Patients with cancer must also have full staging investigations to rule out other sites of disease progression and cannot actively be receiving chemotherapy or radiotherapy. If no exclusion exists, the patient will be randomized to HBO2T or standard of care treatment. HBO2T will consist of 100% oxygen at 2.4 ATA for 90 min daily, at least 5 days per week, for 30 treatments. The selection of this regimen is based both on the safety and efficacy observed in other FDA approved

uses selleck inhibitor including radiation necrosis of non-neural soft tissues. All patients will be monitored throughout their treatment period for progression of symptoms and their steroid requirement. They will also receive repeat MRI scans of the head after completion of the treatment protocol (30 days) and again and at 90 days following completion of treatment protocol. Formal neuropsychological

evaluation will be done at enrollment and repeated at 90 days post-treatment. Quality of this website life measures, such as the EORTC QLQ-C30 and BN 20 will be administered at enrollment and 90 days as well [70] and [71]. Primary outcomes will be progression, stabilization or resolution of symptoms measured by the neurologist, as well as progression, stabilization, or resolution of the lesions on MRI imaging where RECIST (response evaluation criteria in solid tumors) criteria will be applied [72]. Demeclocycline Secondary outcomes will include change in neuropsychological measures and, the steroid requirement as compared to control. All measures will be assessed at 90 days post-treatment. To determine whether use of HBO2T will relieve headache pain in status migrainosus. Migraine is a common disorder. One-year prevalence is approximately

18% and 7% for American woman and men, respectively [73]. Status Migrainosus, as defined by The International Headache Society’s International Classification of Headache Disorders, 2nd edition [74], is a migraine attack lasting more than 72 h that is typical of previous attacks except in duration, and that cannot be attributed to another disorder. While usually felt to be a rare phenomenon, in a recent retrospective study, 20% of migraineurs reported episodes which met these criteria [75]. Current knowledge suggests that primary neuronal dysfunction leads to intracranial and extracranial changes that account for migraine [76]. Those prone to migraine have a genetic migrainous threshold that leaves them susceptible to acute attacks, dependent on the balance of excitation and inhibition at various levels of the nervous system. Genetic and environmental factors both play a role [77]. Nevertheless, it is believed that vasodilatation still plays an integral part in the severe throbbing pain characteristic of migraine, likely secondary to instability in the central neurovascular control mechanism [78].

A maioria dos doentes apresenta evidências de hipersensibilidade a alimentos/alergénios aéreos/história de alergias respiratórias, muitas vezes associados a eosinofilia periférica e aumento de IgE. Os doentes com EE em 50‐80% dos casos são atópicos (rinite alérgica/asma/dermatite atópica/sensibilização alérgica da pele). Doentes

com rinite alérgica apresentam elevações sazonais dos eosinófilos esofágicos. Doentes com EE também apresentam variações sazonais dos seus sintomas. Aproximadamente 2/3 dos doentes têm testes cutâneos positivos a pelo menos um alergénio alimentar4 and 11. BMS-354825 chemical structure Os alimentos mais comumente relacionados são: amendoim, ovo, soja, leite de vaca e trigo. A eliminação de alguns alimentos da dieta conduz a 77% de resolução de alterações histológicas. Desconhece‐se ainda o impacto do tratamento a longo prazo e o dano final da doença12. A supressão ácida com inibidores da bomba de protões é útil no diagnóstico. Sabemos que a acidez irrita mais o esófago, já inflamado, logo é igualmente uma terapia adjuvante. A dilatação esofágica de estenoses é fundamental para o bem‐estar do doente. A dilatação está indicada quando ocorrem sintomas secundários à estenose. Traduz‐se em riscos do próprio procedimento: perfuração, laceração (mucosal tearing) e, apesar do sucesso, 7‐50% dos doentes tem recorrência dos sintomas e necessita de novas dilatações. Epacadostat concentration A corticoterapia sistémica traduz melhoria clínica e histológica.

É útil na necessidade de rápido alívio dos sintomas (disfagia grave, desidratação devida a dificuldade em deglutição, perda de peso, estenose esofágica).

