Disease flares with baricitinib dose reductions and development of flare criteria in patients with CANDLE/PRAAS.

OBJECTIVES: Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop 'flare criteria'. METHODS: Of 10 patients with CANDLE/PRAAS treated with baricitinib in an open-label expanded-access programme, baricitinib doses were reduced 14 times in 9 patients between April 2014 and December 2019. Retrospective data analysis of daily diary scores and laboratory markers collected before and after the dose reductions were used to develop 'clinical' and 'subclinical' flare criteria. Disease flare rates were compared among patients with <25% and >25% dose reductions and during study visits when patients received recommended 'optimized' baricitinib doses (high-dose visits) versus lower than recommended baricitinib doses (low-dose visits) using two-sided χ2 tests. RESULTS: In the 9/10 patients with CANDLE with dose reduction, 7/14 (50%) times the dose was reduced resulted in a disease flare. All four dose reductions of >25% triggered a disease flare (p <0.05). Assessment of clinical and laboratory changes during disease flares allowed the development of disease flare criteria that were assessed during visits when patients received high or low doses of baricitinib. Disease flare criteria were reached during 43.14% of low-dose visits compared with 12.75% of high-dose visits (p <0.0001). Addition of an interferon score as an additional flare criterion increased the sensitivity to detect disease flares. CONCLUSION: We observed disease flares and rebound inflammation with baricitinib dose reductions and proposed flare criteria that can assist in monitoring disease activity and in designing clinical studies in CANDLE/PRAAS.

Transcription-coupled repair of DNA-protein cross-links depends on CSA and CSB.

Covalent DNA-protein cross-links (DPCs) are toxic DNA lesions that block replication and require repair by multiple pathways. Whether transcription blockage contributes to the toxicity of DPCs and how cells respond when RNA polymerases stall at DPCs is unknown. Here we find that DPC formation arrests transcription and induces ubiquitylation and degradation of RNA polymerase II. Using genetic screens and a method for the genome-wide mapping of DNA-protein adducts, DPC sequencing, we discover that Cockayne syndrome (CS) proteins CSB and CSA provide resistance to DPC-inducing agents by promoting DPC repair in actively transcribed genes. Consequently, CSB- or CSA-deficient cells fail to efficiently restart transcription after induction of DPCs. In contrast, nucleotide excision repair factors that act downstream of CSB and CSA at ultraviolet light-induced DNA lesions are dispensable. Our study describes a transcription-coupled DPC repair pathway and suggests that defects in this pathway may contribute to the unique neurological features of CS.

The contribution of brain volume to explain autonomous imbalance during recovery from acute stress in batterers.

AIM: Many authors have suggested that intimate partner violence (IPV) perpetrators present an imbalance between both branches of the autonomous nervous system when coping with acute stress. Concretely, there is a predominance of the sympathetic branches over the parasympathetic ones when recovering from stress. This imbalance can be explained by their tendency toward anger rumination, and more concretely, by their focus on thoughts of revenge during this period. Unfortunately, there is a gap in the scientific literature in terms of using magnetic resonance imaging (MRI) techniques to assess which brain structures would explain this tendency of IPV perpetrators when coping with acute stress. METHOD: The main objective of this study was to assess whether the gray matter volume (GMV) of relevant brain structures, signaled in previous scientific literature, moderates the association between thoughts of revenge and sympathetic activation during the recovery period, based on skin conductance levels (SCL) after being exposed to stress, in a group of IPV perpetrators (n = 58) and non-violent men (n = 61). RESULTS: This study highlighted that the GMV of the left nucleus accumbens, right lobules of the cerebellum, and inferior temporal gyrus in IPV perpetrators moderated the association between thoughts of revenge and SCL during the recovery period. Accordingly, the higher the thoughts of revenge, the higher the sympathetic predominance (or higher SCL levels), especially among IPV perpetrators with the lowest GMV of these brain structures. Nonetheless, those variables were unrelated in the control group. CONCLUSIONS: Our study highlights the involvement of certain brain structures and how they explain the tendency of some IPV perpetrators to ruminate anger or, more precisely, to focus on thoughts of revenge when they recover from acute stress. These results reinforce the need to incorporate neuroimaging techniques during screening processes to properly understand how IPV perpetrators deal with stress, which in turn helps target their needs and design concrete intervention modules.

