Influence of apneic oxygenation on cardiorespiratory system homeostasis

Purpose

The aim of this study was to elucidate the magnitude of variations in oxygenation indices and the pattern of hemodynamic changes in response to the net effect of tracheal apneic oxygenation (AO) with a view to define the safe time limit of its application.

Methods

After obtaining Animal Research Ethics Committee approval, AO was applied in 12 piglets for 40 min. Arterial (a) and mixed venous (v) blood samples for oxygen (O₂) and carbon dioxide (CO₂) tension (PaO₂/PvO₂, PaCO₂/PvCO₂), O₂ saturation (SaO₂/SvO₂), pHa, base excess (BEa), and bicarbonate (HCO₃a) determination and for alveolar O₂ tension (PAO₂), PaO₂/FiO₂ and PaO₂/PAO₂ ratio, arterial–mixed venous O₂ content (AVDO₂), and O₂ extraction ratio (O₂ER) estimation were collected on anesthesia induction, 10, 20, 30, and 40 min during AO and 10 and 20 min after reconnection to the ventilator. Concomitant hemodynamic data were obtained.

Results

Besides PvO₂ and PAO₂, AO adversely influenced PaO₂ (248–113 mmHg), PaCO₂ (35–145 mmHg), PvCO₂, PaO₂/FiO₂, and PaO₂/PAO₂ in a time-depended fashion, whereas SvO₂, AVDO₂, and O₂ER were minimally affected. P(a ? v)CO₂ was reversed throughout AO. Acid–base status derangement, consisting of HCO₃a elevation, BEa widening, and acidemia (pH 6.9) maximized 40 min after AO. During AO, heart rate, systemic and pulmonary circulation pressures, and cardiac output were progressively elevated, whereas systemic vascular resistance was reduced. All the studied parameters reverted almost to baseline within the 20-min period of ventilator reconnection.

Conclusion

Tracheal AO for 40 min ensures acceptable blood oxygenation, promotes notable hypercapnic acidosis, and consequent transient hemodynamic alterations, which are almost completely reversible after reconnection to the ventilator.     

Translation,cross-cultural adaptation and validation of the Bulgarian version of the Dizziness Handicap Inventory

Purpose

The aim of the present study was the translation, cross-cultural adaptation and validation of the Dizziness Handicap Inventory in Bulgarian language (DHI-BG).

Methods

Ninety-seven vestibular patients (19 men and 78 women, mean age 45.08 ± 13.85 years) took part in the investigation. All participants were asked to fill in the DHI-BG. Internal consistency was estimated using Cronbach’s alpha and item-total correlation, reproducibility by calculating Bland–Altman’s limits of agreement and intraclass correlation coefficients (ICCs). Associations were estimated by Spearman’s correlation coefficients.

Results

The Cronbach’s alpha for the total score, functional, physical and emotional subscales of DHI-BG were 0.88, 0.75, 0.72 and 0.81. The floor and ceiling effects of the DHI-BG total scale were evaluated with respect to the limits of agreement which were ±9.4–14.53 points. Intraclass correlation coefficients (ICCs) for all scale and subscales were higher than the recommended value of 0.75 and determined good test–retest reliability. The range of items correlation for DHI-BG was from 0.27 (item 12) to 0.72 (item 3). No significant differences were observed in the Cronbach’s alpha coefficients between the DHI-BG and the original version, the German and Italian versions of the questionnaire. The most significant difference was observed in comparison with the German version of DHI. Construct validity presented a moderate correlation between Romberg coefficients and DHI-BG scores and strong correlation between all scores of DHI and the self-perceived disability. The results suggest that DHI-BG scores show a good discriminative validity between groups with different levels of self-assessed disability.

Conclusion

The Bulgarian version of the DHI is a reliable and valid tool in assessing the impact of dizziness on the quality of life in Bulgarian vestibular patients.     

