of client proteins. In ocular tissue, Hsp90 is widely expressed in the cornea and retina and has multiple roles in these tissues. The expression of HSPs was induced in the retinas of glaucomatous patients and laser-induced glaucoma in monkey while their mechanisms remain to be elucidated. For this reason, we tried to elucidate the role of Hsp90 in intraocular pressure (IOP) regulation in rabbits. METHODS: IOP was measured by a pneumatonometer before and after intracameral injection of Hsp90 inhibitors. The aqueous flow rate was measured by fluorophotometry. Trans-epithelial electrical resistance was measured in primary human trabecular meshwork cells. RESULTS: 17-AAG, a specific Hsp90 inhibitor, significantly lowered IOP at concentrations of more than 30 µm in normotensive rabbits. Other Hsp90 inhibitors also significantly lowered IOP in normotensive rabbits at a dose of 100 µm. No reduction of aqueous humor production was observed by injection of 17-AAG in rabbits. Topical administration of pilocarpine tended to attenuate the IOP-lowering effects induced by the Hsp90 inhibitor. No reduction of trans-epithelial electrical resistance was observed by inhibition of Hsp90 in culture cells. CONCLUSIONS: These results indicated that intraocular Hsp90 regulates IOP, and the inhibition of Hsp90 by Hsp90 inhibitor decreases IOP without affecting aqueous humor production in rabbits. Further research in elucidating the mechanism of Hsp90 inhibitors will result in a better understanding of the role of Hsp90 in the regulation of IOP.

RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy.

Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed, because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation. DMD transcripts from 20 genetically undiagnosed dystrophinopathy patients in whom no exon variants were identified, despite dystrophin deficiency on muscle biopsy, were analyzed by transcriptome sequencing. Genome sequencing captured intronic variants and their effects were interpreted using in silico tools. Targeted long-read sequencing was applied in cases with suspected structural genomic abnormalities. Abnormal DMD transcripts were detected in 19 of 20 cases; Exonization of intronic sequences in 15 cases, exon skipping in one case, aberrantly spliced and polyadenylated transcripts in two cases and transcription termination in one case. Intronic single nucleotide variants, chromosomal rearrangements and nucleotide repeat expansion were identified in DMD gene as pathogenic causes of transcript alteration. Our combined analysis approach successfully identified pathogenic events. Detection of diseasing-causing mechanisms in DMD transcripts could inform the therapeutic options for patients with dystrophinopathy.

Multiplex Detection of Transgenes Using πCode Technology for Gene Doping Control.

To ensure fair competition and sports integrity, gene doping is prohibited in horseracing and equine sports. One gene doping method is by administering exogenous genes, called transgenes, to postnatal animals. Although several transgene detection methods have been developed for horses, many are unsuitable for multiplex detection. In this proof-of-concept study, we developed a highly sensitive and multiplex transgene detection method using multiple πCode with identification patterns printed on the surface. The following steps were employed: (1) multiplex polymerase chain reaction amplification of 12 targeted transgenes in a single tube, (2) detection using a mixture of 12 probes labeled with different πCodes, and (3) median fluorescence intensity measurement of fluorescent πCodes. Twelve transgenes cloned into plasmid vectors were targeted, and 1500 copies of each plasmid were spiked into 1.5 mL of horse plasma. Subsequently, a novel method using πCode succeeded in detecting all the transgenes using their DNA extracts. Additionally, we detected the erythropoietin (EPO) transgene in blood samples from a horse administered solely with the EPO transgene using this method. Therefore, the πCode detection method is considered suitable for multitarget gene detection in gene doping tests.

Activating transcription factor 5 (ATF5) controls intestinal tuft and goblet cell expansion upon succinate-induced type 2 immune responses in mice.

