Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan

As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron‐rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age‐related changes of susceptibility were in good agreement with the findings from R2^* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. Hum Brain Mapp 35:2698–2713, 2014. © 2013 Wiley Periodicals, Inc .     

Obstructive Thebesian valve: anatomical study and implications for invasive cardiologic procedures

Thebesian valve is the embryological remnant of the right sinoatrial valve, guarding the coronary sinus (CS) ostium. Advanced invasive and interventional cardiac diagnostic and management tools involve cannulation of the CS ostium. The presence of obstructive Thebesian valves has been reported to lead to unsuccessful cannulation of the CS. We studied the morphology of the Thebesian valve and CS ostium to assess the possible impact of these structures on invasive cardiological procedures. One hundred fifty randomly selected human cadaveric heart specimens fixed in 10 % formalin were dissected in the customary routine manner. The Thebesian valves were classified according to their shape as semilunar/fenestrated/biconcave band like and according to their composition as membranous/fibromuscular/fibrous/muscular, and the extent to which the valve covered the CS ostium was also noted. An obstructive Thebesian valve that could interfere with the cannulation of the CS was defined as non-fenestrated (semilunar/biconcave band like) and non-membranous (fibromuscular/fibrous/muscular) valves covering >75 % of the CS ostium. Thebesian valves were present in 118 (79 %) heart specimens, of which 27 (18 %) met the criteria of being obstructive. Semilunar was the most common type of Thebesian valve in terms of shape and was observed in 65 (65/118; 55 %) hearts. This type was associated with the least mean craniocaudal (7.9 ± 0.6 mm) and mean transverse (6.25 ± 0.6 mm) diameters of the CS ostium. The mean craniocaudal diameter of the CS ostium (9.4 ± 2.1 mm) was significantly larger (p = 0.004) than the mean transverse diameter (7.15 ± 1.5 mm) in specimens with Thebesian valves, and the cranial margin of the CS ostium was free from any attachment of the Thebesian valve in all the types observed (in terms of shape). Hence, attempts to direct the tip of the catheter toward the cranial margin of the CS ostium under direct vision may lead to successful cannulation of the same when conventional techniques have been unsuccessful because of the presence of an obstructive Thebesian valve.     

Photodynamic therapy of melanoma with new,structurally similar,NIR-absorbing ruthenium (II) complexes promotes tumor growth control via distinct hallmarks of immunogenic cell death

Cancer therapies that generate T cell-based anti-cancer immune responses are critical for clinical success and are favored over traditional therapies. One way to elicit T cell immune responses and generate long-lasting anti-cancer immunity is through induction of immunogenic cell death (ICD), a form of regulated cell death that promotes antigenicity and adjuvanticity within dying cells. Therefore, research in the last decade has focused on developing cancer therapies which stimulate ICD. Herein, we report novel photodynamic therapy (PDT) compounds with immunomodulatory and ICD inducing properties. PDT is a clinically approved, minimally invasive anti-cancer treatment option and has been extensively investigated for its tumor-destroying properties, lower side effects, and immune activation capabilities. In this study, we explore two structurally related ruthenium compounds, ML19B01 and ML19B02, that can be activated with near infrared light to elicit superior cytotoxic properties. In addition to its direct cell killing abilities, we investigated the effect of our PSs on immunological pathways upon activation. PDT treatment with ML19B01 and ML19B02 induced differential expression of reactive oxygen species, proinflammatory response-mediating genes, and heat shock proteins. Dying melanoma cells induced by ML19B01-PDT and ML19B02-PDT contained ICD hallmarks such as calreticulin, ATP, and HMGB1, initiated activation of antigen presenting cells, and were efficiently phagocytosed by bone marrow-derived dendritic cells. Most importantly, despite the distinct profiles of ICD hallmark inducing capacities, vaccination with both PDT-induced dying cancer cells established anti-tumor immunity that protected mice against subsequent challenge with melanoma cells.     

