Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone

Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that α-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.

The nature of the excited state of the reaction center of photosystem II of green plants: A high-resolution fluorescence spectroscopy study

We studied the electronically excited state of the isolated reaction center of photosystem II with high-resolution fluorescence spectroscopy at 5 K and compared the obtained spectral features with those obtained earlier for the primary electron donor. The results show that there is a striking resemblance between the emitting and charge-separating states in the photosystem II reaction center, such as a very similar shape of the phonon wing with characteristic features at 19 and 80 cm−1, almost identical frequencies of a number of vibrational modes, a very similar double-Gaussian shape of the inhomogeneous distribution function, and relatively strong electron-phonon coupling for both states. We suggest that the emission at 5 K originates either from an exciton state delocalized over the inactive branch of the photosystem or from a fraction of the primary electron donor that is long-lived at 5 K. The latter possibility can be explained by a distribution of the free energy difference of the primary charge separation reaction around zero. Both possibilities are in line with the idea that the state that drives primary charge separation in the reaction center of photosystem II is a collective state, with contributions from all chlorophyll molecules in the central part of the complex.

Dendritic cell modulation by 1α,25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo

Dendritic cells (DCs) play a central role in regulating immune activation and responses to self. DC maturation is central to the outcome of antigen presentation to T cells. Maturation of DCs is inhibited by physiological levels of 1α,25 dihydroxyvitamin D3 [1α,25(OH)2D3] and a related analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-vitamin D3 (D3 analog). Conditioning of bone marrow cultures with 10−10 M D3 analog resulted in accumulation of immature DCs with reduced IL-12 secretion and without induction of transforming growth factor β1. These DCs retained an immature phenotype after withdrawal of D3 analog and exhibited blunted responses to maturing stimuli (CD40 ligation, macrophage products, or lipopolysaccharide). Resistance to maturation depended on the presence of the 1α,25(OH)2D3 receptor (VDR). In an in vivo model of DC-mediated antigen-specific sensitization, D3 analog-conditioned DCs failed to sensitize and, instead, promoted prolonged survival of subsequent skin grafts expressing the same antigen. To investigate the physiologic significance of 1α,25(OH)2D3/VDR-mediated modulation of DC maturity we analyzed DC populations from mice lacking VDR. Compared with wild-type animals, VDR-deficient mice had hypertrophy of subcutaneous lymph nodes and an increase in mature DCs in lymph nodes but not spleen. We conclude that 1α,25(OH)2D3/VDR mediates physiologically relevant inhibition of DC maturity that is resistant to maturational stimuli and modulates antigen-specific immune responses in vivo.

Human immunodeficiency virus tat gene transfer to the murine central nervous system using a replication-defective herpes simplex virus vector stimulates transforming growth factor beta 1 gene expression.

The high incidence of neurological disorders in patients afflicted with acquired immunodeficiency syndrome (AIDS) may result from human immunodeficiency virus type 1 (HIV-1) induction of chemotactic signals and cytokines within the brain by virus-encoded gene products. Transforming growth factor beta1 (TGF-beta1) is an immunomodulator and potent chemotactic molecule present at elevated levels in HIV-1-infected patients, and its expression may thus be induced by viral trans-activating proteins such as Tat. In this report, a replication-defective herpes simplex virus (HSV)-1 tat gene transfer vector, dSTat, was used to transiently express HIV-1 Tat in glial cells in culture and following intracerebral inoculation in mouse brain in order to directly determine whether Tat can increase TGF-beta1 mRNA expression. dSTat infection of Vero cells transiently transfected by a panel of HIV-1 long terminal repeat deletion mutants linked to the bacterial chloramphenicol acetyltransferase reporter gene demonstrated that vector-expressed Tat activated the long terminal repeat in a trans-activation response element-dependent fashion independent of the HSV-mediated induction of the HIV-1 enhancer, or NF-kappaB domain. Northern blot analysis of human astrocytic glial U87-MG cells transfected by dSTat vector DNA resulted in a substantial increase in steady-state levels of TGF-beta1 mRNA. Furthermore, intracerebral inoculation of dSTat followed by Northern blot analysis of whole mouse brain RNA revealed an increase in levels of TGF-beta1 mRNA similar to that observed in cultured glial cells transfected by dSTat DNA. These results provided direct in vivo evidence for the involvement of HIV-1 Tat in activation of TGF-beta1 gene expression in brain. Tat-mediated stimulation of TGF-beta1 expression suggests a novel pathway by which HIV-1 may alter the expression of cytokines in the central nervous system, potentially contributing to the development of AIDS-associated neurological disease.

