Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria.

AIM: Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS: Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS: Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION: Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.

Development of an in vitro model to study tooth cystogenesis.

AIM: To describe an in vitro experimental model of cystic structure formation to conduct research on radicular cyst development. METHODOLOGY: To form spheroid structures, various numbers (1 × 104 , 5 × 104 or 1 × 105 ) of epithelial cells (HaCaT and Cal27) were seeded in 96-well plates previously coated with 1.5% low-melting agarose. After 24 h, the spheroids were collected, embedded in 3D collagen matrix and transferred to 24-well plates previously coated with polymerized collagen and kept for up to 21 days. Images of spheroids were captured at each time-point (1, 5, 9, 15 and 21 days), and samples underwent histological and confocal microscopy analyses. Spheroid area, perimeter and cell dispersion were measured. One-way Anova was used for statistical analysis. RESULTS: Both epithelial cell lines were able to generate regular and circular spheroids after 24 h of incubation regardless of cell density. Spheroid structures in the collagen matrix were uniform in most samples until day 15, when several spots that appeared to be new cultures were seen. Spheroids from HaCaT were significantly more stable than those from Cal27 (P < 0.05). Starting on the third day, the examination of histological sections revealed a cavity with epithelial lining morphology, similar to a pathological radicular cyst. CONCLUSIONS: This study describes an experimental model of cystogenesis in vitro that may be used to test theories and investigates the effects of different growth factors during cyst development and maintenance.

Dynamic control over catalytic function using responsive bisthiourea catalysts.

Two novel bisthiourea molecular motor-based catalysts were designed and their dynamic control of activity and stereoselectivity in the Henry reaction using heat and light as external stimuli was investigated. Enantioselective organocatalysis studies established that a basic functional group is not required within the catalyst core to effect efficient dual stereocontrol, illustrating novel stimuli responsive organocatalysts.

The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression.

AIM: To detect cells expressing the stem cell marker ALDH1 (aldehyde dehydrogenase1) in the pulp of human permanent teeth and to investigate the expression of ALDH1 in isolated dental pulp cells. METHODOLOGY: Pulp tissue was collected and processed for immunohistochemistry to detect ALDH1-, STRO-1- and CD90-positive cells. In addition, cells were isolated and analysed by flow cytometry for ALDH1 activity and for the cell surface markers CD44, CD73, CD90, STRO-1 and CD45. Cells were also examined for multidifferentiation capacity. Within these cells, an ALDH1(+) cell subpopulation was selected and evaluated for multidifferentiation capacity. RESULTS: The immunohistochemistry analyses showed that ALDH1-, CD90- and STRO-1-positive cells were located mainly in the perivascular areas and nerve fibres of dental pulps. Cells on the fifth passage had high expression for CD44, CD73 and CD90, whereas moderate labelling was observed for STRO-1 and ALDH1 in flow cytometry analysis. On the same passages, cells were able to differentiate into osteogenic, adipogenic and chondrogenic lineages. The ALDH1(+) cell subpopulation also demonstrated multilineage differentiation ability. CONCLUSIONS: Dental pulp stem cells reside in the vicinity of blood vessels and nerve fibres, indicating the possible existence of more than one stem cell niche in dental pulps. Furthermore, ALDH1 was expressed by isolated dental pulp cells, which had mesenchymal stem cell characteristics. Thus, it can be suggested that ALDH1 may be used as a DPSC marker.

Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group.

Pregnancy loss prior to viability is common and research in the field is extensive. Unfortunately, terminology in the literature is inconsistent. The lack of consensus regarding nomenclature and classification of pregnancy loss prior to viability makes it difficult to compare study results from different centres. In our opinion, terminology and definitions should be based on clinical findings, and when possible, transvaginal ultrasound. With this Early Pregnancy Consensus Statement, it is our goal to provide clear and consistent terminology for pregnancy loss prior to viability.

Deep breathing acutely improves arterial dysfunction in obese children: evidence of functional impairment?