Vascular changes of the retina and choroid in systemic lupus erythematosus: pathology and pathogenesis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems. When eyes are involved, the principle manifestations are hemorrhage, retinal cotton wool spots, microangiopathy and vaso-occlusion. Research in the past two decades has significantly contributed to our understanding about this disease in general and its therapeutic management, although knowledge about the mechanism of ocular involvement and pathogenesis in SLE is limited. This is an important issue, because the ocular symptoms in this disease could be potentially sight threatening in acute cases. Here, we present an overview of the clinical and histopathologic features of retinal and choroidal vascular changes, as seen in patients with SLE. We discuss the role of immune complex deposition in vascular pathogenesis in the eye. Reports indicated an involvement of antiphospholipid antibodies (APAs) in the retinal and choroidal vasculopathy in SLE, although their precise role in this process is uncertain. It is important to look for mechanisms of immune complex-mediated vasculopathy and role of inflammatory mediators in this process in SLE. For this, established animal models can be utilized in research to learn about the precise role of various autoantibodies and complements involved in disease pathogenesis. A clear knowledge about the immunopathogenesis is warranted, and the rationale for the future therapy should be based on reducing vascular inflammation as well as ameliorating autoimmunity in this disease.     

Vitamin profile of cooked foods: how healthy is the practice of ready-to-eat foods?

During recent years importance of B complex vitamins, beta-carotene and vitamin C has been realised in terms of their antioxidative and anticarcinogenic properties. Fruits and vegetables are the rich sources of these vitamins. However, there are considerable cooking losses of vitamins, and information on vitamin contents of cooked foods is essential for assessing the adequacy of vitamin intakes. Secondly, there is a growing trend to consume ready-to-eat foods such as stuffed pancakes (samosa, patties), pastries, French fries; replacing traditional foods for lunch or dinner like roti, vegetable curry, bread, non-vegetarian items. Ready-to-eat foods are considered to give empty calories rather than a balanced diet. A study was undertaken to estimate ascorbic acid, folic acid, riboflavin, thiamine and beta-carotene of 263 cooked food samples and 260 meals representing dietary patterns of Asia, Africa, Europe, USA and Latin America by spectrophotometry and photoflurometry. A broad range of beta-carotene (84-2038 mcg%), riboflavin (0.01-0.48 mg%), thiamine (0.04-0.36 mg%), vitamin C (1-28 mg%) and folate (26-111 mcg%) was observed in individual foods. Bakery products and sweets were found to be poor sources and green leafy vegetables and fruits were good sources of these five vitamins. The differences between ready-to-eat foods and meals consumed during lunch or dinner were prominent for beta-carotene, ascorbic acid, riboflavin and folic acid (P < 0.05). The cooking losses were 34.6, 30, 52.2, 45.9 and 32.2% in case of ascorbic acid, thiamine, riboflavin, beta-carotene and folic acid respectively. Irrespective of whether it is ready-to-eat or a lunch/dinner food item, the contribution of vegetables in the preparations was found to make a marked impact on the vitamin profile. While results justify the concept of a food pyramid, emphasis needs to be given to types of fruits and vegetables rich in vitamins; preferably in their uncooked form, rather than considering their total consumption.     

Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness

Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma in children; however, the mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we examined the effects of in utero cigarette smoke exposure of Balb/c mice on airway responsiveness, as determined by Penh measurements. Animals exposed prenatally but not postnatally to cigarette smoke exhibited increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract. The increased airway hyperresponsiveness was not associated with increased leukocyte migration or mucous production in the lung but was causally related to decreased lung cyclic adenosine monophosphate levels, increased phosphodiesterase-4 enzymatic activity, and phosphodiesterase-4D (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung. Exposure of adult mice to cigarette smoke did not significantly alter airway responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase activity. These results suggest that prenatal exposure to cigarette smoke affects lung airway reactivity by modulating the lung cyclic adenosine monophosphate levels through changes in phosphodiesterase-4D activity, and these effects are independent of significant mucous production or leukocyte recruitment into the lung.     

Training of postgraduates in anatomy

It is recognized that training methods differ among the various medical colleges; however, trained specialists should be competent to discharge their duties independently in any part of the country. Therefore, to maintain uniform standards of education, there is a need to harmonize postgraduate training in anatomy. It is proposed that a structured training programme should be drawn up and monitored regularly at specified intervals, spelling out some clearly defined targets that need to be achieved. The ultimate goal of the postgraduate training programme should be to produce anatomists with sufficient knowledge and practical skills to undertake undergraduate teaching and evaluation in all branches of anatomy, as well as to pursue research independently.