Are associations between physical activity and bone mineral density in adults sex- and age-dependent? An analysis of the UK Biobank study.

Although physical activity (PA) is recognized as a key bone mass determinant across life, athlete studies suggest that it may be less effective in women and older individuals. This has not been explored within the general population. We aimed to address this knowledge gap using data from the UK Biobank Study, a large population-based study of middle-aged and older adults. Free-living PA data collected at 100 Hz for 7 d using wrist-worn accelerometers were classified as sedentary behavior (0-29 milligravities [mg]), light (30-124 mg), or moderate-to-vigorous PA (125 + mg). LS and FN-BMD were assessed using DXA. The associations between PA and BMD were assessed using linear regression models, with formal assessments of sex and age interactions undertaken and adjustments made for accelerometer wear time, height, body mass index, education, ethnicity, disability, and (in women only) menopausal status. In total, 15 133 UK Biobank participants (52% women) had complete PA, bone, and covariate data. In this sample, greater overall and moderate-to-vigorous PA was associated with higher LS BMD. In women, these associations were typically weaker in older individuals, for example, regression coefficients in women aged 70 yr or older were ~50% lower than at 45-54 yr (age-by-PA interactions P < .01 in all models). Similar associations were observed in basic but not full models for FN BMD. Greater sedentary time was associated with lower LS BMD in men only, and greater light PA and sedentary time were associated with higher and lower FN BMD, respectively, in both sexes. These results suggest that associations between PA and bone health at clinically-relevant sites are weaker in older than younger women. That positive associations are evident between overall and moderate-vigorous PA and FN BMD even in women ≥70 yr suggests that PA for bone health should still be promoted in older women.

Retraction: Hemichorea: A Rare Neurological Complication of Diabetes Mellitus.

[This retracts the article DOI: 10.7759/cureus.21131.].

Molecular survey on vector-borne pathogens in clinically healthy stray cats in Zaragoza (Spain).

BACKGROUND: In Europe, feline vector-borne infections are gaining importance because of the changing climate, expanding habitats of potential vectors and expanding pathogen reservoirs. The main objective of this study was to assess the prevalence of vector-borne pathogens (VBPs) in stray cats in Zaragoza, Spain, and to investigate potential risk factors for infection, including feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). METHODS: Blood samples from stray cats presented to the veterinary faculty in Zaragoza between February 2020 and 2022 were tested by polymerase chain reaction (PCR) for the presence of Anaplasma phagocytophilum, Anaplasma platys, Bartonella henselae, Ehrlichia canis, Rickettsia spp., haemotropic Mycoplasma spp., Hepatozoon spp., Leishmania infantum, piroplasms and microfilariae at the LABOKLIN laboratory. The cats were also tested for FeLV and FIV by PCR. RESULTS: Nearly half of the cats (158/332, 47.6%) were positive for at least one VBP. Hepatozoon spp. were detected in 25.6%, haemotropic Mycoplasma spp. in 22.9%, B. henselae in 9.3% and L. infantum in 2.1% of the cats. Male sex had a statistically significant association with test results for haemotropic Mycoplasma spp. (odds ratio 1.38 [1.21;1.57]); regionality with Hepatozoon spp., B. henseale and FIV; and seasonality with Hepatozoon spp., haemotropic Mycoplasma spp., L. infantum and FeLV (P ≤ 0.05 each). A strong positive correlation was reported for the amount of rainfall and the number of cats that tested positive for Hepatozoon spp. (ρ = 753, P = 0.05). None of the cats tested positive for A. phagocytophilum, A. platys, E. canis, Rickettsia spp., piroplasms, or microfilariae. Co-infections with multiple VBPs were detected in 56 out of 332 cats (16.9%). Thirty-one of the 332 cats included in the study (9.3%) tested positive for FeLV (6.9%) and for FIV (3.6%). In 20/31 cats (64.5%) that tested positive for FeLV/FIV, coinfections with VBP were detected (P = 0.048, OR 2.15 [0.99; 4.64]). CONCLUSIONS: VBPs were frequently detected in stray cats in Zaragoza. In particular, regionality and seasonality had a statistically significant association with PCR results for most VBPs included in the study.

Uncovering global lipid accumulation routes towards docosahexaenoic acid (DHA) production in Aurantiochytrium sp. SW1 using integrative proteomic analysis.