BACKGROUND AND AIMS: Similarly to diabetes type 2, patients with obesity show insulin resistance and autonomic and vascular abnormalities associated with increased morbidity and mortality. We tested whether arterial dysfunction in obese children may have a functional nature, reversible with appropriate interventions (e.g., by reduction of sympathetic activity), or else results from anatomic arterial modifications (likely irreversible). For this purpose, we tested whether deep breathing (an intervention known to transiently reduce sympathetic activity) could acutely improve arterial function, hence showing a functional abnormality. METHODS AND RESULTS: A total of 130 obese children and 67 age-matched healthy normal-weight control children were recruited. Arterial function was measured by augmentation index (AIx), by direct analysis of blood pressure contour, and by pulse wave velocity (PWV), during spontaneous and controlled breathing. The markers of metabolic syndrome were evaluated at baseline. AIx showed increased values in obese male participants as compared with the control group. Slow breathing acutely reduced Aix in obese children, to a greater extent than in normal-weight control children. Similarly, the blood pressure contour showed higher values in obese children that were significantly attenuated by slow breathing. Baseline PWV was not altered in obese participants. The markers of metabolic syndrome correlated with AIx and PWV. CONCLUSIONS: Obese subjects showed impaired arterial function. The acute improvement in vascular abnormalities with reduction in sympathetic activity indicates that this alteration was largely functional, likely related to initial autonomic dysfunction and to metabolic abnormalities. As a consequence, this study provides a rationale for strategies aiming at preventing arterial function deterioration in the early ages.

Application Tip and Concentration of a Self-mixing Bleach: Hydrogen Peroxide Inside the Pulp Chamber, Color Change, and Amount of Bleaching Gel Used.

PURPOSE: The objective of this study was to evaluate if the application method (tip with brush or tip without brush) and hydrogen peroxide (HP) concentration (6% or 35% self-mixing) of in-office bleaching gel influences the penetration of HP into the pulp chamber, color change, and the amount of bleaching gel used. METHODS: Forty healthy premolars were randomly divided into the following five groups (n=8): no treatment; HP6% using a tip with a brush, HP6% using a tip without a brush, HP35% using a tip with a brush, and HP35% using a tip without a brush. After treatments, the HP concentration (µg/mL) within the pulp chamber was determined using UV-Vis spectrophotometry. The color change (ΔEab, ΔE00, and ΔWID) was evaluated using a digital spectrophotometer. The amount of gel used (g) in each group was measured using a precision analytical balance. Data from each test were submitted to parametric tests (α=0.05). RESULTS: The tip with a brush resulted in a lower amount of HP inside the pulp chamber and less gel used when compared with the tip without a brush, regardless of HP concentration (p<0.05). However, regarding the tip used, although no significant difference was observed when HP35% was used (p>0.05), a higher whitening effect was observed when the 6% HP was applied without a brush as opposed to with a tip brush (p<0.05). CONCLUSIONS: The use of a tip with a brush, regardless of the in-office bleaching gel concentration (6% or 35% self-mixing), presented a lower penetration and lower volume of spent gel when compared to a tip without brush. However, the whitening effect depended on the concentration of HP used.

Correction to: Joint Family and Work Trajectories and Multidimensional Wellbeing.

[This corrects the article DOI: 10.1007/s10680-021-09583-3.].

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.

PURPOSE: This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. METHODS: The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored. All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. RESULTS: The surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 µSv for neuroradiology diagnostic study, 62 µSv for AVM, 38 µSv for aneurysm embolization, 33 µSv for CA-PTCA, 39 µSv for PM-ICD, 49 µSv for EVAR, 2500 µSv for FEVAR, 153 µSv for CT-guided lung biopsy. CONCLUSIONS: In interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used. Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.

Short-term oxygen administration restores blunted baroreflex sensitivity in patients with type 1 diabetes.

AIMS/HYPOTHESIS: We hypothesised that the blunted baroreflex sensitivity (BRS) typical of type 1 diabetes is caused by a higher degree of tissue hypoxia in diabetes, and tested whether oxygen increased BRS and ventilation less, equally or more than in healthy control participants (the latter suggesting higher tissue hypoxia). In addition, we also considered the possible interference between oxygen and breathing pattern. METHODS: In 96 participants with type 1 diabetes and 40 age-matched healthy controls, we measured BRS (average of six different standard methods), oxygen saturation, end-tidal carbon dioxide and ventilation changes during spontaneous and controlled breathing at 15 and six breaths/min, in normoxia and during 5 l/min oxygen administration. RESULTS: BRS was blunted and blood pressure higher in diabetic participants during spontaneous breathing (p < 0.05). BRS increased with oxygen during spontaneous breathing in diabetic (p < 0.001) but not in control participants, and with oxygen the difference in BRS was no longer significant. Slow breathing in normoxia restored BRS to a similar extent to giving oxygen. Oxygen increased systolic and diastolic blood pressure, RR interval, heart rate variability, minute ventilation and tidal volume to a greater extent in diabetic patients than in controls, and decreased carbon dioxide similarly to controls. CONCLUSIONS/INTERPRETATION: The increased response to hyperoxia suggests a pre-existing condition of tissue hypoxia that functionally restrains parasympathetic activity in patients with type 1 diabetes. Autonomic abnormalities can be partially and temporarily reversed by functional manoeuvres such as slow breathing or oxygen administration through enhancement of parasympathetic activity and/or correction of tissue hypoxia.

