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Xiaoting Yang,1 Zuxing Feng,2 Mei Cai1 1Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, People’s Republic of China; 2Department of Psychiatry, The Psychiatry Hospital of Yunnan, Kunming, Yunnan, 650224, People’s Republic of ChinaCorrespondence: Mei Cai, Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Yunnan-Myanmar Avenue, Kunming, Yunnan, 650101, People’s Republic of China, Tel +86 13888532488, Email caimei5867@163.comObjective: Pro-inflammatory cytokines mediate the course of rosacea, anxiety, and depression through various means such as immunity and inflammation. This study aims to further explore the relationship between rosacea, anxiety, and depression through changes in the levels of pro-inflammatory cytokines.Methods: 280 rosacea patients were included in the rosacea group, divided into: rosacea without mental disorders, rosacea with anxiety, rosacea with depression, and rosacea with combined anxiety and depression. The mental control group included 210 anxiety and depression patients, divided into: anxiety, depression, and combined anxiety and depression. The healthy control group consisted of 70 healthy individuals. Serum specimens were collected and ELISA was used to detect major pro-inflammatory cytokines. CEA, IGA, GFSS, RosaQoL, HAMA, and HAMD-24 were used for the diagnosis and severity assessment of rosacea and anxiety and depression.Results: This study primarily used the Chi-Square test, Kruskal–Wallis H-test, generalized linear model, and binary logistic regression to evaluate the data. IL-1β, IL-17, and IL-8 levels in rosacea patients and anxiety/depression patients were higher than those in the healthy population (P< 0.001), and TNF-α levels in rosacea patients were higher than those in the healthy population (P< 0.001). There was an interaction between rosacea, anxiety, and depression in terms of IL-1β, IL-17, and IL-8 levels (P< 0.001). Elevated levels of IL-1β, IL-17, and IL-8 are positively correlated with anxiety and depression in rosacea (all P

IntroductionAccumulating evidence has supported that gut microbiota and metabolite profiles play indispensable roles in the pathogenesis of colorectal cancer (CRC), which ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide. However, alterations in tumoral or circulating microbiomes in CRC remain incompletely understood. It has been well-documented that tissue or serum microbiomes with low microbial biomass could be screened by use of 2bRAD sequencing for microbiome (2bRAD-M) at the species resolution.MethodsIn order to validate the microbial biomarkers distinguishing CRC and the variations in microorganisms present in serum and tumors, we performed 2bRAD-M to characterize the microbiomes in serum and cancer tissues of CRC patients with and without lymph node or liver metastasis.ResultsThe composition of dominated microbiota in serum was different from that of tissue samples, while the microbial community composition of tumors was similar to that of the tumor-adjacent tissues. The analysis of α-diversity and β-diversity has revealed notable variations in serum microbiota diversities in CRC patients, particularly those with liver metastasis. Multiple CRC-specific microbial species, such as Moraxella A cinereus, Flavobacterium sp001800905, and Acinetobacter albensis, were identified in serum. Complicated functions and KEGG pathways were also confirmed in CRC according to the metastasis status.DiscussionThis study has found significant alterations in the microbial compositions and diversities in CRC and CRC-specific microbial species in both circulation and cancer tissues, which may serve as promising biomarkers for the screening, diagnosis and prognosis prediction of CRC. In particular, CRC-specific bacterial taxa are promising markers, holding transformative potentials in establishing personalized screening and risk stratification, refining much earlier non-invasive diagnostic approaches, and enhancing diagnostic sensitivity.

