PLANT TESTING MAGNETIC CONDITIONING ON KENNECOTT'S Cu-Mo PORPHYRY ORE

Over it's more than 100-year history, the Kennecott operation has often been at the forefront of innovation;driven by the demands of the lower grade ore-body and the higher costs of operating in the US where wages are generally higher and regulation more restrictive. One way of reducing operating costs in c/lb is to increase the lbs produced at minimal cost. Despite the relatively coarse grind at Kennecott - about 30% >150μm, approximately 20% of the Cu lost to tail is liberated chalcopyrite in the <20μm fraction, and about 30%-40% in the <37μm fraction. In 2020 Kennecott undertook a detailed plant scale test of the magnetic aggregation technology to increase copper recovery by reducing fine copper losses. A paired statistical plant test of magnetic conditioning on one rougher line showed a 1.12% increase in Cu recovery to 97% statistical confidence. The next challenge, unforeseen at the start of the project, was the fabrication and transportation to site of the equipment for the three remaining rougher rows, during the severe supply-chain constraints of the Covid pandemic in 2021. This resulted in delays and unforeseen costs as world-wide transportation became chaotic, particularly transportation via west coast USA. Nevertheless, the project was completed and commissioned, with only minor delays and cost increases, due to a flexible approach to overcoming the hurdles encountered. Copyright © 2023 by SME.

Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards.

BACKGROUND: Endothelial dysfunction, assessed by flow-mediated dilation (FMD), is related to poor prognosis in patients with COVID-19 pneumonia (CP). In this study, we explored the interplay among FMD, NADPH oxidase type 2 (NOX-2) and lipopolysaccharides (LPS) in hospitalised patients with CP, community acquired pneumonia (CAP) and controls (CT). METHODS: We enrolled 20 consecutive patients with CP, 20 hospitalised patients with CAP and 20 CT matched for sex, age, and main cardiovascular risk factors. In all subjects we performed FMD and collected blood samples to analyse markers of oxidative stress (soluble Nox2-derived peptide (sNOX2-dp), hydrogen peroxide breakdown activity (HBA), nitric oxide (NO), hydrogen peroxide (H2O2)), inflammation (TNF-α and IL-6), LPS and zonulin levels. RESULTS: Compared with controls, CP had significant higher values of LPS, sNOX-2-dp, H2O2,TNF-α, IL-6 and zonulin; conversely FMD, HBA and NO bioavailability were significantly lower in CP. Compared to CAP patients, CP had significantly higher levels of sNOX2-dp, H2O2, TNF-α, IL-6, LPS, zonulin and lower HBA. Simple linear regression analysis showed that FMD inversely correlated with sNOX2-dp, H2O2, TNF-α, IL-6, LPS and zonulin; conversely FMD was directly correlated with NO bioavailability and HBA. Multiple linear regression analysis highlighted LPS as the only predictor of FMD. CONCLUSION: This study shows that patients with COVID-19 have low-grade endotoxemia that could activate NOX-2, generating increased oxidative stress and endothelial dysfunction.

Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

The Impact of Post COVID Rehabilitation on the Level of Systemic Inflammation in Patients with Post COVID Syndrome

Rationale: Low-grade inflammation is a risk factor for adverse cardiovascular events including death from cardiovascular disease. Cardiovascular events are one of the most common manifestations of post covid syndrome, impacting the mortality in the post covid period. Methods: 260 post covid patients age 48-66 years were examined. All patients underwent rehabilitation in a Crimean sanitorium, that included climatologic therapy on the southern coast of Crimea;dietary therapy;pharmacologic therapy, and if necessary, breathing exercises using a variety of methods of respiratory therapy. The patients were examined for C-reactive protein (CRP) level in peripheral blood before and after the sanatorium rehabilitation. Results: The level of CRP of the patients who underwent rehabilitation did not differ significantly (p>0.05) from the initial values obtained on the day of admission to the rehabilitation center. At admission and upon discharge the CRP values corresponded to the lower limit of the levels characteristic of low-grade inflammation ranging from 3 mg/l to 10 mg/l). Conclusions: The currently available methods of physical rehabilitation of post covid patients as implemented in a Crimean sanitorium did not provide a reduction of the level of systemic inflammation as assessed by CRP determination. New less traditional approaches may be needed to reduce inflammation in post covid syndrome patients who are at risk for cardiovascular adverse consequences.