Deep breathing improves blunted baroreflex sensitivity even after 30 years of type 1 diabetes.

AIMS/HYPOTHESES: Cardiovascular autonomic neuropathy is associated with increased morbidity in patients with type 1 diabetes. Although it is conventionally considered to be an organic, irreversible disorder, we previously demonstrated in patients with short-duration type 1 diabetes that reduced baroreflex sensitivity (BRS) could be corrected by slow, deep breathing, indicating a functional component to the disorder. We have now tested whether autonomic abnormalities in long-term diabetes progress to a stage that cannot be modified by functional manoeuvres, indicating a switch towards predominantly organic dysfunction. METHODS: We studied 117 patients with a short duration (8.9 ± 0.1 years) and 37 patients with a long duration (33.7 ± 0.5 years) of type 1 diabetes, 73 healthy controls and 12 heart-transplanted participants (surgical heart denervation). An autonomic score was calculated from autonomic function tests. Spectral analysis of heart rate and blood pressure variability, and BRS, were obtained from recordings during normal (15 breaths per min) and slow, deep (six breaths per min) controlled breathing. RESULTS: BRS was reduced in all patients, but more in patients with a long duration of diabetes or with increasing autonomic involvement, although the effect of duration disappeared after adjustment for age. Slow breathing increased the BRS to the level of the control participants at a normal rate of breathing (15 per min) in all patients except those with an abnormal autonomic score. CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes have a blunted BRS that in the majority of patients can be restored by slow breathing, irrespective of disease duration. Even after a long duration of diabetes, the abnormal BRS is at least in part of functional origin.

Joint Family and Work Trajectories and Multidimensional Wellbeing.

Informed by the life course perspective, this paper investigates whether and how employment and family trajectories are jointly associated with subjective, relational and financial wellbeing later in life. We draw on data from the Swiss Household Panel which combines biographical retrospective information on work, partnership and childbearing trajectories with 19 annual waves containing a number of wellbeing indicators as well as detailed socio-demographic and social origin information. We use sequence analysis to identify the main family and work trajectories for men and women aged 20-50 years old. We use OLS regression models to assess the association between those trajectories and their interdependency with wellbeing. Results reveal a joint association between work and family trajectories and wellbeing at older age, even net of social origin and pre-trajectory resources. For women, but not for men, the association is also not fully explained by proximate (current family and work status) determinants of wellbeing. Women's stable full-time employment combined with traditional family trajectories yields a subjective wellbeing premium, whereas childlessness and absence of a stable partnership over the life course is associated with lower levels of financial and subjective wellbeing after 50 especially in combination with a trajectory of weak labour market involvement. Relational wellbeing is not associated with employment trajectories, and only weakly linked to family trajectories among men.

Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis.

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.

Early autonomic dysfunction in type 1 diabetes: a reversible disorder?

AIMS/HYPOTHESIS: Cardiac autonomic neuropathy is associated with increased morbidity and mortality rates in patients with type 1 diabetes. The prevalence of early autonomic abnormalities is relatively high compared with the frequency of manifest clinical abnormalities. Thus, early autonomic dysfunction could to some extent be functional and might lead to an organic disease in a subgroup of patients only. If this is true, manoeuvres such as slow deep-breathing, which can improve baroreflex sensitivity (BRS) in normal but not in denervated hearts, could also modify autonomic modulation in patients with type 1 diabetes, despite autonomic dysfunction. METHODS: We compared 116 type 1 diabetic patients with 36 matched healthy control participants and 12 heart-transplanted participants with surgically denervated hearts. Autonomic function tests and spectral analysis of heart rate and blood pressure variability were performed. BRS was estimated by four methods during controlled (15 breaths per minute) and slow deep-breathing (six breaths per minute), and in supine and standing positions. RESULTS: Conventional autonomic function tests were normal, but resting spectral variables and BRS were reduced during normal controlled breathing in patients with type 1 diabetes. However, slow deep-breathing improved BRS in patients with type 1 diabetes, but not in patients with surgically denervated hearts. Standing induced similar reductions in BRS in diabetic and control participants. CONCLUSIONS/INTERPRETATION: Although we found signs of increased sympathetic activity in patients with type 1 diabetes, we also observed a near normalisation of BRS with a simple functional test, indicating that early autonomic derangements are to a large extent functional and potentially correctable by appropriate interventions.

