Hamid, Karachi Sanjiv Mahadeva, Kuala Lumpur Satawat Thongsawat, Chiang Mai Sathaporn Manatsathit, Bangkok Shiv Kumar Sarin, New Delhi Shomei Ryozawa, Yokohama Siam Sirinthornpanya, Bangkok Siew C Ng, Hong Kong Siriboon Attasaran, Bangkok Siriluck Papasivorakul, Bangkok Siwaporn Chainuvati, Bangkok Somchai Leelakusolvong, Bangkok Somying Tumwasorn, Bangkok Soon Koo Baik, Wonju Subrat see more S. K. Acharya, New Delhi Supot Pongprasobchai, Bangkok Supreecha Asavakarn, Bangkok Suthep

Gonchanvit, Bangkok Takao Itoi, Tokyo Takeshi Azuma, Kobe Taned Chitapanarux, Bangkok Tanittha Chatsuwan, Bangkok Tawesak Tanwandee, Bangkok Taya Kitiyakara, Bangkok Teerha Piratvisuth, Bangkok Thawatchai Akaraviputh, Bangkok Theranand Sanpajit, Bangkok Tsang Bih Shiou Charles, Singapore Tsutomu Chiba, Kyoto Uday C Ghoshal, Lucknow Uthai Khow-ean, Songkla Varocha Mahachai, Bangkok Varut Lohsiriwat,

Bangkok Vincent Wong, Hong Kong Voranush Chongsrisawat, Bangkok Wanich Piyaniran, Bangkok Wan-Long Chuang, Kaohsiung Worabuth Taweerutchana, Bangkok Yasushi Sano, Kobe Yi-You Chiou, Taipei Yogesh K. Chawla, Chandigarh Yutaka Saito, Kyoto “
“I read the very interesting article by Finn1 about sorafenib, the first systemic agent showing a survival advantage when it is used to treat patients with hepatocellular carcinoma. Finn1 pointed out common and predictable toxicities, including hand-skin reactions, anorexia, and diarrhea, which were experienced learn more by 15% to 40% of the treated patients.

However, Finn1 did not mention the importance of health-related quality of life (HRQOL) with respect to the potential side effects of hepatocellular carcinoma treatment and wrote only a few words about the cost of the drug. The growth of health care costs continues to outpace our ability to pay for health care in the future. We need to know not only the clinical efficacy of the drug but also its cost-effectiveness and the HRQOL of patients randomized 上海皓元 between a placebo and sorafenib. Studies of HRQOL may add value in a variety of ways, including the provision of data that may contrast with or support the primary outcome and sometimes change a study’s interpretation. Studies of cost-effectiveness and HRQOL may provide valuable sources of additional information useful to both the clinician and the patient when treatment decisions are being made, and they are considered important endpoints together with traditional measures.2 I think that their assessment is particularly worthwhile for trials in which survival rates are low. Natalia Terreni M.D.*, Giancarlo Spinzi M.D.*, * Division of Gastroenterology, Valduce Hospital, Como, Italy. “
“Cheung J, Soo I, Bastiampillai R, Zhu Q, Ma M. Urgent vs.

4B,D). However, Tregs were also found http://www.selleckchem.com/products/hydroxychloroquine-sulfate.html among lymphocytic infiltrates in the tumor bed (Fig. 4A,C) and in the marginal zones separating the tumor from surrounding

liver tissue (Fig. 4A). Furthermore, we analyzed the expression of HLA-DR, CD25, ICOS, GITR, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in blood, TFL, and tumor CD4+ CD25+FoxP3+ Tregs (Fig. 3B). Based on the expression of these markers, we concluded that intrahepatic Tregs displayed a more activated phenotype than circulating Tregs. Interestingly, tumor Tregs expressed significantly more ICOS and GITR than Tregs from TFL and blood. In addition, Tregs from LM-CRC expressed significantly higher levels of CTLA-4, HLA-DR, and CD25 than their counterparts from TFL, indicating a higher state of Treg activation at the

