Differentiation between Chondrosarcoma and Synovial Chondromatosis of the Temporomandibular Joint Using CT and MR Imaging.

BACKGROUND AND PURPOSE: Chondrosarcoma and synovial chondromatosis of the temporomandibular joint share overlapping clinical and histopathologic features. We aimed to identify CT and MR imaging features to differentiate chondrosarcoma from synovial chondromatosis of the temporomandibular joint. MATERIALS AND METHODS: The CT and MR images of 12 and 35 patients with histopathologically confirmed chondrosarcoma and synovial chondromatosis of the temporomandibular joint, respectively, were retrospectively reviewed. Imaging features including lesion size, center, enhancement, destruction/sclerosis of surrounding bone, infiltration into the tendon of the lateral pterygoid muscle, calcification, periosteal reaction, and osteophyte formation were assessed. A comparison between chondrosarcoma and synovial chondromatosis was performed with a Student t test for quantitative variables and the Fisher exact test or linear-by-linear association test for qualitative variables. Receiver operating characteristic analysis was performed to determine the diagnostic performance for differentiation of chondrosarcoma and synovial chondromatosis based on a composite score obtained by assigning 1 point for each of 9 imaging features. RESULTS: High-risk imaging features for chondrosarcoma were the following: lesion centered on the mandibular condyle, destruction of the mandibular condyle, no destruction/sclerosis of the articular eminence/glenoid fossa, infiltration into the tendon of the lateral pterygoid muscle, absent or stippled calcification, periosteal reaction, internal enhancement, and size of ≥30.5 mm. The best cutoff value to discriminate chondrosarcoma from synovial chondromatosis was the presence of any 4 of these high-risk imaging features, with an area under the curve of 0.986 and an accuracy of 95.8%. CONCLUSIONS: CT and MR imaging features can distinguish chondrosarcoma from synovial chondromatosis of the temporomandibular joint with improved diagnostic performance when a subcombination of 9 imaging features is used.

Impact Analysis of Different CT Configurations of Carotid Artery Plaque Calcifications on Cerebrovascular Events.

BACKGROUND AND PURPOSE: CT is considered the standard reference both for quantification and characterization of carotid artery calcifications. Our aim was to investigate the relationship among different types of calcium configurations detected with CT within the plaque with a novel classification and to investigate the prevalence of cerebrovascular events. MATERIALS AND METHODS: Seven hundred ninety patients (men = 332; mean age, 69.7 [SD, 13] years; 508 symptomatic for cerebrovascular symptoms and 282 asymptomatic) who underwent computed tomography of the carotid arteries were retrospectively included in this institutional review board-approved study. The plaque was classified into 6 types according to the different types of calcium configurations as the following: type 1, complete absence of calcification within the plaque; type 2, intimal or superficial calcifications; type 3, deep or bulky calcifications; type 4, adventitial calcifications with internal soft plaque of <2 mm thickness; type 5, mixed patterns with intimal and bulky calcifications; and type 6, positive rim sign. RESULTS: The highest prevalence of cerebrovascular events was observed for type 6, for which 89 of the 99 cases were symptomatic. Type 6 plaque had the highest degree of correlation with TIA, stroke, symptoms, and ipsilateral infarct for both sides with a higher prevalence in younger patients. The frequency of symptoms observed by configuration type significantly differed between right and left plaques, with symptoms observed more frequently in type 6 calcification on the right side (50/53; 94%) than on the left side (39/46; 85%, P < .001). CONCLUSIONS: We propose a novel carotid artery plaque configuration classification that is associated with the prevalence of cerebrovascular events. If confirmed in longitudinal analysis, this classification could be used to stratify the risk of occurrence of ischemic events.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The guideline for coronary artery revascularization replaces the 2011 coronary artery bypass graft surgery and the 2011 and 2015 percutaneous coronary intervention guidelines, providing a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. STRUCTURE: Coronary artery disease remains a leading cause of morbidity and mortality globally. Coronary revascularization is an important therapeutic option when managing patients with coronary artery disease. The 2021 coronary artery revascularization guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularization, with the intent to improve quality of care and align with patients' interests.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. STRUCTURE: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

Imaging features of synovial chondromatosis of the temporomandibular joint: a report of 34 cases.