Analysis on the energy efficiency, thermal performance and infection intervention characteristics of interactive cascade ventilation (ICV)

Floor radiation (FR) is one of the widely used heating modes in winter. However, the widespread and high outbreak of Corona Virus Disease 2019 (COVID-19) has made the disadvantage of floor radiation that lacks fresh air and air movement exposed as a deficiency. To seek a heating mode that can realize a comfortable and healthy indoor environment with low cost, the interactive cascade ventilation (ICV) coupling with multiple low-grade sources was proposed in this study. Energy efficiency, thermal comfort and air quality were investigated by comparing with FR and floor radiation with mixing ventilation (FRMV). The results showed that by elevating the same indoor temperature, ICV can reduce indoor heat transfer by 28.41% and 30.94% than FR and FRMV, respectively. And ICV also presented the highest system COP by introducing multiple low-grade sources. In terms of thermal comfort, the indoor environment served by ICV was closer to thermal neutrality, and the subjective thermal comfort can also be enhanced by 10% and 8% relative to FR and FRMV. The CO2 test results indicated that by introducing the ICV, indoor air quality can be improved by 36.68% and 61.45% over FR and FRMV with the contaminant removal rate significantly accelerated. During the pandemic, ICV can reduce the COVID-19 infection rate by 9.6% and 55.5% within 8 h and 30 min compared with FRMV. The conclusions obtained in this paper can provide new ideas for designing air conditioning systems in the epidemic and the context of carbon reduction.

Evaluating the Relationship Between Obesity and the Humoral Immune Response to COVID-19 Vaccines

Background. The pro-inflammatory state associated with obesity leads to B- and T-lymphocyte dysfunction that may lead to an inadequate immune response to natural infection and vaccination. Preliminary studies, conducted outside of the US, involving multiple COVID-19 vaccines indicate that obesity may impact antibody response. The objective of this study was to evaluate the role of inflammatory status as a mediator in the relationship between obesity and COVID-19 vaccine immune response in a predominantly African-American population. Methods. This cross-sectional analysis involved 54 participants 18 years of age who had completed the primary dosing schedule and booster for Novavax's recombinant COVID-19 vaccine, NVX-CoV2373. Weight, height, and waist circumference (WC) measurements were taken. Medical history including COVID-19 vaccination and known COVID-19 infection were obtained. Blood samples were taken for measurement of c-reactive protein (CRP) and anti-SARS-CoV-2 spike protein IgG levels. Spearman correlation coefficient was used to assess the presence of a relationship between BMI and CRP, WC and CRP, CRP and spike protein IgG, BMI and spike protein IgG, and finally, WC and spike protein IgG. Mediation analysis was used to evaluate the moderating effect of plasma CRP on the relationship between WC and spike protein IgG while adjusting for suspected confounders. Statistical significance was defined as p < .05. Results. There was an expected positive relationship betweenWCand CRP, (rho = 0.37, p< .05). CRP and spike protein IgG trended towards a weak, negative relationship (rho= -0.13, p > .05). WC and BMI both trended towards a positive relationship with anti-SARS-CoV-2 spike protein IgG (rho = 0.29 and 0.15, respectively, p >.05). The mediation analysis showed that WC positively influenced spike protein IgG (p< .05), and this effect was not mediated by CRP. Conclusion. Inflammation may be negatively associated with antibody response to COVID-19 vaccines. WC and antibody response may be positively related in NVX-CoV2373 recipients, in spite of chronic low-grade inflammation. Further research is needed to fully characterize the impact of obesity on COVID-19 vaccine immunogenic responses.

The effects of low-grade inflammation and sleep loss on model-based and model-free control: Results of an experimental double hit model

Methods: In an ongoing study, we recruited 46 individuals who complete three sessions: sleep loss (2 nights of 4h in bed), normal sleep (2 nights of 9h in bed) (within-subjects), and a low-grade inflammation condition (COVID-19 vaccination) preceded by either sleep loss or normal sleep (between subjects). Blood samples were taken (not analyzed), sickness symptoms were assessed (SicknessQ with 10-point scale), and model-based and model-free control was quantified (a sequential decision task). Result(s): Sickness symptoms were highest after vaccination with sleep loss (M = 34.6), followed by vaccination with normal sleep (M = 24.3) and sleep loss (M = 23.8), and normal sleep only (M = 15.3). Model-free control increased in the vaccine as compared to the non-vaccine condition (b = 0.23, 95% CI 0.10, 0.37, p <.001), most clearly in the normal sleep condition. Model-based control decreased after sleep loss versus normal sleep (reward + common: b = -0.47, 95% CI -0.67, -0.28, p <.001, non-reward + rare: b = -0.43, 95% CI -0.63, -0.18, p <.001), which was not modulated by vaccination. Conclusion(s): These results suggest that low-grade inflammation and sleep loss independently attenuate behavioral control towards a cognitively less expensive but inflexible decision style. The potential role of sleep-immune pathways in model-based and model-free control will be discussed. Copyright © 2022

