Choice of population database for forensic DNA profile analysis.
When evaluating the weight of evidence (WoE) for an individual to be a contributor to a DNA sample, an allele frequency database is required. The allele frequencies are needed to inform about genotype probabilities for unknown contributors of DNA to the sample. Typically databases are available from several populations, and a common practice is to evaluate the WoE using each available database for each unknown contributor. Often the most conservative WoE (most favourable to the defence) is the one reported to the court. However the number of human populations that could be considered is essentially unlimited and the number of contributors to a sample can be large, making it impractical to perform every possible WoE calculation, particularly for complex crime scene profiles. We propose instead the use of only the database that best matches the ancestry of the queried contributor, together with a substantial FST adjustment. To investigate the degree of conservativeness of this approach, we performed extensive simulations of one- and two-contributor crime scene profiles, in the latter case with, and without, the profile of the second contributor available for the analysis. The genotypes were simulated using five population databases, which were also available for the analysis, and evaluations of WoE using our heuristic rule were compared with several alternative calculations using different databases. Using FST=0.03, we found that our heuristic gave WoE more favourable to the defence than alternative calculations in well over 99% of the comparisons we considered; on average the difference in WoE was just under 0.2 bans (orders of magnitude) per locus. The degree of conservativeness of the heuristic rule can be adjusted through the FST value. We propose the use of this heuristic for DNA profile WoE calculations, due to its ease of implementation, and efficient use of the evidence while allowing a flexible degree of conservativeness.


Metallic CrP2 monolayer: potential applications in energy storage and conversion.
Phosphorus-rich compounds have emerged as a promising class of energy storage and conversion materials due to their interesting structures and electrochemical properties. Herein, we propose that a metallic CrP2 monolayer, isomorphic to 1H-phase MoS2, is a good prospect as an anode for K-ion batteries and a catalyst for hydrogen evolution through first-principles calculations. The CrP2 monolayer demonstrates not only a desirable high K storage capacity (940 mA h g-1) but also a low K-ion diffusion barrier (0.10 eV) and average open circuit voltage (0.40 V). On the other hand, its Gibbs free energy (0.02 eV)/active site density is superior/comparable to that of commercial Pt, resulting from the contribution of the lone pair electrons of the P atom. Its high structural stability and intrinsic metallicity can ensure high safety and performance during the cyclic process. These interesting properties make the CrP2 monolayer a promising multifunctional material for energy storage and conversion devices.


Correlation Between IVIM-DWI Parameters and Pathological Classification of Idiopathic Orbital Inflammatory Pseudotumors: A Preliminary Study.
To investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs). Nineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation. The true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were obtained. Based on histopathology, the lesions were divided into three types: lymphocytic infiltration, fibrosclerotic, and mixed. The correlation between IVIM-DWI parameters and pathological classification was tested with the histopathological results as the gold standard. The data were analyzed using SPSS version 17.0, with P < 0.05 defined as significant. Among the 19 patients (24 eyes) affected by IOIP, there were no significant differences between IOIP pathological classification and gender or age (P > 0.05). There were statistically significant differences between the D and f values for different pathological types of IOIP and IVIM parameters (P < 0.05), and there was no significant difference in D* value between the different pathological types (P > 0.05). The D and f values showed correlation with different types of IOIP, and the sensitivity of the D value was higher than that of the f value. The D* value showed no significant distinction between pathological types of IOIP.