Não esquecendo os efeitos laterais desta medicação em idade pediátrica. O corticoesteroide tópico tem associada melhoria clínica e histológica. Os efeitos adversos mais frequentes são a candidíase esofágica anti-EGFR antibody inhibitor e sensação de «boca seca». Entre os mais usados a fluticasona (220‐440 ug 2 x /dia) dose inalada; > 750 ug/dia; apesar de não estar ainda aprovado no tratamento da EE, tem uma resposta de 95% aos 3 meses, resposta rápida. Não esquecer que os estímulos se mantêm e portanto a doença tende a perpetuar‐se. Os antagonistas do recetor de leucotrienos promovem alívio dos sintomas, mas sem efeito benéfico na eosinofilia. O tratamento dietético com remoção de antigénios alimentares/alimentos específicos (história clínica + testes) controlam os sintomas, bem como as alterações histopatológicas: ainda é um tratamento controverso. O uso de dieta empírica deve ser monitorizado de perto por nutricionista. A remoção de 6 alimentos (leite, trigo, soja, frutos secos, ovo) durante 4‐6 semanas, seguida de reintrodução individual a cada 4‐6 semanas. A dieta guiada por testes alergológicos (PRICK, PATCH) muitas vezes associada a evicção do leite para ser melhor aceite pelo doente. O uso de fórmula de aminoácidos é o padrão‐ouro para determinar se os antigénios alimentares são responsáveis pela EE.

Patients flexed their knees to 30° and removed the slack from the tubing. As described MK0683 ic50 in previous publications,12, 15, 16 and 26 patients then performed a partial squat against resistance from the start position to full knee extension while squeezing a ball between both knees. Outcome measures

were obtained on 3 separate occasions: at baseline, after 8 weeks of exercise (postintervention), and at 6 months (follow-up). A single tester who was not blinded to group assignment recorded all outcome measurements. For patients with bilateral PFP, the limb reported to be the most painful during initial testing was evaluated for all testing sessions. Self-reported pain intensity was selleck chemicals quantified using a 10-cm visual analog scale (VAS), which ranged from 0 (no pain) to 10 (worst pain possible). Individuals were asked to rate their pain based on activities

that aggravated symptoms during the previous week. The 10-cm VAS is a valid and responsive outcome measure for PFP with a minimal clinically important difference of 2.27 Self-reported health status was quantified using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). The WOMAC is a 24-item questionnaire evaluating pain, stiffness, and physical function.28 This tool is a valid outcome measure for knee osteoarthritis29 and has been reported to be significantly correlated with an outcome measure specifically designed for PFP.30 The total summed score for the Likert scale version used in the current study ranged from 0 to 96 (pain, 0–20; stiffness, 0–8; physical function, 0–68); higher scores indicated worse health status. Independent t tests were used to evaluate group differences at baseline. A 2-factor, mixed-model analysis of variance (ANOVA) (2 groups × 3 time points) was used to compare outcome measures between groups over time. This analysis was repeated for the VAS and WOMAC scores. If a significant interaction was found, paired t tests (2-tailed) were used to assess changes in each group across the 3 time points. Additionally, independent t tests (1-tailed) were used to compare group differences 3-mercaptopyruvate sulfurtransferase at each time point.

Because data were normally distributed and variance was equal between groups, parametric tests were justified. All statistical analyses were conducted with SPSS software b using a significance level of P=.05. At baseline, demographic characteristics, VAS scores, and WOMAC scores were comparable between groups (see table 1). Patients in both groups were moderately to severely impaired with respect to pain intensity and health status. All subjects completed the postintervention and 6-month follow-up assessments. On average, patients assigned to the posterolateral hip exercise group attended 22.4 supervised exercise sessions, whereas subjects assigned to the quadriceps exercise group attended 22.1 supervised exercise sessions.

No MTD of hydralazine was observed in this trial, but as the maximum recommended dose of hydralazine for the treatment of hypertension or congestive heart failure is 300 mg per day,

the phase II dose of hydralazine in combination with valproic acid at therapeutic doses was defined as 300 mg per day; six additional patients were enrolled at this dose level (total of nine) to better define any potential toxicities, without any DLTs observed. A median number of two treatment cycles were administered on this protocol (range = 1 -29). There were no complete responses. One partial response by Response Evaluation Criteria In Solid Tumors (RECIST) criteria was observed in a patient who had metastatic mutant B-RAF V600E-positive melanoma (before the availability of vemurafenib). They received this regimen as a second-line systemic therapy after a combination of temozolomide, paclitaxel, click here and carboplatin and remained on therapy for 29 months. They initially

had stable disease for 4 months, which slowly evolved into a partial response. They developed vitiligo on this experimental combination. On disease progression, they received ipilimumab without response. Five additional subjects experienced stable disease for 3 to 6 months: two with soft-tissue sarcoma (3 and 4 months), ovarian cancer (3 months), squamous cell cancer of the head and neck (4 months), and breast cancer (6 months). At the time of this report, 24 of the 27 subjects have died, with a median overall survival of 3 months (range = 1-18 months); the three survivors are alive at 16, 18, and 18 months.

