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In Africa, bat‐borne zoonoses emerged in the past few decades resulting in large outbreaks or just sporadic spillovers. In addition, hundreds of more viruses are described without any information on zoonotic potential. We discuss important characteristics of bats including bat biology, evolution, distribution and ecology that not only make them unique among most mammals but also contribute to their potential as viral reservoirs. The detection of a virus in bats does not imply that spillover will occur and several biological, ecological and anthropogenic factors play a role in such an event. We summarize and critically analyse the current knowledge on African bats as reservoirs for corona‐, filo‐, paramyxo‐ and lyssaviruses. We highlight that important information on epidemiology, bat biology and ecology is often not available to make informed decisions on zoonotic spillover potential. Even if knowledge gaps exist, it is still important to recognize the role of bats in zoonotic disease outbreaks and implement mitigation strategies to prevent exposure to infectious agents including working safely with bats. Equally important is the crucial role of bats in various ecosystem services. This necessitates a multidisciplinary One Health approach to close knowledge gaps and ensure the development of responsible mitigation strategies to not only minimize risk of infection but also ensure conservation of the species., Hundreds of viruses have been described from bats in Africa, some with proven spillover and causing human deaths, however for the majority there is no information on spillover potential. We summarize and critically analyze the current knowledge on African bats as reservoirs for corona, filo, paramyxo and lyssaviruses, including important characteristics of bats like biology, evolution, distribution and ecology that not only make them unique amongst most mammals but also contribute to their potential as viral reservoirs. We highlight the gaps in knowledge that is often not available to make informed decisions on zoonotic spillover potential. Despite this it is still important to recognize the role of bats in zoonotic disease outbreaks and implement mitigation strategies to prevent exposure to infectious agents, including working safely with bats. Equally important is the crucial role of bats in various ecosystem services.

Diabet. Med. 29, e170–e175 (2012) Abstract Aims To determine whether the frequency and severity of diabetic ketoacidosis and the clinical characteristics of children at diagnosis of Type 1 diabetes mellitus have changed over the past decades among patients under surveillance of a tertiary paediatric centre. Methods In three time-periods, 75 (1986–1987), 86 (1996–1997) and 245 (2006–2007) patients at mean age 10.1 ± 4.7 years (0.6–20.0) were diagnosed with new-onset Type 1 diabetes. Data on clinical characteristics and laboratory evaluation at diagnosis retrieved from the patients’ files . Comparative analysis was performed between the three time periods. Results The frequency of diabetic ketoacidosis at diagnosis was 40% in 1986–1987, 41.8% in 1996–1997 and 29.4% in 2006–2007; the last rate was significantly lower (P = 0.04). No significant differences in the proportions of patients with severe or moderate diabetic ketoacidosis were found over time. Mean weight standard deviation score significantly increased from −0.72 ± 1.8 in 1986–1987 to −0.27 ± 1.2 in 2006–2007 (P

Diabet. Med. 27, 339–347 (2010) Abstract Aims To identify variables that predict glycaemic control in Type 1 diabetic patients switched to a continuous subcutaneous insulin infusion (CSII) regimen, in order to improve patient selection for this treatment. Methods The notes of 421 Type 1 diabetic patients aged 2.6–39.8 years (median 19.4) who initiated CSII treatment in 1998–2007 and used it for ≥ 1 year were reviewed. Details about their background and disease-related and treatment-related variables were recorded. At pump initiation, the mean age was 15.9 ± 7.2 years, mean diabetes duration 6.4 ± 5.8 years. Mean time of CSII use was 4.1 ± 2.1 years. Good glycaemic control was defined by glycated haemoglobin (HbA1c) stratified by age (American Diabetes Association target levels). Improvement in glycaemic control was defined as a reduction of ≥ 0.5% in HbA1c from baseline. The change in the rate of severe hypoglycaemic or diabetic ketoacidosis events was also determined. Results There was a significant sustained decrease in HbA1c with CSII for an average of 6 years, without increased rates of hypoglycaemia. Achievement of target HbA1c was significantly associated with the following parameters at pump initiation: lower HbA1c (P

Objective Central precocious puberty (CPP) causes early epiphyseal maturation, and early initiation of treatment improves final height. Unfortunately, there is no one parameter that can distinguish CPP from premature thelarche (PT), which is self-limited and requires no therapy. In animal models, kisspeptin, the ligand for the G-protein coupled receptor GPR54, was found to induce precocious activation of the gonadotrophic axis. Data on kisspeptin levels in girls with precocious puberty or in healthy prepubertal girls are lacking. We measured blood kisspeptin levels in girls with CPP and evaluated its potential as a clinical marker for CPP. Design This was a case-control study. Patients Thirty-one girls clinically diagnosed with CPP and 14 prepubertal age-matched healthy controls. Measurements Kisspeptin blood levels. Results Kisspeptin levels were significantly higher in the girls with CPP than in the controls: 14.62 +/- 10.2 pmol/l vs. 8.35 +/- 2.98 pmol/l, P 5.0 IU/l and those with a peak LH Conclusions Although kisspeptin is significantly higher in girls with true CPP than in age-matched prepubertal controls, the evident overlap limits its use as a single diagnostic tool until further data obtained in larger studies should prove otherwise.

