The United Nations and One Health: the International Health Regulations (2005) and global health security.

The One Health approach encompasses multiple themes and can be understood from many different perspectives. This paper expresses the viewpoint of those in charge of responding to public health events of international concern and, in particular, to outbreaks of zoonotic disease. Several international organisations are involved in responding to such outbreaks, including the United Nations (UN) and its technical agencies; principally, the Food and Agriculture Organization of the UN (FAO) and the World Health Organization (WHO); UN funds and programmes, such as the United Nations Development Programme, the World Food Programme, the United Nations Environment Programme, the United Nations Children's Fund; the UN-linked multilateral banking system (the World Bank and regional development banks); and partner organisations, such as the World Organisation for Animal Health (OIE). All of these organisations have benefited from the experiences gained during zoonotic disease outbreaks over the last decade, developing common approaches and mechanisms to foster good governance, promote policies that cut across different sectors, target investment more effectively and strengthen global and national capacities for dealing with emerging crises. Coordination among the various UN agencies and creating partnerships with related organisations have helped to improve disease surveillance in all countries, enabling more efficient detection of disease outbreaks and a faster response, greater transparency and stakeholder engagement and improved public health. The need to build more robust national public human and animal health systems, which are based on good governance and comply with the International Health Regulations (2005) and the international standards set by the OIE, prompted FAO, WHO and the OIE to join forces with the World Bank, to provide practical tools to help countries manage their zoonotic disease risks and develop adequate resources to prevent and control disease outbreaks, particularly at the animal source. All these efforts contribute to the One Health agenda.

Functional comparison of rod and cone Gα(t) on the regulation of light sensitivity.

The signaling cascades mediated by G protein-coupled receptors (GPCRs) exhibit a wide spectrum of spatial and temporal response properties to fulfill diverse physiological demands. However, the mechanisms that shape the signaling response of the GPCR are not well understood. In this study, we replaced cone transducin α (cTα) for rod transducin α (rTα) in rod photoreceptors of transgenic mice, which also express S opsin, to evaluate the role of Gα subtype on signal amplification from different GPCRs in the same cell; such analysis may explain functional differences between retinal rod and cone photoreceptors. We showed that ectopically expressed cTα 1) forms a heterotrimeric complex with rod Gß(1)γ(1), 2) substitutes equally for rTα in generating photoresponses initiated by either rhodopsin or S-cone opsin, and 3) exhibited similar light-activated translocation as endogenous rTα in rods and endogenous cTα in cones. Thus, rTα and cTα appear functionally interchangeable. Interestingly, light sensitivity appeared to correlate with the concentration of cTα when expression is reduced below 35% of normal. However, quantification of endogenous cTα concentration in cones showed a higher level to rTα in rods. Thus, reduced sensitivity in cones cannot be explained by reduced coupling efficiency between the GPCR and G protein or a lower concentration of G protein in cones versus rods.

Planning for rapid response to outbreaks of animal diseases transmissible to humans via food.

Planning for rapid response to outbreaks of foodborne zoonoses requires coordination and intersectoral collaboration, making the process inherently complex. Guidance documents have been published by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) on the topics of foodborne outbreak investigation, establishing food safety emergency response plans, applying risk analysis principles during food safety emergencies, and developing national food recall systems. These guides should be used as resources by national authorities to develop national plans which should each reference the other in order to maintain consistency at the country level. FAO and WHO, together with the World Organisation for Animal Health (O1E), are the international organisations responsible at the global level for the health of people and animals and for food safety and security. As such, these organisations need to continue to work together to develop an intersectoral mechanism to conduct robust and timely joint risk assessments in the face of foodborne outbreaks and other food safety emergencies. Three international instruments have the potential to aid countries in their preparedness to face outbreaks of foodborne zoonoses and organise subsequent response efforts: the International Food Safety Authorities Network (INFOSAN), the newly enhanced Global Early Warning System for Major Animal Diseases, including Zoonoses (GLEWS+), and the FAO Emergency Prevention System for Food Safety (EMPRES Food Safety).