Experimental sleep loss and low-grade inflammation attenuate behavioural control towards a cognitively less expensive but inflexible decision style

Introduction: Behavioural control arises from a balance between model-based and model-free behaviour. Model-based behaviour is cognitively costly but enables adaptation to changes in the environment. In contrast, model-free control is fast, cognitively inexpensive, but inflexible. Overreliance on model-free control and/or reduced model-based control is found across various mental health conditions, suggesting that these modes of control may be influenced by common trans diagnostic processes. Since insufficient sleep and low-grade inflammation are highly common in mental ill-health, we assessed how they by themselves and in combination influence behavioural control Methods: In an ongoing study, we recruited 46 individuals who completed three sessions: Sleep loss (2 nights of 4 h in bed), normal sleep (2 nights of 9 h in bed) (within-subjects), and a low-grade inflammation condition (COVID-19 vaccination) preceded by either sleep loss or normal sleep (between subjects). Blood samples were taken (not analysed), sickness symptoms were assessed using the SicknessQ, and model-based and model-free control was quantified (using a sequential decision task). Result(s): Sickness symptoms were highest after vaccination with sleep loss (M = 34.6), followed by vaccination with normal sleep (M = 24.3) and sleep loss (M = 23.8), and normal sleep only (M = 15.3). Modelfree behaviour increased in the vaccine as compared to the nonvaccine condition (b = 0.23, 95% CI 0.10, 0.37, p < 0.001). Modelbased control decreased after sleep loss versus normal sleep (reward + common: B = -0.47, 95% CI -0.67, -0.28, p < 0.001, nonreward + rare: B = -0.43, 95% CI -0.63, -0.18, p < 0.001), which was not modulated by vaccination. Conclusion(s): These results suggest that sleep loss and low-grade inflammation independently attenuate behavioural control towards a cognitively less expensive but inflexible decision style.

IMMUNO-PSYCHIATRY AND INFLAMMATION

: The discovery that the immune system can influence brain function and structure has profoundly changed the landscape of psychiatry. Repeated report of association of pro-inflammatory cytokines with major psychiatric disorders led to exploration of the causes and consequences of this inflammatory background. This low-grade inflammation has been shown to be the consequence of interaction between environmental factors such as infections, stress, pollution, unhealthy lifestyle with immune-genetic background. Association with particular immune-genetic variants of Toll-like receptor genes possibly explain diminished response to infections (TLR, NOD), association with mitochondrial genes contribute to maintenance of inflammation, while association with particular HLA haplotypes explains induction of auto-immune phenomena and/or exaggerated synaptic pruning. For example, association with the complement genes can induce abnormal pruning and microglial activation thereby increasing the risk of neurodevelopmental disorders such as early onset schizophrenia. In the context of the SARS-Cov2 pandemic, increased severity of COVID-19 in psychiatric patients is probably due to their reduced ability to fight infection. Systemic inflammation and persistent infections induce different pathways paving the way to biomarker-guided personalized medicine. One of the best examples is the identification of “autoimmune psychosis” defined by presence of anti-neuronal antibodies that has been confounded for long with atypical, mild, or attenuated forms of autoimmune encephalitis. Persistent infections are associated to activation of Human endogenous retrovirus (HERV). Systemic inflammation induced by microbial infection or psychosocial factors can also be at the origin of the activation of human endogenous retrovirus. Inflammation is also known to be associated with gut dysbiosis and disturbance of the integrity of the digestive barrier leading to behavioral abnormalities. One last example can be found in the immune-metabolic abnormalities that pave the way to metabolic syndrome associated with psychiatric disorders. Although many aspects of the complex relationship between immunity and brain function are not yet fully elucidated, the findings that have accumulated so far have transformed our understanding of psychiatric disorders and favored the consideration of other possible cellular and molecular targets for their treatment than just alterations in neuronal transmitters. Disclosure: Nothing to disclose.