Aurantiochytrium sp., a marine thraustochytrid possesses a remarkable ability to produce lipid rich in polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA). Although gene regulation underlying lipid biosynthesis has been previously reported, proteomic analysis is still limited. In this study, high DHA accumulating strain Aurantiochytrium sp. SW1 has been used as a study model to elucidate the alteration in proteome profile under different cultivation phases i.e. growth, nitrogen-limitation and lipid accumulation. Of the total of 5146 identified proteins, 852 proteins were differentially expressed proteins (DEPs). The largest number of DEPs (488 proteins) was found to be uniquely expressed between lipid accumulating phase and growth phase. Interestingly, there were up-regulated proteins involved in glycolysis, glycerolipid, carotenoid and glutathione metabolism which were preferable metabolic routes towards lipid accumulation and DHA production as well as cellular oxidative defence. Integrated proteomic and transcriptomic data were also conducted to comprehend the gene and protein regulation underlying the lipid and DHA biosynthesis. A significant up-regulation of acetyl-CoA synthetase was observed which suggests alternative route of acetate metabolism for acetyl-CoA producer. This study presents the holistic routes underlying lipid accumulation and DHA production in Aurantiochytrium sp. SW1 and other relevant thraustochytrid.

The study of the strength and significance of four biological parameters on the body weight of goose.

Alternative products such as those from high-value protien animals have increased the demand for the production of high-quality chicken meat in past few years. This study examines the impact of two distinct feeding types on goose body-weight, as well as the genetic variation of growth hormone (GH) and pituitary-specific transcription factor (Pit-1) genes in ten goose populations using single nucleotide polymorphism (SNP) markers and PCR-RFLP analysis. Both genes were seen as very important for productivity, especially in light of the COVID-19 and its effect on poultry industry at the time. The findings suggest that employing genetic indicators in these two genes in conjunction with a high-fat diet may be a feasible strategy for goose selection programme aiming to increase marketing body weight, as the high-fat diet outperformed the balanced diet. The study investigates the effect of gender, 2 types of diets, breeds and the genetic variation of the two genes, four SNPs were reported to be found: two at the GH gene exons C123T and C158T, and two at the Pit-1 gene exons G161A and T282G. Certain genotypes were found to have a substantial effect on the marketing body-weight of goose, which varied depending on the tested breeds. However, in terms of gender, males report higher and better performance levels than females. Diet, breeds and genotype interaction, and breeds, gender and genotype interaction were found to have a minor effect on goose body weight. However, diet, breeds, gender, SNP locus, diet and breeds interaction, and breeds and gender interaction were found to have a significant effect on goose body weight, as indicated by the effect size results.

Revealing holistic metabolic responses associated with lipid and docosahexaenoic acid (DHA) production in Aurantiochytrium sp. SW1.

Aurantiochytrium sp. SW1, a marine thraustochytrid, has been regarded as a potential candidate as a docosahexaenoic acid (DHA) producer. Even though the genomics of Aurantiochytrium sp. are available, the metabolic responses at a systems level are largely unknown. Therefore, this study aimed to investigate the global metabolic responses to DHA production in Aurantiochytrium sp. through transcriptome and genome-scale network-driven analysis. Of a total of 13,505 genes, 2527 differentially expressed genes (DEGs) were identified in Aurantiochytrium sp., unravelling the transcriptional regulations behinds lipid and DHA accumulation. The highest number of DEG were found for pairwise comparison between growth phase and lipid accumulating phase where a total of 1435 genes were down-regulated with 869 genes being up-regulated. These uncovered several metabolic pathways that contributing in DHA and lipid accumulation including amino acid and acetate metabolism which involve in the generation of crucial precursors. Upon applying network-driven analysis, hydrogen sulphide was found as potential reporter metabolite that could be associated with the genes related to acetyl-CoA synthesis for DHA production. Our findings suggest that the transcriptional regulation of these pathways is a ubiquitous feature in response to specific cultivation phases during DHA overproduction in Aurantiochytrium sp. SW1.

Wandering Spleen: A Rare Case From the Emergency Department.

