Transient heating of expressed breast milk up to 65°C inactivates HIV‐1 in milk: A simple,rapid, and cost‐effective method to prevent postnatal transmission

The postnatal transmission of human immunodeficiency virus (HIV) from mothers to children occurs through breastfeeding. Although heat treatment of expressed breast milk is a promising approach to make breastfeeding safer, it is still not popular, mainly because the recommended procedures are difficult to follow, or time‐consuming, or because mothers do not know which temperature is sufficient to inactivate HIV without destroying the nutritional elements of milk. To overcome these drawbacks, a simple and rapid method of heat treatment that a mother could perform with regular household materials applying her day‐to‐day art of cooking was examined. This structured experiment has demonstrated that both cell‐free and cell‐associated HIV type 1 (HIV‐1) in expressed breast milk could be inactivated once the temperature of milk reached 65°C. Furthermore, a heating method as simple as heating the milk in a pan over a stove to 65°C inhibited HIV‐1 transmission retaining milk's nutritional key elements, for example, total protein, IgG, IgA, and vitamin B₁₂. This study has highlighted a simple, handy, and cost‐effective method of heat treatment of expressed breast milk that mothers infected with HIV could apply easily and with more confidence. J. Med. Virol. 85:187–193, 2013. © 2012 Wiley Periodicals, Inc.     

Hydroxychloroquine enhances the endocrine secretion of adenovirus-directed growth hormone from rat submandibular glands in vivo.

Use of gene transfer technology for treating single protein deficiency disorders requires delivery of therapeutic levels of the transgene product. We have suggested that salivary glands may provide a potentially valuable target site for certain systemic applications of gene therapeutics (He et al., Gene Ther. 1998;5:537-541). However, the ability of salivary glands to deliver therapeutic proteins to either the upper gastrointestinal tract via saliva or to the bloodstream, as required, must be carefully evaluated. In the anterior pituitary gland, human growth hormone (hGH) is secreted into the bloodstream via the regulated secretory pathway. However, when expressed from an adenoviral vector delivered to salivary glands, most hGH follows the regulated, tissue-specific, exocrine secretory pathway into saliva, where it is not therapeutically useful. We tested the hypothesis that the commonly used, FDA-approved drug hydroxychloroquine (HCQ) can divert adenovirus-directed hGH from this regulated secretory pathway in rat submandibular glands and enhance delivery into the bloodstream. In untreated rats, there was approximately 20-fold more vector-directed hGH in saliva than in serum. Administration of HCQ led to a shift of hGH secretion into the bloodstream. When delivered at doses of 1 or 10 mg/kg body weight, via intraperitoneal injection plus intraductal infusion, the saliva:serum hGH ratio was approximately 2:1. Such HCQ delivery did not significantly alter the total amount of hGH measured, but increased the serum level of hGH 5- to 6-fold. Also, HCQ had no significant effects on serum chemistries or hematological parameters. We conclude that HCQ is able to significantly enhance hGH secretion from salivary glands into the bloodstream and may be useful to facilitate clinical applications of gene therapeutics via salivary glands.     

Altered neuronal excitability in cerebellar granule cells of mice lacking calretinin

Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mm of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore the calcium-buffering capacity. A proposed mathematical model demonstrates that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium-buffering capacity resulting from the absence of calretinin. This result suggests that calcium-binding proteins modulate intrinsic neuronal excitability and may therefore play a role in information processing in the CNS.     

