MK801 (0 050 1 mg kg-1, intraperitoneal [IP]) caused similar effe

MK801 (0.050.1, intraperitoneal [IP]) caused similar effects, but, with lesser changes in power. Figure 2. Dose-response effects of subcutaneous phencyclidine (PCP) 1 on electroencephalographic (EEG) spectral power in the prefrontal cortex and sensorimotor cortex in conscious rats. The abscissa represents the EEG spectral component between 1 and 30 … In contrast, the noncompetitive AMPA (amino-3hydroxy-5-methyl-4-isoxazole propionic acid) antagonists GYKI 52466 and GYKI 53655 Inhibitors,research,lifescience,medical increased RRG power over the whole power spectrum (1-10, IP). Clozapine, an atypical antipsychotic

agent (0.2, subcutaneous) synchronized the RRG (peak 8 Hz) (Figure 3.) The 5-HT2A antagonist M100907 specifically increased RRG Inhibitors,research,lifescience,medical power at 2 to 3 Hz at low doses (10 and 50 subcutaneous), whereas at higher doses (0.1, subcutaneous) the profile resembled that of clozapine. Figure 3. Dose-response effects of subcutaneous clozapine (0.2 expressed as percentage change of electroencephalographic (EEG) spectral power in the prefrontal cortex and sensorimotor cortex of conscious

rats at each frequency between 1 and 30 Hz. Vertical … Clozapine (0.2, subcutaneous), GYKI 53655 (5, IP), prazosin (0.05 and 0.1, IP), and M100907 (0.01 Inhibitors,research,lifescience,medical and 0.05, subcutaneous) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1, subcutaneous), but not the increase in power at 1 to 3 Hz in prefrontal Inhibitors,research,lifescience,medical cortex (Figure 4.) Figure 4. Coadministration of subcutaneous phencyclidine (PCP) (1 and

clozapine (0.2, expressed as percentage change of electroencephalographic (EEG) spectral power in the prefrontal cortex and sensorimotor cortex of conscious rats at each frequency … Conclusion Thus, clozapine, supposedly the best antipsychotic agent, available, apart from its limiting side effects, clearly increased theta rhythm in prefrontal cortex, indicating beneficial effects on cognition. Clozapine also partially antagonized Inhibitors,research,lifescience,medical the effects of PCP on RRG, but only the desynchronization. These results clearly show that the effects next of PCP on RRG can be used a model for schizophrenia, which may be transposable to man. The profiles of compounds screened for activity in this model are allowing new selleck compound therapies for schizophrenia to be developed, particularly if all the effects of PCP may be antagonized.
Animal models are defined as experimental preparations developed in one species in order to study phenomena existing in another species. When addressing animal models of human psych opathology, attempts are made to reproduce in animals some syndromes or symptoms resembling as far as possible some human syndromes or symptoms in order to study particular aspects of human psychopathology.

Figure S3 Replicate quality analysis plot for the amino acid prof

Figure S3 Replicate quality analysis plot for the amino acid profiling by UPLC-LC-MS/MS in the mutant stock SALK_021108 (AT1G52670). Instructions in how to interpret this plot can be found in the consortium web portal (Figure taken from The numbers in the upper right corner correspond to the correlation coefficients between replicates (ith row, jth column). The x (ith replicate) and y (jth

replicate) coordinates of the scatterplots are the logarithms (base 2) of the ratio of the mean relative abundances (μ) of each amino acid in the wild-type (wt) versus mutant (mt) plant (i.e., log2 (μmt/uwt)). Conflict of Interest Conflict of Interest The Inhibitors,research,lifescience,medical authors declare no conflict of interest.
Arachidonic acid is metabolized to an array of oxidized bioactive lipids by a series of different oxygenases