The spleen is typically located in the left upper quadrant and is held in position by the suspensory ligaments, which include the gastrosplenic ligament, the splenorenal ligament, and the phrenicocolic ligament. Abnormalities within these ligaments result in the mobility of the spleen, so it may be located in the pelvis or iliac region, which is termed a wandering spleen. We present a case of a middle-aged man who presented to the emergency department with generalized abdominal pain and diffuse guarding and tenderness. The patient had a previous history of peptic ulcer disease and multiple emergency department visits for gastritis. Given the assumed diagnosis of perforated viscus, the patient underwent a computed tomography scan that demonstrated the absence of the spleen in its usual location and showed an ectopic pelvic spleen. The patient underwent successful surgical treatment with splenopexy. The wandering spleen is a rare medical condition that presents a clinical diagnostic challenge and requires a high index of suspicion. Despite its rarity, the wandering spleen should be considered in patients with recurrent abdominal pain.

Nano Zinc Oxide Improves Performance, IGF-I mRNA Expression, Meat Quality, and Humeral Immune Response and Alleviates Oxidative Stress and NF-κB Immunohistochemistry of Broiler Chickens.

A 35-day trial was set to explore the effects of different dietary zinc sources on growth, insulin-like growth factor I (IGF-I) mRNA expression, meat quality, immune response, antioxidant activity, and immunohistochemistry of nuclear factor kappa B (NF-κ7B) of broiler chickens. Ross 308 broiler chicks (n = 156) were randomly assigned into four experimental groups. The G1 received the basal control diet without zinc supplementation; the G2, G3, and G4 were supplemented with zinc oxide, zinc lysine, and nano zinc oxide, respectively, at a level of 40 mg Zn/kg diet. The data revealed that nano zinc oxide linearly improved the overall growth performance parameters. Nano zinc oxide linearly elevated (P < 0.001) mRNA expression of IGF-I followed by G3. The pH value of breast muscle in G4 shows a linearly decreasing value (P < 0.001). Also, the linearly highest expressible release volume percentage and lightness (L*) value with the lowest redness (a*) value (P < 0.05) were recorded in G4 and G3. A numerical increase in the total antibody titer was recorded on the 35th day in the G3 and G4. A numerical elevation in the superoxide dismutase (SOD) and a numerical reduction in the serum malondialdehyde (MDA) were recorded in the G4. The section of the liver from G4 revealed significantly very low expression of NF-κB staining. It is concluded that nano zinc oxide is considered the more trending zinc source. It had no negative effects on the health status and can be used in broiler diet premix.

Co-existence of type I fatty acid synthase and polyketide synthase metabolons in Aurantiochytrium SW1 and their implications for lipid biosynthesis.

The key enzymes of lipid biosynthesis in oleaginous filamentous fungi exist as metabolons. However, the existence of a similar organization in other groups of oleaginous microorganisms is still unknown. In this study, we confirmed the occurrence of two separate and distinct lipogenic metabolons in a thraustochytrid, Aurantiochytrium SW1. These involve the Type I Fatty Acid Synthase (FAS) pathway, consisting of six enzymes: fatty acid synthase, malic enzyme (ME), ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), malate dehydrogenase (MD) and pyruvate carboxylase (PC), and the Polyketide Synthase-like (PKS) pathway, consisting of PKS subunits a, b, c, glucose-6-phosphate dehydrogenase (G6PDH) 6-phosphogluconate dehydrogenase (6PGDH), ACL and ACC. This suggests that the NADPH requirement for the FAS pathway is primarily generated and channelled by ME whereas G6PDH and 6PGDH fulfil this role for the PKS pathway. Diminished biosynthesis of palmitic acid (16:0), docosahexaenoic acid (22:6 n-3, DHA) and docosapentaenoic acid (22:5 n-6, DPA) correlated with the dissociation of their respective metabolons thereby suggesting that regulation of the pathways is achieved through the formation and dissociation of the metabolons.

Associations between childhood and adulthood socioeconomic position and grip strength at age 46 years: findings from the 1970 British Cohort Study.