Introduction. Despite the significant advances in the pharmacotherapy of cardiovascular diseases, the increasing prevalence of heart failure (HF) and its poor prognosis constitute one of the leading medical problems worldwide. The complex pathophysiology of HF involves the alterations in the peripheral circulation, particularly the development of endothelial dysfunction (ED). The deepening of understanding the pathology of ED and the spectrum of pharmacological implications, involving its certain pathophysiological aspects, could favor the optimization of the personalized approach to the management of such challenging HF patients. Aim: to provide a literature review of the current data on the alterations in peripheral circulation in HF with the focus on ED, and to outline possible pharmacological implications involving certain pathophysiological aspects of ED in HF patients. Material and methods. The thematic scientific papers, published predominantly during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis. Results and discussion. Currently, the ED considered as a stage of a specific continuum, which is initiated in the form of «activation» of the endothelium, and moves through the stage of its actual «dysfunction» to the stage of endothelial «damage». Taking into account the important pathogenetic and prognostic significance of ED in HF, the endothelium is considered as a target of various pharmacological influences, including renin-angiotensin-aldosterone inhibitors and statins. Among the modern approaches to pharmacological treatment of HF, the correction of reduced nitric oxide (NO) bioavailability by modulating the «NO-soluble guanylate cyclase-cyclic guanosine monophosphate» signaling pathway is a perspective option in terms of preventing the occurrence and progression of ED. Conclusion. The deepening of knowledge about the pathophysiological features of ED in HF allows both to improve the understanding of the pharmacodynamic effects of already approved cardiovascular drugs, and to outline the perspectives for pharmacological direct or indirect impact on endothelium.

Abstract Manual massage, commonly used by healthy individuals for well-being, is an ancient practice requiring the intervention of a trained and experienced physiotherapist. On the other hand, automated massage is carried out by machines or modalities without or with minimal control of a human operator. In the present review, we provide a literature analysis to gather the effects of automated massage on muscle properties, peripheral circulation and psychophysiological variables as reported through psychometric and neurophysiological evaluations of each modality ranging from massage beds and whole-body vibrations to robotic massage. A computerized search was performed in Google Scholar, PubMed, and ResearchGate using selected key search terms, and the relevant data were extracted. The findings of this review indicate that for vibration massage, whole-body vibration exposure with relatively lower frequency and magnitude can be safely and effectively used to induce improvements in peripheral circulation. As for massage chair and mechanical bed massage, while most studies report on positive changes, the lack of strong clinical evidence renders these findings largely inconclusive. As for robotic massage, we discuss whether technological advances and collaborative robots might reconcile active and passive modes of action control during a massage and offer new massage perspectives through a stochastic sensorimotor user experience. This transition faculty, from one mode of control to the other, might definitely represent an innovative conceptual approach in terms of human–machine interactions.

Abstract Objectives The purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS. Methods The proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161− cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients. Results The proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti‐SSA/Ro60 positive, anti‐SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p = .0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA‐DR, Ki67, FasL, TNF‐α, and IFN‐γ on CD161+CD56+ NK cells was lower than that on CD161−CD56+ NK cells in the peripheral blood of pSS patients. Conclusion This study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS.

Background: In patients with liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) is considered a standardized treatment of refractory ascites or variceal bleeding. TIPS thrombosis (TT) and/or portal vein thrombosis (PVT) are possible complications during/after TIPS placement. Previous studies suggested increased clotting activity in portal circulation (PORC). This pilot study aimed to evaluate alterations and differences of coagulation function in PORC and in peripheral circulation (PERC) via rotational thromboelastometry during TIPS. Methods: Blood samples were collected from cirrhotic patients (n = 13; median Model of End Stage Liver Disease, MELD Score: 12; median age: 60 years) undergoing TIPS (10/13 TIPSs were elective procedures due to refractory ascites) as follows: median cubital vein (MCV; PERC)—confluence of the three hepatic veins to the inferior cava vein (HV/ICV; PORC)—portal vein (PV; PORC)—TIPS (PORC). This research utilized four variables of the extrinsic test EXTEM, i.e., clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum lysis (ML). Results: EXTEM results [mean, M (range) ± standard deviation, SD (range)] showed no significant differences for CT [M (70–73) ± SD (9–13); p = 0.93] or CFT [M (137–155) ± SD (75–112); p = 0.97] or MCF [M (51–54) ± SD (9–10); p = 0.90] or ML [M (9–10) ± SD (4–5); p = 0.89] between the compartments, i.e., MCV vs. HV/ICV vs. PV vs. TIPS. Overall, we detected no differences in coagulation function between PERC and PORC. Conclusion: These results are in contrast to previous reports suggesting increased clotting activity in PORC vs. PERC in association with liver cirrhosis. Rotational thromboelastometry-based evaluation of coagulation function in PERC appears to reliably reflect coagulation function in PORC with respect to risk estimation for TT and/or PVT in cirrhotic patients undergoing TIPS. [ABSTRACT FROM AUTHOR]