Zoonotic nematode in the city of La Plata, Argentina: Report of a case of Calodium hepaticum in Rattus rattus.

This study describes a case of Calodium hepaticum (Trichinellida: Capillariidae) infection in an adult rat (Rattus rattus) from the periurban area of the city of La Plata in the province of Buenos Aires, Argentina. The rat was found with neurological signs (ataxia, lethargy, and episodes of unresponsiveness) in the food storage of a goat production facility. The liver was observed with hepatomegaly and diffuse and irregular yellowish-white spots appearing in striae or small nodules on the external surface and inside the liver. Subsequent microscopic and histopathological studies were performed. Eggs were observed by direct microscopy of the impression smear of liver tissue. A multifocal granulomatous tissue reaction with different stages of fibrocellular tissue was observed in the liver parenchyma. The granulomas contained adults and degenerated eggs delimited by an intense infiltrate of mononuclear cells. Macro and microscopic observations and histopathological liver lesions were compatible with C. hepaticum infection. To our knowledge, this is the first confirmation of C. hepaticum infection in R. rattus in Argentina, increasing the host record of this parasite and a new record of distribution in goat production systems in the country.

The Vicious Cycle of Type 2 Diabetes Mellitus and Skeletal Muscle Atrophy: Clinical, Biochemical, and Nutritional Bases.

Today, type 2 diabetes mellitus (T2DM) and skeletal muscle atrophy (SMA) have become increasingly common occurrences. Whether the onset of T2DM increases the risk of SMA or vice versa has long been under investigation. Both conditions are associated with negative changes in skeletal muscle health, which can, in turn, lead to impaired physical function, a lowered quality of life, and an increased risk of mortality. Poor nutrition can exacerbate both T2DM and SMA. T2DM and SMA are linked by a vicious cycle of events that reinforce and worsen each other. Muscle insulin resistance appears to be the pathophysiological link between T2DM and SMA. To explore this association, our review (i) compiles evidence on the clinical association between T2DM and SMA, (ii) reviews mechanisms underlying biochemical changes in the muscles of people with or at risk of T2DM and SMA, and (iii) examines how nutritional therapy and increased physical activity as muscle-targeted treatments benefit this population. Based on the evidence, we conclude that effective treatment of patients with T2DM-SMA depends on the restoration and maintenance of muscle mass. We thus propose that regular intake of key functional nutrients, along with guidance for physical activity, can help maintain euglycemia and improve muscle status in all patients with T2DM and SMA.

Associations of current and childhood socioeconomic status and health outcomes amongst patients with knee or hip osteoarthritis in a Mexico City family-practice setting.

OBJECTIVES: To examine the association of current and childhood socioeconomic status (SES) with patient-reported functional status, quality of life and disability in patients with knee or hip osteoarthritis (OA). METHODS: Cross-sectional study amongst individuals seeking care for any medical reason in a primary care family-practice clinic in Mexico City. We included individuals with self-reported doctor-diagnosed arthritis, recruited through waiting-room posters and invitations by treating family physicians. We administered a survey using validated Spanish language versions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Osteoarthritis of Lower Limbs and Quality of Life (AMICAL), and the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI). To estimate current and childhood SES, we collected data on education level and occupation type for both the patient and their parents, as well as using a validated tool to estimate income quintile. RESULTS: We recruited 154 patients and excluded 8 patients. There was a high correlation between outcome scores. Estimated income and education levels were correlated with WOMAC, AMICAL and HAQ-DI scores, and significant differences were found in all scores by occupation type. The associations for current SES variables and outcome scores remained significant independently of age, sex, BMI, and presence of diabetes or hypertension, and were largely explained by current income in mutually adjusted models. Childhood SES - in particular as measured through maternal education - was best correlated with AMICAL scores, though its effect seemed largely mediated by its association with current SES. CONCLUSIONS: Current Socioeconomic Status impacts functional status, quality of life and disability amongst OA patients in Mexico City. The WOMAC, AMICAL and HAQ-DI scores correlate with each other and are all potentially useful markers of disease severity. More research is needed to elucidate the relationships between childhood SES and OA outcomes. Awareness of life-course SES may be useful in identifying patients at risk for worse outcomes.

COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

Optimizing Diabetes Management Using a Low-Calorie Diet in Saudi Arabia: A Cost-Benefit Analysis.