Ensaio clínico randomizado do uso do curativo gel de clorexidina para a prevenção da colonização do cateter venoso central em pacientes adultos críticos

Os acessos venosos são indispensáveis para assistência do paciente em situação crítica. O cateter venoso central (CVC) é um acesso que viabiliza a terapêutica dessa clientela, mas o seu uso pode levar à infecções. Estas infecções ocasionam maior permanência hospitalar, elevam os custos totais das instituições e aumentam a morbidade e a mortalidade do paciente. O uso de curativos como cobertura do sítio de saída do CVC é eficaz na prevenção das infecções relacionadas a estes cateteres, em particular, o uso de curativos impregnados com antissépticos como o curativo gel de clorexidina. Este estudo teve como objetivo comparar a efetividade do curativo gel de clorexidina com a do filme transparente de poliuretano na prevenção da colonização do cateter venoso central em pacientes adultos críticos. Trata-se de estudo experimental, do tipo ensaio clínico randomizado, com tratamentos em paralelo, prospectivo e monocêntrico, realizado de acordo com as recomendações do Consolidated Standards of Reporting Trials (CONSORT). O estudo foi realizado na Unidade de Terapia Intensiva e na Unidade Coronariana de um hospital de ensino do interior do Estado de São Paulo. Participaram do estudo 102 indivíduos hospitalizados nestes locais, divididos aleatoriamente em dois grupos: grupo intervenção, no qual o tipo de cobertura utilizada foi o curativo de gel de clorexidina e grupo controle, que utilizou como cobertura o filme transparente de poliuretano. O desfecho primário mensurado foi a colonização do cateter e os desfechos secundários foram a infecção clínica do sítio de saída, a infecção microbiológica do sítio de saída e a infecção da corrente sanguínea relacionada ao cateter. Para a coleta de dados foi elaborado um instrumento, e este validado quanto ao seu conteúdo e forma por 13 enfermeiros pertencentes aos locais do estudo. Estes profissionais foram treinados para a realização dos curativos e coleta das pontas dos cateteres centrais, swabs dos sítios de saída e hemoculturas. Análises descritivas foram usadas para todas as variáveis do estudo. O teste Exato de Fisher foi utilizado para comparar as proporções de cada desfecho nos grupos de intervenção e controle, e a regressão logística para explorar se a colonização no CVC poderia ser associada com o tempo de uso do cateter e com o Acute Physiology and Chronic Health Evaluation II (APACHE II) dos pacientes do estudo. De acordo com os resultados não houve diferença estatisticamente significante entre a colonização nos dois grupos (p valor = 1.00), para a infecção microbiológica do sítio de saída (p valor = 0.08), para a infecção clínica do sítio de saída (p valor = 0.77) e para as infecções da corrente sanguínea relacionadas ao cateter (p valor = 1,00). Conclui-se que o presente estudo pode contribuir para que as unidades de saúde tenham subsídios para realizar a escolha do tipo de curativo baseado em suas necessidades institucionais e no desenvolvimento de protocolos relacionados à medidas de inserção e manutenção do cateter, bem como medidas educativas permanentes

Local community perception towards bats (Mammalia: Chiroptera) in Caves in South central Mindanao, Philippines: Threats and Implication for conservation