Intestinal tuft cells, a chemosensory cell type in mucosal epithelia that secrete interleukin (IL)-25, play a pivotal role in type 2 immune responses triggered by parasitic infections. Tuft cell-derived IL-25 activates type 2 innate lymphoid cells (ILC2) to secrete IL-13, which, in turn, acts on intestinal stem or transient amplifying cells to expand tuft cells themselves and mucus-secreting goblet cells. However, the molecular mechanisms of tuft cell differentiation under type 2 immune responses remain unclear. The present study investigated the effects of the deletion of activating transcription factor 5 (ATF5) on the type 2 immune response triggered by succinate (a metabolite of parasites) in mice. ATF5 mRNAs were expressed in the small intestine, and the loss of the ATF5 gene did not affect the gross morphology of the tissue or the basal differentiation of epithelial cell subtypes. Succinate induced marked increases in tuft and goblet cell numbers in the ATF5-deficient ileum. Tuft cells in the ATF5-deficient ileum are assumed to be a subtype of intestinal tuft cells (Tuft-2 cells) marked by the transcription factor Spib. Exogenous IL-25 induced similar increases in tuft and goblet cell numbers in wild-type and ATF5-deficient ilea. IL-13 at a submaximal dose enhanced tuft cell differentiation more in ATF5-deficient than in wild-type intestinal organoids. These results indicate that the loss of ATF5 enhanced the tuft cell-ILC2 type 2 immune response circuit by promoting tuft cell differentiation in the small intestine, suggesting its novel regulatory role in immune responses against parasitic infections.

Distinctive chaperonopathy in skeletal muscle associated with the dominant variant in DNAJB4.

DnaJ homolog, subfamily B, member 4, a member of the heat shock protein 40 chaperones encoded by DNAJB4, is highly expressed in myofibers. We identified a heterozygous c.270 T > A (p.F90L) variant in DNAJB4 in a family with a dominantly inherited distal myopathy, in which affected members have specific features on muscle pathology represented by the presence of cytoplasmic inclusions and the accumulation of desmin, p62, HSP70, and DNAJB4 predominantly in type 1 fibers. Both Dnajb4F90L knockin and knockout mice developed muscle weakness and recapitulated the patient muscle pathology in the soleus muscle, where DNAJB4 has the highest expression. These data indicate that the identified variant is causative, resulting in defective chaperone function and selective muscle degeneration in specific muscle fibers. This study demonstrates the importance of DNAJB4 in skeletal muscle proteostasis by identifying the associated chaperonopathy.

Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial.

OBJECTIVE: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE. METHODS: We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug. RESULTS: A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061). CONCLUSION: The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT. TRIAL REGISTRATION NUMBER: jRCTs031190160.

A Novel de novo KIF1A Mutation in a Patient with Ataxia, Intellectual Disability and Mild Foot Deformity.

Early-onset ataxias are often difficult to diagnose due to the genetic and phenotypic heterogeneity of patients. Whole exome sequencing (WES) is a powerful method for determining causative mutations of early-onset ataxias. We report a case in which a novel de novo KIF1A mutation was identified in a patient with ataxia, intellectual disability and mild foot deformity.A patient presented with sporadic forms of ataxia with mild foot deformity, intellectual disability, peripheral neuropathy, pyramidal signs, and orthostatic hypotension. WES was used to identify a novel de novo mutation in KIF1A, a known causative gene of neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment syndrome (NESCAVS).We report a novel phenotype of NESCAVS that is associated with a novel de novo missense mutation in KIF1A, which provides valuable information for the diagnosis of NESCAVS even in the era of WES. Early rehabilitation of patients with NESCAVS may prevent symptom worsening and improve the disease course.

