Notes

Morphogenesis and also development components involving bacterially-induced struvite.
Some COVID-19 patients develop respiratory failure requiring admission to intensive care unit (ICU). We aim to evaluate the effects of pulmonary rehabilitation (PR) post-ICU in COVID-19 patients.

Twenty-one COVID-19 patients were evaluated pre- and post-PR and compared retrospectively to a non-COVID-19 group of 21 patients rehabilitated after ICU admission due to respiratory failure.

PR induced greater 6-min walking distance improvement in COVID-19 patients (+205 ± 121 m) than in other respiratory failure patients post-ICU (+93 ± 66 m). The sooner PR was performed post-ICU, the better patients recovered.

PR induced large functional improvements in COVID-19 patients post-ICU although significant physical and psychosocial impairments remained post-PR.
PR induced large functional improvements in COVID-19 patients post-ICU although significant physical and psychosocial impairments remained post-PR.Burrowing rodents have a blunted hypercapnic ventilatory response compared to non-burrowing rodents, but semi-fossorial ground squirrels and hamsters are not born with this blunted response when raised in room conditions. This study examined the hypercapnic ventilatory response of rats, hamsters, and ground squirrels raised in burrow-like hypercapnia (∼3 % CO2) through development (embryonic day 16-18 to postnatal day 30) to determine if chronic hypercapnia exerts any effect on the developing and adult semi-fossorial response. Chronic hypercapnia attenuated the ventilatory response to 5 % CO2 by 60 % (rats), 150 % (hamsters), and 70 % (squirrels) in newborns when compared to newborns raised in normal conditions. When raised in burrow conditions, squirrels and hamsters reached the blunted adult response ∼8-12 days sooner in development than their room air counterparts, while burrow-reared rats maintained a consistently blunted response until removal from chronic hypercapnia. Our study revealed no lasting effect of chronic hypercarbia on the ventilatory responses to CO2 in burrowing rodents, but rather a change in the developmental profile such that the blunted adult response was reached earlier in development.
Continuous renal replacement therapy (CRRT) is associated with micronutrients loss. Current recommendations are to administer 1-1.5g/kg/day of proteins during CRRT. We aim to evaluate the net effect of CRRT on amino acids (AA), vitamins A and C (Vit A, Vit C) levels.

This is a prospective observational study embedded within a randomised controlled trial comparing two CRRT doses in patients with septic shock. CRRT was provided in continuous veno-venous haemofiltration mode at a dose of either 35ml/kg/h or 70ml/kg/h. All patients received parenteral nutrition with standard trace elements and vitamins (protein intake 1g/kg/d). We measured serum levels of glutamine, valine and alanine as well as Vit A and Vit C upon randomisation, study day four and eight. In addition, we measured a larger panel of AA in a subset of 11 patients.

We included 30 patients (17 allocated to 70ml/kg/h and 13 to 35ml/kg/h CRRT). Before CRRT initiation, mean plasma levels of glutamine and valine, Vit A and Vit C were low. CRRT was not associated with any significant change in AA levels except for a decrease in cystein. It was associated with an increase in Vit A and a decrease in Vit C levels. CRRT dose had no impact on those nutrients blood levels.

Irrespective of dose, CRRT was associated with a decrease in cysteine and Vit C and an increase in Vit A with no significant change in other AA. Further studies should focus on lean mass wasting during CRRT.
Irrespective of dose, CRRT was associated with a decrease in cysteine and Vit C and an increase in Vit A with no significant change in other AA. Further studies should focus on lean mass wasting during CRRT.
Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses.

Subjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2mL LOR (0.03, 0.07, 0.15, or 0.23mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0-10], WOMAC Pain [0-100], WOMAC Function [0-100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling.

In total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07mg and 0.23mg LOR at Weeks 12 (-0.96, 95% CI [-1.54,-0.37], P=0.001;-0.78 [-1.39,-0.17], P=0.012) and 24 (-0.70 [-1.34,-0.06], P=0.031;-0.82 [-1.51,-0.12], P=0.022). Additionally, 0.07mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P=0.04, P=0.021), and 0.23mg LOR significantly improved both WOMAC subscores at Week 24 (P=0.031, P=0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07mg LOR as the lowest effective dose.

This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07mg LOR.
This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR.
To evaluate the efficacy of carbon-fibre shoe-stiffening inserts in individuals with first metatarsophalangeal joint osteoarthritis.

