Synthesis across studies also requires consideration of how conte

Synthesis across studies also requires consideration of how contextual

influences and AZD9291 ic50 matters of interpretation are addressed [34]. In this synthesis, data collection in the different studies was broadly underpinned by current frameworks for palliative care [9], which provided a consistent reference for interpretation. However we also attempted to synthesise alternative stakeholder views on palliative care within a stroke context. ‘Realist’ work requires a strong stakeholder focus to ensure that emerging theory addresses important issues, and produces useful findings [20]. However, little guidance is available to suggest how different perspectives should Inhibitors,research,lifescience,medical be managed within the process. As we aimed to produce a guiding framework for clinicians and service managers to sustain Inhibitors,research,lifescience,medical the integration of palliative care within stroke services, we ‘focused’ our synthesis through the perspectives of staff drawn from three stroke services. Whilst this should maximise the utility of our findings, we may have under-represented some issues which are important to other stakeholders, including patients and family members. Conclusion Inhibitors,research,lifescience,medical This paper addresses an important gap in the literature by investigating

the interface between stroke and palliative care from the perspectives of patients, family members and stroke service staff. Synthesis of three studies highlights a chain of mechanisms which cumulatively explain these may be integrated around the needs and preferences of patients and family members. Mechanisms relate to the legitimacy of palliative care and individual capacity, engaging with family, the timing of intervention, working with complexity and the recognition of dying. A range of Inhibitors,research,lifescience,medical clinical and service factors appear to influence whether these mechanisms operate, and consequently how palliative care needs are attended to. The beliefs of staff about palliative

care, education and training, communication skills, supported by Inhibitors,research,lifescience,medical partnership working with specialist palliative care provide the basis for the integration of palliative and stroke care to occur. Our findings highlight Ketanserin difficulties in identifying the nature and purpose of palliative care in acute stroke services, including whether palliative care focuses on end of life care, or more general supportive interventions that could (or not) be combined with active treatment strategies. Practical difficulties in identifying when patients require palliative interventions should be the focus of further investigation. Competing interests The authors declare that they have no competing interests. Authors’ contributions CB and SP were involved in the study concept, design, analysis, interpretation of the data and drafting the manuscript. Both authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.

29 The leaves contain huge amount of vitamin C which is used in t

29 The leaves contain huge amount of vitamin C which is used in the treatment of oedema. 30 A decoction of the herb is used as a vermifuge and is useful in rheumatitis. It is also an antidote to alcoholic poison. 31 The present study was carried out with the aim to determine the chemical composition of essential oil isolated from T. decandra using GC–MS and to evaluate its antimicrobial activity and antioxidant activity against clinical bacterial and fungal selleck inhibitor pathogens. The leaves of T. decandra L. were collected from Salem district, Tamil Nadu, India during June 2008. The plant

was taxonomically identified and authenticated by the Botanical Survey of India, Coimbatore (Tamil Nadu) and voucher specimen No.BSI/SRC/5/23/10-11/Tech.975 was deposited in Plant Tissue Culture laboratory, SRM University for future reference. Aerial parts of T. decandra were washed with distilled water to remove dirt and soil, and were shade dried.

The dried plant material was powdered and passed through a 40-mesh sieve. The coarse powder (500 g) was extracted with petroleum ether (60–80°C), removed wax, and then extracted thrice with chloroform (CHCl3). The chloroform crude extract was desalted and dewaxed. It was dissolved in minimum quantity of acetone and absorbed over silica gel and transferred to a column (Column Height: 50 cm, Diameter: JQ1 9 cm) packed with silica gel (60–120 mesh) using petroleum ether and eluted with solvents of increasing polarity. The fractions eluted with petroleum ether: chloroform (3:1) gave a colourless liquid as an essential oil with a yield of 800 mg. To study the antimicrobial activity of various extracts of T. decandra, the strains of bacteria, yeast and fungi were collected from Institute of Microbial Technology, Chandigarh. The selected microorganisms included bacteria such as Staphylococcus aureus (MTCC 29213), Streptococcus faecalis (MTCC 0459), Enterococcus faecalis (MTCC 2729), E. coli (MTCC 443), P. aeruginosa (MTCC 1035), Salmonella typhi (MTCC heptaminol 98), Vibrio cholera (MTCC

