Skin Hyperemia Research Articles

Peripheral whole blood microRNA expression in relation to vascular function: a population-based study

BackgroundAs key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis.MethodsPeripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module’s expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis.ResultsFour modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion.ConclusionsWe identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std β = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std β = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std β = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

Diabetes mellitus during pregnancy — complications for the fetus and newborn

Currently, diabetes mellitus is considered one of the most common problems in obstetrics and neonatology, associated with its high incidence and complications it causes — perinatal loss and morbidity of newborns, as well as further negative consequences for the child’s health. The incidence of diabetes mellitus is increasing in the world every year. According to forecasts of the International Diabetes Federation, there is no tendency to decrease the incidence in the near future. The increase in the incidence of diabetes mellitus is also due to a change in the criteria for diagnosis set out in the Gestational Diabetes Mellitus Treatment Guidelines. In addition, patients often do not understand the seriousness of the complications that occur with the disease, thereby not following the doctor’s treatment recommendations. To date, it has been proven that diabetes mellitus is a main cause of perinatal morbidity and mortality. According to the World Health Organization, even slight hyperglycemia in the mother during pregnancy is associated with the development of diabetic fetopathy.
 This article provides an analytical review of current literature covering the issues of perinatal and neonatal outcomes in the presence of diabetic fetopathy. Its characteristic phenotypic signs include macrosomia (due to increased fat deposition in subcutaneous tissue associated with increased production of somatotropic hormone) or microsomia (due to primary placental insufficiency), general pastiness, skin hyperemia, characteristic сushingoid-type appearance, body disproportion, puffy face in combination with other signs of immaturity, as well as transient hypertrophic cardiomyopathy and hepatosplenomegaly.

A Clinical Scoring System and Impact of Athymic Nude Mouse Age on Corynebacterium bovis Clinical Disease.

Corynebacterium bovis infection in biomedical research is synonymous with skin hyperkeratosis of athymic nude mice. This clinical sign can be obvious and is the namesake for 'scaly skin disease.' Other clinical signs that accompany scaly skin, including early presentation, duration, and rate of resolution, are less well known. The goal of this study was to characterize the clinical signs of C. bovis infection in nude mice under experimental conditions and develop a quantifiable scoring system. For the development, prospective trial, and application of this clinical scoring system, 93 naïve Hsd:Athymic Nude mice were used, of which 81 were exposed to soiled bedding from clinically ill C. bovis -infected NSG mice. The emergence of clinical signs was monitored and scored daily for 14 d. We identified 3 categories of clinical signs including skin hyperemia, skin hyperkeratosis, and surrogate indicators of overall health. Each of these defined categories appeared consistently and progressed and regressed temporally. We subsequently used this scoring system to determine if the age of Hsd:Athymic Nude mice (6 compared with 10 wk) at time of infection affects clinical severity. Our findings demonstrate that 6-wk-old mice demonstrate more severe clinical signs. Ten-week-old mice showed less skin hyperemia and no skin hyperkeratosis and were less affected by the infection based on surrogates of overall health. Here we show the utility of this novel scoring system and the impact of nude mouse age at the time of infection on C. bovis clinical disease.

Pathological changes in aborted fetuses and placental tissue in cows with neosporosis

The failure to obtain offspring due to abortion causes considerable damage to the dairy industry worldwide, costing millions of US dollars. Neospora caninum, a protozoan parasite of the Apicomplexa class, is the causative agent of neosporosis, a disease that leads to abortions or the birth of weak offspring in cows. Therefore, addressing this issue is crucial. The purpose of this study is to describe the pathological changes in aborted fetuses and placental tissue in cows with neosporosis. Macroscopic examination of fetal and placental parts was performed through pathological dissection. The gestation age (days) was determined using the formula: 68 + 2.25×CRL (cm) and/or from historical data. DNA of N. caninum was detected by polymerase chain reaction in all fetuses and/or fetal parts of placentas described in the study. It was found that the majority of abortions occurred at 4-5 months of gestation. External examination revealed isolated instances of skin hyperemia and haemorrhages throughout the body. Some fetuses were mummified. Autolysis of the fetus and placental parts was observed in most cases. Placentitis and oedema of the placental tissue were also noted in some cases. Internal examination of fetuses revealed changes in the brain, skeletal muscles, heart, lungs, liver, spleen, and kidneys, in addition to characteristic autolysis. These changes, including grey foci in the brain with a light grey centre, white foci, and multiple white streaks in skeletal muscles and the tongue, can be attributed to typical pathological changes in aborted fetuses with neosporosis. These changes are rare but can impact the determination of the cause of abortion, narrowing down the factors responsible

Early activation after cochlear implantation: a systematic review.