that can introduce molecular oxygen with extraordinary regioselectivity and stereospecificity (Figure 1). Free arachidonic acid serves as the substrate for cyclooxygenases Inhibitors,research,lifescience,medical (COXs), lipoxygenases (LOXs), and cytochromes P-450 (CYPs); whereas esterified arachidonic acid is primarily metabolized by 15-LOX-1. The ability of COXs to convert arachidonic acid to prostaglandins Inhibitors,research,lifescience,medical (PGs) and thromboxane A2 was recognized over 50 years ago [1,2,3]. Two COX isoforms have been identified, the first of which, COX-1, is Luminespib chemical structure constitutively active [4]. The presence of a second inducible form of COX was first suggested by experiments, which showed a transient increase in the formation of PGE2 from arachidonic acid by canine kidney cells upon stimulation Inhibitors,research,lifescience,medical with tumor promoters and carcinogens [5,6]. The increased PGE2 production was eliminated by inhibition of transcription or translation, Inhibitors,research,lifescience,medical indicating that it was dependent upon de novo COX synthesis. This new isoform (COX-2)

was subsequently cloned, sequenced, and its expression was found to be inducible in human cells [7]. COX-2 and COX-1 share 60% sequence homology [8] and they are both responsible for the metabolism of free arachidonic acid to the bioactive only PGs and TXA2 (Figure 1). Figure 1 Pathways of arachidonic acid metabolism. Abbreviations: COX, cyclooxygenase; CYP, cytochrome P540; EET, epoxyeicosatrienoic acid; EH, epoxide hydrolase; FLAP, 5-lipoxygenase activating protein; GGT, γ-glutamyltranspeptidase; GSH, glutathione; … Arachidonic acid is converted initially to the hydroperoxy-endoperoxide PGG2, which subsequently converts to the hydroxy-endoperoxide PGH2 through the enzyme’s peroxidase (POX) activity (Figure 1) [9]. A variety of bioactive arachidonic acid metabolites are produced from PGH2, varying in function from regulating inflammation, blood clotting, ovulation, initiation of labor, bone metabolism, nerve growth and development, kidney function, and blood vessel tone.

Future studies in depression will further explore these findings,

Future studies in depression will further explore these findings, and promise to add an important group of medications to the treatment repertoire for depression. Beyond this, research is currently under way to delineate the epidemiological,

biochemical, and genetic factors that mediate the effects of psychosocial stress on depressive syndromes. An important aspect of this research will be to better define the interaction between the HPA axis and the monoamine neurotransmitter systems, especially given the apparent role of serotonin Inhibitors,research,lifescience,medical neurotransmission in modulating the effects of stress on the development of depression (see above). For example, we recently reported that 5-HT depletion in humans is associated with dramatic increases Inhibitors,research,lifescience,medical in CSF CRF concentrations, demonstrating an important 5-HT-CRF link.87 HPT axis Hypothyroidism is classically associated with a depressive syndrome that is ameliorated by correcting the underlying thyroid hormone deficit. This suggests a relation between the hypothalamic-pituitary-thyroid (HPT) axis and the neurobiology of depression. In the HPT axis, thyrotropin-releasing hormone (TRH) is secreted by the hypothalamus

and stimulates thyroid-stimulating hormone (TSH) release from the pituitary. Inhibitors,research,lifescience,medical TSH acts on the thyroid to stimulate iodine uptake, follicle cell metabolism, and release of the two thyroid hormones (triiodothyronine [T3] and thyroxine [T4). Thyroid hormones are responsible for a number of homeostatic and metabolic Inhibitors,research,lifescience,medical functions and also provide feedback to the hypothalamus and pituitary to decrease further TRH and TSH release, respectively.