Although oxyclozanide the primary www.selleckchem.com/products/ldk378.html objective of this phase I study was to identify the MTD of the combination of escalating doses of hydralazine with a fixed, steady-state concentration of valproic acid, the significance of the study was to design and test a tolerable combination of agents that may subsequently be evaluated as a regimen for the chemoprevention of lung cancer. Chromatin-modifying agents have demonstrated activity in vitro and in vivo against non–small cell lung cancer. However, the adverse event profiles of current FDA-approved chromatin-modifying agents are not justifiable for chronic delivery in healthy patients at risk for lung cancer. In our trial, the recommended dose for further study is hydralazine at 300 mg per day and valproic acid with a target serum concentration of 0.4 to 0.7 μg/ml. Although the dose of 400 mg per day of hydralazine did not exceed DLT as defined, the rates of mild, symptomatic hypotension and edema were considered unacceptable for the purpose of prolonged administration. This study demonstrates that pharmacological doses of hydralazine and valproic acid may be delivered to patients with heavily pretreated malignancies, with evidence of potential clinical activity in melanoma, soft-tissue sarcoma, and carcinomas of the breast, ovary, and head and neck.

Ecological restoration attempts to return a degraded ecosystem to its historical trajectory [35]. For many ecosystems in the deep sea, although the historical trajectory is not always well understood or well documented, it may be inferred from life history and functional attributes of dominant taxa. For some deep-sea ecosystems selleckchem (e.g., many hydrothermal vent systems), a historical trajectory is understood or can be reasonably established or inferred [36] and [37]. For

others, more research and data would be needed to determine a historical trajectory. This is especially the case where disturbed ecosystems are exceptionally stable, with organisms of centennial or multi-centennial lifespans (e.g., coral reefs) [38] or substrata that grow on millennial time scales (e.g., manganese nodules) [39]. Ensuring that a functional set of flows, interactions, and exchanges with contiguous or inter-connected ecosystems occur in restored deep-sea ecosystems requires an understanding

of local and regional hydrodynamics as well as interactions among populations and species. For some patchy ecosystems in the deep sea, such as hydrothermal vents, cold seeps, and some seamounts, the understanding of how networks MAPK Inhibitor Library ic50 of these ecosystems interact within a bioregion is a fledgling science [40] and [41]; for apparently vast ecosystems, such as abyssal plains and manganese nodule beds, the spatial scale of ecosystem networks and characteristics of their ecological and genetic connectivity are poorly understood [42]. Restored ecosystems consist of indigenous species to the greatest practicable extent [35], but a Thalidomide number of factors make it challenging to recognize indigenous versus non-indigenous species or taxa: ranges of species and subspecies are often poorly known because pre-disturbance baselines (including successional sequences following natural disturbance) do not exist for most deep-sea ecosystems, taxonomic diversity is very high, and most

species have very low abundance in most of the deep sea [43]. While it may be more practical in most deep-sea systems to compare indigenous functional groups (e.g., suspension feeders, deposit feeders, size groups, etc.) rather than attempt to census all indigenous species and taxa, restoration actions based on functional groups could promote a change in community structure and species composition and an over-simplification of structure and diversity [18]. Attributes of restored ecosystems also include “connectivity” attributes that describe their relationship to the rest of the world. These include their integration into a larger landscape, their protection from external threats, and the existence of governance in support of restoration. Although all ecosystems are three-dimensional in space, this particular attribute is especially important for the ocean and linkages among its ecosystems.