BACKGROUND: Low-calorie diets, high in protein and low in carbohydrates, are commonly recommended for patients with pre-diabetes and type 2 diabetes. The objective of this study was to carry out a cost-benefit analysis (CBA) of a low-calorie versus a standard diet from the perspective of the Saudi Arabian health system. METHODS: The CBA compares costs and benefits of the two diet strategies over a 1-year time horizon. Costs included diet and diabetes treatment-related resources while benefits were measured in terms of the costs of diabetes complications avoided. Data on costs and benefits were collected from published literature and subject matter experts. Incremental costs were estimated as the cost difference between low-calorie and standard diet. Incremental benefits were estimated as cost difference from medical complications when following a low-calorie or standard diet. The incremental absolute cost-benefit ratio was calculated to show the difference between the costs and benefits of the low-calorie diet. Incremental relative cost-benefit ratio was calculated to show the cost per dollar of benefit obtained. Monte Carlo simulation modeled variability in outcomes due to variation in costs and uncertainty of diabetes complications. RESULTS: The 1 year cost of standard diet was US$2515 ± 156 compared to US$2469 ± 107 per patient for a low-calorie diet. Incremental benefit is estimated at US$21,438 ± 7367 per patient. The estimated incremental absolute cost-benefit ratio was US$ - 21,360 establishing that benefits are greater than costs, while the estimated incremental relative cost-benefit ratio is 0.0037, establishing that benefits are 270 times greater than costs. CONCLUSION: The low-calorie diet was the dominant strategy compared to the standard diet in modeled scenarios. These findings highlight the importance of a low-calorie diet as part of diabetes management programs for outpatients with type 2 diabetes.

Increased femoral anteversion in females with anterior knee pain relates to both the neck and the shaft of the femur.

INTRODUCTION: Increased femoral anteversion (FAV) can have many clinical manifestations, including anterior knee pain (AKP). To our knowledge, no studies have measured the location of FAV in a cohort of female AKP patients. The objective of this research is to determine whether the increased FAV in AKP females originates above the lesser trochanter, below the lesser trochanter or at both levels. MATERIALS AND METHODS: Thrity-seven consecutive AKP female patients (n = 66 femurs) were recruited prospectively. There were 17 patients (n = 26 femurs; mean age of 28 years) in whom the suspicion for the increased FAV of the femur was based on the clinical examination (pathological group-PG). The control group (CG) consisted of 20 patients (n = 40 femurs; mean age of 29 years) in whom there was no increased FAV from the clinical standpoint. All of them underwent a torsional computed tomography of the lower limbs. FAV was measured according to Murphy´s method. A segmental analysis of FAV was performed using the lesser trochanter as a landmark. RESULTS: Significant differences in the total FAV (18.7 ± 5.52 vs. 42.46 ± 6.33; p < 0.001), the neck version (54.88 ± 9.64 vs. 64.27 ± 11.25; p = 0.0006) and the diaphysis version (- 36.17 ± 8.93 vs. - 21.81 ± 11.73; p < 0.001) were observed between the CG and the PG. The difference in the diaphyseal angle between CG and PG accounts for 60% of the total difference between healthy and pathological groups, while the difference between both groups in the angle of the neck accounts for 40%. CONCLUSION: In chronic AKP female patients with increased FAV, the two segments of the femur contribute to the total FAV, with a different pattern among patients and controls, being the compensation mechanism of the diaphysis much lower in the pathological femurs than in the controls.

Bone Grafting Options for Single-Level TLIF: So Many Options, What Is the Evidence?