Circadian rhythms of locomotor activity have been investigated in several African mole-rat species. Even though mole-rats spend most of their lives in underground burrows devoid of light, studies have shown that they do possess circadian rhythms to some extent. We investigated the circadian rhythms of locomotor activity in 11 male Ansell’s mole-rats Fukomys anselli from Zambia. In order to determine whether these animals can entrain to light and have endogenous rhythms, they were subjected to different light regimes: first, 12 h light/12 h dark, followed by constant darkness, then returned to 12 h light/12 h dark, which was later inversed to 12 h dark/12 h light. Only two individuals displayed arrhythmic activity patterns whereas the other nine (81.8%) exhibited entrainment of their activity to the light regimes. Locomotory activity of Ansell’s mole-rat was predominantly during the dark phase in all light regimes. During constant darkness (DD), only five individuals (45.5%) displayed very weak circadian rhythms that free ran but became more indistinct towards the end of the cycle. Under the second LD light cycle, 90.1% of the animals were active during the night phase of the cycle and when placed under an inverse light cycle, seven individuals still displayed activity predominantly during the dark phase. In conclusion, these results suggest that Ansell’s mole-rat does have a weak circadian clock and is able to perceive light and entrain to light cycles.

Summary The 1990s policy trend of intervening at the specification level over a broad range of products has ended. Today's environmental product policies focus, rather, on a few arbitrary product groups. Selectiveness should serve absolute environmental impact reduction, which asks for a rational product-selection and target framework. The authors propose “life-cycle impact per consumer expenditure” as a key criterion. This criterion helps to connect macro environmental impact reduction aims with product innovation targets, even under continuous economic growth, consumption pattern shifts, and rebound threats. The authors analyze the Dutch economy as an exercise. This results in 44 product groups, labeled “Hyenas” by the authors, that need to improve their ratio score drastically between now and 2040. Some magnitudes of desired change are given. Finally, intervention processes at the Hyena group level along the lines of sustainable transition management are proposed. Joint visioning, experimental portfolios, interaction between micro, meso, and macro change levels, and gradual pressure building are crucial elements in this concept of complex change management.

CHRISTINA L. DE VRIES [*] Health issues are now, more than ever, issues of social justice and peace, of values in respect of human life and dignity, and of the striving for "wholeness". The need for the empowerment of women and for the care of the marginalized increases. This becomes painstakingly clear from the societal devastation following the AIDS epidemic. Health issues invade all segments of society and of individuals' lives. Thus churches cannot ignore health issues as "non-theological" aspects of the churches' mission. The shift of attention for health concerns from the religious domain towards the medical profession was accentuated during the 20th century, when, due to revolutionary new technology, health issues became more medical-technological issues, to be addressed by health professionals. In the second half of the century, health issues were not just defined as an issue between a patient and his/her doctor, but became an object of nationally and internationally managed intervention programmes. The realization arose that health seemed no longer just the opposite of disease, but that the health of populations and individuals was constantly under threat from poverty, violence and wars. Globalization, the power of multinational companies and the passive attitude of many governments towards health needs made the scenario even more gloomy: would health now become just another free market issue, and drugs merely an economic commodity? Would health be attained only by those who were willing and able to pay for it? Would healt h cease to be a basic human right for all? Where are the mechanisms left for societies to exercise solidarity for the weak and the poor? Do global economic principles overrule local societal values at national and sub-national level? What could and should be the role of churches? An excellent overview article by Sigrun Mogedal and Mirjam Bergh that addressed the global health situation and the churches' response was published in this journal in 1994. [1] It is still valid today, yet the scenario has become even more urgent. This present article will further highlight some of the challenges in health and health care, which urgently need to be addressed by the churches. Stocktaking Achievements of the 20th century The 20th century has become part of our shared history, now we can look at it and marvel at what it has brought to humankind: * Standards of living improved for large segments of populations, especially in Europe and the Americas. There is now better housing, greater access to clean water, sewage systems and latrines, which have all contributed greatly towards reducing the occurrence of tuberculosis, cholera and child mortality through diarrhoea. * There was an improvement in knowledge about healthy diets coupled with an increased availability of foods, and the development of vitamin and iron supplements for children and pregnant women. All of these increased people's life expectancy. * The discovery of antibiotics contributed towards reducing deaths from communicable diseases. * The development of vaccines in conjunction with the establishment of the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) resulted in global programmes for the prevention of diseases. The results were impressive: the eradication of smallpox and the Extended Programme for Immunizations (EPI) against major childhood diseases are truly the highlights. * Revolutionary new technologies changed hospital care: more diagnostic and imaging facilities changed the role of doctors and hospitals, in the sense that technology became more prominent at the expense of care and comfort. * The development and adoption of family planning methods on a large scale (whether compulsory or voluntary) resulted in a demographic transition in many countries resulting in populations containing relatively less youth and more elderly people. …