Understanding mental stress and skin aging connection among dermatologists and psychologists through real world evidence

Preaging is an emerging concept in China whereby young women are looking for skin aging solutions. Among the intrinsic and extrinsic causes of skin aging, mental stress was highlighted as a possible cause of preaging in young women. The COVID-19 pandemic has further impacted the mental well-being of the younger generation, with 44% of Asian women aged 18 to 34 under poor mental well-being based on WHO-5. While 76.5% of dermatologists agreed that there is a strong connection between stress and skin aging, there is limited evidence on the pathophysiology. The aim of this research is to explore how clinicians understand the impact of stress and the biologic pathways connecting stress and skin aging. A quantitative survey with 60 dermatologists and 60 psychologists from China and Japan was conducted to assess the link between stress and skin aging. Overall, 69.2% of both health care professionals agree that psychological stress has a significant link to skin aging. Three meta-themes were perceived by clinician as possible pathways connecting psychological stress and skin aging, including stress hormone, inflammation, and overactive immune system. While all health care professionals have heard of inflammaging, only 52% are very familiar with the concept. Both groups agree that unresolved acute inflammatory response can accelerate skin aging. Surprisingly, a significant difference was observed in that psychologists believe more strongly than dermatologists that chronic low-grade inflammation accelerates skin aging. This study highlights the need for further fundamental research, which could help clinicians provide appropriate recommendations for patients under psychological stress.

OA Biology

Purpose: The field of osteoarthritis (OA) biology is rapidly evolving and brilliant progress has been made this year as well. Methods: Landmark studies of OA biology published in 2021 and early 2022 were selected through PubMed searches and classified by their molecular mechanisms, and it was largely divided into the intra-cellular mechanisms and the inter-compartment or inter-cellular interaction in OA progression. Results: The intra-cellular mechanisms involving OA progression included 1) Piezo1/TRPV4-mediated calcium signaling, 2) low grade inflammation by TLR-CD14-LBP complex and IKKβ-NFkB signaling, 3) PGRN/TNFR2/14-3-3ε/Elk-1 anabolic cascade, 4) G protein-coupled receptor (GPCR) signaling, 5) mechanical loading-cilia/Ift88-hedgehog signaling, 6) mitochondrial fission by ERK1/2-DRP1 pathway, and 7) hypoxia-DOT1L-H3K79 methylation pathway. The studies on inter-compartment or inter-cellular interaction in OA progression included the following subjects: 1) the anabolic role of Lubricin, a proteoglycan from superficial zone cells, 2) osteoclast-chondrocyte interaction via exosomal miRNA and sphingosine 1-phosphate (S1P), 3) αV integrin-mediated TGFβ activation by mechanical loading, 4) TGFβ-mediated suppression of sclerostin in osteocytes, 5) catabolic role of Flightless I as a DAMPs-triggering molecule, and 6) catabolic role of paracrine signaling from fat. Conclusions: Despite the disastrous Covid-19 pandemic situation, many outstanding studies have expanded the boundary of OA biology. They give us not only critical insight on pathophysiology, but also clue for the treatment of OA.

Persistent Fever and Positive PCR 90 Days Post-SARS-CoV-2 Infection in a Rituximab-Treated Patient: A Case of Late Antiviral Treatment.

Background: Persistent fever after SARS-CoV-2 infection in rituximab-treated patients has been reported. Due to reduced sensitivity in conventional sampling methods and unspecific symptoms in these patients, distinguishing between low-grade viral replication or hyperinflammation is challenging. Antiviral treatment is recommended as prophylactic or early treatment in the at-risk population; however, no defined treatment approaches for protracted SARS-CoV-2 infection exist. Results: We present a case of 96 days of persistent fever and SARS-CoV-2 infection in a patient receiving B cell depletion therapy for multiple sclerosis. Migratory lung infiltrates and positive PCR tests from serum (day-58 post infection) and lower airways (day-90 post infection) confirmed continuous viral replication. The dominant symptoms were continuous high fever, dyspnea and mild to moderate hypoxemia, which never developed into severe respiratory failure. The patient was hospitalized three times, with transient improvement after late antiviral treatment and full recovery 6 months post-rituximab infusion. Conclusions: A strategy for securing samples from lower airways and serum should be a prioritization to strengthen diagnostic certainty in immunocompromised patients. B-cell-deprived patients could benefit from late treatment with SARS-CoV-2-specific monoclonal antibodies and antivirals. Importantly, increased intervals between immunosuppressive therapy should be considered where feasible.