3906), Proteus vulgaris (MTCC 1771), Bacillus subtilis (MTCC 121), Yersinia enterocolitica (MTCC 840) and fungi such as Candida albicans (MTCC 183) and Cryptococcus neoformans (MTCC 1346). The in vitro antimicrobial activity of the sample was studied by disc diffusion method. Sterile nutrient agar (Himedia) plates were inoculated with a loopful broth culture of each organism. Sterile discs (6 mm diameter) were impregnated with 20 μl (1 mg/disc) quantity of dimethyl sulfoxide solution of essential oil were air dried and placed on the seeded agar plates. The plates were incubated at 37 °C for 24 h. Libraries Chloramphenicol and nystatin (30 μg) were used as positive control. 32 After incubation, the DIZ was measured. Minimal inhibition concentration assay was performed in nutrient broth supplemented with resazurin according to the method.

Encapsulation of the doxorubicin analog, epirubicin into PEGylate

Encapsulation of the doxorubicin analog, epirubicin into PEGylated thermoresponsive liposomes increased blood residency and tumor accumulation over unresponsive liposomes or free drug, resulting in a 20% higher tumor growth inhibition in animals treated with thermoresponsive liposomes over unresponsive epirubicin-loaded liposomes [368]. Paasonen et al. used gold-nanoparticles

as “energy collectors” to lower the threshold energy required to induce photo-sensitive Inhibitors,research,lifescience,medical drug release [369]. After heat transfer from gold nanoparticles to lipids promoting liquid crystal-to-gel phase transition, a UV-induced liberation of the model compound calcein was evidenced with virtually no release Inhibitors,research,lifescience,medical without irradiation. Magnetic fluid hyperthermia involves heat transfer from magnetic particles after exposure to a magnetic field that results in localized elevation of temperature and induction of cell death [370]. To improve the selectivity, doxorubicin thermo-responsive liposomes coloaded with doxorubicin and magnetic nanoparticles were armed

with folic acid and resulted in improved cytotoxicity in vitro over nonresponsive liposomes or untargeted thermo-responsive doxorubicin-loaded liposomes [371]. Intra-tumoral injection of anti-HER2 immunoliposomes Selleckchem Dasatinib containing magnetite followed by alternate Inhibitors,research,lifescience,medical magnetic field heating promoted iron retention in tumors

in a HER2-specific manner 48h after injection [372]. A 3-fold higher iron content was detected in Inhibitors,research,lifescience,medical HER2-overexpressing BT474 breast cancer xenografts over low HER2-expressing SKOV3 ovarian cancer xenografts, and magnetite retention in BT474 xenografts correlated with stable tumor regression [372]. Inhibitors,research,lifescience,medical In line with these studies, conjugation of HER2 antibody to thermo-sensitive doxorubicin-loaded liposomes improved the doxorubicin-mediated toxicity over controls [373]. Boron capture neutron therapy relies on delivery of 10B boron followed by γ-irradiation and capture of neutrons by 10B, leading to the production of toxic α-particles, 4H and 7Li for cell death induction [374]. Maruyama encapsulated Non-specific serine/threonine protein kinase 10B into PEGylated transferrin-armed liposomes for targeted delivery to colon carcinoma xenografts, this led to higher 10B tumor accumulation compared to the free isotope or untargeted liposomes and resulted in superior therapeutic efficacy after irradiation over free isotope or untargeted 10B liposomes [36]. Lastly, the group led by Miyata reported a 3.6-fold higher 10B tumor concentration in orthotopic gliomas after intratumoral convection-enhanced delivery using PEGylated transferrin armed liposomes over untargeted liposomes with a lower retention in normal brains [375].