BACKGROUND: This review seeks to investigate the clinically relevant bone graft materials in single-level transforaminal lumbar interbody fusion (TLIF) procedures as defined by (1) primary outcomes (ie, fusion rates and complication rates) and (2) patient-reported outcomes (ie, visual analog scale [VAS] and Oswestry disability index [ODI]). Because of the advantages in stimulating bone growth, autologous bone grafts such as the iliac crest bone graft (ICBG) have been the gold standard. Numerous alternatives to ICBG have been introduced. Understanding the risks and benefits of bone graft options is vital to optimizing patient care. METHODS: A PubMed search was performed for all clinical studies published between January 2008 and March 2023 that referenced the single-level TLIF procedure as well as one of the following grafts: autograft, allograft, bone morphogenetic protein (BMP), demineralized bone matrix, or mesenchymal stem cells (MSCs). Case studies and reports were excluded. RESULTS: Twenty-eight studies met the inclusion criteria. Studies from the PubMed search demonstrated similarly high fusion rates across nearly all graft materials, the lone exception being MSCs, which showed lower fusion rates. ICBG grafts experienced higher rates of postoperative graft site pain. The BMP graft material had high rates of radiculitis, heterogeneous ossification, and vertebral osteolysis. Patients saw an overall improvement in VAS and ODI scores with all graft materials. CONCLUSION: Local autografts and ICBG have been the most studied. Fusion rates during single-level TLIF were similar across all graft materials except MSCs. Patient-reported pain levels improved after TLIF surgery regardless of the type of grafts used. While BMP implants have shown promising benefits, they have introduced a new array of complications not normally seen in ICBG implants. The study is limited by the lack of evidence of certain graft materials as well as nonuniformity in metrics evaluating the efficacy of graft materials.

Lactate: an alternative pathway for the immunosuppressive properties of mesenchymal stem/stromal cells.

BACKGROUND: The metabolic reprogramming of mesenchymal stem/stromal cells (MSC) favoring glycolysis has recently emerged as a new approach to improve their immunotherapeutic abilities. This strategy is associated with greater lactate release, and interestingly, recent studies have proposed lactate as a functional suppressive molecule, changing the old paradigm of lactate as a waste product. Therefore, we evaluated the role of lactate as an alternative mediator of MSC immunosuppressive properties and its contribution to the enhanced immunoregulatory activity of glycolytic MSCs. MATERIALS AND METHODS: Murine CD4+ T cells from C57BL/6 male mice were differentiated into proinflammatory Th1 or Th17 cells and cultured with either L-lactate, MSCs pretreated or not with the glycolytic inductor, oligomycin, and MSCs pretreated or not with a chemical inhibitor of lactate dehydrogenase A (LDHA), galloflavin or LDH siRNA to prevent lactate production. Additionally, we validated our results using human umbilical cord-derived MSCs (UC-MSCs) in a murine model of delayed type 1 hypersensitivity (DTH). RESULTS: Our results showed that 50 mM of exogenous L-lactate inhibited the proliferation rate and phenotype of CD4+ T cell-derived Th1 or Th17 by 40% and 60%, respectively. Moreover, the suppressive activity of both glycolytic and basal MSCs was impaired when LDH activity was reduced. Likewise, in the DTH inflammation model, lactate production was required for MSC anti-inflammatory activity. This lactate dependent-immunosuppressive mechanism was confirmed in UC-MSCs through the inhibition of LDH, which significantly decreased their capacity to control proliferation of activated CD4+ and CD8+ human T cells by 30%. CONCLUSION: These findings identify a new MSC immunosuppressive pathway that is independent of the classical suppressive mechanism and demonstrated that the enhanced suppressive and therapeutic abilities of glycolytic MSCs depend at least in part on lactate production.

High-sensitivity whole-genome recovery of single viral species in environmental samples.

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. This work presents a method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A novel gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. Validation experiments using a sewage sample spiked with two known viruses demonstrate the method's efficacy. We achieve 100% recovery of the spiked-in SV40 (Simian virus 40, 5243bp) genome sequence with uniform coverage distribution, and approximately 99.4% for the larger HAd5 genome (Human Adenovirus 5, 35938bp). Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables targeted characterizations of rare viral species and whole-genome amplification of single genomes for accessing the mutational profile in single virus genomes, contributing to an improved understanding of viral ecology.

Brain network functional connectivity changes in patients with anterior knee pain: a resting-state fMRI exploratory study.