ALTERED GUT MICROBIOTA and RESPIRATORY DYSFUNCTION 3 MONTHS after SEVERE COVID-19

Background: Although COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and associate with long-term respiratory dysfunction is unknown. Methods: From the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition (Fig. 1), with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2-(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and were associated with low-grade inflammation and respiratory dysfunction after three months. Figure 1 legend: Gut microbial composition in patients with respiratory dysfunction at the three-month follow-up (DLCO<="" div=""> Conclusion: Respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

Association of Low-Grade Glioma Diagnosis and Management Approach with Mental Health Disorders: A MarketScan Analysis 2005-2014.

Low-grade gliomas (LGGs) comprise 13-16% of glial tumors. As survival for LGG patients has been gradually improving, it is essential that the effects of diagnosis and disease progression on mental health be considered. This retrospective cohort study queried the IBM Watson Health MarketScan® Database to describe the incidence and prevalence of mental health disorders (MHDs) among LGG patients and identify associated risk factors. Among the 20,432 LGG patients identified, 12,436 (60.9%) had at least one MHD. Of those who never had a prior MHD, as documented in the claims record, 1915 (16.7%) had their first, newly diagnosed MHD within 12 months after LGG diagnosis. Patients who were female (odds ratio (OR), 1.14, 95% confidence intervals (CI), 1.03-1.26), aged 35-44 (OR, 1.20, 95% CI, 1.03-1.39), and experienced glioma-related seizures (OR, 2.19, 95% CI, 1.95-2.47) were significantly associated with MHD incidence. Patients who underwent resection (OR, 2.58, 95% CI, 2.19-3.04) or biopsy (OR, 2.17, 95% CI, 1.68-2.79) were also more likely to develop a MHD compared to patients who did not undergo a first-line surgical treatment. These data support the need for active surveillance, proactive counseling, and management of MHDs in patients with LGG. Impact of surgery on brain networks affecting mood should also be considered.

Preliminary results of a complex program: Care for metabolic state of musculoskeletal system-a key to long-life independence in patients with osteoporosis and osteopenia

Objective: Ever since the times of ancient physicians and surgeons like Sushruta (600 BC) or Hippocrates (400 BC), it is clear that physical development of individuals with sedentary lifestyle is different from the one of the physically active individuals. Only after the year 2000, with the first discovery of causality of IL-6 and muscular movement, an intensive study of this problematics has begun. Currently, there are about 600 known operations (myokins) that are interrelated with muscle functions. Muscular tissue interrelates with others mechanistically, but it also forms humoral harmony in which the muscular tissue has a dominant and determining role. This phenomenon is relevant for pathophysiology of chronical low-grade inflammation, muscle loss, origin and development of noncommunicable diseases. These cause approx. 75% of deaths in population. Solution of this problem has been considerably affecting cost-effectivity in the health care system today and thus the state economy as well. Therapeutic recommendations together with the whole health care strategy need to be adjusted according to the above mentioned findings, including the patients with osteoporosis and osteopenia. There are, so far, no known suitable medicaments which would be used for solving problematics of muscular loss. This is a reason why more attention needs to be paid to the recommended physical regime (150 min/week, according to WHO) and dietary regime (basic diet + proteins). We have built a complex diagnostic and therapeutic program for our patients. Definition of pathological values follows EWGSOP and WHO. Methods: Patient cohorts: Osteoporosis 60-70 y, 70-80 y, osteopenia 60- 70 y and 70-80 y. Control group for osteopenia 60-80 y. We followed information about the control group during the COVID-19 time period, particularly their physical activity regime. 1) Instructions for patients used to be delivered in a form of lectures for different age groups. Now, during the COVID-19 time period, instructions are provided individually. 2) SarQol (Sarcopenia and Quality of Life) questionnaire (Beaudart 2015). Czech version used with agreement from sarqol.org. Assessment is now done individually only. 3) Measuring hand-grip is standardised according to Southampton protocol with a dynamometer Jamar. Values of 20 kg are found pathological (female values). 4) Determination of BMI, according to WHO, the border figure is 25 or 30 kg/m2 . 5) DXA method determination of selective muscle index as a measure for muscle mass. ALM/Ht2 for age above 60 y, border value for sarcopenia is ≤5.45 kg/m2 . 6) From laboratory examinations we aimed at IL-6 and CRP(hs) - these are not a subject of this report. Results: Conclusion: We have been running a physical activity and dietary program for our patients for more than 2 y. Physical activity is aimed at 150 min/week (WHO) and basic diet aims at the Mediterranean type + protein saturation, considerable stress is given to whey proteins enriched with Leucin. Patients have been instructed. Due to adherence to this regime we are able to report on statistically relevant changes in muscle power and also in complex muscle mass, even during the current pandemic situation. (Table Presented).

Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study.

OBJECTIVE: Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. METHODS: Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. RESULTS: We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4-5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10-17-fold increased risk of prevalent PCS. CONCLUSIONS: The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

Was it COVID19 or the vaccine a rare case of SARS-COV2 infection or post-vaccine triggered flare in juvenile dermatomyositis

Introduction: Vaccines and infection can cause flares of inflammatory conditions. Objectives: We describe a rare, rapid flare of Juvenile Dermatomyositis (JDM) preceded by confirmed Sars-Cov2 antibodies (asymptomatic infection or first vaccination). Methods: Data was extracted from electronic medical records and a literature review undertaken. Results: We present a 16 year old female of Bangladeshi origin with JDM diagnosed August 2019 (CK 29691, CMAS 23;Mi-2b, Ku, Mi-2a positive). On a background of suboptimal control with low grade inflammation (CK 659;CMAS 51) medications were altered in May 2020 adding Adalimumab and Mycophenolate Mofitil (MMF), to Methotrexate and Intravenous Immunoglobulin (IVIG). CK rose in August 2020 (15969). IVIG continued and physiotherapy input increased. After a stable 5 months (CK 100-300), CK grew to 2307 but as CMAS remained 50 treatment was not altered. Four weeks prior (Jan 2021) the patient received their first dose of Pfizer SARS-CoV2 vaccination. A family member was confirmed to be COVID-19 positive 8 weeks prior and the family isolated together. Our patient did not report any known COVID-19 symptoms. In March 2021 she presented with a 4 day history of acute active inflammation as demonstrated by malaise, increased rash, muscle pain and reduced function (CMAS 3, CK 52848). She was admitted for Multidisciplinary management of an acute flare and found to be SARS-CoV2 IgG positive consistent with prior infection. Adalimumab and MMF were swopped with tacrolimus alongside intravenous methylprednisolone, oral prednisolone and physiotherapy. CMAS scores remained considerably low (5) over the following 6 weeks, with a rapid rise (34) at week 7 with the patient discharged home. Literature review has identified a case of Anti-MDA5 JDM increased interstitial lung disease associated with active SARS-CoV2 infection1. Similarly there is a case presentation of Macrophage Activation Syndrome in Systemic Onset Juvenile Idiopathic Arthritis temporally associated with SARS-CoV2 infection2. There are no reported cases of vaccine mediated hyperinflammation of muscle or skin disease in JDM or Paediatric Inflammatory Multisystem Syndrome Temporally associated with COVID-19 (PIMSTS)3. Conclusion: This was a rare case of a rapid deterioration in function and hyperinflammation at a time of PIMSTS and other similar reactions in adolescents with Rheumatic diseases. We hypothesise that this such case may have been triggered by recent asymptomatic COVID-19 infection or following SARS-Cov2 vaccination.

Epithelial-Myoepithelial Carcinoma of the Minor Salivary Glands: Case Series with Comprehensive Review.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor that is histologically characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells, which is especially uncommon in the minor salivary glands (MSG). Because of its histologic variety, complexity, and heterogeneity, it is sometimes challenging to make the accurate diagnosis. Here, we report a literature review of EMC of the MSGs with our experience of two cases. Incisional biopsy was suggestive of pleomorphic adenoma in Case 1 and pleomorphic adenoma or a low-grade salivary gland carcinoma in Case 2. Both cases were performed intraoral tumor resection, and they have good postoperative courses and are alive with no evidence of local recurrence or metastasis at 31 and 16 months, respectively. Considering that the anatomy, structure, and size of salivary glands are quite different from MSGs, it might be difficult to predict EMCs of the MSG similarly to EMCs of the major salivary glands. This comprehensive review also reports the features of EMC of the MSG cases and the trends of diagnosis and discusses treatment strategy.