Thereby, spontaneous fluctuations in blood pressure Bafetinib and cerebral blood flow velocity (assessed by transcranial

Doppler sonography) are analyzed to extract information about how quickly and appropriately autoregulatory action occurs [2]. A recent systematic review of TCD autoregulation studies in acute ischemic stroke revealed a considerable heterogeneity in autoregulation methodology and time points of measurement [3]. Most of the included studies comprised a small number of patients with various types and locations of ischemic stroke. In this review we summarize data of our previous studies on autoregulation assessed by TCD in acute ischemic stroke. We focus on the time course of autoregulation in acute stroke and clinical factors associated with autoregulation in acute stroke and will discuss future challenges in the field of autoregulation in acute stroke. This review comprises a total of 45 patients from two previous studies [4] and [5]. Patients were admitted with acute ischemic stroke in the middle cerebral artery (MCA) territory to our stroke unit and had no relevant obstructive carotid artery disease. The protocol for the studies included an early measurement of autoregulation (within 48 h after stroke onset) and a late measurement

around days 5–7. Flow velocity PD98059 molecular weight in both MCA was measured by TCD and blood pressure was recorded noninvasively via finger plethysmography. Cerebral autoregulation was assessed from spontaneously occuring fluctuations in blood pressure during a period of 10 min in each study. In this review we focus on results of the correlation coefficient analysis. With this approach (index Mx), mean values of ABP and CBFV are correlated by Pearson’s correlation coefficient. In Endonuclease case of a high correlation, CBFV fluctuations depend on those of ABP. Higher Mx values thus reflect poorer autoregulation [6]. In a group of 45 patients with acute MCA stroke, the index Mx increased significantly between an early measurement within 48 h after

stroke onset and a second (late) measurement around day 6 (late). This increase indicates worsening autoregulation and was larger on the MCA side affected by the stroke, but was also significant on the contralateral side (Fig. 1a). Group mean values did not differ from those of controls. A separate analysis of patients with large MCA stroke, however, showed that Mx is clearly impaired in the MCA ipsilateral to the stroke side around day 6 after stroke onset but not during the first day after stroke (Fig. 1). Deteriorating autoregulation (increasing Mx) on ipsi- more than contralateral sides between days 1–2 and days 5–7 was associated with larger infarcts [7]. Furthermore, there was a positive relation between poorer ipsilateral autoregulation and poorer clinical status (NIH stroke scale) at the early and late measurement. On contralateral sides, a similar but non significant trend was observed.

The effect of DON on the number of affected genes (≥ 1.5× up- or downregulated, p value < 0.01) was highest after 3 h for the lowest and middle dose and much lower after 24 h, indicating a reversible effect. In contrast, the highest concentration of 25 mg/kg DON had an AZD2281 nmr irreversible effect on the number of genes affected. The biological interpretation of the microarray data led to the hypothesis that DON induces thymocyte depletion via induction of the

T cell activation response that is quickly followed by negative selection of thymocytes. The DON in vivo study was performed with 7-week-old male C57BL/6 mice that were obtained from Harlan (Horst, The Netherlands). Animals were kept at a housing temperature of 22 °C and at a relative humidity of 30–70%. Lighting cycle was 12-h light and 12-h dark. The treatment protocol was approved by the ethical committee for animal experiments at Wageningen University, Wageningen, The Netherlands. The experiment included 60 mice, which were randomly divided into 12 different groups. DON was dissolved in ethanol and then diluted with endotoxin-free water. The amount of ethanol was kept the same for all mice (2.5 μl/g

bw). The mice obtained one dose of DON by oral gavage (5, 10, or 25 mg/kg bw). The control groups per time point received only the vehicle ethanol. DON or vehicle was administered to one mouse each every selleck inhibitor 10 min to keep the treatment times constant. After 3, 6, or 24 h, the mice were sacrificed by cervical dislocation under isoflurane anesthesia. The thymus was isolated, immediately

frozen in liquid nitrogen, and kept frozen until further gene expression analysis. The doses used in this study were chosen based on literature. The lowest dose used (5 mg/kg DON) was chosen, Autophagy activator because it resembles the total daily consumption of DON in mice digesting a diet of 25 ppm DON. This level has been shown to result in an increase of circulating IgA and changes in the expression levels of different genes encoding cytokines, such as Il6 and TNFα, in the spleen (Azconaolivera et al., 1995 and Amuzie et al., 2008). The highest dose of 25 mg/kg DON is one-third of the LD50 of DON in mice (Azconaolivera et al., 1995). Thymuses were homogenized in 1 ml of TRIzol reagent (Invitrogen, Breda, The Netherlands) per 50–100 mg tissue, using a homogenizer (Pro Multi-Gen 7, PRO Scientific, Oxford, CT). Subsequently, RNA was isolated following supplier’s instructions. After purification using the RNeasy Mini Kit (Qiagen, Venlo, The Netherlands), integrity, purity, and concentration were assessed by automated gel electrophoresis (Experion, Biorad, Veenendaal, The Netherlands) and spectrophotometrically at wavelengths of 230, 260, and 280 nm. One microgram of each individual RNA sample was amplified using a low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies, Amstelveen, The Netherlands).