BackgroundHand-arm vibration disease is harmful to human body, but there are no effective diagnosis and treatment so far, and current occupational exposure limits underestimate the health damage caused by high-frequency vibration exposure. ObjectiveTo evaluate and compare the damage to workers' peripheral circulation and peripheral nerve caused by different frequencies of vibration operation. MethodsDrilling workers (n=187) from a mining company in Shandong Province and golf club head grinding workers (n=228) from a sports equipment factory in Guangdong Province were selected as study subjects. Hand symptoms were investigated. SV106 vibration meter was used to measure the target operation-associated vibration frequency spectrum. The 8 h energy-equivalent frequency weighted acceleration, cumulative vibration exposure level (CVEL), and the working age related to causing white finger in 10% of an exposed group were calculated.ResultThe study subjects were all male. More grinding workers reported hand symptoms than the drilling workers, e.g. peripheral circulation injury (52.6% vs 19.3%), peripheral nerve injury (71.5% vs 23.0%), hand stiffness (64.0% vs 7.0%), and deformed fingers (69.7% vs 4.3%) (all P

Denileukin diftitox (ONTAK) is a diphtheria/IL-2R fusion protein able to deplete regulatory T cells in peripheral blood. Regulatory T cells in the local immune microenvironment have been shown to be associated with poor prognosis in ovarian cancer. This study examined whether denileukin diftitox (ONTAK) could be safely administered intraperitoneal in patients with advanced refractory ovarian cancer and assessed its effects on regulatory T cells and tumor associated cytokines in ascites and peripheral blood. A phase I dose escalation study of intraperitoneal denileukin diftitox (ONTAK) enrolled 10 patients with advanced, refractory ovarian carcinoma at 3 doses (5 μg/kg, 15 μg/kg, and 25 μg/kg). Serial CA-125 measurements assessed clinical response. Regulatory T cells were quantified using RT-PCR and cytokine levels measured by Luminex. The maximum tolerated dose was 15 μg/kg with a dose limiting toxicity observed in 1 out of 6 patients in the expansion group. The majority of adverse events were transient grades 1–2. One patient treated at the 25 μg/kg dose experienced cytokine storm with prolonged hospitalization. 3 patients had decreases in CA-125 after treatment but none met criteria for partial response. Treatment with denileukin diftitox (ONTAK) decreased regulatory T cells in peripheral blood and ascites. Treated patients did not show any significant changes in IL-8, TGF-β, sIL2Ra in ascites or peripheral blood. Denileukin diftitox (ONTAK) can be safely administered intraperitoneally to recurrent refractory ovarian cancer patients. Regulatory T cells were reduced in ascites and peripheral blood, but there were no significant changes in cytokine levels. Clinical Trial Registration: ClinicalTrials.gov # NCT00357448 • Ovarian cancer has an immunosuppressive tumor microenvironment that has proven resistant to many immunotherapies. • Denileukin diftitox can be safely given intraperitoneally to treatment refractory ovarian cancer patients. • Intraperitoneal denileukin diftitox reduces regulatory T cells both locally, in ascites, and in the peripheral circulation. • Intraperitoneal immunotherapy is feasible and may decrease immunosuppression in the tumor microenvironment. • The effects of local administration should be considered as novel immunotherapies are developed for ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is the most common disease of the circulatory system. The most relevant area in the assessment of individual human health is the constitutional approach. Many studies have shown that most indicators of the blood circulation are related to anthropometric parameters of the body, which is why studying the features of peripheral hemodynamics in representatives of different somatotypes with normal and high blood pressure is especially relevant. The purpose of the study was to determine the features of peripheral circulation in young people, aged 18 to 22 years, of different somatotype with normal and high blood pressure. Materials and methods: two groups of subjects selected: a control group (CG) — those in which the value of BP consistent optimum level by the WHO classification (125 people), the second group — those in which systolic blood pressure higher than 130 mmHg and (or) diastolic — 85 mmHg (135 people). Somatotyping performed using techniques by Carter and Heath. To study the condition of peripheral hemodynamics used rheovasography of the lower extremities. Results and discussion: statistical analysis of the results by the Kruskal-Wallis method in the individuals of both groups showed a significant difference in the majority of rheovasography indices among subjects of different somatotypes. The method of multiple comparisons showed significant differences in the values of peripheral circulation among representatives of different somatotypes with normal and high blood pressure. Conclusions: peripheral hemodynamics in subjects with normal blood pressure and predominance of the endomorphic component was characterized by significantly higher vascular tone of mainly medium and small diameter compared to ectomorphs. The peripheral circulation of individuals with high blood pressure and predominance of the endomorphic component, compared to ectomorphs and to lesser extent mesomorphs, was characterized by a significantly higher increase in the tone of the small arteries and a decrease in the tone of the large arteries.

