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Platelet volume indices: markers of carotid atherosclerosis in type 2 diabetes mellitus?

Background. Platelet volume indices (PVI) such as mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P‑LCR) are the indicators of platelet activity and may have a role in subclinical atherosclerosis and microvascular complications in type 2 diabetes mellitus (T2DM). We evaluated PVI in diabetics for their association with carotid intima media thickness (CIMT) and micro-vascular complications. Methods. Participants — 105 T2DM patients and age, gender matched 105 controls were evaluated by history and complete blood counts (CBC) including PVI, blood sugars, HbA1c, lipid profile and microvascular complications. PVI were compared between cases and controls. Carotid Doppler was done and CIMT was correlated with PVI. Results. PVI were found significantly higher in diabetic patients compared to controls. Mean MPV in cases vs. controls was (11.09 ± 1.02 fL vs. 10.28 ± 0.96 fL, p ≤ 0.001), mean PDW (13.46 ± 1.96 fL vs. 12.85 ± 3.54 fL, p = 0.12), mean P-LCR (31.92 ± 6.23% vs. 27.94 ± 5.94%, p ≤ 0.001). CIMT showed a positive significant association with MPV, PDW and PLCR, dyslipidemia and negative with glycemic control. PVI, especially MPV was significantly elevated in those with neuropathy, nephropathy and retinopathy. Conclusion. PVI i.e. MPV, PDW, P-LCR are increased in diabetic patients. They correlate positively with CIMT, implying cardiovascular risk. PVI have a positive association with microvascular complications also. PVI as determined by simple automated CBC can be used as markers of subclinical atherosclerosis and predictor of future cardiovascular events in T2DM.

The use of neural integrity monitor [NIM flextm] tube in patients undergoing posterior fossa surgery: our institutional experience

Neurosurgery for cerebellopontine angle tumour involves handling and dissection of cranial nerves at their origin from the brainstem. Lower cranial nerves or their nuclei may be affected by lesions arising from or extending up to the medulla. Preserving their structural and functional integrity is an important goal during surgical resection. Important functions of vagus nerve include swallowing, speech, respiration and heart rate control and its damage is one of the devastating complications of posterior fossa tumour resection. Electromyographic monitoring for recurrent branch of vagus nerve has been done in thyroid surgeries using a specially designed neural integrity monitor (NIM flexTM) electromyogram (EMG) endotracheal tube containing embedded stimulating electrodes placed at the level of vocal cords. We present our experience with the use of this NIM flexTM EMG endotracheal tube for vagus nerve monitoring in neurosurgery for posterior fossa tumours in four patients. Use of this tube in neurosurgery has been less reported in the Indian literature

Transient facial nerve palsy after scalp block for awake craniotomy: A case report

Awake craniotomy is a unique clinical setting that needs anesthesiologist to provide variable states of sedation and analgesia to ensure optimal operating conditions without compromising patient safety. Scalp block is an integral part of awake craniotomy as it provides regional anesthesia to the nerves innervating the scalp. It minimizes response to noxious stimuli of cranial pin application and craniotomy. We report a case of transient facial nerve palsy after scalp block in awake craniotomy in a patient with a lesion in the motor cortex. Facial nerve palsy has been described as a rare complication of scalp block and is less reported

Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection

On Earth, biological systems have evolved in response to environmental stressors, interactions dictated by physical forces that include gravity. The absence of gravity is an extreme stressor and the impact of its absence on biological systems is ill-defined. Astronauts who have spent extended time under conditions of minimal gravity (microgravity) experience an array of biological alterations, including perturbations in cardiovascular function. We hypothesized that physiological perturbations in cardiac function in microgravity may be a consequence of alterations in molecular and organellar dynamics within the cellular milieu of cardiomyocytes. We used a combination of mass spectrometry-based approaches to compare the relative abundance and turnover rates of 848 and 196 proteins, respectively, in rat neonatal cardiomyocytes exposed to simulated microgravity or normal gravity. Gene functional enrichment analysis of these data suggested that the protein content and function of the mitochondria, ribosomes, and endoplasmic reticulum were differentially modulated in microgravity. We confirmed experimentally that in microgravity protein synthesis was decreased while apoptosis, cell viability, and protein degradation were largely unaffected. These data support our conclusion that in microgravity cardiomyocytes attempt to maintain mitochondrial homeostasis at the expense of protein synthesis. The overall response to this stress may culminate in cardiac muscle atrophy