tumor site. When comparing expression of these markers between both patient groups, we observed that expression of the activation CHIR-99021 markers HLA-DR and CD25 was higher on Tregs from LM-CRC than HCC tumors (HLA-DR LM-CRC, 3,398 ± 2,182 mean fluorescence intensity (MFI) versus HCC, 1,681 ± 1,064 MFI, P = 0.0337; and CD25 LM-CRC, 5,257 ± 3,110 MFI versus HCC, 2,022 ± 1,189 MFI, P = 0.0018), whereas expression of the other markers was similar. Thus, tumor-derived Tregs were characterized by the expression of high levels of GITR and ICOS and Tregs in LM-CRC displayed an even more activated phenotype than those in medchemexpress HCC. To analyze whether the enhanced activation status of tumor-derived Tregs was reflected in superior suppressive functionality compared with their counterparts from PB, cocultures of Tregs from blood or tumor with CD4+CD25− T cells from PB stimulated

with PHA, TL, or CMV were performed. PHA-stimulated CD4+CD25− T cells responded with a robust proliferation, and both circulating and tumor-derived Tregs inhibited T cell proliferation in a dose-dependent manner (Supporting Fig. 4). However, tumor Tregs showed stronger inhibitory capacity than circulating Tregs. To compare inhibition of tumor-specific T cell responses, autologous peripheral CD4+CD25− T cells were stimulated with DCs pulsed with TL and cocultured with Tregs (Fig. 5). Both HCC- and LM-CRC–derived Tregs were more potent suppressors of tumor-specific T cell proliferation than circulating Tregs, but only LM-CRC–derived and not HCC-derived Tregs convincingly inhibited the cytokine production of responder T cells better than circulating Tregs. However, CMV-specific T cell proliferation and cytokine production in both HCC and LM-CRC are more potently suppressed by tumor-derived Tregs than blood-derived Tregs. Whereas no significant differences were found between HCC patients with and without cirrhosis with regard to tumor-infiltrating CD4+ T cells, including Tregs and their functionality (Supporting Fig. 5), phenotypic and functional differences were noted comparing tumor-infiltrating Tregs from patients with HCC and LM-CRC. As seen in Fig.

15 The study has since expanded to include eight clinical sites. Network investigators were charged with identifying and enrolling persons who developed DILI, carefully phenotyping the clinical condition, and collecting appropriate biological samples. Details concerning the planning, initial study design, study outcomes, eligibility criteria, and conduct of the study have been reported,14 and the clinical features of the first 300 patients enrolled have been summarized.16 The study protocols were approved

by the institutional review boards at all participating institutions and were registered at ClinicalTrials.gov. In brief, enrollees in the prospective study were persons receiving single

or multiple drugs, herbals, or other over-the-counter BAY 80-6946 products identified to have biochemically defined liver dysfunction, provided that they could be evaluated within 6 months of onset of the liver disease.14 Biochemical buy MDV3100 criteria for enrollment included (1) two consecutive serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values > 5 times the upper limit of normal (ULN) or > 5 times the baseline abnormal value, (2) two consecutive serum alkaline phosphatase (AP) values greater than twice the ULN or twice the baseline abnormal value, or (3) an otherwise unexplained total serum bilirubin MCE value > 2.5 mg/dL or an international normalized ratio (INR) > 1.5 on two consecutive occasions. Symptoms or signs of liver injury were not required. Exclusion criteria were liver injury due to acetaminophen, preexisting autoimmune hepatitis or sclerosing cholangitis, and previous receipt of

a bone marrow or liver transplant. Persons were not excluded for preexisting chronic hepatitis B or C or human immunodeficiency virus infection, provided that baseline laboratory test results were available. Sequential steps in causality assessment are outlined in Fig. 1. Complete clinical data, including serial laboratory test results together with the local ULN values, were extracted from the clinical records and entered into a 65-page case report form (CRF). To exclude conditions that can mimic drug-induced liver disease, the patients and their medical records were screened for previous liver disease, alcohol use, serological and virological evidence of hepatitis A, B, or C infection, autoantibodies, ceruloplasmin, alpha-1-antitrypsin, ferritin, and iron; additionally, results of imaging studies were reviewed. Patients who had not been fully evaluated when they were first identified underwent testing for any missing laboratory data at enrollment. Liver biopsy was not required for adjudication purposes, but if it was performed as part of routine clinical care, the results were collected and made available to reviewers.