Factors influencing the decision to introduce alternative nutrition in patients with Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Nutritional management of adults with Duchenne muscular dystrophy (DMD) is an important clinical issue. However, it is not clear which dysphagia-related factors should prompt introduction of alternative nutrition (AN). We aimed to determine which patients with DMD were introduced to AN. METHODS: This retrospective study included 56 patients with DMD (median age, 23.5 years). They were divided into patients able to continue oral feeding (OF) and those introduced to AN. Body weight, frequency of ventilator use, daily meals, history of steroid treatment, results of videofluoroscopic examination of swallowing (VF), and awareness of dysphagia were evaluated. RESULTS: Of 56 patients, 19 were in the AN group. After AN introduction, 93% of the patients continued oral intake. The proportion of patients who consumed chopped and liquid diets was higher, and body weight was lower, in the AN than in the OF group. There were no significant differences in age, upper limb function of feeding, frequency of ventilator use, or history of steroid therapy between the two groups. The frequencies of aspiration and residue in the pyriform sinus in VF were higher in the AN group than in the OF group. Decision-tree analysis showed that food form and subjective difficulty swallowing solid foods were the most important factors affecting the decision-making for AN. DISCUSSION: Patients with DMD who had difficulty eating solid foods were started on AN because they were unable to maintain their weight. These findings provide information for future longitudinal studies to assess the value of AN.

Minimal cross-trial generalization in learning the representation of an odor-guided choice task.

There is no single way to represent a task. Indeed, despite experiencing the same task events and contingencies, different subjects may form distinct task representations. As experimenters, we often assume that subjects represent the task as we envision it. However, such a representation cannot be taken for granted, especially in animal experiments where we cannot deliver explicit instruction regarding the structure of the task. Here, we tested how rats represent an odor-guided choice task in which two odor cues indicated which of two responses would lead to reward, whereas a third odor indicated free choice among the two responses. A parsimonious task representation would allow animals to learn from the forced trials what is the better option to choose in the free-choice trials. However, animals may not necessarily generalize across odors in this way. We fit reinforcement-learning models that use different task representations to trial-by-trial choice behavior of individual rats performing this task, and quantified the degree to which each animal used the more parsimonious representation, generalizing across trial types. Model comparison revealed that most rats did not acquire this representation despite extensive experience. Our results demonstrate the importance of formally testing possible task representations that can afford the observed behavior, rather than assuming that animals' task representations abide by the generative task structure that governs the experimental design.

Correlation between the regional brain volume and glymphatic system activity in progressive supranuclear palsy.

INTRODUCTION: Tau protein accumulation in the brain is thought to be one of the causes of progressive supranuclear palsy (PSP). The glymphatic system was discovered a decade ago as a waste drainage system in the brain that promotes the elimination of amyloid-beta and tau protein. We here evaluated the relationships between glymphatic system activity and regional brain volumes in PSP patients. METHOD: Subjects were 24 patients with PSP and 42 healthy participants who underwent diffusion tensor imaging (DTI). We computed the diffusion tensor image analysis along the perivascular space (DTI­ALPS) index as a proxy of glymphatic system activity, and estimated the relationships between the DTI­ALPS index and regional brain volume in PSP patients by whole-brain and region-of-interest analyses, including analyses of the midbrain and third and lateral ventricles. RESULTS: The DTI­ALPS index was significantly lower in patients with PSP, compared with healthy subjects. Further, there were significant correlations between the DTI­ALPS index and the regional brain volumes in the midbrain tegmentum, pons, right frontal lobe, and lateral ventricles in patients with PSP. CONCLUSIONS: Our data suggest that the DTI­ALPS index is a good biomarker for PSP and might be effective to distinguish PSP from other neurocognitive disorders.

Effect of triamcinolone acetonide on retinal inflammation and angiogenesis induced by pericyte depletion in mouse.