A mixed database supports some role for the HPT axis in the pathophysiology of depression. In depressed patients, CSF TRH has been shown to be elevated (suggesting decreased feedback from thyroid hormones) Inhibitors,research,lifescience,medical compared with controls,88,89 though discordant findings have been reported.90 Several studies have revealed a blunted TSH response to TRH stimulation in depressed patients despite normal thyroid hormone levels,91 consistent with downregulation of TRH receptors in the pituitary, Ixazomib in vitro perhaps secondary to elevated TRH levels. Alternatively, thyroid hormone in the periphery may not be efficiently transported into the CNS in depressed patients; CSF levels of transthyretin – the protein responsible Digestive enzyme for transporting thyroid hormones across the bloodbrain barrier at the choroid plexus – have been shown to be decreased in depressed patients.92,93 Thyroid hormone augmentation (primarily with T3) has been reported to exert antidepressant effects, even in the absence of clinical hypothyroidism,94-95 though several negative studies are available (P. Ninan and C. B. Nemeroff, unpublished observations).96 Future studies will help clarify the role of the HPT axis in the pathophysiology and treatment of depression. As with the HPA axis, areas of interest include the interaction of the HPT system with other neuromodulatory systems.

It is also possible that interactions with other substances, such

It is also possible that interactions with other substances, such as ethanol, may potentiate the toxic potential of a compound present in the preparation. Because of the expense of newer medications as well as safety and efficacy concerns about some older or alternative medications, the possibility still remains that for many patients with anxiety disorders, the best, available treatment will be a benzodiazepine. Understanding what has been learned about benzodiazepine use and the development, of dependence may be helpful in ensuring

that, these patients are not denied effective Inhibitors,research,lifescience,medical treatment.41 Dependence The reported potential of a class of prescription drugs to result, in dependence in some patients needs to be viewed as part, of an overall risk-benefit analysis in the same way as that process is applied Inhibitors,research,lifescience,medical to nonpsychiatric medical illness. Many other authors have commented

on the historical biases that, have been present in shaping social views on the acceptability of treating illnesses such as anxiety and depression with pharmacological intervention. The presence of what, has Selleckchem KRX0401 eloquently been called “pharmacological Calvinism” is still a factor in the acceptability of the appropriateness of Inhibitors,research,lifescience,medical biologically based treatments Inhibitors,research,lifescience,medical for these disorders.26 The context in which medications are used includes the suffering and disability caused by the condition being treated as well as the overall risks of a proposed therapy for a given patient. Definitions of substance dependence often lack consistency, but, they usually include a number of criteria composed of issues relating to psychological dependence and/or physical dependence.1 In many characterizations, there are overlaps with Inhibitors,research,lifescience,medical abuse and addiction. Table I summarizes the Diagnostic: and Statistical Manual of Mental Disorders,

Fourth Edition1 (DSM-LV) criteria for dependence. A central concept is the exhibition of a Urease maladaptive pattern of substance use leading to clinically significant impairment or distress. Accompanying features may include tolerance, which can result in an escalation in dose, and patients may spend inordinate amounts of time obtaining, using, and recovering from the drug. Drug seeking and drug use may become more important, than customary social, recreational, and occupational obligations and activities, and the patient, often knows that, the use of the drug may be causing physical and/or psychological problems. Attempts to control or reduce substance use are unsuccessful, and a withdrawal syndrome characteristic for the given substance may occur.

The SCJ was incised and drained, and the

The SCJ was incised and drained, and the abscess cavity was enlarged to include the abscess of the left sternocleidomastoid muscle. Sulbactam/ampicillin administration was started immediately. Aspirated pus, urine, and two sets of blood cultures all indicated S. aureus infection. FK228 order According to the results of antibiotic susceptibility testing, the patient’s antibiotic therapy was changed to cefotiam. After one week of antibiotic therapy, blood and wound cultures were negative for pathogens. Follow-up MRI clearly

showed abscess formation in the left paraspinal muscle at L1-L3, but culture of fluid aspirated from the abscess showed Inhibitors,research,lifescience,medical no growth. Figure 3 The left SCJ. Aspiration of the SCJ and culture of the obtained fluid Inhibitors,research,lifescience,medical yielded a growth of S. aureus. The patient’s general condition improved significantly and his fever subsided after 4days. The wound at the SCJ was irrigated daily. Twelve days after the onset of treatment, his plasma