BACKGROUND: This study investigates the functional brain connectivity in patients with anterior knee pain (AKP). While biomechanical models are frequently employed to investigate AKP, it is important to recognize that pain can manifest even in the absence of structural abnormalities. Leveraging the capabilities of functional magnetic resonance imaging (fMRI), this research aims to investigate the brain mechanisms present in AKP patients. METHODS: Forty-five female subjects (24 AKP patients, 21 controls) underwent resting-state fMRI and T1-weighted structural MRI. Functional brain connectivity patterns were analyzed, focusing on pain network areas, and the influence of catastrophizing thoughts was evaluated. RESULTS: Comparing patients and controls, several findings emerged. First, patients with AKP exhibited increased correlation between the right supplementary motor area and cerebellum I, as well as decreased correlation between the right insula and the left rostral prefrontal cortex and superior frontal gyrus. Second, in AKP patients with catastrophizing thoughts, there was increased correlation of the left lateral parietal cortex with two regions of the right cerebellum (II and VII) and the right pallidum, and decreased correlation between the left medial frontal gyrus and the right thalamus. Furthermore, the correlation between these regions showed promising results for discriminating AKP patients from controls, achieving a cross-validation accuracy of 80.5%. CONCLUSIONS: Resting-state fMRI revealed correlation differences in AKP patients compared to controls and based on catastrophizing thoughts levels. These findings shed light on neural correlates of chronic pain in AKP, suggesting that functional brain connectivity alterations may be linked to pain experience in this population. RELEVANCE STATEMENT: Etiopathogenesis of pain in anterior knee pain patients might not be limited to the knee, but also to underlying alterations in the central nervous system: cortical changes might lead a perpetuation of pain. KEY POINTS: • Anterior knee pain patients exhibit distinct functional brain connectivity compared to controls, and among catastrophizing subgroups. • Resting-state fMRI reveals potential for discriminating anterior knee pain patients with 80.5% accuracy. • Functional brain connectivity differences improve understanding of pain pathogenesis and objective anterior knee pain identification.

Assessment of coagulation assays on Roche Cobas t711 analyzer: performance and clinical implications.

OBJECTIVES: We performed an analytical assessment of five coagulation tests [i.e. prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin time (TT) and D-dimer] on the Roche Cobas t711 analyzer and a comparison study with the methodology in use at our laboratory (i.e. Werfen ACL Top 750 analyzer), expanding the analysis to the clinical implications of Cobas t711 implementation. METHODS: Imprecision studies were performed following the Clinical and Laboratory Standards Institute (CLSI) H57 A:2008 guideline. Linearity of D-dimer and fibrinogen tests was analysed according to the CLSI EP06-A: 2003 recommendations. For method comparison, the results were analyzed using the Bland-Altman plot and Passing-Bablok regression. RESULTS: Imprecision met manufacturer claims for PT, aPTT and TT. D-dimer and fibrinogen tests showed a coefficient of variation (CV)% over manufacturer claims at certain concentration levels. Linearity ranges could not be verified. Comparison study revealed that results are not interchangeable for any test, a lower correlation for aPTT test and lower D-dimer results from Roche Cobas t711. CONCLUSION: The strength of this study relies on the analysis of the clinical implications of reporting Cobas t711 results compared to those obtained with the methodology in use at our laboratory. Different sensibility to factor deficiency, anticoagulant therapy and interferences might explain lower correlation rates obtained for the aPTT test. Different monoclonal antibodies used for D-dimer determination might explain the lower results obtained with the Cobas t711 analyzer. This aspect needs further studies given the relevance of D-dimer test to exclude thrombotic events and reinforces the need of harmonization in the haemostasis laboratory.

Central sensitization negatively influences the level of disability in female patients with anterior knee pain.

PURPOSE: To define the prevalence of Central Sensitization (CS) in patients with Anterior Knee Pain (AKP) and determine whether there is an association between CS and the magnitude of pain, disability, quality-of-life and psychological impairment. METHODS: The data of a total of 44 AKP female patients with a mean age of 27.7 years (15-50) recruited consecutively from hospital outpatient knee clinics were prospectively included in this study. The patients had no antecedents of knee trauma or surgery and no history of injury or disease of the nervous system. There were also 50 healthy female controls with a mean age of 26.1 years (16-46). CS was evaluated using the Central Sensitization Inventory (CSI). Quality-of-life was evaluated using the EuroQoL-5D questionnaire. Self-reporting of clinical pain intensity was obtained using the Visual Analogue Scale. The Kujala Knee Scale and IKDC form were used to evaluate disability. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Subscale (HAD). Kinesiophobia was measured with the Tampa Scale for Kinesiophobia (TSK-11) and catastrophizing by means of the Pain Catastrophizing Scale (PCS). RESULTS: Sixteen AKP patients (36%), and 2 (4%) of the healthy controls presented with central sensitization (p < 0.01). AKP patients with CS have a greater degree of disability based on the Kujala Scale and higher levels of anxiety and depression than AKP patients without CS. The score of AKP patients in the CSI correlated weakly with disability and quality of life and moderately with anxiety and depression. However, no association was seen between CSI score and pain intensity, nor with catastrophizing and kinesiophobia. A multivariate logistic regression analysis showed that only depression was statistically significant in the prediction of the presence of CS (odds ratio 1.45; 95% CI 1.07 to 1.96). CONCLUSIONS: AKP patients have a significantly higher prevalence of CS in comparison with what has been reported for the general population. This finding suggests the presence of altered pain modulation in a subgroup of AKP patients. LEVEL OF EVIDENCE: Level III.