Slow (1 Hz) repetitive transcranial magnetic stimulation (rTMS) induces a sustained change in cortical excitability in patients with Parkinson's disease.
Low-frequency (< or =1 Hz) rTMS (LF-rTMS) can reduce excitability in the underlying cortex and/or promote inhibition. In patients with Parkinson's disease (PD) several TMS elicited features of motor corticospinal physiology suggest presence of impaired inhibitory mechanisms. These include shortened silent period (SP) and slightly steeper input-output (I-O) curve of motor evoked potential (MEP) size than in normal controls. However, studies of LF-rTMS effects on inhibitory mechanisms in PD are scarce. In this companion paper to the clinical paper describing effects of four consecutive days of LF-rTMS on dyskinesia in PD (Filipović et al., 2009), we evaluate the delayed (24h) effects of the LF-rTMS treatment on physiological measures of excitability of the motor cortex in the same patients. There are very few studies of physiological follow up of daily rTMS treatments. Nine patients with PD in Hoehn and Yahr stages 2 or 3 and prominent medication-induced dyskinesia were studied. This was a placebo-controlled, crossover study, with two treatment arms, "real" rTMS and "sham" rTMS (placebo). In each of the treatment arms, rTMS (1800 pulses; 1 Hz rate; intensity of the real stimuli just-below the active motor threshold) was delivered over the motor cortex for four consecutive days. Motor cortex excitability was evaluated at the beginning of the study and the next day following each of the four-day rTMS series (real and sham) with patients first in the practically defined "off" state, following 12h withdrawal of medication, and subsequently in a typical "on" state following usual morning medication dose. The SP was significantly longer following real rTMS in comparison to both baseline and sham rTMS. The effect was independent from the effects of dopaminergic treatment. There was no difference in MEP size, rest and active motor threshold. The I-O curve, recorded from the relaxed muscle, showed a trend towards diminished slope in comparison to baseline, but the difference was not significant. There was no consistent correlation between prolongation of SP and concomitant reduction in dyskinesia following real rTMS. Low-frequency rTMS delivered over several consecutive days changes the excitability of motor cortex by increasing the excitability of inhibitory circuits. The effects persist for at least a day after rTMS. The results confirm the existence of a residual after-effect of consecutive daily applications of rTMS that might be relevant to the clinical effect that was observed in this group of patients and could be further exploited for potential therapeutic uses.


[Effect of ACTH injection and graft of bursa of Fabricius on the adrenocortical activity of bursectomized chicks at 80 hours of incubation].
Early embryonic bursectomy (BFX) disturbed the adrenocortical functioning. The stress-unresponsive period that occurred in controls, and lasted for 2-3 weeks after hatching, no longer appeared in BFX chicks. In contrast, the magnitude of the stress-induced hypercorticosteronemia was much lower in BFX than in sham-operated 5 week-old chicken. It was assumed that such adrenocortical dysfunction was due to bursal deprivation, since grafting bursal buds onto the chorio-allantoic membrane of BFX embryos restored all the parameters under study, i.e., the post-hatching stress unresponsive period and the high magnitude of stress-induced responses in adults. Factor(s) involved in such interregulation are not known but do not seem to affect directly adrenocortical cells because intramuscular injection of a moderate dose of ACTH resulted in the same hypercorticosteronemia whether 3 day-old and 5 week-old chicks had been bursectomized or sham-operated.


Neurosyphilis with oral‑facial‑lingual dyskinesia: A case report.
The present study describes the case of a 52-year-old male patient who presented with subacute onset dysarthria and oral-facial-lingual dyskinesia, with normal blood glucose and acanthocyte levels, and no history of drug use. The patient tested negative for autoimmune encephalitis-related antibodies and paraneoplastic-related antibodies. The level of cerebrospinal fluid (CSF) protein was slightly elevated, and the Treponema pallidum hemagglutination assay and rapid plasma reagin test were positive in both serum and CSF samples. After 1 month of treatment with doxycycline, the patient's oral-facial-lingual dyskinesia was significantly improved, suggesting the diagnosis of neurosyphilis.