WBC was 7,050/mm3 with 78% neutrophils. Two weeks after admission, there was a still a non-tender swelling over the left SCJ, but the purulent Inhibitors,research,lifescience,medical secretion had completely resolved. Neurological examination of the lower limbs was unchanged. Eight weeks after admission, he was transferred to the spinal surgery unit to undergo evaluation for operative treatment of his spondylitis and epidural abscess. Discussion It is likely that this patient’s epidural block caused the paraspinal muscle abscess Inhibitors,research,lifescience,medical and nearby lumbar spondylodiscitis,

and that this iatrogenic infection spread hematogenously to the SCJ. Septic arthritis most commonly affects the weight-bearing joints of the lower limb, which account for 61-79% of all reported cases of septic arthritis [8]. The knee is the most commonly affected joint, followed by the hip, shoulder, wrist, ankle, and elbow. There is usually no limiting basement plate under the well-vascularized synovial membrane, facilitating the Inhibitors,research,lifescience,medical entry of hematogenously carried bacteria into the joint space [9]. Septic arthritis of the SCJ is extremely rare, comprising 0.5–1% of all joint infections Megestrol Acetate [10], but results in abscess formation in 20% of cases [11,12]. The SCJ is the only joint connecting the trunk with the pectoral girdle, and is therefore involved in all major movements of the upper limb. The function of the articular disc on the clavicular side of the SCJ is to resist the compressive load [13]. SCJ infection can cause life-threatening complications, because the joint capsule is unable to distend and infection spreads beyond the joint quickly, leading to fistula formation, cutaneous abscess or, rarely, mediastinitis and superior vena cava syndrome [14,15]. The pathogenesis of SCJ infection is not well understood, but it appears to result from either hematogenous or contiguous spread.

05 Results Patient and tumor characteristics We analyzed 106 pat

05. Results Patient and tumor characteristics We analyzed 106 patients with esophageal cancer that underwent NAC followed by esophagectomy from Alvespimycin in vivo September 1996 to May 2011. Patient characteristics as well as tumor histology and staging are presented in Table 1. The vast majority of patients in this study were male (n=88, 83%) and the median age was 61 (range, 31-86) years at Inhibitors,research,lifescience,medical the time of diagnosis. The predominant histology was adenocarcinoma (n=92, 87%) while 13% were squamous cell carcinoma (n=14). Prior to treatment, nearly two-thirds of patients presented with stage III disease (n=66, 62%), with stage IIIA being the

most frequent presenting stage (n=51, 48%), while one-third had stage II (n=33, 31%) and 7% had stage I (n=7) disease. Median follow up was 6.7 (range, 2.6-17.5) years. Table 1 Patient characteristics, histology, and staging Pathologic response

and post-operative staging Following NAC Inhibitors,research,lifescience,medical and esophagectomy, a pCR with no evidence of disease histologically was achieved in 31 patients (29%) of the cohort. Moreover, the majority of patients had an R0 resection with negative margins microscopically (n=98, 92.5%). Grossly, 14 patients (13.2%) had an R1 resection with confirmed positive margins in 8 patients (7.5%). Expectedly, post-operative pathologic staging determined that 62 patients (59%) were downstaged following NAC while 9 patients (8%) were upstaged and 34 patients Inhibitors,research,lifescience,medical (32%) remained at the same stage (Table 1). Survival analysis The median OS was 31.2 months (range, 2 months -17 years) for all patients in this cohort (Figure 1). When analyzed by histologic subtype, there was a trend toward Inhibitors,research,lifescience,medical increased OS in patients with squamous cell carcinoma vs. adenocarcinoma (53 vs. 29 months, respectively; P=0.06, Figure 2). Interestingly there was a similar extent of downstaging between squamous cell carcinomas and adenocarcinomas (50% vs. 51.9%, respectively). Inhibitors,research,lifescience,medical However 35.7% (n=5 of 14) of squamous cell carcinomas had a pCR compared to only 24.5% (n=23 of 92) of adenocarcinomas. Moreover, there were a greater proportion of patients who had squamous cell carcinoma with stage