AIM: To investigate the imaging features of synovial chondromatosis of the temporomandibular joint (TMJ), which is a rare benign arthropathy with cartilaginous proliferation. MATERIALS AND METHODS: Computed tomography and magnetic resonance imaging examinations of 34 patients with histopathologically confirmed primary synovial chondromatosis of the TMJ were reviewed retrospectively. Imaging features including the lesion epicentre, destruction/sclerosis of surrounding bone, calcification, periosteal reaction, osteophyte, lesion size, and joint space dimensions were assessed. RESULTS: Thirty-one of thirty-four patients (91.2%) showed the superior joint space as the lesion epicentre. For the mandibular condyle, more than one-third of patients (14/34; 41.2%) showed no destruction, and more than half of patients (19/34; 55.9%) showed no sclerosis. Conversely, >70% of patients showed destruction and sclerosis of the articular eminence/glenoid fossa, while >80% of patients (28/34; 82.4%) presented with various calcifications, including the ring-and-arc (9/34; 26.5%) and popcorn (13/34; 38.2%) types. The mean joint space on the affected side was significantly larger than that of the unaffected side (p<0.001). More than three-fourths of patients (76.9%) experienced no interval increase in lesion size during an average of 1.6 years of follow-up. CONCLUSION: Synovial chondromatosis of the TMJ demonstrated several imaging features, including the lesion centre being located in the superior joint space, resultant articular eminence/glenoid fossa-oriented bone changes, ring-and-arc and popcorn calcification, joint space widening, and self-limiting growth. These imaging features may be helpful in differentiating synovial chondromatosis from other lesions of the TMJ.

Support from superiors reduces depression in Republic of Korea military officers.

BACKGROUND: The prevalence of depression is relatively high in the Korean military. Social support is a protective factor against depression and is classified into four categories: emotional support-having the sense of feeling loved; instrumental support-receiving material assistance; informational support-receiving advice; appraisal support-feeling valued and respected for one's abilities. OBJECTIVE: To investigate the effect of support from one's superior on depression among Republic of Korea (ROK) military officers. METHODS: 2047 participants from the 2015 Military Health Survey were included in the study. The Korean version of the Beck Depression Inventory was used to measure depression, and a self-reported questionnaire was used to assess support from one's superior. A chi-squared test and multiple logistic regression were used to analyse the data. RESULTS: Of the 2047 participants, 177 (8.6%) had depression. Military officers who did not receive support from their superior were more likely to have depression than than those who did receive support (OR=2.09, 95% CI 1.30 to 3.36). Additionally, military personnel who did not receive emotional or appraisal support were more likely to have depression (emotional support: OR=2.37, 95% CI 1.31 to 4.29; appraisal support: OR=1.56, 95% CI 1.48 to 2.75). CONCLUSIONS: Our study found that depression in military officers was associated with lack of support from superiors. In particular, emotional support and appraisal support had a statistically significant effect. Therefore, we suggest that the ROK armed forces consider early intervention and management for high-risk groups. A social support programme and organisational atmosphere are also needed to improve supportive ability and skills of superiors.

Imaging features of chondrosarcoma of the temporomandibular joint: report of nine cases and literature review.

AIM: To investigate the imaging features of chondrosarcoma of the temporomandibular joint (TMJ) and review the literature. MATERIALS AND METHODS: Computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)/CT images of nine patients with histopathologically confirmed chondrosarcoma of the TMJ were reviewed retrospectively. Imaging features regarding the direction of lesion growth, bone destruction, infiltration into the tendon of the lateral pterygoid muscle (LPM) in the pterygoid fovea, enhancement pattern, calcification, periosteal reaction, markedly hyperintense T2 signal area, and qualitative PET signal intensity were evaluated. RESULTS: Seven of nine patients (77.8%) presented with lesion growth that was outward from the medulla of the mandibular condyle. Infiltration into the tendon of LPM in the pterygoid fovea was observed in all cases, and 77.8% (7/9) of them demonstrated >50% infiltration. All the lesions showed a mixed peripheral and internal enhancement, and revealed a markedly hyperintense T2 signal intensity area, which showed no enhancement. Although five of nine cases demonstrated higher FDG uptake compared with that of the liver, the other four cases showed less FDG uptake than that of the liver. CONCLUSION: Chondrosarcoma of the TMJ demonstrated several imaging features, including outward growth from the mandibular condyle, resultant infiltration into the tendon of LPM in the pterygoid fovea, various patterns of internal enhancement, and a markedly hyperintense T2 signal intensity area. These imaging features may be helpful to differentiate chondrosarcoma from other lesions of the TMJ.

Vimentin citrullination probed by a novel monoclonal antibody serves as a specific indicator for reactive astrocytes in neurodegeneration.