For an outpatient visit the median cost was Rs 225 Weighting th

For an outpatient visit the median cost was Rs. 225. Weighting these costs by the estimated healthcare seeking patterns at each level, we estimate that hospitalization due to rotavirus diarrhea cost the country INR 4.9 billion (3.3 to 6.9 billion) annually. Additionally the country spends about INR 5.38 billion (3.6–7.6 billion) on outpatient visits. The total cost of the rotavirus immunization program for the 2011 India birth cohort of 27,098,000 children was calculated at Rs. 4.47 billion or USD 74.5 million, which is less than rotavirus associated

hospitalization costs. Despite gains in child survival and increased availability of effective interventions such as ORS, zinc and access to healthcare, rotavirus diarrhea Imatinib chemical structure continues Abiraterone cell line to result in substantial mortality and morbidity for children in India and is a significant economic

burden to the healthcare system and Modulators society. Each year in India, rotavirus causes an estimated 78,500 deaths, 872,000 hospitalizations, and over 3.2 million outpatient visits in children <5 years of age. In other words, by 5 years of age, 1 in every 334 – 356 Indian children will die from rotavirus diarrhea, 1 in every 22 – 45 children will be hospitalized, and 1 in every 6 – 12 children will have visited an outpatient clinic for rotavirus diarrhea (Fig. 1). Despite the lower vaccine efficacy of oral rotavirus vaccines in developing countries, because of the large disease burden these vaccines are predicted to alleviate substantial rotavirus mortality and morbidity [26]. Introduction of Rotavac® at current national PDK4 coverage, will avert 27,000 deaths, 291,000 hospitalizations and 686,000 outpatient visits annually. The national estimates of rotavirus deaths are slightly lower than rates previously estimated and are likely due to overall decline in diarrheal mortality. Rotavirus continues to contribute

39% of all diarrhea hospitalizations reiterating its position as the most important cause of diarrheal mortality. This reduction in mortality may reflect a greater impact of interventions to improve sanitation and hygiene on the burden of bacterial diarrhea, which is often transmitted through contaminated food and water, as opposed to rotavirus, which has multiple modes of transmission. The decline in child mortality in the past two decades may also be a function of better access to fluid replacement therapy and in-patient healthcare [3]. Our estimates of rotavirus hospitalizations are higher than previous estimates [9] and [19]. This may, in part, be a result of lower threshold for hospitalization in intensely followed up cohorts, but is also more likely to represent the true need for hospitalization where there is no constraint to accessing healthcare and contributes significantly to better survival.

The 1-adamantanethiol (AD) SAMs were prepared by immersing the go

The 1-adamantanethiol (AD) SAMs were prepared by immersing the gold films in a 10mM ethanolic AD solution at room temperature for 24 hours [36]. The AD

SAM on gold was rinsed first with ethanol, and then with Milli Q water, before the deposition of the loaded or unloaded micelles. 2.5. Loading of PTX into HS-PEG5k-CA8 Micelles and Characterization 6mg of PTX and 20mg of HS-PEG5k-CA8 were dissolved in 3mL of chloroform Inhibitors,research,lifescience,medical in a 10mL single neck flask to form a homogeneous solution. The solvent was removed by rotavaporation, and the sample was further dried on high vacuum pump for 30min. Then, 1mL of phosphate buffered saline (PBS) was added into the flask to disperse the solid film via vortex Inhibitors,research,lifescience,medical and further sonication for 30min to yield a homogenous micelle solution. The particle sizes of the micelles before and after PTX loading were measured with DLS Zetatrac (Microtrac) to be 16nm and 23nm, respectively. The drug loading capacity was measured using high-performance liquid chromatography (HPLC) calibrated with PTX solutions in dimethyl sulfoxide (DMSO) with known concentrations. 2.6. AFM Imaging AFM measurements of micelles and dendrimers were Inhibitors,research,lifescience,medical performed on a

MFP3D AFM (Asylum Research Inc., Santa Barbara, Calif, USA). When imaging HS-PEG5k-CA8 and PTX-loaded HS-PEG5k-CA8 micelles in SAMs, tapping mode was utilized in aqueous solution. The probe is a MSNL-10 silicon cantilever (Veeco, Camarillo, Calif, USA) with Inhibitors,research,lifescience,medical a force constant of k = 0.1 N/m. During AFM tapping, the cantilever was modulated by a driving frequency of 68kHz and an amplitude range from 0.30 to 0.71V, with damping from 30 to 70%. When imaging PAMAM dendrimers, a silicon cantilever (AC-240, Olympus)