III disease compared to those in the adenocarcinoma group (78.6% vs. 51.9%, respectively). Figure 1 Overall survival much for the 106 patients in our cohort. Figure 2 Overall survival (OS) by histological subtype in all 106 patients in our cohort (P=0.06). Importantly, there was also a trend toward increased OS for downstaged patients following NAC and esophagectomy (P=0.08, Figure 3).The OS for downstaged patients was 40 months, upstaged patients was 20.6 months, and 27 months for those who remained at the same stage. Patients that had no evidence of disease on histological exam at surgery (pCR) had a median OS of 52 months. Figure 3 Overall survival as a function of post-operative tumor stage compared to initial stage following NAC and esophagectomy (P=0.08, n=106). NAC, neoadjuvant chemoradiotherapy.

Immunohistochemisery test on paraffin embedded tissue revealed po

Immunohistochemisery test on paraffin embedded tissue revealed positive reaction for P504 antibody. Figure 5: Nephrogenic adenoma. Immunohistochemisery test on paraffin embedded tissue revealed negative reaction for P63 antibody. Figure 6: Nephrogenic adenoma. Immunohistochemisery test on paraffin embedded tissue revealed negative reaction

for PSA antibody. Discussion Nephrogenic adenoma is a rare bladder lesion presented with well-defined mass located mostly beneath the epithelium. In the past, it was believed that nephrogenic adenoma represented metaplasia of the urinary epithelium in response to inflammatory process. However, it has been demonstrated to result from urothelial shedding, and implant in injured area. Adenocarcinoma Inhibitors,research,lifescience,medical of the bladder was reported to occur two year after nephrogenic adenoma in a 25-year-old man.8 Few reports have examined the use of immunohistochemical findings in the diagnosis of nephrogenic adenoma. Inhibitors,research,lifescience,medical Alsanjary et al. studied the morphological

and immunohistochemical features for differential diagnosis of nephrogenic adenoma from clear cell adenocarcinoma.9 Immunohistochemical study can differentiate nephrogenic adenoma from malignant process, and define the origin of adenoma. Immunohistochmistery studies have shown that PAX2 was positive only in remnant of fetal renal tubules and nephrogenic adenoma, Inhibitors,research,lifescience,medical and negative in malignant process such as prostatic adenocarcinoma.10 Cytoplasmic staining for CK7 and absence of staining for PSA is in favor of nephrogenic adenomaAlpha-methylacyl-CoA racemase (AMACR, P504S), which is the most useful marker for the diagnosis Inhibitors,research,lifescience,medical of prostatic adenocarcinoma,

is detected in nephrogenic adenoma of urinary bladder.10,11 There are some problems in the differential diagnosis of nephrogenic Inhibitors,research,lifescience,medical adenoma from clear cell carcinoma of bladder, because it shows foci with tubular, cystic and papillary configuration, but no dysplastic changes. Nephrogenic adenom can be differentiated from clear cell carcinoma by PAX2 marker.12 Reporting eight patients with nephrogenic adenoma, Chen et al. found high postoperative recurrence, and recommended careful long-term follow up.13 Olivia and Young reviewed 80 cases of nephrogenic adenoma, which showed a trend of male Carnitine palmitoyltransferase II predominance.14 Koirala et al. reported a case of ureter nephrogenic adenoma with intraluminal PAS positive material.15 Jalpota reported an extensive involvement of bladder by nephrogenic adenoma in see more patient with renal allograft transplant.16 Nephrogenic adenoma is a benign metaplastic response to urothelial injury, and may mimic malignant process. In the present case bladder biopsy was done with high suspicion for malignant lesion. However, immunohisthochmical examination of the biopsy revealed positive findings for CK7, EMA, CD10 and AMACR, and negative findings for PSA, P63 and CK20. Such findings are in favor of nephrogenic adenoma as benign lesion.