Dizajniranje i optimizacija mikrokapsula artemetera za maskiranje gorkog okusa

The objective of the present investigation was to reduce the bitterness of artemether (ARM). Microparticles were prepared by the coacervation method using Eudragit E 100 (EE) as polymer and sodium hydroxide solution as nonsolvent for the polymer. A 32 full factorial design was used for optimization wherein the amount of drug (A) and polymer (B) were selected as independent variables and the bitterness score, particle size and drug release at pH, 1.2 and 6.8 were selected as dependent variables. Optimization was carried out using the desirability function. The optimized microparticles batch was characterized by FT-IR and DSC. Multiple linear regression analysis revealed that reduced bitterness of ARM can be obtained by controlling the drug release of microparticles at pH 6.8 and increasing the amount of EE. The increase in the amount of polymer leads to reduction in drug release from microparticles at pH > 5 due to its insolubility and thus reduces bitterness. However, the increase in the amount of polymer results in improved dissolution, suggesting improved availability of ARM in stomach. Optimized microparticles prepared using 0.04 g of ARM and 15 mL of 1% m/V solution of EE showed complete bitter taste masking with improved drug release at pH 1.2.Cilja ovog rada je bio maskirati gorki okus artemetera (ARM) mikrokapsuliranjem. Mikročestice su pripravljene metodom koacervacije pomoću Eudragita E 100 (EE) kao polimerne komponente i natrijevog hidroksida u kojem se polimer ne otapa. 32 faktorijalni dizajn upotrebljen je za optimizaciju. Količine ljekovite tvari (A) i polimera (B) izabrane su kao nezavisne varijable, a intenzitet gorkog okusa, veličina čestica i oslobađanje ljekovite tvari pri pH 1,2 i 6,8 izabrane su kao zavisne varijable. Optimizirane mikročestice karakterizirane su pomoću FT-IR i DSC. Multipla linearna regresijska analiza otkrila je da se smanjenje gorčine artemetera može postići kontroliranjem oslobađanja ljekovite tvari pri pH 6,8 i povećanjem količine EE. Povećanje količine polimera dovodi do smanjenja oslobađanja ljekovite tvari pri pH > 5 pa se smanjuje i gorčina. Međutim, povećanje količine polimera povećava topljivost ljekovite tvari, a time potencijalno i njenu raspoložljivost u želucu. U optimiziranim mikročesticama pripravljenim pomoću 0,04 g ARM i 15 mL 1% m/v otopine EE potpuno se maskirao gorki okus, a oslobađanje ljekovite tvari pri pH 1,2 bilo je poboljšano

Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC

OBJECTIVE The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS The strongest associations in the MHC class II region (rs3957146, beta [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (beta [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, beta [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.Peer reviewe

Mice expressing a human KATP channel mutation have altered channel ATP sensitivity but no cardiac abnormalities

AIMS/HYPOTHESIS: Patients with severe gain-of-function mutations in the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, have neonatal diabetes, muscle hypotonia and mental and motor developmental delay-a condition known as iDEND syndrome. However, despite the fact that Kir6.2 forms the pore of the cardiac K(ATP) channel, patients show no obvious cardiac symptoms. The aim of this project was to use a mouse model of iDEND syndrome to determine whether iDEND mutations affect cardiac function and cardiac K(ATP) channel ATP sensitivity. METHODS: We performed patch-clamp and in vivo cine-MRI studies on mice in which the most common iDEND mutation (Kir6.2-V59M) was targeted to cardiac muscle using Cre-lox technology (m-V59M mice). RESULTS: Patch-clamp studies of isolated cardiac myocytes revealed a markedly reduced K(ATP) channel sensitivity to MgATP inhibition in m-V59M mice (IC(50) 62 μmol/l compared with 13 μmol/l for littermate controls). In vivo cine-MRI revealed there were no gross morphological differences and no differences in heart rate, end diastolic volume, end systolic volume, stroke volume, ejection fraction, cardiac output or wall thickening between m-V59M and control hearts, either under resting conditions or under dobutamine stress. CONCLUSIONS/INTERPRETATION: The common iDEND mutation Kir6.2-V59M decreases ATP block of cardiac K(ATP) channels but was without obvious effect on heart function, suggesting that metabolic changes fail to open the mutated channel to an extent that affects function (at least in the absence of ischaemia). This may have implications for the choice of sulfonylurea used to treat neonatal diabetes

Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes

Background: In adulthood, autoimmune diabetes can present as non-insulin-requiring diabetes, termed as 'latent autoimmune diabetes in adults' (LADA). In this study, we investigated established type 1 diabetes (T1D) and type 2 diabetes (T2D) genetic loci in a large cohort of LADA cases to assess where LADA is situated relative to these two well-characterized, classic forms of diabetes. Methods: We tested the association of T1D and T2D GWAS-implicated loci in 978 LADA cases and 1057 nondiabetic controls of European ancestry using a linear mixed model. We then compared the associations of T1D and T2D loci between LADA and T1D and T2D cases, respectively. We quantified the difference in genetic risk between each given disease at each locus, and also calculated genetic risk scores to quantify how genetic liability to T1D and T2D distinguished LADA cases from controls. Results: Overall, our results showed that LADA is genetically more similar to T1D, with the exception of an association at the T2D HNF1A locus. Several T1D loci were associated with LADA, including the major histocompatibility complex region, as well as at PTPN22, SH2B3, and INS. Contrary to previous studies, the key T2D risk allele at TCF7L2 (rs7903146-T) had a significantly lower frequency in LADA cases, suggesting that this locus does not play a role in LADA etiology. When constrained on antibody status, the similarity between LADA and T1D became more apparent; however, the HNF1A and TCF7L2 observations persisted. Conclusion: LADA is genetically closer to T1D than T2D, although the genetic load of T1D risk alleles is less than childhood-onset T1D, particularly at the major histocompatibility complex region, potentially accounting for the later disease onset. Our results show that the genetic spectrum of T1D extends into adult-onset diabetes, where it can clinically masquerade as T2D. Furthermore, T2D genetic risk plays a small role in LADA, with a degree of evidence for the HNF1A locus, highlighting the potential for genetic risk scores to contribute towards defining diabetes subtypes

Elena+ Care for COVID-19, A Pandemic Lifestyle Care Intervention: Intervention Design and Study Protocol

Background: The current COVID-19 coronavirus pandemic is an emergency on a global scale, with huge swathes of the population required to remain indoors for prolonged periods to tackle the virus. In this new context, individuals’ health-promoting routines are under greater strain, contributing to poorer mental and physical health. Additionally, individuals are required to keep up to date with latest health guidelines about the virus, which may be confusing in an age of social-media disinformation and shifting guidelines. To tackle these factors, we developed Elena+, a smartphone-based and conversational agent (CA) delivered pandemic lifestyle care intervention.Methods: Elena+ utilizes varied intervention components to deliver a psychoeducation-focused coaching program on the topics of: COVID-19 information, physical activity, mental health (anxiety, loneliness, mental resources), sleep and diet and nutrition. Over 43 subtopics, a CA guides individuals through content and tracks progress over time, such as changes in health outcome assessments per topic, alongside user-set behavioral intentions and user-reported actual behaviors. Ratings of the usage experience, social demographics and the user profile are also captured. Elena+ is available for public download on iOS and Android devices in English, European Spanish and Latin American Spanish with future languages and launch countries planned, and no limits on planned recruitment. Panel data methods will be used to track user progress over time in subsequent analyses. The Elena+ intervention is open-source under the Apache 2 license (MobileCoach software) and the Creative Commons 4.0 license CC BY-NC-SA (intervention logic and content), allowing future collaborations; such as cultural adaptions, integration of new sensor-related features or the development of new topics.Discussion: Digital health applications offer a low-cost and scalable route to meet challenges to public health. As Elena+ was developed by an international and interdisciplinary team in a short time frame to meet the COVID-19 pandemic, empirical data are required to discern how effective such solutions can be in meeting real world, emergent health crises. Additionally, clustering Elena+ users based on characteristics and usage behaviors could help public health practitioners understand how population-level digital health interventions can reach at-risk and sub-populations