In the tropics, bats are an essential component of many native ecosystems, through providing various ecological services including pollination and insect pest control, in addition to seed dispersal. Many Philippine bat species roost in caves and underground habitats. However, many caves are disturbed by people, to exploit resources for food, recreation, and mineral and guano extraction. The misunderstanding of the importance of bats to the ecosystem is also considered a threat to many cave roosting species. Understanding the conflicts between humans and ecosystems which provide essential services is important to maintain ecosystem service provision. A total of 100 local respondents from the village of Pisan, Kabacan North Cotabato in south central Mindanao were interviewed through semi-structured interviews and focus group discussions. Respondents were asked about their views, levels of knowledge, use, interaction, and awareness towards both the caves and bats in their locality. Our survey found that most of the respondents are aware of the presence of bats from the caves in their locality. Unfortunately, a large proportion of the respondents noted that bats are hunted in caves for bush meat and trade, and most people perceived bats as pest to fruit crops such as durian. These factors are among the main factors of the execution of many bat colonies in caves of south central Mindanao. In general, cave bats are under appreciated species in caves. The unregulated tourism, hunting for bush meat and trade, and guano extraction are among the alarming threats occurring for both caves and bats in the locality and possibly to other localities in the country. Furthermore, the establishment of strong and effective model conservation education programs and the strengthening the participation of local government, academic, and community are essential steps to preserve the current state of cave bats in the area.

The European Central Bank in the age of banking union. Bruegel Policy Contribution 2013/13, 1 October 2013

During the crisis the European Central Bank’s roles have been greatly extended beyond its price stability mandate. In addition to the primary objective of price stability and the secondary objective of supporting EU economic policies, we identify ten new tasks related to monetary policy and financial stability. We argue that there are three main constraints on monetary policy: fiscal dominance, financial repercussions and regional divergences. By assessing the ECB’s tasks in light of these constraints, we highlight a number of synergies between these tasks and the ECB’s primary mandate of price stability. But we highlight major conflicts of interest related to the ECB’s participation in financial assistance programmes. We also underline that the ECB’s government bond purchasing programmes have introduced the concept of ‘monetary policy under conditionality’, which involves major dilemmas. A solution would be a major change towards a US-style system, in which state public debts are small, there are no federal bail-outs for states, the central bank does not purchase state debt and banks do not hold state debt. Such a change is unrealistic in the foreseeable future.

Bail-in Provisions in State Aid and Resolution Procedures: Are they consistent with systemic stability? CEPS Policy Brief No. 318, 21 May 2014

This CEPS Policy Brief examines the provisions for bail-in in the European Union – that is, the principle whereby any public measure to recapitalise a bank with insufficient prudential capital must be preceded by a write-down or conversion into equity of creditors’ claims – in state aid policies and in the new resolution framework for failing banks, with two aims: i) to assess whether and how they are coordinated and ii) more importantly, whether they address satisfactorily the question of systemic stability that may arise when investors fear that creditors’ claims are likely to be bailed-in in a bank crisis. The issue is especially relevant in the present context, as the comprehensive assessment exercise underway for EU banks falling under the direct supervision of the European Central Bank may lead supervisors to require substantial capital injections simultaneously for many of the banks involved, possibly shaking investors’ confidence across EU banking markets. The authors conclude that the two sets of rules are, broadly speaking, mutually consistent and that they already contain sufficient safeguards to address systemic stability concerns. However, the balance of the elements underpinning the European Commission’s decisions in individual cases may not be clear to bank creditors and potential investors in financial markets. The impression of unneeded rigidity on this very sensitive issue has been heightened by official statements over-emphasising that each case will be assessed individually under competition rules, thus feeding the concern that the systemic dimension of the issue may have been underestimated. Therefore, further clarification by the Commission may be needed on how the various criteria will be applied during the ongoing transition to banking union – perhaps through a new communication completing the state aid framework for banks in view of the adoption of the new resolution rules.