Triamcinolone acetonide (TA) has been shown to improve morphological and functional outcome in diabetic macular edema (DME) patients. However, the functional mechanism of TA has not been elucidated yet. In this study we investigated the detailed functional mechanism of TA using culture cells and retinopathy mouse models in which retinal inflammation and abnormal angiogenesis were induced by pericyte depletion. TA significantly prevented retinal hemorrhage, edema and partially improved abnormal angiogenesis. TA decreased retinal vascular endothelial growth factor (VEGF) concentration, presumably by preventing recruitment of macrophages into retina and TA also inhibited expression of inflammatory cytokines in retina. TA inhibited proliferation/migration of vascular endothelial cells and vessel sprouting. No direct inhibition of VEGF receptor 2 (VEGFR2) autophosphorylation was observed by TA. These results suggested that TA improved inflammatory retinal events which were induced in pericyte-deleted mice by mainly decreasing macrophage-derived VEGF and expression of inflammatory cytokines followed by attenuation of vascular permeability and proliferation/migration of endothelial cells. Furthermore, in these processes, translocation of glucocorticoid receptor (GR) was partially involved.

The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study.

BACKGROUND: Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study. METHODS: Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 µg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events. RESULTS: Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%). CONCLUSIONS: Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.

Explorative Clustering of the Nitrogen Balance Trajectory in Critically Ill Patients: A Preliminary post hoc Analysis of a Single-Center Prospective Observational Study.

BACKGROUND: The nitrogen balance estimates a protein net difference. However, since it has a number of limitations, it is important to consider the trajectory of the nitrogen balance in the clinical course of critically ill patients. OBJECTIVES: We herein exploratively classified the nitrogen balance trajectory using a machine learning method. METHOD: This is a post hoc analysis of a single-center prospective study for the patients admitted to our Emergency and Critical Center ICU. The nitrogen balance was evaluated with 24-h urine collection from ICU days 1-10 with 9 points. K-means clustering was performed to classify the nitrogen balance trajectory. We also evaluated factors associated with uncovered clusters. RESULTS: Seventy-six eligible patients were included in the present study. After clustering, the nitrogen balance trajectory was classified into 4 classes. Class 1 was trajected as a negative balance over 10 days (24 patients). Class 2 had a positive conversion on day 3 or 4 (8 patients). Class 3 had a positive conversion on day 8 or 9 (28 patients). Class 4 initially had a positive balance and then converted to a negative balance (16 patients). Sepsis complication and steroid use were associated with negative nitrogen balance trajectory. Class 2 was associated with lower length of hospital stay and femoral muscle volume loss, however, frequently had frailty and sarcopenia on admission. Active nutrition therapy intention was not correlated with positive trajectory. CONCLUSIONS: The nitrogen balance trajectory in critically ill patients may be classified into 4 classes for clinical practice. Among patients emergently admitted to the ICU, the positive conversion of the nitrogen balance might be delayed over 10 days.

Comparing Inertial Measurement Units to Markerless Video Analysis for Movement Symmetry in Quarter Horses.

BACKGROUND: With an increasing number of systems for quantifying lameness-related movement asymmetry, between-system comparisons under non-laboratory conditions are important for multi-centre or referral-level studies. This study compares an artificial intelligence video app to a validated inertial measurement unit (IMU) gait analysis system in a specific group of horses. METHODS: Twenty-two reining Quarter horses were equipped with nine body-mounted IMUs while being videoed with a smartphone app. Both systems quantified head and pelvic movement symmetry during in-hand trot (hard/soft ground) and on the lunge (left/right rein, soft ground). Proportional limits of agreement (pLoA) were established. RESULTS: Widths of pLoA were larger for head movement (29% to 50% in-hand; 22% to 38% on lunge) than for pelvic movement (13% to 24% in-hand; 14% to 24% on lunge). CONCLUSION: The between-system pLoAs exceed current "lameness thresholds" aimed at identifying the affected limb(s) in lame horses. They also exceed published limits of agreement for stride-matched data but are similar to repeatability values and "lameness thresholds" from "non-lame" horses. This is encouraging for multi-centre studies and referral-level veterinary practice. The narrower pLoA values for pelvic movement asymmetry are particularly encouraging, given the difficulty of grading hind limb lameness "by eye".