A Mediterranean-like breakfast affects energy intake and appetite-related feelings

Energy intake and appetite feelings after the consumption of two different types of breakfast, a high-fiber, traditional, Mediterranean-type breakfast and a low-fiber, Western-type breakfast were compared. Sixteen non-obese young men received the two treatments on separate days: the Mediterranean- and the Western-type breakfasts were isocaloric, similar in volume and macronutrient content, but different in fiber content. Following a 4-hour fast, subjects offered an ad libitum lunch. Food consumed and subjective feelings of hunger, fullness, and desire to eat were evaluated. Energy intake in the ad libitum lunch was significantly lower after the Mediterranean-type, compared to the Western-type breakfast, adjusting for previous day’s energy intake (1488?±?468 versus 1674?±?416?kcal, respectively), whereas no energy compensation was made throughout the day. Furthermore, those who had the Mediterranean-type breakfast reported lower values in the desire to eat during study's course. These findings propose a fulfilling effect of a traditional, Mediterranean, high in fiber breakfast.     

Long non-coding RNAs in development and disease: conservation to mechanisms

Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein-coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the ‘dark matter’ of our genomes, our understanding of which is extremely limited. Part of this ‘dark matter’ includes regions that give rise to RNAs that do not code for proteins. A subset of these non-coding RNAs are long non-coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Gestational sleep deprivation is associated with higher offspring body mass index and blood pressure

Study ObjectivesThe objective of this study was to evaluate the association between gestational sleep deprivation and childhood adiposity and cardiometabolic profile.MethodsData were used from two population-based birth cohorts (Rhea study and Amsterdam Born Children and their Development study). A total of 3,608 pregnant women and their children were followed up until the age of 11 years. Gestational sleep deprivation was defined as 6 or fewer hours of sleep per day, reported by questionnaire. The primary outcomes included repeated measures of body mass index (BMI), waist circumference, body fat, serum lipids, systolic and diastolic blood pressure (DBP) levels in childhood. We performed a pooled analysis with adjusted linear mixed effect and Cox proportional hazards models. We tested for mediation by birthweight, gestational age, and gestational diabetes.ResultsGestational sleep deprivation was associated with higher BMI (beta; 95% CI: 0.7; 0.4, 1.0 kg/m²) and waist circumference (beta; 95% CI: 0.9; 0.1, 1.6 cm) in childhood, and increased risk for overweight or obesity (HR; 95% CI: 1.4; 1.1, 2.0). Gestational sleep deprivation was also associated with higher offspring DBP (beta; 95% CI: 1.6; 0.5, 2.7 mmHg). The observed associations were modified by sex (all p-values for interaction < 0.05); and were more pronounced in girls. Gestational diabetes and shorter gestational age partly mediated the seen associations.ConclusionsThis is the first study showing that gestational sleep deprivation may increase offspring’s adiposity and blood pressure, while exploring possible mechanisms. Attention to glucose metabolism and preterm birth might be extra warranted in mothers with gestational sleep deprivation.     

Genome-wide screening of DNA copy number alterations in cervical carcinoma patients with CGH+SNP microarrays and HPV-FISH

Alterations in the genome that lead to changes in DNA sequence copy number are characteristic features of solid tumors. We used CGH+SNP microarray and HPV-FISH techniques for detailed screening of copy number alterations (CNAs) in a cohort of 26 patients with cervical carcinoma (CC). This approach identified CNAs in 96.2% (25/26) of tumors. Array-CGH discovered CNAs in 73.1% (19/26) of samples, HPV-FISH experiments revealed CNAs in additional 23.1% (6/26) of samples. Common gains of genetic sequences were observed in 3q (50.0%), 1q (42.4%), 19q (23.1%), while losses were frequently found in 11q (30.8%), 4q (23.1%) and 13q (19.2%). Chromosomal regions involved in loss of heterozygosity were observed in 15.4% of samples in 8q21, 11q23, 14q21 and 18q12.2. Incidence of gain 3q was associated with HPV 16 and HPV 18 positive samples and simultaneous presence of gain 1q (P = 0.033). We did not found a correlation between incidence of CNAs identified by array-CGH and HPV strain infection and incidence of lymph node metastases. Subsequently, HPV-FISH was used for validation of array-CGH results in 23 patients for incidence of hTERC (3q26) and MYC (8q24) amplification. Using HPV-FISH, we found chromosomal lesions of hTERC in 87.0% and MYC in 65.2% of specimens. Our findings confirmed the important role of HPV infection and specific genomic alterations in the development of invasive cervical cancer. This study also indicates that CGH+SNP microarrays allow detecting genome-wide CNAs and copy-neutral loss of heterozygosity more precisely, however, it may be less sensitive than FISH in samples with low level clonal CNAs.     