To systematically review the outcomes of early activation following cochlear implantation (CI) based on the findings from different studies in the literature. A comprehensive search strategy was conducted through different databases to identify relevant articles. Our outcomes included impedance levels, rates of complications, hearing and speech perception performance, and patients' satisfactionlevels. The total number of included studies in this systematic review is 19, which recruited 1157 patients, including 857 who underwent early activation following CI. Seventeen studies investigated impedance levels or feasibility rates of early activation approaches. Most of these studies (n = 10) reported that mean impedance levels remarkably decreased within the first day-to-month (first measurement) post-activation. In addition, all 17 studies showed that impedance levels finally normalize and become comparable with intraoperative levels or the conventional activation group. Seventeen studies reported the occurrence of complications in their population. Ten of these studies indicated that none of their patients developed any post-operative complications after early activation. Seven studies reported the development of some minor complications, including pain 9.2% (28/304), infection 4.7% (13/275), swelling 8.2% (25/304), vertigo 15.1% (8/53), skin hyperemia 2.2% (5/228), and others 16.4% (9/55). Hearing and speech perception was assessed in six studies, which showed a remarkable improvement in their patients. Three studies investigated patients' satisfaction and showed high satisfaction levels. Only one report investigated the economic advantages of early activation. Early activation is safe and feasible and does not impact the hearing and speech outcomes of thepatients undergoing CI procedures.

Rare clinical cases of tularemia

The most common clinical form of tularemia in Europe is ulcerative bubonic , which has a summer-autumn seasonality . When infected with water and food , the development of oropharyngeal and abdominal forms is possible . The rarity of registration of such forms is associated not only with the low frequency of such cases of infection , but also with the complexity of diagnosing diseases with an atypical clinic . Important for the correct diagnosis are the results of specific laboratory diagnostics and a qualitatively collected epidemiological history . The results of zooparasitological monitoring allow assessing the risk of infection in certain territories . The article provides descriptions of two cases of severe abdominal tularemia , registered in autumn 2021 – winter 2022 in the Republic of Karelia , which has been one of the most disadvantaged regions of Russia in recent years . In the first case , in a 15-year-old boy , the disease began acutely , the main symptoms were high fever , abdominal pain , vomiting , loose stools , foci of skin hyperemia with clear uneven edges without infiltration in the left knee joint and right inguinal region , hepatomegaly , mesoadenitis . In indirect gemagglutination reaction with tularemia diagnosticum on the third day from the onset of the disease antibodies in titer 1:640. Infection probably occurred when eating food during a trip to the forest zone of the city , where infected rodents were previously detected . In the second case , a 17-year-old girl living in a village was diagnosed with a peritonsillar abscess 3 weeks before a sharp rise in temperature , abdominal pain , vomiting and loose stools . Later he developed renal and hepatic insufficiency , polyserositis . The antibodies titer was 1:320 after 3 weeks and 1:2650 after 5 weeks . Infection probably occurred through consumption of rodent-contaminated v egetables .

Differences in the Basal Flow and Occlusion-induced Reactive Hyperemia of the Apical and Non-apical Cutaneous Microcirculation. Effect of Botulinum Toxin

Introduction: In general, two types of skin are distinguished: apical (glabrous, A) and non-apical (hairy, NA), but less is known regarding the differences in their microcirculation. Thus we aimed to measure changes in subcutaneous microcirculation in these two skin types and its modulation by botulinum toxin (BT). Materials and Methods: Perimed 5000 Laser Doppler flowmetry was used to measure the perfusion (perfusion unit, PU) of skin in the temporal (A) and lower arm (NA) regions. The temporal artery or the upper arm was occluded for 2 min, then released, which was followed by reactive hyperemia. Also the effects of 25 IU BT injected under the forehead skin on PU were observed. Results: In the skin of temporal region PU changed from control PU: 73,01±15,4 to occlusion: 51,64±7,16, then after release to 110,76±22,56. In the skin of upper arm, PU changed from control PU: 10,4±1,2, to occlusion: 1.9±05, then after release to 48,8±25,5. In the forehead skin BT elicited a biphasic response then PU returned close to control, whereas BT inhibited reactive hyperemia; PU changed from 70,63 ±16,08 to occlusion 55,73 ± 6,75 and after release to 71,37±29,22. Conclusion: Thus there is 1) a higher level of microcirculation in the temporal region of the forehead skin than that of the forearm, 2) ischemia/reperfusion elicited greater reactive hyperemia (RH) in the forearm skin then in the temporal skin 3) BT interferes with the mechanisms eliciting reactive hyperemia.

