Emerging Treatment Targets for Migraine and Other Headaches

Migraine is a complex disorder that is characterized by an assortment of neurological and systemic effects. While headache is the most prominent feature of migraine, a host of symptoms affecting many physiological functions are also observed before, during, and after an attack. Furthermore, migraineurs are heterogeneous and have a wide range of responses to migraine therapies. The recent approval of calcitonin gene-related-peptide based therapies has opened up the treatment of migraine and generated a renewed interest in migraine research and discovery. Ongoing advances in migraine research have identified a number of other promising therapeutic targets for this disorder. In this review, we highlight emergent treatments within the following biological systems: pituitary adenylate cyclase activating peptdie, 2 non-mu opioid receptors that have low abuse liability – the delta and kappa opioid receptors, orexin, and nitric oxide-based therapies. Multiple mechanisms have been identified in the induction and maintenance of migraine symptoms; and this divergent set of targets have highly distinct biological effects. Increasing the mechanistic diversity of the migraine tool box will lead to more treatment options and better patient care.     

γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe

Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA⁺]/[NAA–NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA⁺]/[NAA–NAAG] and perfusion (R=−0.46; P=0.037), yet no relationship between AAT and [GABA⁺]/[NAA–NAAG] (R=−0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA⁺]/[NAA–NAAG] and perfusion (R=−0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission.     

Gait characteristics of patients with phobic postural vertigo: effects of fear of falling,attention, and visual input

Phobic postural vertigo (PPV) is the most common cause of chronic dizziness in middle-aged patients. Many patients report symptoms involving gait. We investigated the gait performance and its relationship to the fear of falling and attention of PPV patients in a prospective study of 24 patients with PPV and 24 healthy subjects (HS) using a pressure-sensitive mat (GAITRite^®). Subjects walked at three different speeds (slow, preferred, fast), both during cognitive dual tasks (DTc) and with eyes closed (EC). Falls efficacy and balance confidence were rated by the Falls Efficacy Scale-International (FES-I) and the Activities-specific Balance Confidence Scale (ABC). PPV patients walked slower, with reduced cadence (all p < 0.01), stride length (p < 0.05), and increased double support (p < 0.01) compared to HS. These changes correlated with FES-I (R = ?0.528, p < 0.001) and ABC (R = 0.481, p < 0.01). Walking deterioration under DTc did not differ between PPV patients and HS, but patients showed a reduced cognitive processing speed (p < 0.05). When walking with EC, gait speed decreased more in PPV patients compared to HS (p < 0.05). Patients with PPV show gait changes which correlate with their fear of falling and balance confidence. Absent visual feedback leads to more pronounced gait deteriorations in PPV patients than in HS, indicating a higher reliance of patients on visual information during walking. These findings support the view that the gait characteristics of PPV can be attributed to an inadequate, cautious gait control.     

Congenitally corrected transposition and mitral atresia complicated by restrictive atrial septum

Congenitally corrected transposition (ccTGA), also known as L-transposition of the great arteries (L-TGA), is a rare cardiac malformation accounting for approximately 0.05% of congenital heart disease, characterized by ventricular inversion, discordant ventriculo-arterial connections with a normal visceroatrial relationship. It was first described by Baron Rokitansky in 1875, and prenatal sonographic diagnosis can be difficult. Symptomatology and clinical presentation of this malformation are related to the associated intracardiac defects. We report a rare case of severe, complex cardiac disease: prenatally diagnosed ccTGA with atrial restriction, mitral atresia, Ebsteinoid tricuspid valve, and severe pulmonary valve stenosis, who subsequently developed left pulmonary vein stenosis.     

Hematological and plasma biochemistry in Cirrhinus mrigala (Hamilton 1822)

Hematological and plasma chemistry indices are important parameters for the evaluation of fish physiological status. In this study, we determined the results of selected hematological and plasma biochemical profiles in Cirrhinus mrigala captured from the wild in a tropical climate of India. Blood was analyzed using standard techniques, and differences in hematological parameters including hemoglobin concentration, erythrocyte count, total leukocyte count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) of fish were compared according to sex and different seasons. Analysis of variance showed that there were significant differences (p?<?0.05) between sexes, and the results indicated that blood parameters levels between the sexes in summer were significantly different than that measure in other seasons except MCH and MCHC value. The number of total leukocyte levels was found to be higher in female fish especially in reproductive seasons (summer), but the levels of hemoglobin, hematocrit, and MCV values were high in male fish in an annual period. However, there was no difference in MCH and MCHC values between the sexes and seasons throughout the study period. These may be related to season of sampling and changing physiological cycles during these months. Differences were noted in plasma lipid, cholesterol, and glucose level in the summer season, but the higher amount of plasma protein was found in spring and winter in male and female fish, respectively. In conclusion, monitoring fish hematological and biochemical parameters essentially can be a way to evaluate the physiological and health status of their populations, which may be a useful indicator of the environmental status.     

Prevalence,distribution, and social determinants of tobacco use in 30 sub-Saharan African countries

Background

Although the Framework Convention on Tobacco Control prioritizes monitoring of tobacco use by population-based surveys, information about the prevalence and patterns of tobacco use in sub-Saharan Africa is limited. We provide country-level prevalence estimates for smoking and smokeless tobacco (SLT) use and assess their social determinants.