Hybrid braided 3-D scaffold for bioartificial liver assist devices

Three-dimensional ex vivo hepatocyte culture is a tissue-engineering approach to improve the treatment of liver disease. The extracorporeal bioartificial liver (BAL) assists devices that are used in patients until they either recover or receive a liver transplant. The 3-D scaffold plays a key role in the design of bioreactor that is the most important component of the BAL. Presently available 3-D scaffolds used in BAL have shown good performance. However, existing scaffolds are considered to be less than ideal in terms of high-density cultures of hepatocytes maintaining long-term metabolic functions. This study aims to develop a 3-D hybrid scaffold for a BAL support system that would facilitate high-density hepatocyte anchorage with long-term metabolic functions. The scaffolds were fabricated by interlacing polyethylene terephthalate (PET) fibers onto the polysulfone hollow fibers utilizing a modern microbraiding technique. Scaffolds with various pore sizes and porosities were developed by varying braiding angle which was controlled by the gear ratio of the microbraiding machine. The morphological characteristics (pore size and porosity) of the scaffolds were found to be regulated by the gear ratio. Smaller braiding angle yields larger pore and higher porosity. On the other hand, a larger braiding angle causes smaller pore and lower porosity. In hepatocyte culture it was investigated how the morphological characteristics (pore size and porosity) of scaffolds influenced the cell anchorage and metabolic functions. Scaffolds with larger pores and higher porosity resulted in more cell anchorage and higher cellular functions, like albumin and urea secretion, compared to that of smaller pores and lower porosity.     

Knowledge,attitude and behaviour regarding dietary salt intake among medical students in Angola

High salt (sodium chloride) consumption is an important determinant of high blood pressure and cardiovascular risk. According to World Health Organisation (WHO) statistics, over 80% of cardiovascular disease (CVD) deaths take place in low-and middle-income countries, and elevated blood pressure levels were a major cause of these CVD deaths in those countries.1 Lifestyle factors such as unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol have been considered the most important behavioural risk factors for heart disease and stroke.2Among dietary factors, high salt intake has been the most strongly associated with raised blood pressure and increased risk of stroke and CVD.3 Therefore dietary sodium restriction has been recommended as a non-pharmacological approach to blood pressure lowering,4-6 and for the prevention and control of non-communicable diseases at the population level.7,8Cumulative evidence has shown that even a modest reduction in salt intake was associated with blood pressure lowering and therefore with a significant reduction in incidence of cardiovascular events.9-12 Furthermore, data from the most recent systematic review and meta-analyses has shown the benefit of lowering sodium intake in apparently healthy adults and children,13 and in both hypertensive and normotensive individuals, irrespective of gender and ethnic group.9Since hypertension is associated with CVD worldwide, a public health intervention to reduce high blood pressure must target the role of lifestyle, particularly reduced sodium intake.7 Therefore, several countries have initiated strategies to reduce dietary salt intake in the general population by a combination of various procedures such as public education, food labelling, and collaboration with the food industry to reduce the salt content of processed food.14Among sub-Saharan African countries, only Nigeria and South Africa have developed dietary guidelines regarding salt intake.15 Recently, the South African government implemented important specific legislation towards decreasing salt intake in the population by reducing sodium content of processed foods by industries.16 Therefore, the current public health recommendation is that countries should launch national initiatives to reduce the over-consumption of salt as part of non-communicable disease prevention and healthy nutrition policies for limiting salt intake to less than 5 g/day for the general population including children.7 Despite of this guideline, however, high sodium intake remains prevalent around the world, with average daily salt intake varying from 5 to 18 g/day per person.17Although processed foods have been found to be the principal source of excessive dietary salt intake,18 sources of dietary sodium vary largely worldwide and may be influenced by cultural context and dietary habits of the population.19 In sub-Saharan African countries experiencing demographic and epidemiological transition, the rapid rise in prevalence of CVD (chiefly hypertension) has been attributed to lifestyle change, including high dietary sodium intake.20,21 However, consistent data from studies on risk factors are lacking for the majority of these countries.With regard to Angola, available data from a cross-sectional study reported a high prevalence of multiple cardiovascular risk factors, such as hypertension, sedentary lifestyle, electrocardiographic left ventricular hypertrophy,22 and high rate of the metabolic syndrome23 in an apparently healthy middle-aged population of university public employees living in urban and peri-urban areas.Determining the level of sodium intake in the population is crucial to establish intervention strategies and policy on reduction of sodium intake. For medical students in particular, it is very important to assess their awareness regarding dietary salt intake, since they are the future providers of healthcare information for the counselling of people about the need to reduce salt consumption. The aim of this study was to determine salt intake and to assess the knowledge, attitude and behaviour regarding dietary salt among medical students.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