Effect of iron deficiency on skeletal muscle metabolism in heart failure with preserved ejection fraction

Abstract Background Iron deficiency (ID) is suggested to be one of the key comorbidities contributing to heart failure with preserved ejection fraction (HFpEF) and concomitant exercise intolerance, possibly by inducing systemic inflammation and microvascular dysfunction (MVD). ID is associated with poorer prognosis in HFpEF, but its exact impact on exercise capacity in HFpEF patients remains to be further investigated. Purpose To evaluate the effect of ID on exercise capacity in HFpEF patients by assessing skeletal muscle metabolism. Additionally, to assess the association between ID and MVD in HFpEF patients. Methods This prospective study included patients diagnosed with HFpEF according to the ESC Heart Failure 2016 guidelines between January 2018 and May 2021. Patients were excluded if they were of childbearing potential, had any iron supplementation 6 months or chemotherapy 1 year prior to inclusion, were known with significant peripheral artery disease, or had any contraindication for phosphorus-magnetic resonance spectroscopy (31P-MRS). Iron status was defined as absolute ID (serum ferritin <100μg/L), relative ID (serum ferritin 100–299μg/L and transferrin saturation <20%), and no ID. Skeletal muscle oxidative capacity of the upper leg was evaluated by determining phosphocreatine (PCr) recovery kinetics with 31P-MRS in the vastus lateralis muscle after isometric knee extension exercise. Microvascular function was assessed as heat-induced skin hyperemia using laser-Doppler flowmetry. Clinical data up to 6 months prior to or after inclusion was used. Results Twenty-four HFpEF patients without ID and 18 with ID were included, including 14 patients with absolute ID. Clinical characteristics of patients without ID and with ID were comparable: median age 74 [69–79] vs. 77 [69–81] years, 13 (54%) vs. 14 (78%) were females, and 20 (83%) vs. 16 (89%) had a history of hypertension (Table 1). Both groups showed similar halftime of PCr recovery after exercise (29.2 [22.8–33.2] vs. 27.0 [21.1–31.4] seconds, p=0.416), and similar skin hyperaemic flow increase (1142 [576–2247] vs. 1023 [574–1511] %, p=0.554). These measures of skeletal muscle metabolism and microvascular function were not correlated. In a subset of patients (11 without ID and 13 with ID), elevated high-sensitive C-reactive protein (hsCRP) was correlated with PCr recovery halftime in those with ID (R2 0.565, p=0.003). This correlation was not found in patients without ID (R2 0.119, p=0.300) in the original data (Figure 1), but was found after removal of a prominent outlier (R2 0.654, p=0.005). Conclusion HFpEF patients without ID showed comparable skeletal muscle oxidative capacity and microvascular skin hyperaemia compared to HFpEF patients with ID. Post-hoc analysis suggests that inflammation affects skeletal muscle metabolism in HFpEF patients, possibly regardless of ID. Future studies on the effects of ID and inflammation on cellular metabolism could suggest therapeutic targets in HFpEF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was funded by Vifor Pharma. The funder had no influence on the study results.

GENERALISED MICROVASCULAR DYSFUNCTION IS NONLINEARLY ASSOCIATED WITH HIGHER EXERCISE BLOOD PRESSURE – THE MAASTRICHT STUDY