AIMS: Vimentin citrullination, the calcium (Ca2+ )-dependent peptidylarginine deiminase (PAD)-mediated conversion of an arginine residue of vimentin to a citrulline residue, has emerged as a pathophysiological outcome of autoimmune diseases and neurodegeneration. However, the roles, functions, and expression of citrullinated vimentin have not yet been elucidated because available antibodies are limited. METHODS: We developed mouse monoclonal IgG1 and IgM specific for vimentin citrullinated at position R440 or R450 and applied Western blotting, immunohistochemistry, and immunofluorescent staining to investigate the pathogenesis of prion diseases in animal models, in patients with prion diseases, and in vitro. RESULTS: Vimentin was found to be highly citrullinated at R440 and R450, and these citrullinated forms were mainly expressed in reactive astrocytes in the brain tissues of scrapie-infected mice. Full-length and cleaved forms of citrullinated vimentin were found in the cerebral cortices of sporadic Creutzfeldt-Jakob disease (sCJD) patients. The distribution of citrullinated vimentin was mainly confirmed in vimentin-, GFAP-, and YKL-40-positive reactive astrocytes. Biochemically, citrullination promoted resistance to the caspase-3- and caspase-9-mediated fragmentation of vimentin. Additionally, citrullination led to increased cytoplasmic and integral membrane/organelle vimentin enrichment, which indicated changes in the intrinsic solubility and distribution of vimentin. CONCLUSIONS: Our observations suggest that citrullinated vimentin acts as a specific indicator for the reactive state of astrocytes under abnormal neurological conditions. In addition, these novel antibodies will be helpful for studying the role of citrullinated vimentin in the pathogenesis of human disorders.

Factors affecting the dormancy and germination of bleeding heart [Lamprocapnos spectabilis (L.) Fukuhara] seeds.

Information on the optimal conditions to promote the germination of Lamprocapnos spectabilis (L.) Fukuhara seeds is limited; consequently, this study was conducted to establish the requirements to break seed dormancy and promote germination. The selected seeds had morphophysiological dormancy and had not begun embryo development. To study the dormancy breaking and embryo development processes, seeds were subjected to constant or changing temperature treatments during moist stratification. High temperature and humidity resulted in vigorous embryo growth, with the longest embryos occurring after 1 month of incubation at 20 °C. At 4 °C, the seeds required incubation period of at least 3 months to germinate. Embryo growth and germination were higher with changing high and low temperatures than under a constant temperature, and changing temperatures also considerably changed the endogenous hormone levels, embryo development and germination. Bioactive gibberellin (GA) content was higher in seeds incubated at 20 °C for 1 month, then at 4 °C for 2 months. The content of endogenous abscisic acid in seeds subjected to the same treatment decreased by 97.6% compared with that of the untreated seeds. Embryo growth and seed germination require changing high and low temperatures; however, exogenous GA3 could substitute for high temperatures, as it also causes accelerated germination. In this study, the seeds of L. spectabilis were identified as an intermediate simple type, a sub-level of morphophysiologically dormant seeds.

Surface reconstruction and charge modulation in BaFe2As2 superconducting film.

Whether or not epitaxially grown superconducting films have the same bulk-like superconducting properties is an important concern. We report the structure and the electronic properties of epitaxially grown Ba(Fe1-x Co x )2As2 films using scanning tunneling microscopy and scanning tunneling spectroscopy (STS). This film showed a different surface structure, [Formula: see text]R45° reconstruction, from those of as-cleaved surfaces from bulk crystals. The electronic structure of the grown film is different from that in bulk, and it is notable that the film exhibits the same superconducting transport properties. We found that the superconducting gap at the surface is screened at the Ba layer surface in STS measurements, and the charge density wave was observed at the surface in sample in the superconducting state.

Structural and electronic transformation pathways in morphotropic BiFeO3.

Phase boundaries in multiferroics, in which (anti-)ferromagnetic, ferroelectric and ferroelastic order parameters coexist, enable manipulation of magnetism and electronic properties by external electric fields through switching of the polarization in the material. It has been shown that the strain-driven morphotropic phase boundaries in a single-phase multiferroic such as BiFeO3 (BFO) can exhibit distinct electronic conductivity. However, the control of ferroelectric and phase switching and its correlation with phase boundary conductivity in this material has been a significant challenge. Supported by a thermodynamic approach, here we report a concept to precisely control different switching pathways and the associated control of electronic conductivity in mixed phase BFO. This work demonstrates a critical step to control and use non-volatile strain-conductivity coupling at the nanoscale. Beyond this observation, it provides a framework for exploring a route to control multiple order parameters coupled to ferroelastic and ferroelectric order in multiferroic materials.

Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy.

BACKGROUND AND OBJECTIVES: Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. RESULTS: Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. CONCLUSION: The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field.