was used. The probe has a force constant of k = 1.0N/m as measured by thermal noise method. During tapping mode imaging, the cantilever was modulated by a driving frequency of 74kHz and amplitude of 67.0nm (0.63V), with the damping set to 85%. For displacing adsorbates such as dendrimers or alkanethiolates, tips were placed in contact with the surface Inhibitors,research,lifescience,medical with increasing load beyond threshold [28, 29]. Data display and analysis were conducted using MFP-3D’s software package written on Igor Pro platform (Wavemetrics). The surface coverage of micelle was calculated based on AFM topography images. 2.7. STM Imaging The STM has a walker-type scanner (UHV 300, RHK Technologies, Inc.) and was used under ambient conditions for this investigation. The Rolziracetam STM tips were cut W wires which were electrochemically etched at 2.0V in 3.0M NaOH solutions. A homemade potentiostat monitored the etching process [34, 37]. All STM images were acquired in constant current mode with typical bias voltages ranging from 0.3 to 0.7V and tunneling currents from 5 to 25pA. The piezoelectric scanners were calibrated laterally using a decanethiol SAM (PFI-2 lattice constant = 0.50nm) and vertically using a Au(111) single atomic step (0.235nm). 3. Results and Discussion 3.

However, it does block reextinction when the extinction retention

However, it does block reextinction when the extinction retention test occurs in a context different from that of initial acquisition and initial extinction,50 suggesting that NMDA receptor activation is required when extinction events are relatively novel but not when they are relatively familiar.50

On the other hand, novelty does not seem to matter for fear conditioning itself because disruption of the NMDA Inhibitors,research,lifescience,medical receptor blocks fear acquisition in both a novel and a familiar context.33,49 Effects of localized infusions of NMDA receptor antagonists prior to second extinction are more complex and are reviewed Inhibitors,research,lifescience,medical elsewhere (see ref 51). Role of D-cycloserine in fear extinction Because blockade of the NMDA receptor impairs extinction, we wondered whether enhancing the functioning of that receptor would enhance extinction. To test this we administered a compound called D-cycloserine (DCS) either systemically Inhibitors,research,lifescience,medical or directly into the rats’ amygdala prior to extinction training

and then tested retention of extinction the next day.52 DCS does not bind to the NMDA receptor itself, but to another receptor on the NMDA protein called the glycine regulatory site. Activation of Inhibitors,research,lifescience,medical this site improves the ability of the NMDA receptor protein to flux calcium which initiates a variety of intracellular events that are critical for extinction. As predicted, when DCS was given in combination with repeated exposure to the feared stimulus without a shock, extinction

retention was enhanced, when testing took place after DCS had worn off. This did not occur in control rats that received the drug alone, Inhibitors,research,lifescience,medical without extinction training. Based on these results, we concluded that the positive effects of the DCS else were specifically connected with extinction and did not result from a general dampening of fear expression. These effects have now been replicated in a large number of studies. Systemic administration of DCS either before52-61 or after54 extinction training facilitates extinction. Local infusion of DCS into the basolateral nucleus of the amygdala prior to52,62 or after54 fear extinction training mimics the effects of systemic administration. Chang and Maren63 recently Afatinib showed that although DCS infusions directly into infralimbic cortex did not facilitate extinction, these infusions did facilitate the subsequent reextinction of fear when animals were trained in a drug-free state.

1,2 As the pace of innovation increases, even more biomedical app

1,2 As the pace of innovation increases, even more biomedical applications will be developed. The extrapolation of these current technological trends into the future is based on the fact that these systems are all web-based and therefore do not encounter communication barriers. In addition, the advanced computational technology and the unrestricted sensing devices, which are unnoticeable, leave the limits unbounded.1,2 Advanced technologies comprising

microprocessors have become more powerful, cheaper, Inhibitors,research,lifescience,medical and consume less energy.1,2 Sensing technologies have become highly specific, microminiaturized, and even implantable. Multiple ubiquitous wireless infrastructures now exist for cellular phones, WiFi, and WiMax network accounts, enabling integration Inhibitors,research,lifescience,medical of information to become the norm. Human ABT-263 purchase anatomy models, produced with different technologies combining images captured in the digital imaging and communications in medicine (DICOM) format, are processed using specific three-dimensional reconstruction software. This software has a minimum material deposition thickness to form a build layer. The thinner this layer, the better the surface finishing, and the smoother the prototype surface.3 Inhibitors,research,lifescience,medical In 1965, Gordon Moore sketched his