BACKGROUND: Muscle weakness is a key criterion for important age-related conditions, including sarcopenia and frailty. Research suggests lower childhood socioeconomic position (SEP) may be associated with muscle weakness in later life but there is little evidence on associations in younger adults closer to peak muscle strength. We aimed to examine relationships between indicators of SEP in childhood and adulthood and grip strength at age 46y. METHODS: We examined 7,617 participants from the 1970 British Cohort Study with grip strength measurements at 46y. We used sex-specific linear regression models to test associations between five different indicators of SEP in childhood and adulthood (paternal occupational class and parental education levels at age 5 and own occupational class and education level at age 46) and maximum grip strength. Models were adjusted for birth weight, BMI in childhood and adulthood, adult height, disability in childhood, leisure-time physical activity in childhood and adulthood, sedentary behaviour in childhood and adulthood, occupational activity and smoking at age 46. RESULTS: Among women, lower SEP in childhood and adulthood was associated with weaker grip strength even after adjustments for covariates. For example, in fully-adjusted models, women whose mothers had no qualifications at age five had mean grip strength 0.99 kg (95% CI: -1.65, -0.33) lower than women whose mothers were educated to degree and higher. Among men, lower levels of father's education and both adult SEP indicators were associated with stronger grip. The association between own occupational class and grip strength deviated from linearity; men in skilled-manual occupations (i.e. the middle occupational group) had stronger grip than men in the highest occupational group (Difference in means: 1.33 kg (0.60, 2.06)) whereas there was no difference in grip strength between the highest and lowest occupational groups. Adjustment for occupational activity largely attenuated these associations. CONCLUSION: Findings highlight the need to identify age and sex-specific interventions across life to tackle inequalities in important age-related conditions related to weakness.

Red flags for spinal pain in patients diagnosed with spinal infection in Nigeria: A 10-year medical records review.

BACKGROUND: Spinal infection is a diagnostic challenge, the personal and economic consequences of misdiagnosis can be significant resulting in paralysis and instability of the spine and can ultimately be fatal. To aid identification of those at risk of spinal infection, a better understanding of the red flags for spinal infection is needed. OBJECTIVE: To better understand which red flags may help to identify spinal infection. DESIGN: and Methods: A 10-year medical records review of red flags for spinal infection in Nigeria, using a bespoke data extraction tool. Univariable and multivariable logistic regression was used to identify the main independent predictors of spinal pain. RESULTS: 124,913 records were reviewed, 1,645 patients were diagnosed with spinal infection. 79% of patients presented with spinal pain Univariable analysis revealed nine factors (some centres, all age groups above 16 years, co-morbidities, environmental factors, history of TB, radicular pain, pins and needles, numbness and spine tenderness.) were associated with greater odds (OR = 1.77-21.7, p < 0.001), whilst four (some centres, fatigue, fever and myotomal weakness) were associated with lower odds (OR = 0.51-0.59) of spine pain. Six factors were included in the final multivariable model associated with higher odds of spine pain: age groups above 16 years (OR 2.57 to 5.33, p < 0.05), co-morbidity (OR = 1.68, p < 0.05), history of TB (OR = 3.02, p < 0.05), weight loss (OR = 1.75, p < 0.01), radicular pain (OR = 19.88, p < 0.001); spine tenderness (OR = 6.54, p < 0.001). Myotomal weakness (OR = 0.66, p < 0.05) and fatigue (OR = 0.50, p < 0.01) were associated with lower odds of spinal pain in the final model. CONCLUSION: Using data from ten hospitals in Nigeria within a ten-year period, we have produced a shortlist of red flags that can inform clinical decision making about potential spinal infection.

Variables and Mechanisms Affecting Electro-Membrane Extraction of Bio-Succinic Acid from Fermentation Broth.

The production of succinic acid from fermentation is a promising approach for obtaining building-block chemicals from renewable sources. However, the limited bio-succinic yield from fermentation and the complexity of purification has been making the bio-succinic acid production not competitive with petroleum-based succinic acid. Membrane electrolysis has been identified to be a promising technology in both production and separation stages of fermentation processes. This work focuses on identifying the key operational parameters affecting the performance of the electrolytic cell for separating succinic acid from fermentation broth through an anionic exchange membrane. Indeed, while efforts are mainly focused on studying the performance of an integrated fermenter-electrolytic cell system, a lack of understanding remains in how to tune the electrolytic cell and which main parameters are involved. The results show that a single electrolytic cell of operating volume 250 mL was able to extract up to 3 g L-1 h-1 of succinic acid. The production of OH- ions by water electrolysis can act as a buffer for the fermenter and it could be tuned as a function of the extraction rate. Furthermore, as the complexity of the solution in terms of the quantity and composition of the ions increased, the energy required for the separation process decreased.