Objective: Exercise blood pressure (BP), both high and low responses, is associated with the development of cardiovascular disease and all-cause mortality. However, it is unclear whether microvascular dysfunction is a determinant of exercise BP. Therefore, we investigated whether microvascular dysfunction was (nonlinearly) associated with exercise BP. Design and method: In the population-based Maastricht Study (n = 1,688; age 59 ± 8 years; 51% men), generalised microvascular dysfunction was constructed by a composite score of features of cerebral small vessel disease, retinal microvascular features, albuminuria, heat-induced skin hyperaemia and plasma biomarkers of microvascular dysfunction. Similarly, we constructed a composite score of exercise systolic BP and diastolic BP by combining BP at moderate workload, at peak exercise, change per minute and at 4 minutes after recovery. We used linear regression with adjustments for age, sex, lifestyle and cardiovascular risk factors, including resting BP. Nonlinearity was investigated by adding a quadratic term of generalised microvascular dysfunction Results: After adjustments, generalised microvascular dysfunction was nonlinearly associated with both the composite score of exercise SBP and DBP in an inverted U-shape fashion (p-nonlinear for exercise SBP < .001; for exercise DBP .001). When we divided microvascular dysfunction into quintiles, exercise SBP and DBP did not become higher after the middle quintile, and plateaued or were lower in the highest quintiles of microvascular dysfunction. Conclusions: Generalised microvascular dysfunction is nonlinearly associated with higher exercise SBP and DBP in an inverted U-shape fashion. These findings support the hypothesis that generalised microvascular dysfunction is a determinant of both high and low exercise BP responses.

Reactive hyperaemia augments local heat-induced skin hyperaemia.

What is the central question of this study? It is valuable to be able to monitor disease- or treatment-related changes in the microcirculation. Laser Doppler flowmetry with local heating allows non-invasive monitoring of the skin microcirculation and its ability to vasodilate. Does reactive hyperaemia augment the increase in skin blood flow elicited by local heating? What is the main finding and its importance? The addition of reactive hyperaemia to local heating results in greater vasodilatation than heating alone. Thus, reactive hyperaemia can augment local heat-induced hyperaemia in the skin. The skin circulation has been proposed as a model of generalized microvascular function that could be monitored non-invasively using laser Doppler flowmetry (LDF). The response to heat hyperaemia (HH) is commonly used to monitor disease- or treatment-related changes in microvascular function. We hypothesized that reactive hyperaemia would augment the increase in skin blood flow elicited by local heating. Fourteen healthy young adults were subjected to three different conditions: reactive hyperaemia (RH; skin temperature controlled at 33°C), heat hyperaemia (HH; 42°C held for 40min) and HH+RH. Two Peltier-controlled thermomodules with LDF probes were placed on the right forearm to monitor skin blood flow continuously. A cuff was placed on the right upper arm to elicit RH by inflation to 220mmHg for 5min. This procedure was performed with the skin temperature at 33°C and again after 40min of local heating to 42°C. Beat-by-beat mean arterial pressure (MAP) obtained by a photoplethysmographic sensor on the middle finger of the left hand allowed calculation of cutaneous vascular conductance (CVC) as LDF/MAP. Both HH and RH increased LDF (P<0.0001 and P<0.0001, respectively) and CVC (P=0.0001 and P<0.0001, respectively) above baseline values. The LDF and CVC values were significantly higher during HH+RH when compared with RH or HH alone (P<0.0001). In summary, HH+RH resulted in greater vasodilatation when compared with HH or RH alone. These results indicate that RH can augment local heat-induced hyperaemia in the skin.

ОПТИМИЗАЦИЯ УХОДА ЗА ХИРУРГИЧЕСКОЙ РАНОЙ ПОСЛЕ УРЕТРОПЛАСТИКИ У ДЕТЕЙ С ГИПОСПАДИЕЙ

Objectives. To develop optimal postoperative wound care tactics for boys with hypospadias. Methods. The patients (128) with hypospadias aged from 11 months to 7 years were examined. The main group A consisted of 83 (64.8%) patients in whom we used a special bandage. It includes layer by layer of soft polyamide net two-sided onlay coated with soft silicone and adhesive properties, abundantly treated with an antimicrobial ointment containing an osmotic agent, sterile absorbent wipes with non-woven material, a circularly applied elastic bandage and an adhesive plaster with porous non-woven material. The dressing usually held up to 5 days. Group B included 45 (35.2%) patients with hypospadias, in whom we used a conventional sterile circular gauze bandage with antimicrobial ointment. The gauze bandage changed daily. For all clinical symptoms the groups were comparable in age. Postoperative wound healing had been monitored for 10 days after urethroplasty. The emphasis was made on such criteria as bleeding with hematoma formation, copious exudate excretion, penis skin hyperemia, «soft» and «dense» edema, drying crust (scab), skin sutures dehiscence, hypergranulation and necrosis. Results. In group A, problems with the skin flap and postoperative wound were detected only in 17 (20.5%) boys on the second or third day after removal of the special bandage. In the postoperative period, 41 (91.1%) patients in group B had «painful» skin changes in the area of the postoperative wound, which appeared almost the next day after surgery. Conclusion. The use of special bandage delays in time the contact of microbiota penis tissues compromised by surgery and the external environment, which, no doubt, improves the healing of skin grafts in the early postoperative period, and therefore reduces the number of urethroplasty complications. What this paper adds For the first time in patients with hypospadias, the process of postoperative wound healing was analyzed depending on the type of dressing. It was established that the use of a long-term bandage with a soft polyamide mesh doublesided pad with a silicone contact layer and adhesive properties compared to a traditional gauze bandage, which was changed daily, optimized the tactics of postoperative wound care in boys with hypospadias and minimized the number of urethroplasty complications.