This was a randomised, sham-controlled, participant- and assessor-blinded trial. One hundred participants with first metatarsophalangeal joint osteoarthritis received rehabilitation therapy and were randomised to receive either carbon fibre shoe-stiffening inserts (n=49) or sham inserts (n=51). The primary outcome measure was the Foot Health Status Questionnaire (FHSQ) pain domain assessed at 12 weeks.

All 100 randomised participants (mean age 57.5 (SD 10.3) years; 55 (55%) women) were included in the analysis of the primary outcome. At the 12 week primary endpoint, there were 13 drop-outs (7 in the sham insert group and 6 in the shoe-stiffening insert group), giving completion rates of 86 and 88%, respectively. Both groups demonstrated improvements in the FHSQ pain domain score at each follow-up period, and there was a significant between-group difference in favour of theduals may not experience a clinically worthwhile improvement.
Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (μCT), and to compare the local microstructural organization between OA and donor samples.

We collected posterior horns of both medial and lateral human menisci from 10 end-stage medial compartment knee OA patients undergoing total knee replacement (medial & lateral OA) and 10 deceased donors without knee OA (medial & lateral donor). Posterior horns were dissected and fixed in formalin, dehydrated in ascending ethanol concentrations, treated with hexamethyldisilazane (HMDS), and imaged with μCT. We performed local orientation analysis of collagenous microstructure in 3D by calculating structure tensors from greyscale gradients within selected integration window to determine the polar angle for each voxel.

In donor samples, m important part of meniscus degradation.
To examine the cross-sectional and longitudinal associations of dietary patterns with knee symptoms and structures in patients with knee osteoarthritis (OA).

Participants with symptomatic knee OA were recruited from a randomised, placebo-controlled trial conducted in Tasmania (N=259) and Victoria (N=133). Diet was assessed by the Anti-Cancer Council of Victoria food frequency questionnaire. Factor analysis was used to identify dietary patterns. Knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) and structures using MRI. Multivariable linear regressions were used to examine associations.

Three dietary patterns ("high-fat", "healthy" and "mixed") were identified in whole sample. Participants with higher "healthy pattern" score had lower total WOMAC, pain, function and stiffness scores at baseline but the associations were not significant over 24 months. Three ("western", "vegetable and meat" and "mediterranean") and two ("processed" and "vegetable") patterns were identified in Tasmania and Victoria, respectively. Cross-sectionally, only "mediterranean pattern" and "vegetable pattern" scores were significantly and negatively associated with total WOMAC or function scores. Longitudinally, participants with higher "western pattern" had worsening function (β 0.35, 95%CI 0.03, 0.67) and total WOMAC (β 0.40, 95%CI 0.07, 0.72) scores; furthermore, "vegetable pattern" was associated with decreased WOMAC stiffness score (β-0.47, 95%CI-0.93,-0.02). In contrast, dietary patterns were largely not associated with structural changes.

Some healthy dietary patterns were associated with reduced joint symptoms but dietary patterns were not associated with joint structure in this sample with knee OA. Further studies are required to confirm these findings.
Some healthy dietary patterns were associated with reduced joint symptoms but dietary patterns were not associated with joint structure in this sample with knee OA. Further studies are required to confirm these findings.Larval lake sturgeon, Acipenser fulvescens, reared in hatcheries for stock enhancement of wild populations may be susceptible to early opportunistic bacterial infection. Thus, we examined survival and whole-body mRNA expression of both stress- and immune-related genes (MyD88, IL-1β, StAR, GR1, and HSP70) in 30 days post fertilization larval lake sturgeon following immune challenge with lipopolysaccharides (LPS). Larval sturgeon were exposed to 0, 25, 50, 100, 150, and 200 μg ml-1 LPS and sampled after 30 min, 4 h, and 48 h. Mortality was zero in 0 and 25 μg ml-1 LPS; 37.5% in 50 μg ml-1 LPS and 100% in the higher concentrations. Expression of MyD88 and StAR mRNA were positively correlated and increased with time in the 50 μg ml-1 LPS treatment. There was an influence of both treatment and time on IL-1β mRNA, with expression 10-fold higher than controls after 4 h. Expression of HSP70 mRNA was suppressed within 30 min of 50 μg ml-1 LPS exposure and remained so throughout the time course. Correlated mRNA expression of GR1 with MyD88, StAR and IL-1β suggests a potential relationship between the innate immune and glucocorticoid responses of larval lake sturgeon during this early developmental stage. Data presented suggest that larval lake sturgeon largely responded with predicted changes in gene expression of immune related and stress response genes following LPS challenge. This study provides a foundation for future research examining the effects of hatchery and naturally occurring stressors on the immune responses of larval lake sturgeon.
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