prediction of the pace of silicon technology.4 Decades later, Moore’s law (Figure 1) has remained true, as the number of transistors on a chip roughly doubles every Inhibitors,research,lifescience,medical two years. Consequently the scale continues to become smaller, while transistor counts climb. Along the same trend the ability to increase device complexity and integrate many capabilities onto one chip is growing. The cumulative impact of these spiraling advancements in capabilities empower the economy and the Internet, running on everything from digital phones and PCs to stock markets, spacecraft, and medical devices, facilitating

today’s information-rich, converged digital world. Figure 1 Moore’s law diagram—suited to 2010. KEY APPLICATION AREAS Inhibitors,research,lifescience,medical FOR CRANIOFACIAL SURGERY Anatomical Databases: Data for Simulation and Planning Three-dimensional (3D) anatomic relationships are difficult to learn. Advanced visualization techniques can help people learn better. The use of advanced imaging modalities such as computerized tomography (CT), surface imaging, serial section, and synchrotron can improve visualization Ketanserin and lead to a better understanding of anatomical data and structural relationships. With the development of information technology, 3D models can be devised and built, based on virtual prototypes by means of a computer numerical control (CNC) device. Computers can now be used to create accurately detailed projects that can be assessed from different perspectives in a process known as computer-aided design (CAD). To materialize virtual objects using CAD, a computer-aided manufacturing (CAM) process has been developed.

37,38 In sum, there is a strong, bidirectional relationship betwe

37,38 In sum, there is a strong, bidirectional relationship between depression

and migraine headaches. In patients with a history of depression or who are currently depressed, topiramate and flunarizine should be avoided when possible; if treatment with these medications is required, depressive symptoms should be monitored. For these patients, acute treatment with serotonin agonists and prophylactic treatment with TCAs might be considered, as such treatment could alleviate symptoms of both depression and migraine headaches. Medications for the treatment of multiple sclerosis Patients with multiple sclerosis (MS) are at significantly increased Inhibitors,research,lifescience,medical risk for depression; Inhibitors,research,lifescience,medical one study found a 2.3-fold increase in depression risk, even after controlling for age and gender.39 At present there is no consensus regarding the pathophysiological link between depression and MS; while some researchers suggest increased rates of depression in patients with lesions in specific areas of the brain (eg, right temporal lobe, superior frontal or parietal regions), others have found no such relationship.40 In patients with MS, depression has been associated with worse quality of life,41 increased levels of disability,42 worse adherence to MS treatment,43,44 and an increased risk of suicide Inhibitors,research,lifescience,medical in some studies.45 Interferon (IFN)-ß-1a and IFN-ß-1b

are two of the most common disease-modifying agents used to treat MS. Given the risk of depression using IFN-α in patients with HCV AZD2281 chemical structure infection (see Inhibitors,research,lifescience,medical Anti- infective agents section), there has been significant concern that IFN-ß similarly causes depressive symptoms. Although a few early studies found that IFN-ß-1b-treated patients suffered from high rates of depression and suicidal ideation,43,46 these findings have not Inhibitors,research,lifescience,medical been replicated. In a secondary

analysis of a double-blind, placebo-controlled study evaluating the efficacy of IFN-ß-1a in 365 MS patients, Patten and associates47 found no significant differences in depression between IFN-ß-1a and placebo at 36-month follow-up. Others similarly found no increased risk of depression with IFN-ß treatment in patients with MS who were re-evaluated at 65 months; they suggested that pretreatment depression and disability were the biggest predictors of depression at follow-up.48 Other agents used in the treatment of MS include 4aminopyridine, glatiramer, because fingolimod, mitoxantrone, and natalizumab. Unfortunately, few data exist regarding the rates of depression in patients taking these medications. Depression, specifically, has been studied for only two of these medications: natalizumab and fingolimod. Two randomized controlled trials (RCTs) of natalizumab found no increased risk of depression.49,50 A randomized trial of fingolimod similarly found no increase in depression compared with placebo.