The peripheral circulation of typhoon forms sustained ozone episodes. However, how it impacts the day-to-day ozone pollution levels during the episodes has not been clearly studied, which is crucial for better prediction of the daily ozone variation. In this study, the analysis of ground observation, wind profile data, and model simulation is integrated. By analysing the wind profile radar observations, we found a weak wind deepening (WWD; vertical depth of the weak winds increased), more correlated with the ground-level ozone variation than surface weak wind. Long-term statistical analyses showed that the WWD is a common weather phenomenon in the peripheral subsidence region of typhoons and is generally accompanied by ozone pollution episodes. The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) with process analysis simulation showed that the peripheral subsidence chemical formation (CHEM) and vertical mixing (VMIX) effects are two major contributors to the enhancement of ozone levels to form the episode, while the advection (ADV) showed negative values. However, the day-to-day variation of the daytime ozone levels during the episode is not determined by the daily variation of daytime CHEM and VMIX but is dominated by the ADV terms. Therefore, the ozone and its precursors accumulation, including the enhancement during the night-time, contribute to the daytime ozone increase in the following day. A detail day-to-day process analysis showed that in additional to decrease of negative ADV values (e.g. the weakened advection outflow or dispersion) on the ground, the integrated effect of the daily variation of the accumulative CHEM and ADV above the ground throughout the planetary boundary layer (PBL) together determined the overall day-to-day daytime ozone variation on the ground through the VMIX process. The results indicate that the peripheral characteristics of approaching typhoon not only form the ozone episode by the enhanced photochemical reactions, but also could increase the day-to-day daytime ozone levels via pollution accumulation throughout the PBL due to the WWD up to 3–5 km. These results illustrate the important role of the WWD in the lower troposphere for the formation of sustained ozone episodes due to the peripheral circulation of the typhoon, which helps to better predict the daily changes of daytime ozone levels.