Malnutrition in COVID-19 survivors: prevalence and risk factors.

BACKGROUND: Nutritional status is a critical factor throughout COVID-19 disease course. Malnutrition is associated with poor outcomes in hospitalized COVID-19 patients. AIM: To assess the prevalence of malnutrition and identify its associated factors in COVID-19 survivors. METHODS: Study cohort included 1230 COVID-19 survivors aged 18-86 attending a post-COVID-19 outpatient service. Data on clinical parameters, anthropometry, acute COVID-19 symptoms, lifestyle habits were collected through a comprehensive medical assessment. Malnutrition was assessed according to Global Leadership Initiative on Malnutrition (GLIM) criteria. RESULTS: Prevalence of malnutrition was 22% at 4-5 months after acute disease. Participants who were not hospitalized during acute COVID-19 showed a higher frequency of malnutrition compared to those who needed hospitalization (26% versus 19%, p < 0.01). Malnutrition was found in 25% COVID-19 survivors over 65 years of age compared to 21% younger participants (p < 0.01). After multivariable adjustment, the likelihood of being malnourished increased progressively and independently with advancing age (Odds ratio [OR] 1.02; 95% CI 1.01-1.03) and in male participants (OR 5.56; 95% CI 3.53-8.74). Malnutrition was associated with loss of appetite (OR 2.50; 95% CI 1.73-3.62), and dysgeusia (OR 4.05; 95% CI 2.30-7.21) during acute COVID-19. DISCUSSION: In the present investigation we showed that malnutrition was highly prevalent in a large cohort of COVID-19 survivors at 4-5 months from acute illness. CONCLUSIONS: Our findings highlight the need to implement comprehensive nutritional assessment and therapy as an integral part of care for COVID-19 patients.

Ultrasound-Based Recovery of Anti-Inflammatory and Antimicrobial Extracts of the Acidophilic Microalga Coccomyxa onubensis.

In the present study, the recovery of valuable molecules of proven anti-inflammatory and antimicrobial activity of the acidophilic microalga Coccomyxa onubensis (C. onubensis) were evaluated using green technologies based on ultrasound-assisted extraction (UAE). Using a factorial design (3 × 2) based on response surface methodology and Pareto charts, two types of ultrasonic equipment (bath and probe) were evaluated to recover valuable compounds, including the major terpenoid of C. onubensis, lutein, and the antimicrobial activity of the microalgal extracts obtained under optimal ultrasound conditions (desirability function) was evaluated versus conventional extraction. Significant differences in lutein recovery were observed between ultrasonic bath and ultrasonic probe and conventional extraction. Furthermore, the antimicrobial activity displayed by C. onubensis UAE-based extracts was greater than that obtained in solvent-based extracts, highlighting the effects of the extracts against pathogens such as Enterococcus hirae and Bacillus subtilis, followed by Staphylococcus aureus and Escherichia coli. In addition, gas chromatography-mass spectrometry was performed to detect valuable anti-inflammatory and antimicrobial biomolecules present in the optimal C. onubensis extracts, which revealed that phytol, sterol-like, terpenoid, and even fatty acid structures could also be responsible for the antibacterial activities of the extracts. Moreover, UAE displayed a positive effect on the recovery of valuable molecules, improving biocidal effects. Our study results facilitate the use of green technology as a good tool in algal bioprocess engineering, improving energy consumption and minimizing environmental impacts and process costs, as well as provide a valuable product for applications in the field of biotechnology.

Association of the Stroke Ready Community-Based Participatory Research Intervention With Incidence of Acute Stroke Thrombolysis in Flint, Michigan.