Localized massive staphylococcal pericardial abscess with atypical presentation.

Introduction and importance: Localized staphylococcal pericardial abscess (PA) is extremely rare and highly mortal complication of Staphylococcus aureus bacteremia with only a few reported cases in English-language medical literature. Clinical manifestations are fulminant, and early management is necessary. Case presentation: Here we report a case of end stage renal disease (ESRD) with isolated localized massive staphylococcal PA and had masked signs and symptoms of pericardial staphylococcal infection. Contrast-enhanced computed tomography scan suggested anterior massive localized pericardial cyst like image. Surgical drainage of the abscess with localized pericardiectomy conjugated with antibiotic therapy led to a successful management. Clinical discussion: Staphylococcus aureus is the leading cause of hemodialysis catheter-related bloodstream infections, contributing 33-80% of the organisms cultured from blood samples. Nature of staphylococcal pericardial infection is aggressive and life threatening with generalized involvement of the pericardium although our patient presented with masked signs and symptoms. Conclusion: CT image of localized pericardial lesion with masked signs and symptoms does not exclude the presence of live threating pericardial infection, especially in immunocompromised patients.

Reporting of Model Performance and Statistical Methods in Studies That Use Machine Learning to Develop Clinical Prediction Models: Protocol for a Systematic Review.

BACKGROUND: With the growing excitement of the potential benefits of using machine learning and artificial intelligence in medicine, the number of published clinical prediction models that use these approaches has increased. However, there is evidence (albeit limited) that suggests that the reporting of machine learning-specific aspects in these studies is poor. Further, there are no reviews assessing the reporting quality or broadly accepted reporting guidelines for these aspects. OBJECTIVE: This paper presents the protocol for a systematic review that will assess the reporting quality of machine learning-specific aspects in studies that use machine learning to develop clinical prediction models. METHODS: We will include studies that use a supervised machine learning algorithm to develop a prediction model for use in clinical practice (ie, for diagnosis or prognosis of a condition or identification of candidates for health care interventions). We will search MEDLINE for studies published in 2019, pseudorandomly sort the records, and screen until we obtain 100 studies that meet our inclusion criteria. We will assess reporting quality with a novel checklist developed in parallel with this review, which includes content derived from existing reporting guidelines, textbooks, and consultations with experts. The checklist will cover 4 key areas where the reporting of machine learning studies is unique: modelling steps (order and data used for each step), model performance (eg, reporting the performance of each model compared), statistical methods (eg, describing the tuning approach), and presentation of models (eg, specifying the predictors that contributed to the final model). RESULTS: We completed data analysis in August 2021 and are writing the manuscript. We expect to submit the results to a peer-reviewed journal in early 2022. CONCLUSIONS: This review will contribute to more standardized and complete reporting in the field by identifying areas where reporting is poor and can be improved. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020206167; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=206167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/30956.

Hemichorea: A Rare Neurological Complication of Diabetes Mellitus.

Diabetes mellitus is a prevalent metabolic disorder that has a wide range of complications. Neurological complications are common and include stroke and peripheral neuropathy. However, hemichorea is a very rare manifestation of diabetes mellitus. Chorea can be due to primary inherited conditions or secondary to other disorders. Careful evaluation of patients with chorea is crucial since secondary chorea can be managed with the treatment of the underlying cause. We report the case of a 51-year-old man who presented to the emergency department with a two-week history of sudden involuntary and random-appearing movements of the right upper and lower extremities. These movements were non-suppressible and disappeared during sleep. Further, the movements were not associated with any neurological symptoms, including headache, dizziness, weakness, sensory deficits, or loss of consciousness. The patient had a longstanding history of hypertension and diabetes mellitus. He reported that he was not compliant with his medications. Laboratory investigation revealed a very high level of blood glucose (580 mg/dL) with associated pseudohyponatreamia (127 mEq/L). Head computed tomography scan showed increased density in right caudate nuclei and putamen with no surrounding edema or mass effect. The findings were suggestive of non-ketotic hyperglycemic hemichorea based on the clinical, laboratory, and radiological laboratory findings. The patient received insulin therapy according to sliding-scale protocol. The chorea movements gradually improved and completely disappeared after the fourth day of admission with the normalization of glucose level. In view of this, emergency medicine physicians should consider non-ketotic hyperglycemia as a potential underlying etiology of acute hemichorea.

Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain-containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy. METHODS: Using a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. RESULTS: Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8+ T cells, CD4+ T cells, and CD56+ natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis. CONCLUSIONS: Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.

Effect of poultry offal silage with or without betaine supplementation on growth performance, intestinal morphometry, spleen histomorphology of Nile tilapia (Oreochromis niloticus) fingerlings.

Fishmeal (FM) is the main protein source in fish feed. However, it is quite expensive due to its limited resources. Therefore, finding a dietary alternative to the FM to sustain fish production is crucial, and the current study was performed to assess the impact of poultry offal silage (POS) with or without betaine supplementation; as an effective and cheaper alternative to FM; on feed efficiency, growth performance, spleen morphology and intestinal morphometry of Nile tilapia (Oreochromis niloticus) fingerlings. Four dietary treatments were formulated: (1) FM based diet, (2) FM-B; FM diet +0.7% betaine, (3) POS diet and (4) POS-B; POS diet +0.7% betaine. Each dietary treatment consisted of three replicates (n = 10/replicate), and the experiment was continued for 16 weeks. By the end of the experiment, spleen and intestine specimens were collected from 15 fish (n = 5/replicate) for histopathological assessment. The results were statistically analysed using GLM procedures of SAS 9.4. Feed efficiency increased in both POS-B and FM-B groups (p = 0.01), while body weight and body weight gain showed only weak tendencies towards an increase (p = 0.10 and 0.12, respectively). The villi length was the highest in POS-B fed group (p < 0.01). In addition, melanomacrophage centres of the spleen increased in both betaine-supplemented groups (p < 0.01). From our findings, we conclude that betaine supplementation with poultry offal silage improved production performance and immune status of Nile tilapia fish.

Enhancement of harvesting efficiency and polyunsaturated fatty acid-rich lipid production of Aurantiochytrium sp. SW1 by co-cultivation with oleaginous fungus Cunninghamella bainieri 2A1

Aims@#Thraustochytrids have been shown to be excellent lipid producers due to their ability to accumulate over 50% lipid (g/g biomass) containing up to 50% docosahexaenoic acid (DHA). However, efficient and cost-effective cell recovery of lipid-rich biomass has become a significant challenge at the industrial scale. In this study, we attempted to enhance the harvesting efficiency (HE) and the DHA content of Aurantiochytrium sp. through co-cultivation with a γ-linolenic acid (GLA)-producing oleaginous filamentous fungus, Cunninghamella bainieri 2A1.@*Methodology and results@#A 72 h old C. bainieri 2A1 culture in the form of loose mycelia or pellets of various sizes was added into 72 h old Aurantiochytrium sp. cultures and further incubated for 48 h. The HE of Aurantiochytrium sp. was then determined by comparing the remaining OD values of the supernatant with and without minimal centrifugation at 4000× g. Results showed that 63.23% of HE was achieved without centrifugation from co-cultivation with dispersed mycelia. Higher HE between 96.71-99.55% was achieved when centrifugation was implemented, with the highest value resulting from co-cultivation with dispersed mycelia. These are higher than HE of centrifuged control cultures (80%) consisting of Aurantiochytrium sp. monocultures, suggesting that co-cultivation with C. bainieri 2A1 facilitates the recovery of Aurantiochytrium sp. cells. Moreover, the co-cultivation also resulted in a 28% increase in DHA compared to non-optimized cultures.@*Conclusion, significance and impact of study@#This study provides the first evidence of enhancement in harvesting and DHA content of oleaginous thraustochytrids that could be achieved through co-cultivation with oleaginous fungi.

TREATMENT WITH SOLUBLE CD24 ATTENUATES COVID-19-ASSOCIATED SYSTEMIC IMMUNOPATHOLOGY.

BACKGROUND: SARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy. METHODS: We studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial (NCT04317040) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. FINDINGS: Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8+ T cells, CD4+ T cells, and CD56+ NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity. INTERPRETATION: Our data demonstrates that CD24Fc treatment rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19. FUNDING: NIH.