The long journey: a brief review of the eradication of rinderpest.

In 2011, the 79th General Session of the World Assembly of the World Organisation for Animal Health (OIE) and the 37th Food and Agriculture Organization of the United Nations (FAD) Conference adopted a resolution declaring the world free from rinderpest and recommending follow-up measures to preserve the benefits of this new and hard-won situation. Eradication is an achievable objective for any livestock disease, provided that the epidemiology is uncomplicated and the necessary tools, resources and policies are available. Eradication at a national level inevitably reflects national priorities, whereas global eradication requires a level of international initiative and leadership to integrate these tools into a global framework, aimed first at suppressing transmission across all infected areas and concluding with a demonstration thatthis has been achieved. With a simple transmission chain and the environmental fragility of the virus, rinderpest has always been open to control and even eradication within a zoosanitary approach. However, in the post-1945 drive for more productive agriculture, national and global vaccination programmes became increasingly relevant and important. As rinderpest frequently spread from one region to another through trade-related livestock movements, the key to global eradication was to ensure that such vaccination programmes were carried out in a synchronised manner across all regions where the disease was endemic - an objective to which the European Union, the United States Agency for International Development, the International Atomic Energy Agency, the African Union-Interafrican Bureau of Animal Resources, FA0 and OIE fully subscribed. This article provides a review of rinderpest eradication, from the seminal work carried out by Giovanni Lancisi in the early 18th Century to the global declaration in 2011.

Assessment of national strategies for control of high-pathogenicity avian influenza and low-pathogenicity notifiable avian influenza in poultry, with emphasis on vaccines and vaccination.

Twenty-nine distinct epizootics of high-pathogenicity avian influenza (HPAI) have occurred since 1959. The H5N1 HPAI panzootic affecting Asia, Africa and Eastern Europe has been the largest among these, affecting poultry and/or wild birds in 63 countries. A stamping-out programme achieved eradication in 24 of these epizootics (and is close to achieving eradication in the current H5N2 epizootic in South African ostriches), but vaccination was added to the control programmes in four epizootics when stamping out alone was not effective. During the 2002 to 2010 period, more than 113 billion doses of avian influenza (AI) vaccine were used in at-risk national poultry populations of over 131 billion birds. At two to three doses per bird for the 15 vaccinating countries, the average national vaccination coverage rate was 41.9% and the global AI vaccine coverage rate was 10.9% for all poultry. The highest national coverage rate was nearly 100% for poultry in Hong Kong and the lowest national coverage was less than 0.01% for poultry in Israel and The Netherlands. Inactivated AI vaccines accounted for 95.5% and live recombinant virus vaccines for 4.5% of the vaccines used. Most of these vaccines were used in the H5N1 HPAI panzootic, with more than 99% employed in the People's Republic of China, Egypt, Indonesia and Vietnam. Implementation of vaccination in these four countries occurred after H5N1 HPAI became enzootic in domestic poultry and vaccination did not result in the enzootic infections. Vaccine usage prevented clinical disease and mortality in chickens, and maintained rural livelihoods and food security during HPAI outbreaks. Low-pathogenicity notifiable avian influenza (LPNAI) became reportable to the World Organisation for Animal Health in 2006 because some H5 and H7 low-pathogenicity avian influenza (LPAI) viruses have the potential to mutate to HPAI viruses. Fewer outbreaks of LPNAI have been reported than of HPAI and only six countries used vaccine in control programmes, accounting for 8.1% of the total H5/H7 AI vaccine usage, as compared to 91.9% of the vaccine used against HPAI. Of the six countries that have used vaccine to control LPNAI, Mexico, Guatemala, El Salvador and Italy have been the biggest users. In countries with enzootic HPAI and LPNAI, development and implementation of exit strategies has been difficult.

Optimal processing of photoreceptor signals is required to maximize behavioural sensitivity.