Importance: Acute stroke treatment rates in the US lag behind those in other high-income nations. Objective: To assess whether a hospital emergency department (ED) and community intervention was associated with an increased proportion of patients with stroke receiving thrombolysis. Design, Setting, and Participants: This nonrandomized controlled trial of the Stroke Ready intervention took place in Flint, Michigan, from October 2017 to March 2020. Participants included adults living in the community. Data analysis was completed from July 2022 to May 2023. Intervention: Stroke Ready combined implementation science and community-based participatory research approaches. Acute stroke care was optimized in a safety-net ED, and then a community-wide, theory-based health behavior intervention, including peer-led workshops, mailers, and social media, was conducted. Main Outcomes and Measures: The prespecified primary outcome was the proportion of patients hospitalized with ischemic stroke or transient ischemic attack from Flint who received thrombolysis before and after the intervention. The association between thrombolysis and the Stroke Ready combined intervention, including the ED and community components, was estimated using logistic regression models, clustering at the hospital level and adjusting for time and stroke type. In prespecified secondary analyses, the ED and community intervention were explored separately, adjusting for hospital, time, and stroke type. Results: In total, 5970 people received in-person stroke preparedness workshops, corresponding to 9.7% of the adult population in Flint. There were 3327 ischemic stroke and TIA visits (1848 women [55.6%]; 1747 Black individuals [52.5%]; mean [SD] age, 67.8 [14.5] years) among patients from Flint seen in the relevant EDs, including 2305 in the preintervention period from July 2010 to September 2017 and 1022 in the postintervention period from October 2017 to March 2020. The proportion of thrombolysis usage increased from 4% in 2010 to 14% in 2020. The combined Stroke Ready intervention was not associated with thrombolysis use (adjusted odds ratio [OR], 1.13; 95% CI, 0.74-1.70; P = .58). The ED component was associated with an increase in thrombolysis use (adjusted OR, 1.63; 95% CI, 1.04-2.56; P = .03), but the community component was not (adjusted OR, 0.99; 95% CI, 0.96-1.01; P = .30). Conclusions and Relevance: This nonrandomized controlled trial found that a multilevel ED and community stroke preparedness intervention was not associated with increased thrombolysis treatments. The ED intervention was associated with increased thrombolysis usage, suggesting that implementation strategies in partnership with safety-net hospitals may increase thrombolysis usage. Trial Registration: ClinicalTrials.gov Identifier: NCT036455900.

Spent coffee grounds as feedstock for the production of biosurfactants and the improved recovery of melanoidins.

Spent coffee grounds (SCG) are wastes generated in high amounts worldwide. Their composition makes them a promising feedstock for biotechnological processes. Here we show that the production of the biosurfactant surfactin by submerged culture of a Bacillus subtilis strain growing on SCG is possible, reaching concentrations up to 8.8 mg/L when using SCG at 8.3 g/L in the medium. In addition, we report a synergy between the production of surfactin and the recovery of melanoidins, an added-value compound already present in SCG. More specifically, the concentration of melanoidins in the culture medium increased between 2.1 and 2.5 times thanks to the presence of the B. subtilis in the culture. Furthermore, we have observed a strong interaction between surfactin and melanoidin aggregates through dynamic light scattering measurements, and that both of them can be co-purified with an acid precipitation. We have also characterized the interfacial and antioxidant properties of the cell-free supernatant and surfactin extract, as well as the distribution of the congeners of the biosurfactant. Altogether, this work describes a promising approach to obtain biosurfactants and antioxidant molecules in a single operation, which can be used to design several new formulations of interest for bioremediation, amendment of soils, food and cosmetics.

Exploring Social Determinants of Health in Healthy Aging Among Older Adults: A Qualitative Study.

BACKGROUND: The U.S. population is aging and diversifying. Older Black Americans comprise the largest racial minority group and experience greater disability than White Americans. OBJECTIVES: Within a long-standing, community-based research partnership, we explored the determinants of healthy aging in Flint Michigan, a low-income, predominantly Black American community recovering from a water crisis. METHODS: Focus groups were conducted among older adults residing in Flint, Michigan. A grounded theory approach and constant comparison method was utilized for data analysis. RESULTS: Five focus groups were conducted with 49 total participants. We identified four themes that impacted healthy aging: economic instability, health care access and quality, neighborhood and built environment, and social and community context. Economic instability heavily influenced the other themes. CONCLUSIONS: Economic instability is a barrier to healthy aging. As a result, we are testing an innovative cross-sector partnership combining older adult affordable housing and health care.