Background: Off-pump coronary artery bypass grafting (OPCAB) is an alternative to on-pump coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). During OPCAB, the temporary use of an intracoronary shunt and inotropic medication or catecholamines should keep the central hemodynamics constant. Nevertheless, the need for conversion to on-pump CABG often occurs unexpectedly, most likely due to circulation instability. Circulation instability can appear first in peripheral body parts; therefore, peripheral microcirculation might serve as a predictor for the upcoming conversion to on-pump CABG. We investigated the impact of coronary artery ligation and shunt insertion during OPCAB on cutaneous microcirculation (cLDP) with Laser Doppler Perfusion Technology and transcutaneous oxygen partial pressure (tcpO2). Methods: In a pig model of OPCAB, peripheral circulation was evaluated after cLDP (N = 17) and tcpO2 (N = 6) monitoring. Systolic, diastolic, and mean arterial pressure were also observed to prove the independence of perfusion measurement results from hemodynamic parameters. Results: Ligation time during cLDP and tcpO2 monitoring were 101 ± 49 s and 83 ± 33 s, respectively. Shunt time was 11 ± 3 min during cLDP and 13 ± 2 min during tcpO2 measurement. Ligation of the left anterior descending coronary artery (LAD) reduced cLDP significantly to 88 ± 14% (p = 0.007) and tcpO2 to 71 ± 25% (p = 0.038). Inserting a temporary shunt into the LAD significantly improved cLDP (p = 0.006) and tcpO2 (p = 0.015) compared to ligation. cLDP was restored to 99%, and tcpO2 was restored to 91% of the baseline level before ligation. All hemodynamic parameters remained stable and did not change significantly during OPCAB. Conclusions: Although hemodynamic parameters stayed constant, peripheral microcirculation was influenced markedly during OPCAB. Inserting a temporary shut into the LAD leads to a complete normalization of peripheral microcirculation, regarding evaluation by cLDP and tcpO2.

IntroductionThe emergence of SARS-CoV-2, which causes COVID-19, has led to over 400 million reported cases worldwide. COVID-19 disease ranges from asymptomatic infection to severe disease and may be impacted by individual immune differences.MethodsWe used multiparameter flow cytometry to compare CD4+ and CD8+ T cell responses in severe (ICU admitted) and non-severe (admitted to observational unit) hospitalized COVID-19 patients.ResultsWe found that patients with severe COVID- 19 had greater frequencies of CD4+ T cells expressing CD62L compared to non-severe patients and greater frequencies of perforin+ CD8+ T cells compared to recovered patients. Furthermore, greater frequencies of CD62L+ CD4+ and CD8+ T cells were seen in severely ill diabetic patients compared to non-severe and non-diabetic patients, and increased CD62L+ CD4+ T cells were also seen in severely ill patients with hypertension.DiscussionThis is the first report to show that CD62L+ T cells and perforin+ T cells are associated with severe COVID-19 illness and are significantly increased in patients with high-risk pre-existing conditions including older age and diabetes. These data provide a potential biological marker for severe COVID-19.

Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)). C57BL/6 mice were fed a high-fat diet or low-fat diet from 8 weeks before mating and during pregnancy. At GD12, we analyzed the gut microbiota composition in the feces and immune responses in the intestine (Peyer's patches, mesenteric lymph nodes) and the peripheral circulation (spleen and peripheral blood). Maternal obesity reduced beneficial bacteria (e.g., Bifidobacterium and Akkermansia) and changed intestinal and peripheral immune responses (e.g., dendritic cells, Th1/Th2/Th17/Treg axis, monocytes). Numerous correlations were found between obesity-associated bacterial genera and intestinal/peripheral immune anomalies. This study shows that maternal obesity impacts the abundance of specific bacterial gut genera as compared to lean mice and deranges maternal intestinal immune responses that subsequently change peripheral maternal immune responses in mid-pregnancy. Our findings underscore the opportunities for early intervention strategies targeting maternal obesity, ideally starting in the periconceptional period, to mitigate these obesity-related pregnancy effects. [ABSTRACT FROM AUTHOR]