Migration in the Central Mediterranean. Jean Monnet Occasional Papers 02/2013

In the last decade irregular immigration has emerged as a “security” challenge (in the language of International Relations military “threat”) in the Mediterranean region particularly in the central, sub-region1. The designation of this issue as a “security challenge” or “threat” is itself controversial and will be discussed further down. This paper focuses on the situation in the central Mediterranean involving mainly four countries namely Italy, Libya, Malta and Tunisia all of which have long standing historic links and bilateral relations and participate in the so called “5+5” Dialogue in the Western Mediterranean. Two of these Central Mediterranean countries (Italy, Malta) are EU member states and Tunisia has a long standing relationship with the EU [Association Agreement, Barcelona Process (EMP), Neighbourhood Policy (ENP), Union for the Mediterranean (UfM)] while Libya so far has no formal relations at all with the EU. This paper analyses some of the aspects of migration in the central Mediterranean focusing on the link between the domestic and international politics of the issue in Italy and Malta and contrasting the different approaches taken. For example, although Italy and Malta both resort to self-help and both try to involve the EU in helping them tackle the problem, they do this in a markedly different way: Italy uses the EU as a supplement to its independent and bilateral efforts while Malta looks to the EU as the major solution to the problem. Lacking the power and influence to deal with the issue, Malta tends to see the problem as primarily a multilateral issue or one that can only be tackled in concert with stronger powers in the region preferably within an EU context. On the other hand, Italy has been keen in involving the EU but decided to go it alone when this option turned out to be a dead end. In this paper I also try to show the extent (or limitations) to which multilateral initiatives such as the “5+5” and Euro operation really play a decisive role in incentivizing or facilitating inter-state cooperation or joint solutions. This paper also refers to the EU acquis, the notion of solidarity (norms) and the extent to which it is implemented as well as a number of connected issues. The subjects of this paper, the Mediterranean Boat People, have been referred to by various names in the literature, all of which may be more or less deficient in actually defining them all. They have been referred to as “illegal” or “irregular” immigrants, “refugees” in search of international protection, “migrants at sea” and “boat people”. The use of “boat people” dispenses with the need of having to define the various categories of migrants involved and is thus preferred in this paper.

State-building in Iraq since 2003: the Challenges and Lessons. Jean Monnet Occasional Paper No. 12/2014

Introduction. In 2003, Iraq was invaded by the US coalition forces that ousted Saddam Hussein’s regime from power before occupying the whole country. The intension, declared by the then American George W. Bush, was to ‘build a decent and democratic society at the centre of the Middle East’ that ‘will become a place of progress and peace.’1 In 2014, three years after the withdrawal of the last American soldier, however, it is difficult to overestimate or exaggerate what is at stake. National unity and territorial integrity have never been so seriously threatened since the country is experiencing the internal fighting in its modern history. Many parts of Iraq, including the northern oil city of Kirkuk, long claimed as an integral part of the semi-autonomous region of Kurdistan, are out of the control of the central government. Large areas in the north including the strategic city of Mosul were seized by the fighters of the Islamic State, an Al-Qaeda offshoot, formerly known as ISIS, who threatened to invade the Kurdistan region before being attacked by airstrikes by the US. They proclaimed a caliphate on both sides of the border with Syria, where they also control vast territory.

The Border Management Programme in Central Asia: Explaining the European Union's Choice of Implementing Partners. Bruges Regional Integration & Global Governance Papers 3/2014

Between 2003 and 2014 the European Union’s (EU) Border Management Programme in Central Asia was implemented by the United Nations Development Programme (UNDP). However, the latter’s implementing responsibilities have just come to an end, with the next phase of the programme to be implemented by an EU member state consortium. This paper seeks to explain why the EU chose the UNDP to implement the programme in the first place; why the programme was redelegated to the UNDP over successive phases; and why, in the end, the EU has opted for a member state consortium to implement the next phase of the programme. The paper will draw on two alternative accounts of delegation: the principal-agent approach and normative institutionalism. Ultimately, it will be argued that both the EU’s decision(s) to delegate (and redelegate) implementing responsibilities to the UNDP, and its subsequent decision to drop the organisation in favour of an EU member state consortium, were driven for the most part by a rationalist ‘logic of consequentiality’. At the same time, a potential secondary role of a normative institutionalist ‘logic of appropriateness’ – as a supplementary approach – will not be discounted.