Oxygen affinity and electrolyte distribution of human blood: changes induced by propranolol.

Propranolol causes a massive leakage of potassium ions from red cells, which results in an alteration of the Gibbs-Donnan equilibrium across the red cell membrane. According to such a mechanism, the presence of propranolol significantly increases the hydrogen ion activity of the interior of the red cell, causing a decreased oxygen affinity of hemoglobin according to the classical Bohr effect. No release of 2,3-diphosphoglycerate which may be bound to the membrane is thus necessary to explain the effect of propranolol on the oxygen dissociation curve of blood.

Intermittent hypoxia increases exercise tolerance in patients at risk for or with mild COPD.

The effects of repeated short-term hypoxia on exercise tolerance in patients at risk for, or with mild COPD were investigated. Eighteen patients (10 males, 8 females; 33-72 years) were randomly assigned in a double-blind fashion to receive 15 sessions of intermittent hypoxia (FiO(2): 0.15-0.12) or normoxia within 3 weeks. Three weeks of intermittent hypoxia increased total haemoglobin mass (+4% vs. 0%, p<0.05), total exercise time (+9.7% vs. 0%, p<0.05) and the exercise time to the anaerobic threshold (+13% vs. -7.8%, p<0.05) compared to controls. Changes in the total exercise time were positively related to the changes in total haemoglobin mass (r=0.59, p<0.05) and changes in the time to the anaerobic threshold were positively related to the changes in the lung diffusion capacity for carbon monoxide (r=0.48, p<0.05). Intermittent hypoxia treatment may be a valuable addition to therapy designed to improve exercise tolerance in patients at risk for, or with mild COPD.

[TNFalpha blockers and infectious risk in rheumatoid arthritis]. / I farmaci biologici anti-TNFalpha e il rischio infettivo nell'artrite reumatoide.

Patients suffering from rheumatoid arthritis have increased risk of infections when compared with general population. The risk depends directly from disease activity and severity. Furthermore, risk increases with aging, immunosuppressive agents and comorbidities such as diabetes, pulmonary and cardiac diseases. In particular corticosteroids, even at low doses, are a major risk factor. Due to disease related risk it is difficult to separate the risk deriving from the use of TNF alpha blockers. Data from clinical trials, meta-analysis and national registers are somewhat contradictory. In patients with rheumatoid arthritis on routine follow-up, treatment with TNF alpha blockers seems to carry an increased risk of infections compared to traditional DMARDs but not associated with increased risk of overall serious infection. Physicians should carefully monitor for signs of infection when using TNF alpha blockers, particularly shortly after treatment initiation.

Lonomia obliqua bristle extract modulates Rac1 activation, membrane dynamics and cell adhesion properties.

Lonomia obliqua is a caterpillar of potential therapeutic interest whose venom is able to induce severe blood leakage and modulate leukocyte migration. Since both phenotypes are associated with changes in cytoskeleton dynamics and cell adhesion properties, the aim of this study was to analyze the effects of Lonomia obliqua bristle extract (LOBE) in cell adhesion and migration signaling. Proteomic analysis revealed that epithelial cells (CHO-K1) exposed to LOBE (30 µg/mL, 30 min) exhibited changes in levels of actin regulatory proteins, including RhoGTPases. These changes correlated with an increase in the activity of the RhoGTPase family member Rac as measured by Förster resonance energy transfer (FRET). When plated in migration promoting conditions, CHO-K1 cells exposed to LOBE (10 µg/mL) showed an increase in membrane ruffling after short (30 min) period of incubation that was accompanied by changes in the distribution of the adhesion markers paxillin, vinculin and an increase of focal adhesion kinase autophosphorylation levels (Y397), suggesting changes in cell-extracellular matrix (ECM) adhesion properties and signaling. These data suggest that LOBE possesses bioactive molecules that are capable to modulated cell migration signaling, cytoskeletal dynamics and cell-ECM properties of several cell types.