The complete nucleotide sequences of the begomovirus (JX270684, 2745 nucleotides), obtained by rolling circle amplification, showed the highest sequence identity (98.1%) with the weed-infecting

begomovirus, Croton yellow vein mosaic virus. Analysis of recombination indicated the probable occurrence of many overlapping inter- and intraspecific recombination events. The sequence of betasatellite (JX270685, 1355 nucleotides) showed the highest sequence CYC202 price identity (95.7%) with Croton yellow vein mosaic betasatellite. Begomoviruses were not previously known to naturally infect rapeseed-mustard. This is the first report of the emergence of a weed-infecting begomovirus–betasatellite complex in rapeseed-mustard germplasm in India and raises the concern on utilization of such susceptible germplasm in crop improvement programmes. “
“The technique consisting

of the co-operational PCR coupled with dot blot hybridization and posterior colorimetric visualization was developed for the detection of Phaeomoniella chlamydospora, one of the major pathogenic fungi involved in the Petri disease of grapevine. A partial region of the fungal rDNA including the internal transcribed spacer (ITS) region was amplified through co-operational PCR for P. chlamydospora and 17 additional grapevine-associated fungi included in the genera Botryosphaeria, Cryptovalsa, Cylindrocarpon, Dematophora, Diplodia, Dothiorella, Eutypa, Fomitiporia, Lasiodiplodia, Neofusicoccum, Phaeoacremonium, Phomopsis and Stereum, MCE公司 by using the primer pairs NSA3/NLC2 Selleck LDK378 (external pair) and NSI1/NLB4 (inner pair). A specific

probe (Pch2D) targeting the ITS2 region in the rDNA was developed for the detection of P. chlamydospora. Dot blot hybridizations carried out with the PCR products showed the specificity of the probe. Results indicated that Pch2D only hybridized with DNA amplicons of P. chlamydospora isolates, thus proving the specific detection of this fungus, while the 17 remaining species tested for the Pch2D probe resulted in negative results. Sensitivity of the technique was established below 0.1 pg of genomic DNA. This technique was further validated using artificially inoculated grapevine cuttings with P. chlamydospora. The efficacy of detection was established at 80% after two independent blind assays. “
“Based on the observation that Acidovorax citrulli switches from saprobic to pathogenic growth for seed-to-seedling transmission of bacterial fruit blotch of cucurbits (BFB), we hypothesized that quorum sensing (QS) was involved in the regulation of this process. Using aacI (luxI homologue) and aacR (luxR homologue) mutants of AAC00-1, we investigated the role of QS in watermelon seed colonization and seed-to-seedling transmission of BFB.

There is no association between the autoantibody and the efficacy of antiviral therapy for CHC patients. Key Word(s): 1. chronic hepatitis C; 2. autoantibody; 3. IFN; 4. Meta-analysis; Presenting Author: KA ZHANG Additional Authors: YIJIA LIANG, XIAHAI SUN, FEIXING PAN, HUANQI XU Corresponding Author: KA ZHANG Affiliations: Third Affiliated Hospital of Sun Yat-sen University Objective: To investigate the influence factors on HBV relapse after withdrawal of nucleos(t)ide analogues (NAs) treatment in patients with chronic hepatitis B (CHB). Methods: There were 136 CHB patients enrolled in this study. Hepatic biochemical parameters, HBV serological markers and hepatitis B virus

(HBV) DNA testing were determined at baseline and follow-up after this website 1, 2, 3, 4, 5, 6, 9, 12 months the following every

6 months after cessation of NAs treatment respectively. The relapse was defined as HBV DNA > 1.0*103copies/ml. 15 probable influence factors on relapse which were sex, age, HBV family history, interferon treatment history, baseline HBV DNA load, HBeAg status, ALT, AST, TBIL, ALB, time of virological responses, total duration of treatment, duration of extended consolidation therapy, initial treatment or retreatment. The cumulative relapse was calculated by the Kaplan-Meier method. Area under the receiver operator characteristics (ROC) curve was performed to assess the predictive cut off values of age, baseline ALT and duration of extended consolidation therapy at the end of therapy. Results: The results showed Smoothened Agonist mouse that age (RR = 1.045, 95%CI 1.021–1.069, P = 0.000), baseline ALT (RR = 0.999, 95%CI 0.997–1.000, P = 0.016) and duration of extended consolidation therapy (RR = 0.974, 95%CI 0.951–0.998, P = 0.031) were independent predictors. The cut off value of age, baseline ALT and duration of extended consolidation therapy