40, 95% CI: 0 19–0 82; Bull et al 2002) Therefore, increasing f

40, 95% CI: 0.19–0.82; Bull et al. 2002). Therefore, increasing frequency of the follow-ups with focus to manage expectation on side effects and de-stigmatization over depression should be explored as a way to improve the noncontinuous use. These highlighted the importance of the need for systematic psychoeducation on the depressive illness and reinforcement

of patients’ drug adherence as suggested in another local study conducted in patients with mood disorders Inhibitors,research,lifescience,medical (Lee et al. 1992). Limitations While this study evaluated both the prescription record and also the electronic and written medical records of patients, limitations related to retrospective data retrieval still apply when interpreting our findings. The use of retrospective data retrieved from the prescription database and

medical records may have underestimated the rate of noncontinuous use. As the data relied on patient reporting and prescription Inhibitors,research,lifescience,medical PP242 in vitro filling, it does not reflect the actual drug use of the patients. The sample size was relatively modest compared to previous studies using only claims database as source of data. However, the difference in relapse rate between the continuous and Inhibitors,research,lifescience,medical noncontinuous users was highly significant. Therefore, it is unlikely that our modest sample size critically affected our results and conclusions, although it is possible that not all relevant predictors for noncontinuous use were identified. Meanwhile, Inhibitors,research,lifescience,medical the exclusion of comorbid diagnosis or a past history of suicide may have potentially excluded a group of most severe depressive patients. Some studies have previously suggested an impact of concurrent use of benzodiazepine on the continuity of antidepressants, but this Inhibitors,research,lifescience,medical is beyond the scope of this study (Morgan et al. 2011). Finally, the unavailability of standardized, quantitative measurement for defining disease severity, relapses or remission was also one of the limitations in this study. Noncontinuous antidepressant

use is an important predictor of relapse and recurrence with significant implication for long-term prognosis. The results found in this Chinese population highlighted the high early recurrence second rate. Collaborative multidisciplinary approach utilizing various health care professionals to provide systematic psychoeducation on depressive illness and drug aspects should be explored. Acknowledgments None. Conflict of interest None declared.
Dopamine (DA) dysfunction is implicated in the modulation of pain perception and analgesia (Chudler and Dong 1995; Wasner and Deuschl 2012) and DA depletion plays a central role in this modulation. Indeed, hyposensitivity to pain is common in patients with schizophrenia, which is linked to excessive DA neurotransmission.

GAA-KO mice injected with an advanced generation Ad vector began

GAA-KO mice injected with an advanced generation Ad vector began expressing, and more importantly, secreting high P450 inhibitor levels of precursor hGAA from their transduced liver hepatocytes. Since this form of hGAA is likely correctly processed by the mammalian Golgi

apparatus to contain the “motifs”: (i.e.: mannose-6-phosphate residues) required for receptor mediated uptake and lysosomal targeting, liver derived hGAA was taken up by all affected muscle cells in the Ad treated GAA-KO animals. This resulted in both cardiac and skeletal muscle glycogen clearance within 12 days of the gene therapy treatment, and like Inhibitors,research,lifescience,medical ERT, was most effective in cardiac and diaphragm muscles (17). This report was the first to demonstrate the complete systemic correction of a form of muscular dystrophy by a simple intravenous injection technique. This observation Inhibitors,research,lifescience,medical has been subsequently repeated by us and others using Ad or AAV based approaches, as well in alternative species, such as the AMD quail model of GSD-II (18–20). Long term Ad mediated hGAA gene therapy studies showed that hepatically derived hGAA enzyme persisted