Funding agencies aiming to increase the reach and translation of

Funding agencies aiming to increase the reach and translation of their efforts may seek to implement this type of mentoring and training as part of their funding requirements. As the fields of translational science and community-based participatory research continue to evolve, communities will increasingly be called upon to share click here their expertise within the published literature. The process outlined here offers one way for communities

to engage in these efforts. The authors declare that there are no conflicts of interests. The authors would like to acknowledge and thank the creators of the data and writing workshops: George Rutherford, M.D., Christina Lindan, M.D., Randahl Kirkendall, M.P.H., Kathleen Whitten, Ph.D., and Phyllis Ottley, Ph.D. We would like to thank Simone Peart Boyce, Ph.D., the statistician who worked inhibitors closely with the participants. The Centers for Disease Control and Prevention (CDC) supported awardees in the Communities Putting Prevention to Work initiative through cooperative agreements. However, the findings and conclusions in this paper are those of the authors and

do not necessarily represent the official position of the Centers for Disease Control and Prevention. Users of this document should be aware that every funding source has different requirements governing the appropriate use of those funds. Under US law, no Federal STI571 molecular weight funds are permitted to be used for lobbying

or to influence, directly or indirectly, specific pieces of pending or proposed legislation at the federal, state, or local levels. Organizations should consult appropriate legal counsel to ensure compliance with all rules, regulations, and restriction of any funding sources. CDC supported staff training and review by scientific writers for the development of this manuscript through a contract with ICF International (Contract No. 200-2007-22643-0003). CDC staff reviewed also the paper for scientific accuracy. CDC invited authors to submit this paper for the CDC-sponsored supplement through a contract with ICF International (Contract No. 200-2007-22643-0003). “
“The evolution of public health has led to substantial changes in approaches to improving the health of members of communities. In the United States, these changes reflect the influence of many community-centered health developments, including the creation of national-level programs enacted by Congress, the establishment of dedicated governmental units at federal and state levels, and the implementation of innovative health programs at the community level by a variety of other organizations.

To avoid false positives, daily internal control dosage are perfo

To avoid false positives, daily internal control dosage are performed, and in case of a patient with elevated concentration of a substance (in absence of a known addiction), the analysis is repeated Moreover, on scene drugs are recorded,

as well as first aid medical treatments. The impact of road accident dynamics and lesions on the outcome are studied by recording length of stay, PF-01367338 supplier mortality at 6 months, Inhibitors,research,lifescience,medical and the follow-up program at 6 months on the ICU database. As an indicator of the quality of life recovered at 6 months after the event (follow-up at 6 months) the Glasgow Outcome Scale (GOS) [38] is used, as well as the questionnaire EuroQol5 EQ5-D with scale EQ5-D-VAS [39], which includes a medical examination. In case a patient cannot sustain a medical visit, a telephone interview is performed. Patient pre-accident drug treatment and pre-existing medical conditions seem to correlate with worse outcome, in terms of complication, ICU and Hospital length of stay, and lower functional Inhibitors,research,lifescience,medical outcome [40-43]. For this reason these data are recorded in a dedicated section of the database

that includes the type and number of pre-existing medical conditions, and the type and dosage of each drug (ethanol, cannabis, cocaine, amphetamine, benzodiazepine, barbiturate, opioids). Despite some limitations due to risk related to ionizing radiation, CT remains Inhibitors,research,lifescience,medical the most sensitive imaging exam to assess trauma lesions [44-47]: for this reason for head, Inhibitors,research,lifescience,medical neck, face, chest and abdomen CT slices are chosen. In addition to the encoding of each lesion using the AIS code, these are identified by means of a three-dimensional localization tool that uses a discretization of the human body based on a set of CT slices equipped with an active matrix (Figure 7). Figure 7 Graphical method for the active injuries’ localization. This was done by dividing a human body not affected by clinical pathologies

through cross sections of CT scan made at regular intervals in the sagittal plane (z axis). Each slice (or plane) is divided into a point’s matrix. In this way, each point has its Cartesian Inhibitors,research,lifescience,medical coordinate (x, y, z) fixed, where x and y are read in the transverse Phosphoprotein phosphatase plane (CT slice) while the z coordinate is the height of the CT slice, with zero value at top of the head. The matrix dimension depends on of the size of the section. The body regions head-face, neck, thorax, and abdomen are divided, respectively, into 8, 3, 15 and 13 slices. For the facial bones, vertebrae, rib cage, pelvis, and limbs, an active matrix built on the anatomical atlas figure is used to localize lesions with more sensitivity. This type of localization of the lesions, for example, provides a means to compare the distribution of the damage (in terms of extent of the lesion) among different people, or even to realize the frequency distributions of the damage (mean and standard deviation) relative to a certain region of the body.