predicting re1apse is 37-year-old, 80 U/L and 11 months respectively. The cumulative relapse rate of patients above 37-year-old was higher than that of under 37-year-old (including 37) (62.5% vs 45.3%, P = 0.045); baseline ALT ≤ 80 U/L higher than >80 U/L (66.7% vs 44.7%, P = 0.011). Conclusion: Age, baseline ALT and duration of extended consolidation therapy were independent predictors medchemexpress for relapse. Age was the most dangerous risk factor of relapse, the following was baseline ALT, and duration of extended consolidation therapy. Key Word(s): 1. Chronic Hepatitis B; 2. Influence Factors; 3. Withdrawal; 4. Relapse; Presenting Author: KA ZHANG Additional Authors: YIJIA LIANG, XIAHAI SUN, FEIXING PAN, HUANQI XU Corresponding Author: KA ZHANG Affiliations: Third Affiliated Hospital of Sun Yat-sen University Objective: To investigate the relapse rates of CHB patients after nucleos(t)ide analogues (NAs) treatment with different duration of extended consolidation. Methods: 136 CHB patients were enrolled in this study.

Specimens were stained for nitric oxide synthase 2 (NOS2) (also denoted iNOS) as a marker for the M1 macrophage

phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The expression level of COX-2 was examined both by immunohistochemistry and western blot. Results: Stroma of Apc (Min/+)mouse polyps was infiltrated by TAMs that were premodinantly polarized to M2 phenotypes. Berberine reduced the size and number of polyps, and also reduced the number of F4/80 positive macrophages. Concomitantly, Ceritinib cell line the expression of iNOS was significantly upregulated and the expression of COX-2 was decreased by berberine, although the expression of CD163 were not significantly altered. Conclusion: Berberine inhibits the growth of polyps and alters the phenotype of TAMs in stroma of Apc (Min/+)mouse polyps possibly through inhibiting the expression of COX-2. Key Word(s): 1. Berberine; 2. Apc (Min/+) mouse; 3. TAMs; 4. COX-2; Presenting Author: YU-MING WANG Additional Authors: YING CHANG, YUAN-YUAN CHANG, JING CHENG, JING LI, TAO WANG, QING-YU ZHANG, DONG-CHUN LIAJNG, BEI Atezolizumab purchase SUN, BANG-MAO WANG Corresponding

Author: YU-MING WANG Affiliations: Tianjin Medical University General Hospital Objective: To evaluated the links between the serotonin transporter gene polymorphism and SERT expression levels. We examined SERT mRNA, SERT protein levels as well as the ultrastructure in colon biopsies from patients with different 5-HTTLPR genotypes. Methods: Two hundred and fifty-four patients with IBS and 120 healthy subjects were studied. DNA 上海皓元医药股份有限公司 samples were extracted from

peripheral blood and genotyped by polymerase chain reaction. SERT mRNA and protein levels were evaluated by quantitative real time PCR and western blotting. The promoter efficiency of the serotonin transporter promoter was evaluated with luciferase reporter system. The ultrastructures of colon were performed by means of cryogenic transmission electron microscopy. Results: The frequency of the L/L genotype in C-IBS group was significantly higher than that in the control and D-IBS. However, the S/S genotype in D-IBS was significantly higher than that in C-IBS. The transcriptional efficiency of the L/L genotype was significantly higher than that in the L/S and S/S genotype. Patients with the L/L genotype demonstrated increased production of the SERT protein when compared with L/S and S/S patients. The l variant increased SERT promoter activity by 2.43-fold when compared with the s variant. The caliciform cells dense of D-IBS were higher than that of A-IBS and C-IBS. The intra-cellular mucocysts were significantly increase and productive. The neuroendocrine cells were grow in number, and were full of electron-dense secretory granules which were casted off to mesenchymal on occasion. The cell population of plasmocytes were increased in C-IBS. The labrocytes with electron-dense secretory granules and a few vacuolus were significantly increased in mesenchymal of colonic mucosa in D-IBS.