Abstract. The significance and role of peripheral blood circulation sufficiency in the formation of disorders of the muscular system in children with diabetes mellitus remain insufficiently studied. At the same time, the formation of some chronic complications of diabetes is associated with a deficient muscular system function. Aim of study. To discover the state of blood supply to the lower extremities in children with type 1 diabetes mellitus, according to the ankle-brachial index and to determine the value of deviations in the development of diabetic myopathy. Materials and methods. We examined 137 children with type 1 diabetes mellitus. The control group included 41 apparently healthy children. Assessment of the functional state of skeletal muscles, determination of the skeletal muscle index, hand force index and ankle-brachial index before and after exercise were studied in all patients. The ROC analysis was used to calculate cut-off points for the hand force index and the skeletal muscle index in order to determine the diagnostic criteria for dynapenia and diabetic myopathy. Results. We observed functional disorders of skeletal muscles and a decrease in the skeletal muscle index already in the first year of diabetes mellitus. In dynamics, the progression of violations was noted. Found a negative correlation between the level of glycated hemoglobin and the skeletal muscle index (r = -0.49, p

Objectives: The purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS. Methods: The proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161− cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients. Results: The proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti‐SSA/Ro60 positive, anti‐SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p =.0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA‐DR, Ki67, FasL, TNF‐α, and IFN‐γ on CD161+CD56+ NK cells was lower than that on CD161−CD56+ NK cells in the peripheral blood of pSS patients. Conclusion: This study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS. [ABSTRACT FROM AUTHOR]

Insulin has important vasodilatory effects in the peripheral circulation, but less is known about insulin's role in cerebrovascular control. Herein, we hypothesized both systemic (intravenous) and local (intranasal) insulin administration would increase indices of cerebral blood flow and reduce cerebrovascular compliance (Ci) in young adults. Participants were assigned to one of four separate protocols. Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) and blood pressure (BP, finger photoplethysmography) were measured at baseline and at 1) 2 min of carbon dioxide (CO2) air breathing (high flow control), 2) 60 min of euglycemic intravenous insulin infusion (40 mU/m2 body surface area/min), 3) 60 min following 160 IU of intranasal insulin, 4) 60 minutes of time control. Ci was calculated (modified Windkessel model). Intravenous insulin increased serum insulin (6.0 ± 2.6 to 52.7 ± 12.7 μIU/mL, P < 0.001), whereas serum insulin was reduced following intranasal insulin (6.9 ± 4.5 to 4.9 ± 1.8 μIU/mL, P = 0.030). MCAv increased in response to CO2 (60 ± 13 to 69 ± 11 cm/s, P < 0.001) but was unchanged with time control (50 ± 7 to 49 ± 8, P = 0.658) and both insulin conditions (intravenous: 61 ± 13 to 62 ± 17 cm/s, P = 0.531; intranasal: 57 ± 12 to 51 ± 15 cm/s; p = 0.061). In contrast, Ci remained at baseline levels over time (P = 0.438) and was reduced from baseline under CO2 and both insulin conditions (CO2, P < 0.001; intravenous, P = 0.021; intranasal, P = 0.001). Contrary to our hypothesis, there was no effect of systemic or local insulin administration on resting MCAv in young adults; however, both systemic and local insulin administration reduced Ci. These findings advance our understanding of the cerebrovascular response to acute insulin exposure. NEW & NOTEWORTHY: Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Contrary to our hypothesis, there was no effect of systemic (intravenous) nor local (intranasal) insulin administration on middle cerebral artery blood velocity; however, both systemic and local insulin administration reduced cerebrovascular compliance. Our findings advance our understanding of the cerebrovascular response to insulin and may have implications in the context of known metabolic disturbances. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic prompted unprecedented vaccine development efforts against SARS-CoV-2. India, which was one of the countries most impacted by COVID-19, developed its indigenous vaccine in addition to utilizing the ones developed by other countries. While antibody levels and neutralizing antibody titres are considered initial correlates of immune protection, long-term protection from the pathogen relies on memory B and T cells and their recall responses. In this regard, global research has primarily focused on mRNA-based vaccines. The studies on immune memory response, particularly B cell memory response induced by the vaccines given to Indians, remain relatively obscure. Methods: We assessed Receptor Binding Domain-specific memory B cells in the peripheral circulation and their ability to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D), and Sputnik Light, as well as unvaccinated individuals. Results: Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses over time compared to other groups. Conclusions: These findings contribute to our understanding of vaccine-induced immune memory in the Indian population; providing insights that could inform future vaccine strategies. [ABSTRACT FROM AUTHOR]