in the heart and diaphragm for at least 6 months post injection. However, we also noted that plasma levels of hGAA diminished over time in the vector treated GAA-KO Inhibitors,research,lifescience,medical mice (21). We have subsequently confirmed in numerous publications that the loss of plasma hGAA following intravenous injection of an Ad-hGAA vector was not due to loss of the vector, but rather was due to the onset of anti-hGAA antibodies (11, 22–24). These anti-hGAA antibodies prevent Inhibitors,research,lifescience,medical efficient, high level skeletal or cardiac muscle cell uptake of hepatically expressed hGAA, and limited long term efficacy of the approach, a limitation also noted after ERT treatments of GSD-II patients (4, 25). In our most recent studies, use of an optimized Inhibitors,research,lifescience,medical Adenovirus vector expressing hGAA via a tissue specific promoter in adult, hGAA tolerant GAA-KO mice permitted glycogen correction and muscle strength to be preserved in hGAA tolerant, GAA-KO mice for greater than one year. This result was

primarily Etomidate achieved by avoiding the elicitation of anti-hGAA antibody production in the treated animals (26). To begin to investigate the potential for disease reversibility in older GSD-II mice, we studied their responsiveness to hGAA gene therapy. This became especially relevent, since ERT in older mice had been shown to have significant limitations (27). Upon intravenous Ad-hGAA vector injection, we found that extremely high amounts of hepatically secreted hGAA could be produced, and subsequently taken up by multiple muscle tissues in old (12-17 months) GAA-KO mice. As a result, all muscle groups in the hGAA gene treated mice showed significant glycogen reductions, relative to that of age-matched, but mock-injected old GAA-KO mice.

This shows that PLCC is perceived

as much more burdensome

This shows that PLCC is perceived

as much more burdensome for those surrounding the patients and for society at large than it is for the patients themselves. So in examining the claim that PLCC patients should not be tortured by being kept alive with no hope of recovery, one should be very careful “to think whether we’re quite certain it’s the patient who’s being tortured or us.”12 It is important to acknowledge that we may sometimes have Inhibitors,research,lifescience,medical a problem with such patients’ presence; in Professor Meilaender’s words in relation to patients with advanced dementia, “there’s a part of us, there’s a part of me that inevitably wishes they’d go away not because it’s such a problem, but because they’re one of us. They show us our future, and they make us very uneasy.”12 Social attitudes towards loss of cognitive capacities and the perception of personhood Inhibitors,research,lifescience,medical Stephen Post suggests that “we live in a culture

that is … dominated by heightened expectations of rationalism and economic productivity, so clarity of mind and productivity inevitably influence our sense of the worth of a human life.”5 In such “hypercognitive culture”5 it is only natural that loss Inhibitors,research,lifescience,medical of cognitive capacities may be perceived as loss of personhood. Different approaches to personhood have implications for the definition of PLCC patients as “persons” or “non-persons.” Inhibitors,research,lifescience,medical For those who advocate that it is necessary to possess certain cognitive capacities to qualify as a

person, PLCC patients would not be BMS345541 regarded as such. Yet, they are definitely persons within the perception of inherent/ transcendental personhood, for which being a human is equated with being a person. According to interpersonal theories, their personhood depends on its recognition by others.21 The recognition of PLCC patients as persons is relevant to the question whether these patients should be treated like their fellow dependent cognitively Inhibitors,research,lifescience,medical competent patients, or differently; namely, whether they should or should not be offered life-sustaining treatment when such treatment would be offered to other dependent patients. IS THERE A MORAL OBLIGATION TO PROVIDE LIFE-SUSTAINING TREATMENT see more TO PLCC PATIENTS? Good Ethics Starts with Good Facts The preliminary guiding principle of any ethical deliberation is that good ethics starts with good facts. In this discussion, however, there are more mysteries than facts. We know that PLCC patients are human beings, that some are sentient, and that their life depends on on-going medical care. We also know that most people would not wish to be kept alive in this state, which is regarded by our society as “worse than death”; and there are even cases in which we have the patient’s advance directives not to be kept alive in such circumstances. Yet, we do not know for certain that they lack consciousness22 or fail to perceive pain.