If the only standard we apply is evidence-based medicine, or standard-of-practice medicine, or FDA-approved medicine, not only will we fall short of fulfilling our charge, but we will miss clinical opportunities which could well transform how we

manage disease. And perhaps more importantly, we do a disservice to our patients when we do not explore every avenue open to them. Every one of the medicines (for want of a better word) that AG is taking has some basis in the treatment of headache in one or another medical system.[4] Some have an evidence-based rationale, PLX4032 while others have a historical rationale dating back thousands of years. Some are based on a Western diagnosis such as migraine without aura, while others are based on a classical Chinese medicine diagnosis of cool, damp headache, or an Ayurvedic diagnosis headache due to too much pitta dosha (see Dr. Gokani’s accompanying explanation). A couple trace back to traditional American folk treatments. It is not reasonable, practical, or perhaps even appropriate for Western physicians to be skilled in classical Chinese, Ayurvedic

and homeopathic medicine. But an awareness of the reality that other medical systems exist, check details and perhaps more importantly, are practiced by our patients, is critical to our ability to properly care for patients. When these differing approaches conflict or complement each other, shouldn’t we broaden our knowledge base to allow for 上海皓元医药股份有限公司 interaction? That this is not

the current practice is evidenced by the fact that more than 50% of complementary and alternative medicine (CAM) users do not discuss their CAM activities with their health care provider.[2] Contrast this with data indicating that less than 20% of headache specialists routinely use CAM in their practice, while more than 90% ask their patients if they presently or in the past have tried CAM approaches for their headaches.[3] What we have here is a failure to communicate. If we are to find a common ground for treating patients utilizing varied and disparate medical systems, a common vocabulary must be established. The National Institutes of Health have proposed, through the National Center for Complementary and Alternative Medicine, some definitions. CAM is defined as a group of diverse medical and health care systems, practices, and products not generally considered part of conventional medicine.

Over time, these data have also allowed WFH to track programme progress, target resources and identify development needs [14]. Historically, WFH country development programmes focused on one or two elements of the WFH Model. To advance care further and faster, O’Mahony had an idea for a new intensive programme that would work on all five development elements at once to close the gap

in diagnosis, access to treatment products and mortality that existed between developed and developing countries. On World Hemophilia Day (April 17) in 2003, the WFH launched the Global Alliance for Progress (GAP) Program, which was a culmination of all that the WFH had learned about building sustainable care. This 10-year health care development initiative aimed to greatly increase the diagnosis LY2835219 and treatment of people with haemophilia in 20 developing Rapamycin purchase countries. An overarching goal was to identify 50 000 people with haemophilia globally. In 2013, GAP celebrated its tenth anniversary and a decade of success in achieving

demonstrable change in each of the 20 participating countries (Algeria, Armenia, Azerbaijan, Belarus, China, Ecuador, Egypt, Georgia, Jordan, Lebanon, Mexico, Moldova, Morocco, Peru, Philippines, Syria, Thailand, Tunisia, Russia and South Africa). In these countries, to date 26 381 patients with haemophilia were identified and national care programmes were established in 16 countries. Globally, the number people diagnosed with haemophilia increased from 105 971 in 2003 [15] to 167 110 in 2011 [16]. Although the success of health care development projects like GAP depend on a winning coalition it is often the patient leaders, those who have the most to gain or lose, who are the local drivers for change. To better prepare the WFH NMOs in the late 1990s, the WFH began developing workshops to help patient leaders develop the skills to lobby their government for improved care. This grew into a global advocacy in action training programme launched in 2006. So far, over 1000 patient organization leaders have been trained and gone on to improve care

MCE公司 in their own countries. Soon after being elected WFH president in 2004, Mark Skinner (US) led the WFH to adopt the vision of Treatment for All, which is the foundation upon which the WFH’s global development strategy is built today [17]. Treatment for All means that one day treatment will be available for all patients with inherited bleeding disorders regardless of where they live. It also means more than simply access to treatment products. It means: Proper diagnosis, management and care by a multidisciplinary team of trained specialists; Safe, effective treatment products are available for all people with inherited bleeding disorders; Expansion of services beyond haemophilia, to those with von Willebrand’s disease (VWD), rare factor deficiencies and inherited platelet disorders.