Numerous studies highlight the significant role of exercise therapy in patients with peripheral artery disease (PAD), emphasizing how regular physical exercise enhances vascular endothelial function and promotes metabolic adaptations in skeletal muscles, ultimately improving walking performance. There are currently discussions in the medical world on optimizing noninvasive therapy to prevent the development of lower limb ischemia. This study aimed to assess the impact of a supervised training program combined with whirlpool massage treatment on improving peripheral circulation and physical performance in patients suffering from peripheral artery disease. Methods: One hundred participants (both male and female) aged between 39 and 79 years old (60.0 ± 11.6) were included in the analysis, all diagnosed with peripheral circulation disorders. The participants were assigned to two groups. The study group received 10 whirlpool treatments of the lower limbs and a personalized training program. The control group only participated in the training sessions. Pre- and post-intervention evaluations included impedance plethysmography and the six-minute walk test (6MWT). Results: Assessing the results of local flow parameters, after the procedures, a statistically significant increase in the pulse wave amplitude (PAmpl, p < 0.001) and systolic slope (PSlope, p < 0.001) values was found, as well as a statistically significant decrease in the crest time (CT, p < 0.001) and propagation time (PT, p = 0.007) values in the study group, which indicates an improvement in blood flow in the peripheral circulation. Also, in the 6 min walk test, a statistically significant increase in the walking distance was noted in the study group after the procedures. Conclusions: Physical training, combined with whirlpool massage treatment, has a beneficial effect on improving peripheral blood flow assessed by impedance plethysmography, as well as patients' tolerance to physical exercise. The inclusion of hydrotherapy as part of cardiovascular rehabilitation protocols in patients with peripheral ischemia is a promising form of conservative treatment. [ABSTRACT FROM AUTHOR]

Hyperthermia is thought to increase limb blood flow through the activation of thermosensitive mechanisms within the limb vasculature, but the precise vascular locus in which hyperthermia modulates perfusion remains elusive. We tested the hypothesis that local temperature‐sensitive mechanisms alter limb hemodynamics by regulating microvascular blood flow. Temperature and oxygenation profiles and leg hemodynamics of the common (CFA), superficial (SFA) and profunda (PFA) femoral arteries, and popliteal artery (POA) of the experimental and control legs were measured in healthy participants during: (1) 3 h of whole leg heating (WLH) followed by 3 h of recovery (n = 9); (2) 1 h of upper leg heating (ULH) followed by 30 min of cooling and 1 h ULH bout (n = 8); and (3) 1 h of lower leg heating (LLH) (n = 8). WLH increased experimental leg temperature by 4.2 ± 1.2ºC and blood flow in CFA, SFA, PFA, and POA by ≥3‐fold, while the core temperature essentially remained stable. Upper and lower leg blood flow increased exponentially in response to leg temperature and then declined during recovery. ULH and LLH similarly increased the corresponding segmental leg temperature, blood flow, and tissue oxygenation without affecting these responses in the non‐heated leg segment, or perfusion pressure and conduit artery diameter across all vessels. Findings demonstrate that whole leg hyperthermia induces profound and sustained elevations in upper and lower limb blood flow and that segmental hyperthermia matches the regional thermal hyperemia without causing thermal or hemodynamic alterations in the non‐heated limb segment. These observations support the notion that heat‐activated thermosensitive mechanisms in microcirculation regulate limb tissue perfusion during hyperthermia. [ABSTRACT FROM AUTHOR]

Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra‐intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter‐kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet‐induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super‐resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage‐specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation‐related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well‐established biological effects induced by gut bacteria on distant organs. [ABSTRACT FROM AUTHOR]