Diagnostic performance of C-reactive protein and D-dimer test in acute varicothrombophlebitis

Diagnostic value of C-reactive protein (CRP) and D-dimer test in acute varicothrombophlebitis (VTP) was studied in a cohort of 45 patients; female – 60%, median age – 59 (25-75% IQR 48-64) years. In patients with normal value of CRP the rate of VTP type II-III (Verrel-Steckmeier) was 4% vs 25% – in those with CRP ≥10 mg/L; while the thrombus growth rate was 2 times lower – 2.33 (25-75% IQR 0.74-8.18) cm3/day and 5.74 (25-75% IQR 1.82-15.02) cm3/day, respectively (P=0.07 in both cases). A larger area of skin hyperemia and soft tissue perivenous infiltrate were identified in patients with CRP ≥10 mg/L vs normal values of CRP: 153.2 (25-75% IQR 49.35-248.8) vs 48.4 (25-75% IQR 40.45-85.7) cm2 and 86.25 (25-75% IQR 26.08-131.3) vs 32.35 (25-75% IQR 17.95-52.33) cm2, P=0.05 and 0.06, respectively. The level of D-dimers in types II-III of VTP exceeded the respective index in cases of type I of VTP and isolated thrombosis of varicose tributaries: 876 (25-75% IQR 611-1637) ng/mL vs 395 (25-75% IQR 216-710) ng/mL (p&lt;0.05). Analysis of the ROC curve demonstrated an optimal cut-off value for the exclusion of types II-III of acute VTP equal to 611 ng/mL (sensitivity = 85.7%; specificity = 65.7%). Negative predictive value of the model – 95.8% (95% CI 73.6-98.1).

Clinical and sub-clinical characteristics of rickettsioses at 108 Military Central Hospital from 2020 to 2021

Objective: Rickettsioses remains one of the most common infectious diseases in Vietnam, the atypical disease’s manifestation often leads to misdiagnosis with other diseases and results in a delayed proper treatment. The study aimed to characterise the clinical and laboratory features of rickettsioses. Subject and method: This was a retrospective cohort study. The clinical and sub-clinical features of rickettsioses were described. All patients admitted to the 108 Military Central Hospital, Hanoi from May 2020 to September 2021. Result: There were 22 patients enrolled into the study and 15/22 (68.2%) hospitalised 5 days after fever onset. The most common clinical features were abrupt fever (100%), headache (100%), myalgia (100%), and skin hyperemia (100%). Some rare signs were recorded: Eschars (9.1%), lymphadenopathy (0%), and rash (4.8%). The laboratory findings showed 95% of the patients with elevated liver transaminases and 51.1% cases with thrombocytopenia. All of the patients were treated with doxycycline and 100% (22/22) fully recovered. The defervescence time was 74.9 ± 38.6 hours and the hospitalisation time was 7.1 ± 1.4 days. Conclusion: The study demonstrated that the appearance of longer than five days fever, severe headache, thrombocytopenia, and elevated liver transaminase could suggest a diagnosis of rickettsioses.

Dynamics of skin microvascular blood flow in 4-6-year-old children in association with pre- and postnatal black carbon and particulate air pollution exposure.