The sensitivity of receptor cells places a fundamental limit upon the sensitivity of sensory systems. For example, the signal-to-noise ratio of sensory receptors has been suggested to limit absolute thresholds in the visual and auditory systems. However, the necessity of optimally processing sensory receptor signals for behaviour to approach this limit has received less attention. We investigated the behavioural consequences of increasing the signal-to-noise ratio of the rod photoreceptor single-photon response in a transgenic mouse, the GCAPs-/- knockout. The loss of fast Ca2+ feedback to cGMP synthesis in phototransduction for GCAPs-/- mice increases the magnitude of the rod single-photon response and dark noise, with the increase in size of the single-photon response outweighing the increase in noise. Surprisingly, despite the increased rod signal-to-noise ratio, behavioural performance for GCAPs-/- mice was diminished near absolute visual threshold. We demonstrate in electrophysiological recordings that the diminished performance compared to wild-type mice is explained by poorly tuned postsynaptic processing of the rod single-photon response at the rod bipolar cell. In particular, the level of postsynaptic saturation in GCAPs-/- rod bipolar cells is not sufficient to eliminate rod noise, and degrades the single-photon response signal-to-noise ratio. Thus, it is critical for retinal processing to be optimally tuned near absolute threshold; otherwise the visual system fails to utilize fully the signals present in the rods.

Efficacy of atorvastatin therapy in ischaemic heart disease - effects on oxidized low-density lipoprotein and adiponectin.

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 +/- 148.6 to 286.9 +/- 88.5 nmol/l, and adiponectin increased from 9.7 +/- 7.4 to 13.9 +/- 9.98 microg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.

Food safety in international trade.

International approaches are indispensable in the management of foodborne risks to health. The contributions made by WHO and the World Trade Organization to achieving food safety are discussed below, and particular reference is made to the Agreement on the Application of Sanitary and Phytosanitary Measures and to the work of the Codex Alimentarius Commission.

Healthy Marketplaces.

PIP: This article discusses approaches of the World Health Organization's (WHO) Healthy Cities Program (HCP) to create environments that are supportive to good health. Creation of healthy marketplaces is part of the HCP strategy. Marketplaces offer consumers low-cost fresh produce and other foods direct from the producers and ready-to-eat foods prepared by vendors. Marketplaces serve an important social role for exchanging ideas and information. These locations offer an opportunity for health education. Many marketplaces set a poor example with unsanitary conditions and unhygienic practices. A Joint Food and Agriculture Organization (FAO)-WHO Expert Committee on Food Safety recommends drafting and enforcing food laws, provision of infrastructure and services, training and education of vendors, and increased consumer awareness. Hygiene should be equal to requirements for fixed facility retail stores. A Hazard Analysis Critical Control Point (HACCP) system is a cost-effective method for assessing food safety and controlling health hazards. HACCP priorities take into consideration the physical and socioeconomic context and cultural characteristics of vendors and customers. A first step in ensuring food safety is the establishment of an organizational structure for implementing controls. Healthy marketplaces should include market administration, healthy sanitation and drainage, waste disposal, and education of food vendors and customers. The physical layout should provide the best conditions for preventing contamination.^ieng

[A survey of goals and the utilization of numerical goals in the health planning of 47 prefectures].

Health plans of 47 prefectural governments based on the Medical Law of 1985, were evaluated regarding four health planning factors: final goal, implementation plan, development of resources, and evaluation planning. Results of the evaluation showed that 8.5% of the 47 prefectures had defined future level of health based on numerical goals. On the other hand, all of the prefectures had developed numerical goals specifying the number of hospital beds in each medical district. A major component of health planning is improvement in the accomplishment of the implementation plan. There were 14 prefectures which had numerical goals for the upgrading of facilities and for manpower development to meet future health care activities. The following factors are required in the health planning to meet the needs for improving the health status of the population. 1) Including in the future health goals, in addition to the number of medical bed in regional areas, objective levels of health that should be attained. 2) Development of practical plans for evaluation of effectiveness of health planning.

[Continuous hyperthermic peritoneal perfusion (CHPP) therapy in advanced gastric cancer].