Phospholipase D1 decreases type I collagen levels in hepatic stellate cells via induction of autophagy.

Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-ß/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy.

Portal cavernoma cholangiopathy: consensus statement of a working party of the Indian national association for study of the liver.

Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the extrahepatic biliary system including the cystic duct and gallbladder with or without abnormalities in the 1st and 2nd generation biliary ducts in a patient with portal cavernoma. Presence of a portal cavernoma, typical cholangiographic changes on endoscopic or magnetic resonance cholangiography and the absence of other causes of these biliary changes like bile duct injury, primary sclerosing cholangitis, cholangiocarcinoma etc are mandatory to arrive a diagnosis. Compression by porto-portal collateral veins involving the paracholedochal and epicholedochal venous plexuses and cholecystic veins and ischemic insult due to deficient portal blood supply or prolonged compression by collaterals bring about biliary changes. While the former are reversible after porto-systemic shunt surgery, the latter are not. Majority of the patients with PCC are asymptomatic and approximately 21% are symptomatic. Symptoms in PCC could be in the form of long standing jaundice due to chronic cholestasis, or biliary pain with or without cholangitis due to biliary stones. Endoscopic retrograde cholangiography has no diagnostic role because it is invasive and is associated with risk of complications, hence it is reserved for therapeutic procedures. Magnetic resonance cholangiography and portovenography is a noninvasive and comprehensive imaging technique, and is the modality of choice for mapping of the biliary and vascular abnormalities in these patients. PCC is a progressive condition and symptoms develop late in the course of portal hypertension only in patients with severe or advanced changes of cholangiopathy. Asymptomatic patients with PCC do not require any treatment. Treatment of symptomatic PCC can be approached in a phased manner, coping first with biliary clearance by nasobiliary or biliary stent placement for acute cholangitis and endoscopic biliary sphincterotomy for biliary stone removal; second, with portal decompression by creating portosystemic shunt; and third, with persistent biliary obstruction by performing second-stage biliary drainage surgery such as hepaticojejunostomy or choledochoduodenostomy. Patients with symptomatic PCC have good prognosis after successful endoscopic biliary drainage and after successful shunt surgery.

Evaluation of hybrid PET/CT gastrography in gastric cancer.

AIM: With the recent advances in multidetector-row CT, a fusion of functional PET with three dimensional (3D) CT gastrography may provide enhanced diagnostic capability and help surgeons during preoperative planning. The diagnostic value of hybrid PET/CT gastrography was compared with that of conventional PET/CT alone in gastric cancer staging. PATIENTS, METHODS: Patients with gastric cancer (n = 101) confirmed by endoscopic biopsy specimens underwent conventional PET/CT and regional PET with contrast enhanced CT, followed by gastrectomy with lymphadenectomy at our institution from November 2007 to November 2008. These images were fused into a hybrid PET/CT gastrography using the cardiac IQ fusion software. Conventional PET/CT and hybrid PET/CT gastrography were evaluated for staging of gastric cancer. After gastrectomy, these were compared with pathologic reports respectively. RESULTS: Gastric cancer was diagnosed as 50 early gastric cancer (EGC) and 51 advanced gastric cancer (AGC) on pathologic examination. In EGC, hybrid PET/CT gastrography and PET/CT identified 36 (72%) and 7 (14%) tumours, respectively. Hybrid PET/CT gastrography correctly delineated the subtype of 25 EGC. In AGC, all 51 (100%) tumours were identified on the hybrid PET/CT gastrography compared to 39 (76.5%) tumours on PET/CT. Hybrid PET/CT gastrography correctly classified the morphology of 42 AGC using the Bormann classification. Additionally, depth of invasion was correctly presented in 38 of 51 AGC. Hybrid PET/CT gastrography for regional lymph node (LN) metastasis in the EGC and AGC showed the sensitivity of 75% and 83.9%, and specificity 90.5% and 55%, respectively. CONCLUSION: Hybrid PET/CT gastrography is the more intuitive and comprehensive method for the preoperative evaluation of gastric cancer than conventional PET/CT.

Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study.

The incidence and severity of Clostridium difficile infections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.

Tetrahydro-naphthols as orally available TRPV1 inhibitors.

Starting from a naphthol-based lead series with low oral bioavailability, we have identified potent TRPV1 antagonists with oral bioavailability in rats. These compounds emerged from SAR studies aimed at replacing the lead's phenol structure whilst maintaining potency. Compound rac-6a is an orally available TRPV1 antagonist with single-digit nanomolar activity. The enantiomers show a low eudismic ratio at the receptor level.