Use of diuretics or laxative abuse was not informed by hearing of her history. On admission, the patient was 157.0 cm tall and weighed 27.0 kg, with a body mass index of 11.0 kg/cm2. Her blood pressure was 80/48 mm Hg, her pulse rate was 96/min, and her temperature was 36.7 °C. Physical examination revealed severe malnutrition, but she had no bone pain. Laboratory data were as follows: the white blood cell (WBC) count was 4900/μL, hemoglobin (Hb) was 10.0 g/dL, platelet count was 329 × 103/μL, total serum protein was 7.2 g/dL, and serum albumin was 3.2 g/dL. Sodium was 132 mmol/L, potassium was 3.0 mEq/L, chloride was 100 mmol/L, serum calcium was 9.2 mg/dL, phosphate

was 3.8 mg/dL, pH was 7.38, pCO2 was 33 Torr, pO2 was 114 Torr, HCO3 was 19 mmol/L, base excess was − 4.9 mmol/L, urea was 34 mg/dL, Ipilimumab in vivo creatinine was 1.8 mg/dL, and uric acid was 12.3 mg/dL. In addition, total cholesterol was 170 mg/dL, triglycerides were 41 mg/dL, and

glucose was 107 mg/dL. Furthermore, serum alkaline phosphatase (ALP) was 83 IU/L, parathyroid hormone (PTH) was 27.7 pg/mL, osteocalcin was 6.9 ng/mL, 1,25-dihydroxyvitamin D was 7.0 ng/mL (normal: 20 to 60), and 25-hydroxyvitamin D was 18.7 μg/L (normal: 10 to 33). Serum renin was 87 pg/mL (normal: 10 to 20) and serum aldosterone was 136.0 ng/dL (normal: 3 to 15). Serum levels of adrenocorticotrophic learn more hormone, cortisol, and thyroid hormone were normal. Her 24-h urinary protein excretion was 0.17 g, N-acetyl-β-D-glucosaminidase (NAG) excretion was 54.0 IU (normal; less than 5.0), and β2-microglobin excretion was 2828 μg (normal; less than 400). Creatinine clearance was 36.5 mL/min and the estimated GFR was 36.5 mL/min. Urinary calcium excretion was low (55.5 mg/day). Sodium was 5.0 mmol/day, and potassium excretion was low (3.0 mmol/day). Radiographs showed severe generalized osteoporosis, but there were no pseudofractures (Fig. 1). Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA), revealing T-scores of − 4.8 SD and − 2.9 SD for the lumbar (-)-p-Bromotetramisole Oxalate spine (L2–L4) in the lateral and anterior–posterior

views, respectively, as well as a T-score of − 3.9 SD for the femoral neck. These findings were consistent with a diagnosis of osteoporosis (less than − 2.5 SD) according to the WHO classification. After informed consent was given, renal biopsy was performed for the assessment of her kidney dysfunction, and right iliac crest bone biopsy was performed after double-tetracycline labeling (with a schedule of 3 days on-7 days off-3 days on-24 days off using doxycycline of 200 mg daily) for the examination of her bone disease. Histomorphometric analysis of bone was performed using undecalcified thin (5 μm) sections of the biopsy specimen stained by the Villanueva method. This analysis was done by Mrs. Akemi Ito of the Ito Bone Science Institute (Niigata, Japan).