However, the recent work of Treiber et al. (2012) that questions the structure and location of magnetoreceptors could actually be viewed as a strength and sign of health: of a field that welcomes new results that may force revisions of current models of understanding. While many aspects of navigation are unresolved, as this review indicates, that does not mean that

there is no data. While the models for studying navigation are imperfect, closer links between laboratory work and field work are being established, and the addition of new technology for studying animals in the wild will broadened our understanding of the behaviour of migrating birds and the challenges they face (Guilford et al., 2011). The integration of neurobiology, RXDX-106 manufacturer physics and molecular biology into the discipline is now well established and has led to a number of breakthroughs in our understanding of the magnetic sense as well as Selleckchem Ulixertinib the role of the olfactory sense in navigation. The integration of these disciplines

has led to testable predictions about the structure of sensory systems and potentially the mechanisms of navigation. For the field to advance further, the link between these disciplines and behavioural biology needs to strengthen further, in order to reduce the ‘black box’ understanding of some of the systems involved. For example, a better knowledge of the structure of the ferromagnetic sense will allow better predictions

about the effect of magnetic pulse treatments to understand how receptors are changed by the treatment. Strengthening this integration of other disciplines, while maintaining the roots as a behavioural biology discipline, will ultimately lead to the solution of the ‘mystery’ of bird navigation. I will finish this review by highlighting some of the key issues that should be resolved in order for the field of true navigation in migratory birds to advance. (1)  Is the true navigation map unimodal, that is one environmental cue provides all information on location, bimodal, medchemexpress that is two separate environmental cues provide different aspects of the location (e.g. latitude and longitude), or redundant, that is do multiple cues provide the same information for different aspects of the location. Solving this will help to understand some of the inconsistencies and conflicting evidence in the field, as it will establish whether failure to repeat is a consequence of experimental design rather than redundancy of cues. I thank John Phillips and two anonymous reviewers for helpful comments on the paper. Aspects of this review also came as a result of enjoyable discussions with the Navigation Special Interest Group at the MIGRATE NSF funded meeting in Konstanz, 2010 with Susanna Åkesson, Verner Bingman, Tim Guilford, Anna Gagliardo, Henrik Mouritsen, Rachel Muheim, Rosie Wiltschko and Wolfgang Wiltschko.

Compared to other modalities, US requires additional expertise in interpretation, and is user dependent. Although imaging has helped in understanding the integrity of the haemophilic joint reasonably well, scoring systems for MRI and US are likely still evolving. The challenges http://www.selleckchem.com/products/ganetespib-sta-9090.html in the use of radiological tools include availability,

cost, expertise, long durations required for the studies and sometimes long waiting periods. Better understanding of how the radiological changes correlate with progression of joint arthropathy, clinical significance of Doppler and early MRI findings and the physician’s need (question to be answered) are essential, and will determine the use and future directions of imaging. Quality of life (QoL) is a ubiquitous term that has been used for centuries, initially ZD1839 molecular weight describing a country’s standard of living. More recently: the term quality of life is used to evaluate the general well-being of individuals and societies [37]. The World Health Association has defined quality of life in this way: Quality of life is defined as individuals’ perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations,

standards and concerns [38]. As such, QoL is necessarily subjective and very broad in its construction. For many individuals, including persons with haemophilia, 上海皓元 physical health makes only a very small contribution to their assessment of QoL [39]. Many other factors, like romantic and social relationships, wealth, material possessions, achievements in school or work and so on, are included

when an individual assesses his or her own QoL. The most important goals in treating persons with haemophilia are arguably preventing mortality and improving QoL; however, as health practitioners we may not be able to have an impact on aspects of QoL other than health. For that reason, many groups have developed ways of measuring health impact or health status. Questionnaires assessing health or health status, and reported by patients themselves, have often been labelled ‘health related quality of life’ (HRQL) measures [40]. The World Health Organization definition of health is a: state of complete physical, mental and social well-being and not merely the absence of disease or infirmity [41]. Their ICF model provides an organized way to conceive of health in the context of a disease like haemophilia. It posits that the disease has a direct impact on body structures and functions, activities and participation. Furthermore, these domains are influenced by environmental and personal factors. Given the descriptions above of health and QoL, it follows that a good measure of HRQL would measure the impact of disease(s) at the physical, mental and social levels. It would do this using the domains of structure and function (anatomy, physiology, etc.