According to the two state receptor model, the β2-adrenergic receptor (β2-AR) isomerizes between an inactive state and a constitutively active state, which couples to the stimulatory G-protein in the absence of agonist. In bovine tracheal smooth muscle (BTSM), we investigated the effect of short and long term β2-AR activation by fenoterol on constitutive receptor activity. Preincubation of the BTSM strips for 5 min, 30 min and 18 h with 10 μM fenoterol, followed by extensive washout (3 h, 37°C), caused a rapid and time-dependent inhibition of KCl-induced contraction, reaching 68±10, 51±6 and 46±4% of control, respectively, at 40 mM KCl (Palprenolol⩾sotalol>labetalol. At 25 mM KCl-induced tone, the contraction induced by cumulative timolol administration was competitively antagonized by the less efficacious inverse agonist labetalol, indicating that the fenoterol-induced effects cannot be explained by residual β-agonist binding. In conclusion, fenoterol treatment of BTSM causes a time- and concentration-dependent development of constitutive β2-AR activity, which can be reversed by various inverse agonists. The β-agonist-induced changes could represent a novel regulation mechanism of β2-AR activity. Keywords: β2-adrenergic receptor, constitutive receptor activity, inverse agonism, fenoterol, timolol, β-adrenergic receptor antagonists, bovine tracheal smooth muscle, contraction, KCl Introduction It has been demonstrated that some mutations in the C-terminal part of the third intracellular loop of the human β2-adrenoceptor (β2-AR) result in constitutive activation of the receptor (Samama et al., 1993). Besides agonist-independent activation of adenylyl cyclase, the mutant receptor displays a higher affinity for agonists, even in absence of G-proteins, an increased potency of agonists for stimulation of adenylyl cyclase, and an increased intrinsic activity for partial agonists as compared to the wild type receptor (Samama et al., 1993). Because the G-protein independent increase in agonist affinity for the mutant receptor cannot be explained by the classical Ternary Complex Model (De Lean et al., 1980) this model has been extended assuming isomerization of the receptor between an inactive and a constitutively active conformation. In this model, only the constitutively active conformation of the receptor can couple to the G-protein and elicit a biological response. Mutation of the human β2-AR would lead to a shift in the receptor equilibrium in favour of the constitutively active conformation by an impaired ability of the receptor to constrain peptide regions in the third intracellular loop from their interaction with the G-protein (Samama et al., 1993). The constitutively active conformation of the wild type β2-AR can also be visualized by overexpression of the receptor, which is consistent with the concept that a small fraction of the total receptor pool may exist in the activated conformation even in the absence of agonist (Chidiac et al., 1994). Transgenic mice with cardiac-specific overexpression of the β2-AR showed an increased basal atrial contractility, which, in the highest overexpressing transgenic animals, was not responsive to further increase by isoprenaline (Milano et al., 1994). In myocardial membranes of these transgenic mice both basal and isoprenaline-stimulated adenylyl cyclase activity were increased as compared to controls, accompanied by an increased isoprenaline sensitivity in the transgenic membranes (Milano et al., 1994). The activity of both the overexpressed and mutant constitutively active β2-AR's can be inhibited by antagonists with negative intrinsic activity (inverse agonists), such as ICI 118551 and betaxolol for the mutant receptor (Samama et al., 1994) and for example timolol and propranolol for the overexpressed human wild type receptor (Chidiac et al., 1994). Recently, it has been reported by Wang et al. (1994) that chronic activation of the Gi-coupled μ opioid receptor in human SH-SY neuroblastoma cells by the agonist morphine gradually caused a constitutively active receptor state. The evidence for this was based on the observation that after morphine exposure, followed by thorough washing, the antagonist naloxone acutely enhanced cyclic AMP accumulation. This inverse agonistic behaviour of naloxone has also been demonstrated in morphine-pretreated guinea-pig ileum preparations (‘abstinence response') whereas in control tissues naloxone was without effect (Cruz et al., 1996). Based on these findings, we examined whether short and long term activation of native β2-ARs in bovine tracheal smooth muscle (BTSM), using the selective β2-agonist fenoterol, would induce constitutive receptor activity.

A macromolecular “antifreeze” is present in the blood serum of fishes that inhabit subzero waters in winter. During the summer the “antifreeze” is not present. The effect of temperature and photoperiod on this circ-annual cycle of “antifreeze” production was investigated. Fishes collected from subzero waters were acclimated to various temperature and photoperiod regimes. Only the combination of a long photoperiod and warm temperature resulted in the disappearance of “antifreeze” from the serum, thus providing for an efficient failsafe system. The time necessary for the complete loss of the macromolecular “antifreeze” ranged from 3 to 5 weeks. When summer fish were acclimated to various combinations of temperature and photoperiod, low temperatures resulted in the production of “antifreeze” regardless of the photo-period. Serum Na and Cl− levels were significantly higher in cold acclimated than in warm acclimated fish. In general, fishes collected from more northerly latitudes had lower serum freezing points than the same species from warmer, more southerly waters. There seemed to be a genetic difference between populations of Anoplarchus purpurescens from Amchitka, Alaska and San Simeon, California since the California fish were unable to produce “antifreeze” when acclimated to cold temperatures.