PCaGuard: A Software Platform to Support Optimal Management of Prostate Cancer

Background and Objective  Prostate cancer (PCa) is a severe public health issue and the most common cancer worldwide in men. Early diagnosis can lead to early treatment and long-term survival. The addition of the multiparametric magnetic resonance imaging in combination with ultrasound (mpMRI-U/S fusion) biopsy to the existing diagnostic tools improved prostate cancer detection. Use of both tools gradually increases in every day urological practice. Furthermore, advances in the area of information technology and artificial intelligence have led to the development of software platforms able to support clinical diagnosis and decision-making using patient data from personalized medicine. Methods  We investigated the current aspects of implementation, architecture, and design of a health care information system able to handle and store a large number of clinical examination data along with medical images, and produce a risk calculator in a seamless and secure manner complying with data security/accuracy and personal data protection directives and standards simultaneously. Furthermore, we took into account interoperability support and connectivity to legacy and other information management systems. The platform was implemented using open source, modern frameworks, and development tools. Results  The application showed that software platforms supporting patient follow-up monitoring can be effective, productive, and of extreme value, while at the same time, aiding toward the betterment medicine clinical workflows. Furthermore, it removes access barriers and restrictions to specialized care, especially for rural areas, providing the exchange of medical images and patient data, among hospitals and physicians. Conclusion  This platform handles data to estimate the risk of prostate cancer detection using current state-of-the-art in eHealth systems and services while fusing emerging multidisciplinary and intersectoral approaches. This work offers the research community an open architecture framework that encourages the broader adoption of more robust and comprehensive systems in standard clinical practice.     

Depletion of microglia in developing cortical circuits reveals its critical role in glutamatergic synapse development,functional connectivity,and critical period plasticity

Microglia populate the early developing brain and mediate pruning of the central synapses. Yet, little is known on their functional significance in shaping the developing cortical circuits. We hypothesize that the developing cortical circuits require microglia for proper circuit maturation and connectivity, and as such, ablation of microglia during the cortical critical period may result in a long-lasting circuit abnormality. We administered PLX3397, a colony-stimulating factor 1 receptor inhibitor, to mice starting at postnatal day 14 and through P28, which depletes >75% of microglia in the visual cortex (VC). This treatment largely covers the critical period (P19-32) of VC maturation and plasticity. Patch clamp recording in VC layer 2/3 (L2/3) and L5 neurons revealed increased mEPSC frequency and reduced amplitude, and decreased AMPA/NMDA current ratio, indicative of altered synapse maturation. Increased spine density was observed in these neurons, potentially reflecting impaired synapse pruning. In addition, VC intracortical circuit functional connectivity, assessed by laser scanning photostimulation combined with glutamate uncaging, was dramatically altered. Using two photon longitudinal dendritic spine imaging, we confirmed that spine elimination/pruning was diminished during VC critical period when microglia were depleted. Reduced spine pruning thus may account for increased spine density and disrupted connectivity of VC circuits. Lastly, using single-unit recording combined with monocular deprivation, we found that ocular dominance plasticity in the VC was obliterated during the critical period as a result of microglia depletion. These data establish a critical role of microglia in developmental cortical synapse pruning, maturation, functional connectivity, and critical period plasticity.