A growing body of evidence indicates that cardiovascular health in adulthood, particularly that of the microcirculation, could find its roots during prenatal development. In this study, we investigated the association between pre- and postnatal air pollution exposure on heat-induced skin hyperemia as a dynamic marker of the microvasculature. In 139 children between the ages of 4 and 6 who are followed longitudinally within the ENVIRONAGE birth cohort, we measured skin perfusion by Laser Doppler probes using the Periflux6000. Residential black carbon (BC), particulate (PM10 and PM2.5) air pollution, and nitrogen dioxide (NO2) levels were modelled for each participant's home address using a high-resolution spatiotemporal model for multiple time windows. We assessed the association between skin hyperemia and pre- and postnatal air pollution using multiple regression models while adjusting for relevant covariates. Residential BC exposure during the whole pregnancy averaged (IQR) 1.42 (1.22-1.58) µg/m3, PM10 18.88 (16.64 - 21.13) µg/m3, PM2.5 13.67 (11.5 - 15.56) µg/m3 and NO2 18.39 (15.52 - 20.31) µg/m3. An IQR increment in BC exposure during the third trimester of pregnancy was associated with an 11.5 % (95% CI: -20.1 to -1.9; p=0.020) lower skin hyperemia. Similar effect estimates were retrieved for PM10, PM2.5 and NO2 (respectively 13.9 % [95% CI: -21.9 to -3.0; p=0.003], 17.0 % [95% CI: -26.7 to -6.1; p=0.004] and 12.7% [95 % CI: -22.2 to -1.9; p=0.023] lower skin hyperemia). In multipollutant models, PM2.5 showed the strongest inverse association with skin hyperemia. Postnatal exposure to BC, PM10, PM2.5 or NO2, was not associated with skin hyperemia at the age of 4 to 6, and did not alter the previous reported prenatal associations when taken into account. Our findings support that BC, particulate air pollution, and NO2 exposure, even at low concentrations, during prenatal life, can have long-lasting consequences for the microvasculature. This proposes a role of prenatal air pollution exposures over and beyond postnatal exposure in the microvascular alterations which were persistent into childhood.

Extracerebral microvascular dysfunction is related to brain MRI markers of cerebral small vessel disease: The Maastricht Study

BackgroundCerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated with structural cSVD MRI markers.MethodsCross-sectional data of the population-based Maastricht Study was used (n = 1872, mean age 59 ± 8 years, 49% women). Measures of eMVD included flicker light-induced retinal arteriolar and venular dilation response (retina), albuminuria and glomerular filtration rate (kidney), heat-induced skin hyperemia (skin), and plasma biomarkers of endothelial dysfunction (sICAM-1, sVCAM-1, sE-selectin, and von Willebrand factor). These measures were standardized into z scores and summarized into a compound score. Linear and logistic regression analyses were used to investigate the associations between the compound score and white matter hyperintensity (WMH) volume, and the presence of lacunes and microbleeds, as measured by brain MRI.ResultsThe eMVD compound score was associated with WMH volume independent of age, sex, and cardiovascular risk factors (St β 0.057 [95% CI 0.010–0.081], p value 0.01), but not with the presence of lacunes (OR 1.011 [95% CI 0.803–1.273], p value 0.92) or microbleeds (OR 1.055 [95% CI 0.896–1.242], p value 0.52).ConclusionA compound score of eMVD is associated with WMH volume. Further research is needed to expand the knowledge about the role of systemic MVD in the pathophysiology of cSVD.

Pododermatite plasmocitária felina: relato de caso

Feline Plasmacytic Pododermatitis is an uncommon dermatological disorder that affects one or multiple paw pads and leads to swelling, ulceration, hemorrhage, scaling, erythema, and striation. Its etiopathogenesis is poorly understood, however, an immune-mediated basis is strongly suggested. A two-year-old neutered, mixed breed, male cat was referred to the Veterinary Clinic of the Federal University of Santa Catarina (UFSC), Curitibanos Campus, with a brief clinical history of progressive lesions on palmar and plantar pads for one month. On physical examination, the patient had enlarged popliteal and inguinal lymph nodes, and paw pads with thin, swollen, hyperemic, erythematous, and purple color skin with multiple white striations. Histopathological diagnosis confirmed plasmacytic pododermatitis, and glucocorticoid therapy with prednisolone was prescribed. In the present report, the patient's clinical follow-up was compromised, as the tutor did not perform the prescribed treatment and did not return with the animal for further evaluations.