In CHPP therapy for advanced gastric cancer, a perfusate containing 20 mg CDDP and 8 mg MMC in 1,000 ml physiologic saline warmed at 47 degrees C was infused at a constant rate of 200 ml/min into the pouch of Douglas. The intraperitoneal temperature at the supra-pancreatic region was around 39.0 degrees C. To obtain a more stable and higher intraperitoneal temperature, the infusing rate was increased to 400 ml/min. This yielded a 3 degrees C higher temperature (42 degrees C) at the same measuring site. However, the temperature recorded at various intraperitoneal sites did not always reach such an effective range. The maximal plasma concentrations of MMC determined during CHPP at the 200 and 400 ml/min infusion were 0.09 +/- 0.03 and 0.11 +/- 0.03 microgram/ml, and those of CDDP 1.6 +/- 0.4 and 1.7 +/- 0.3 microgram/ml, respectively, all of which were not significantly different. When an intraperitoneal dosage of 20 mg MMC was given to 3 patients, the portal venous blood, at 10 min after the administration, produced a 1.7 times higher concentration of the agent than did the peripheral venous blood. This discrepancy between the two concentrations was much smaller than found by other investigators in animal experiments.

[Total body hyperthermia and continuous hyperthermic peritoneal perfusion as an adjuvant therapy in advanced gastric cancer].

Between September 1986 and July 1989, adjuvant hyperthermic therapy, consisting of either total body hyperthermia (TBHT) or continuous hyperthermic peritoneal perfusion (CHPP), was given to a total of 41 patients immediately following gastric resection for cancer. TBHT was performed in 1 curative- and 11 noncurative-gastrectomized patients (1 stage III and 11 stage IV), and CHPP in 18 curative- and 11 noncurative-gastrectomized patients (6 stage I/II, 10 stage III and 13 stage IV). For TBHT, the blood was warmed and maintained at 42 degrees C for 3 hours by means of a V-V bypass connected to an extracorporeal heater-pumping system. When the hyperthermic condition was established, anti-cancer drugs were administered intravenously. In CHPP, 46 degrees C saline containing anti-cancer drugs were infused at a constant rate through a tube placed at the Douglas fossa. The perfusate was drained out through another tube positioned at an uppermost part of the abdominal cavity. The hyperthermic condition was monitored by measuring the outflow temperature. Complications encountered were bone marrow depression, liver damage and pyrexia, and were more frequently experienced by the TBHT patients. Patients under 65 years of age who had had an absolute noncurative gastrectomy but with TBHT survived significantly longer than those without TBHT. When the patients who had undergone gastrectomy with CHPP for a cancer of more than se penetration were compared with those without CHPP, there was no significant difference in survival found between these two populations. This unsatisfactory result could be partly attributable to difficult maintenance of appropriate (sufficiently high) and constant perfusate temperature.

[Adenoid cystic carcinoma of the esophagus].

A 56-year-old man was admitted with the complaint of dysphagia. X-ray studies and endoscopy revealed a protruding tumor at the middle third of esophagus. Under the diagnosis of esophageal cancer, subtotal esophagectomy was performed. A Borrmann type I like tumor measuring 6.7 X 3.8 X 2.2 cm was identified on the resected specimen. The surface of the tumor was irregular, nodular and covered with thin compressed esophageal mucosa. The histology of the tumor was consistent with adenoid cystic carcinoma. Incidentally, small foci of invasive squamous cell carcinoma were found adjacent to this tumor. There was no lymph node or remote organ metastasis.

[Primary adenosquamous carcinoma of the stomach--a case report].

A 56-year-old man was hospitalized with the complaint of upper abdominal discomfort. A gastrointestinal series revealed a filling defect in the body of the stomach. Under the diagnosis of gastric cancer, total gastrectomy was performed. Borrmann III type cancer measuring 5 X 4 cm, extending to the antrum and the upper portion of the body of the stomach, was identified in the body. Histologically, most of the tumor consisted of squamous cell carcinoma. Adenocarcinoma and a small nest of squamous metaplasia were observed at the peripheral wall of this tumor. The pathological diagnosis was adenosquamous carcinoma. In some regional lymph nodes, metastasis of adenocarcinoma was observed.