However, ERK 1/2 phosphorylation was shown to be involved in apoptotic morphological changes induced by heat stress at jejunal level ( Yu

et al., 2010). Similarly, a recent paper has indicated a correlation between decreased intestinal barrier function, decreased expression of tight junction proteins and the intestinal activation of MAPK ( Hu et al., 2012). So, the present results taken together with previous works allow to hypothesize that intestinal morphological alterations, such apical lyses of enterocytes and villi atrophy, were associated with changes in the tight junctions of the epithelium and the apoptosis induced by MAPK activation after exposure to DON. In conclusion, we demonstrated that, ABT-199 clinical trial in in vivo and ex vivo models, the histological changes induced by DON are similar as well as the response observed for the expression of MAPK in both models. This strongly suggests that intestinal toxicity of DON involve MAPK activation. In addition, using histological and protein expression analysis, we confirmed that the explant model is a good alternative for the studies focused on gastrointestinal toxicity following exposure to low doses of toxins. This work was financially supported by the CAPES/COFECUB (593/08) international cooperation program, CNPq grant (474583/2010-4) and the French ANR Project DON & Co. “
“The Phoneutria nigriventer spider, popularly known as the wandering armed spider or banana spider accounts

for most notified cases of accidents in Brazil. The Proteases inhibitor majority of accidents only cause local edema and pain; less than 1% is considered severe ( Bucaretchi et al., 2000). Patients severely envenomed oxyclozanide show tachycardia, hypertension, priapism, agitation, blurred vision, convulsion, and in some cases pulmonary edema and death. P. nigriventer venom (PNV) contains a notable amount of biologically active peptides, most of which are Na+, K+ and Ca2+ channel-acting neuropeptides which affect neurotransmitter release ( Fontana and Vital Brazil, 1985; Love and Cruz-Höfling, 1986; Gomez et al., 2002). In rats, the

venom induces excitatory effects such as intense salivation, lachrymation, piloerection, priapism, tonic convulsion and spastic and flaccid paralysis of the hindlimbs ( Diniz, 1963; Schenberg and Pereira Lima, 1971; Le Sueur et al., 2003; Rapôso et al., 2007; Mendonça et al., 2012). Transmission electron microscopy has shown that the venom can cause BBBb, evidenced by extravasation of extracellular tracer from brain microvessels and the presence of perivascular edema and edematous electron lucent endfeet of the perivascular astrocyte population ( Le Sueur et al., 2003, 2004; Rapôso et al., 2007). Swelling of astrocytic endfeet that follows BBB impairment may result from osmotic imbalance and accumulation of fluid into the brain provoking edema. The regulation of water permeability across the BBB is fundamental to maintain brain homeostasis.

In pelagic plankton ecosystems, the number of zooplankton species in a certain taxon (e.g., copepods) can be used, because there are a sufficient number of samples to provide accurate estimates. The number of benthic species can also be used for deep-sea ecosystems. Thus, simple and common indices such as species richness

(i.e., the number of species) can be used for different ecosystem types. The next step is to develop better indices considering the evenness of species distribution as well as phylogenetic relatedness. This is especially important for comparisons among different ecosystems because of large differences in lifetimes and speed of evolution [42]. More importantly, problems associated with the effects of research efforts on the estimation of species diversity should be

considered as in the case of criterion 1 (Nakajima et al. 2015). This criteria is defined as an “area with a comparatively higher Ku-0059436 price degree of naturalness as a result of the lack of or low level of human-induced disturbance or degradation,” [5]. This criterion is a relative measure in that “pristine conditions” are most important and should be preserved as best as possible. In selleck kinase inhibitor this research program, data such as the area of natural reserves, ratio of natural to artificial coastline, and human population size per catchment area are available and can be used for coastal ecosystems like kelp forests, seagrass beds, and coral reefs. On the other hand, offshore pelagic plankton and deep-sea benthic ecosystems, of which we are not yet able to determine the direct effect on fisheries, are mostly regarded as relatively natural; therefore, it is difficult to find relevant data showing variations in “naturalness.” For offshore pelagic ecosystems, data recorded from fisheries can be used, although the available species are limited. Distance from the coast can also be used as a rough approximation of fishing intensity. For deep-sea ecosystems, depth can be used as an approximation of fishing effort. The possible exploitation of deep-sea

energy and mineral resources must also be aminophylline considered, because deep-sea research that is based on long-term observations is insufficient to analyze the dynamics of unique ecosystems such as hydrothermal vents [43]. In theory, criterion 7 must be identified by quantifying human activity and its impacts on ecosystems. Available quantitative indices are mostly from the statistics of the Japanese government. In order to apply these indices to other countries in Asia, satellite images such as nighttime images of artificial light density and changes in coastline structures can be used to measure spatial and temporal variations in human impacts. Globally, the human impact model [44] can be used as an index of naturalness. For the open ocean, the use of fisheries statistics should be considered.