Dynamics of skin microvascular blood flow in 4-6 year old children in association with pre- and postnatal black carbon and particulate air pollution exposure

Background: A growing body of evidence shows that cardiovascular disease in adulthood, in particular that of the microcirculation, could find its roots during prenatal development. In this study we investigated the association between pre- and postnatal black carbon and particulate air pollution exposure on heat-induced skin hyperemia as a dynamic marker of the microvasculature. Methods: In 139 children between the age of 4 to 6 who are followed longitudinally within the ENVIRONAGE birth cohort, we measured skin perfusion by Laser Doppler probes using the Periflux6000. Residential black carbon (BC) and particulate (PM10 and PM2.5) air pollution levels were modelled for each participant’s home address using a high-resolution spatiotemporal model. We assessed the association between skin hyperemia and pre- and postnatal air pollution using linear regression models while adjusting for relevant covariates. Results: Prenatal residential BC exposure averaged (IQR) 1.38 (1.05 - 1.62) µg/m³, PM10 18.72 (14.44 - 22.78) µg/m³ and PM2.5 13.43 (9.19 - 17.26) µg/m³. An IQR increment in BC exposure during the third trimester of pregnancy was associated with a 13.8 % (95% CI: -22.7 to -3.9; p = 0.008) lower skin hyperemia. Similar effect estimates were retrieved for PM10 and PM2.5 (respectively 11.7 % (95% CI: -20.6 to -1.8; p = 0.022) and 14.2 % (95% CI: -25.1 to -1.8; p = 0.027) lower skin hyperemia). Postnatal exposure to BC, PM10 or PM2.5 was not associated with skin hyperemia at the age 4 to 6 and did not alter the previous reported prenatal associations. Conclusion: These findings support that BC and particulate air pollution exposure even at low concentrations during prenatal life can have long-lasting consequences on the microvasculature. This proposes a role of prenatal air pollution exposures in the microvascular origin of cardiovascular disease development later in life.

Synthesis of functionally substituted esters of nicotinic and isonicotinic acid

Nicotinic (3-pyridinecarboxylic) acid is one of the most important vitamins as well as substance with versatile physiological activity, since it plays significant role in the human organism. Nicotinic acid (niacin, vitamin PP, vitamin B3) is widely used in medicine as drug which has a vasodilating effect, prevents the accumulation of cholesterol and normalizes the heart function. Isonicotinic (4-pyridinecarboxylic) acid is used for the production of valuable anti-tuberculosis drugs, antidepressants, etc. However, nicotinic and isonicotinic acids have various side effects: skin hyperemia, pruritus, formation of stomach peptic ulcers, liver dysfunction and hyperglycemia. To reduce the severity of side effects, their slightly soluble salts, esters or amides are obtained. The synthesis of nicotinic and isonicotinic acid esters with vanillin benzaldehydes, cholesterol, 8-hydroxyquinoline, quinine and (4,5-dichloroisothiazol-3-yl)methanol is described. Esters were obtained by acylation of hydroxybenzaldehydes and alcohols with nicotinic and isonicotinic acid hydrochlorides in the presence of triethylamine in anhydrous methylene chloride. The IR- UV- and NMR spectra of the compounds obtained are presented.

Novel use of lip balm under tracheostomy ties to prevent skin irritation in the pediatric patient

ObjectivesTo study the effectiveness of lip balm in reducing skin irritation and preventing pressure induced injury in tracheostomy dependent children. MethodsThe skin of tracheostomy patients presenting to a pediatric otolaryngology clinic over a 12 month period from 2018 to 2019 was assessed and categorized as hyperemic blanchable (abnormal pre-pressure injury), hyperemic non-blanchable, partial thickness skin loss, or full thickness skin loss. Caregivers were instructed to apply lip balm to the skin under soft ties three times per day and with tracheostomy tie changes. Patients were followed prospectively by a tracheostomy care nurse. Results24 patients enrolled and reported daily adherence with lip balm use. Median age was 7.3 years (interquartile range, IQR, = 1.3–12.4) with 10 females and 14 males. The majority of patients (n = 20) were identified as having hyperemic blanchable skin. 96% (23/24) of caregivers reported a subjective benefit. 79.2% (95% CI: 57.8%–92.9%) of patients with hyperemic skin (n = 24) demonstrated complete resolution with continued application, and was found to be significant: all patients had skin hyperemia before application, while 20.8% (5/24) continued to have hyperemia after application (P < .001). Infants and ventilation dependent patients demonstrated recovery rates of 88.9% and 75% respectively. Median duration of follow-up was 6.3 months (IQR = 3.4–11.3). There were no documented allergic reactions, accidental decannulations, or skin deterioration in the cohort. ConclusionsLip balm appears to be a low cost, hydrophobic, and friction-reducing agent that is potentially useful in preventing at risk pressure injuries in tracheostomy dependent pediatric patients.