Energy and material flows of megacities

Understanding the drivers of energy and material flows of cities is important for addressing global environmental challenges. Accessing, sharing, and managing energy and material resources is particularly critical for megacities, which face enormous social stresses because of their sheer size and complexity. Here we quantify the energy and material flows through the world’s 27 megacities with populations greater than 10 million people as of 2010. Collectively the resource flows through megacities are largely consistent with scaling laws established in the emerging science of cities. Correlations are established for electricity consumption, heating and industrial fuel use, ground transportation energy use, water consumption, waste generation, and steel production in terms of heating-degree-days, urban form, economic activity, and population growth. The results help identify megacities exhibiting high and low levels of consumption and those making efficient use of resources. The correlation between per capita electricity use and urbanized area per capita is shown to be a consequence of gross building floor area per capita, which is found to increase for lower-density cities. Many of the megacities are growing rapidly in population but are growing even faster in terms of gross domestic product (GDP) and energy use. In the decade from 2001–2011, electricity use and ground transportation fuel use in megacities grew at approximately half the rate of GDP growth.The remarkable growth of cities on our planet during the past century has provoked a range of scientific inquires. From 1900–2011, the world’s urban population grew from 220 million (13% of the world’s population) to 3,530 million (52% of the world’s population) (1, 2). This phenomenon of urbanization has prompted the development of a science of cities (3, 4), including interdisciplinary contributions on scaling laws (5, 6), networks (7), and the thermodynamics of cities (8, 9). The growth of cities also has been strongly linked to global challenges of environmental sustainability, making the study of urban energy and material flows, e.g., for determining greenhouse gas emissions from cities and urban resource efficiency (10–19), important.At the pinnacle of the growth of cities is the formation of megacities, i.e., metropolitan regions with populations in excess of 10 million people. In 1970, there were only eight megacities on the planet (SI Appendix, Fig. S1). By 2010, the number had grown to 27, and a further 10 megacities likely will exist by 2020 (20). In 2010, 460 million people (6.7% of the global population) lived in the 27 megacities. The sheer size and complexity of megacities gives rise to enormous social and environmental challenges. Megacities often are perceived to be areas of high global risk (i.e., threatened by economic, environmental, geopolitical, societal, and technological risks with potential impacts across entire countries) with extreme levels of poverty, vulnerability, and social–spatial fragmentation (21–24). To provide adequate water and wastewater services, many megacities require massive technical investment and appropriate institutional development (25, 26). Many inhabitants of megacities also suffer severe health impacts from air pollution (27). However, these factors present only one side; the megacities include some of the wealthiest cities in the world (albeit with large disparities between citizens). Even the poorer megacities are seen by some as potential centers of innovation, where high levels of resource efficiency might reduce global environmental burdens (21, 28, 29). Whether megacities can develop as sustainable cities depends to a large extent on how they obtain, share, and manage their energy and material resources.The aims of our study are first to quantify the energy and material flows for the world’s 27 megacities, based on 2010 population, and second to identify physical and economic characteristics that underlie these resource flows at multiple scales. This goal entailed developing a common data-collection process applied to all the megacities. The cities were identified based on Brinkhoff’s database of metropolitan regions (www.citypopulation.de/world/Agglomerations.html; SI Appendix, Fig. S2). The megacities are essentially common commuter-sheds of more than 10 million people; most are contiguous urban regions, but a contiguous area is not a requirement; for example, the London megacity includes a ring of commuter towns outside the Greater London area. Megacities can spread across political borders. They include large tracts of suburban regions, which can have higher per capita resource flows than central areas (30, 31). We quantify energy flows for the dominant direct forms of consumption in megacities. A wide and complex range of materials flow through cities; here the focus is on water, concrete, steel, and waste. We show how values of aggregate resource use of all megacities generally are consistent with the scaling laws that have been developed for cities (5, 6). We then analyze factors correlated with energy and material flow at macro- and microscales; discuss megacities with low, high, and efficient use of resources; and examine changes over time.