Ever further from Moscow. Russia's stance on Central Asia. OSW Study 48/2014

The post-Soviet countries of Central Asia are important for Moscow as a potential source of danger; as a site of its relationships with China, the West and the Islamic world; and not least as a space covered by Russia’s integration initiatives. Since the collapse of the USSR, Russian influence in this region has undergone a far-reaching erosion. The Kremlin’s consistent actions to build up the Eurasian Union, as well as the threat of destabilisation in region after the ISAF operation in Afghanistan winds up in 2014, have slowed down this process, although it is unlikely to be reversed. The current ‘state of possession’ (i.e. the instruments and assets which Russia possesses) still ensures Moscow a minimum level of control over the region, which means that the activity of other global players is limited. This situation may change in tandem with a rise in their ambitions, especially with the possible involvement of China in the field of ‘hard’ security.

Kazakhstan: the regional success story; Tajikistan: a trial period; Uzbekistan: the major source of instability in Central Asia? OSW Study 15/2004

Kazakhstan: Kazakhstan can boast economic development like no other country in Central Asia. In contrast to other countries of the region, which have rich natural resources, Kazakhstan has managed to use its economic potential in a way that yields concrete benefits now and, at the same time, creates prospects for further sustainable economic growth. Tajikistan: Tajikistan in its present state has been built on the civil war experiences and provisions of the peace accords signed in 1997. These have had a great impact on the present form of the state, its political scene and power mechanisms. President Emomali Rakhmonov is the central figure in the state. The political system, which he has cocreated, is based on - unique in this region - political pluralism (the existence of the Islamic party), decentralisation (far-going independence of the regions and relatively limited potential of the central structures) and compromise as the basic way of resolving conflicts. Such a system has so far guaranteed stabilisation and normalisation of the country. Uzbekistan: With its geographic location, potential, ambitions and political priorities, Uzbekistan could play a leading role in Central Asia. The international community has perceived the country as the pillar of stability in the region. This perception was further reinforced after 11th September 2001 and was certainly among the factors that inspired the United States to start closer political and military cooperation with Tashkent. The administration in Washington had expected that closer contacts might galvanise political, economic and social change in Uzbekistan, thus reinforcing positive trends in other countries of the region as well. But the relations between Washington and Tashkent are in crisis (which the United States will certainly try to overcome), and we have seen rapprochement between Uzbekistan and Russia and China.

The EU’s Rule of Law Initiative for Central Asia: From Initiative to More Substance? EUCAM Policy Brief No. 18, June 2011

All five Central Asian states are weak in terms of rule of law, good governance and democracy. The EU chose to devote specific attention to the rule of law through a regional initiative with Central Asian partners' participation. What is the current state of the initiative and is the EU on track?

The Emergence of a Network of ‘European Embassies’: Increasing Cooperation between EU Delegations and Member State Diplomatic Missions. EU Diplomacy Paper No. 10, December 2014

Five years after the entry into force of the Treaty of Lisbon and at the end of the first mandate of the High Representative of the Union for Foreign Affairs and Security Policy/Vice-President of the European Commission (HR/VP), this analysis provides an in-depth view of the on-going institutional socialisation between Member State Embassies and EU Delegations. Specifically, it focuses on the Member States’ perceptions of the role of EU Delegations. These perceptions can back up or restrain the EU Delegations in fulfilling their mandate. More precisely, the paper examines to what extent the socialisation between EU Delegations and EU Member State Embassies helps the Delegations to fulfil their mandate in bilateral diplomacy. It argues that EU Delegations are still under dynamic processes of institutional socialisation with the Member States’ Embassies which increasingly accept and expect EU Delegations’ actions. The post-Lisbon context of EU Diplomacy is consolidating a primus inter pares role of Delegations being central hubs coordinating and implementing EU policies on the spot.