Methods

We analyzed population-based data of the most recent Demographic Health Surveys performed between 2006 and 2013 involving men and women in 30 sub-Saharan African countries. Weighted country-level prevalence rates were estimated for ‘current smoking’ (cigarettes, pipe, cigars, etc.) and ‘current SLT use’ (chewing, snuff, etc.). From the pooled datasets for men and women, social determinants of smoking and SLT use were assessed through multivariate analyses using a dummy country variable as a control and by including a within-country sample weight for each country.

Results

Among men, smoking prevalence rates were high in Sierra Leone (37.7%), Lesotho (34.1%), and Madagascar (28.5%); low (<10%) in Ethiopia, Benin, Ghana, Nigeria, and Sao Tome & Principe; the prevalence of SLT use was <10% in all countries except for Madagascar (24.7%) and Mozambique (10.9%). Among women, smoking and SLT prevalence rates were <5% in most countries except for Burundi (9.9%), Sierra Leone (6%), and Namibia (5.9%) (smoking), and Madagascar (19.6%) and Lesotho (9.1%) (SLT use). The proportion of females who smoked was lower than SLT users in most countries. Older age was strongly associated with both smoking and SLT use among men and women. Smoking among both men and women was weakly associated, but SLT use was strongly associated, with education. Similarly, smoking among men and women was weakly associated, but SLT use was strongly associated, with the wealth index. Smoking and SLT use were also associated with marital status among both men and women, as well as with occupation (agriculturists and unskilled workers).

Conclusions

Prevalence of smoking among women was much lower than in men, although the social patterns of tobacco use were similar to those in men. Tobacco control strategies should target the poor, not/least educated, and agricultural and unskilled workers, who are the most vulnerable social groups in sub-Saharan Africa.

     

Support to the Safe Motherhood Programme in Nepal: an integrated approach

Evidence gathered from 1997 to 2006 indicates progress in reducing maternal mortality in Nepal, but public health services are still constrained by resource and staff shortages, especially in rural areas. The five-year Support to the Safe Motherhood Programme builds on the experience of the Nepal Safer Motherhood Project (1997-2004). It is working with the Government of Nepal to build capacity to institute a minimum package of essential maternity services, linking evidence-based policy development with health system strengthening. It has supported long-term planning, working towards skilled attendance at every birth, safe blood supplies, staff training, building management capacity, improving monitoring systems and use of process indicators, promoting dialogue between women and providers on quality of care, and increasing equity and access at district level. An incentives scheme finances transport costs to a health facility for all pregnant women and incentives to health workers attending deliveries, with free services and subsidies to facilities in the poorest 25 districts. Despite bureaucracy, frequent transfer of key government staff and political instability, there has been progress in policy development, and public health sector expenditure has increased. For the future, a human resources strategy with career paths that encourage skilled staff to stay in the government service is key.     

Automated Detection of Caffeinated Coffee-Induced Short-Term Effects on ECG Signals Using EMD,DWT, and WPD

The effect of coffee (caffeinated) on electro-cardiac activity is not yet sufficiently researched. In the current study, the occurrence of coffee-induced short-term changes in electrocardiogram (ECG) signals was examined. Further, a machine learning model that can efficiently detect coffee-induced alterations in cardiac activity is proposed. The ECG signals were decomposed using three different joint time–frequency decomposition methods: empirical mode decomposition, discrete wavelet transforms, and wavelet packet decomposition with varying decomposition parameters. Various statistical and entropy-based features were computed from the decomposed coefficients. The statistical significance of these features was computed using Wilcoxon’s signed-rank (WSR) test for significance testing. The results of the WSR tests infer a significant change in many of these parameters after the consumption of coffee (caffeinated). Further, the analysis of the frequency bands of the decomposed coefficients reveals that most of the significant change was localized in the lower frequency band (<22.5 Hz). Herein, the performance of nine machine learning models is compared and a gradient-boosted tree classifier is proposed as the best model. The results suggest that the gradient-boosted tree (GBT) model that was developed using a db2 mother wavelet at level 2 decomposition shows the highest mean classification accuracy of 78%. The outcome of the current study will open up new possibilities in detecting the effects of drugs, various food products, and alcohol on cardiac functionality.     

Coronavirus and cardiovascular manifestations-getting to the heart of the matter

Coronavirus disease has unarguably been the largest pandemic of recent times. Over 150 million cases have occurred worldwide, and more than 3 million have succumbed to the disease. Cardiac manifestations can have varied presentations from an asymptomatic troponin rise to fulminant myocarditis. The pathogenesis of myocardial damage could be direct or indirect, including inflammation, coronary spasm, plaque rupture, and cytokine storm. Thromboembolism is also an important feature of cardiovascular affliction with both arterial and venous systems being affected. Hence, anticoagulation has also been a matter of debate. Fulminant myocarditis is the most severe form and can lead to circulatory shock with a high mortality. Management of cardiac patients with coronavirus disease 2019(COVID-19) infection is not considerably different from non-COVID-19 cardiovascular disease, but interaction between cardiovascular drugs and antiCOVID-19 therapy requires careful attention. More recently, vaccines have emerged as a ray of hope for the disease. But simultaneously, there have been reports of thromboembolism following vaccination. In this review, we discuss the various aspects of coronavirus disease affecting of heart and its management.