Development of a prolonged warm ex vivo perfusion model for kidneys donated after cardiac death.
Ex vivo perfusion of marginal kidney grafts offers the chance to expand the donor pool, but there is no current clinical standard for the prolonged warm perfusion of renal grafts. This exploratory pilot study seeks to identify a stable ex vivo kidney perfusion model that can support low intravascular resistance and preserve histologic architecture in a porcine donation after cardiac death (DCD) model. 15 kidneys were preserved in 1 of 3 settings: normothermic whole blood (NT-WB), normothermic Steen Solution™ (XVIVO Perfusion) with whole blood (NT-Steen/WB), or subnormothermic Steen Solution™ at 21°C (SNT-Steen). Kidneys were primarily assessed using hemodynamic parameters and histologic analysis. NT-WB perfusion resulted in high vascular resistance and glomerular necrosis. NT-Steen/WB and SNT-Steen resistance ranged between 0.18-0.45 mmHg/mL per minute and 0.25-0.53 mmHg/mL per minute, respectively, enabling stable perfusion for up to 24 hours. NT-Steen/WB demonstrated tubular and glomerular necrosis, while the histologic architecture of SNT-Steen was preserved with the exception of numerous proteinaceous casts. Our results suggest that ex vivo kidney perfusion with Steen Solution™ at 21°C supports low and stable vascular resistance and provides adequate histologic preservation during 24-hour perfusion.


Plasma-assisted immobilization of heparin onto low-density polyethylene surface.
In this study heparin was covalently immobilized onto LDPE-VEMAC sheet fabricated by the introduction of carboxyl groups to the surface of low-density polyethylene (LDPE) using a plasma technique. The plasma irradiation time influenced the density of carboxyl groups on the LDPE-VEMAC sheet. Heparin was immobilized on the LDPE-VEMAC sheet using a condensation reagent, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). We confirmed the immobilization of heparin from the ATR-FT-IR spectrum of the sheet obtained. Where heparin was directly immobilized on the LDPE-VEMAC sheet, the density of the immobilized heparin depended on that of the carboxyl groups. Heparin was also immobilized with a spacer, hexamethylene diamine, and the density of such heparin was about 1.6 times that of the directly immobilized heparin. This result suggests that the introduction of a spacer may be an effective way to increase the density of immobilized heparin.


Imaging of an invasive malignant thymoma on PET Scan: CT and histopathologic correlation.
Thymomas are common primary mediastinal neoplasms. They can be benign or malignant. The diagnosis of malignant thymomas is based on capsular invasion, cellular atypia and distant metastases. We present a case of invasive malignant thymoma as diagnosed on PET and CT scan with histologic correlation and review of literature. A seventy year old Asian man presented with cough and dyspnea. A CT scan showed an anterior mediastinal mass, and a PET scan showed a hypermetabolic mass in the corresponding location. Resection of the mass revealed a minimally invasive thymoma based on evidence of capsular invasion. PET scan proved invaluable in correctly diagnosing, staging the lesion, and excluding any extramediastinal involvement.


Pulmonary blastoma metastatic to the ovary.
Pulmonary blastoma (PB) is a rare and aggressive pulmonary malignancy. A 38-year-old woman was diagnosed as biphasic PB (1 subgroup of sarcomatoid carcinoma) and treated by surgery, radiotherapy, and chemotherapy. Six months later, the patient presented with menstrual disorder and a mass in the abdominal-pelvic cavity. Abdominal hysterectomy and bilateral salpingo-oophorectomy showed the morphology of metastatic PB in both ovaries. The metastatic tumor was composed exclusively of epithelial components resembling well-differentiated fetal adenocarcinoma. To our knowledge, this is the first reported case of bilateral ovarian metastasis from biphasic PB.


Tolerance to inhaled fenoterol.
Fenoterol ( Berotec ; Th 1165a , Boehringer- Ingelheim , Spa., Firenze , Italy) is an effective, widely used bronchodilator. It has been suggested by some investigators that, as in the case of other beta-adrenergic agonists, its clinical usefulness may be limited by the development of tolerance; others have found no tolerance. These conflicting results appear to be related to differences in study designs. We studied for 3 months the effects of inhaled fenoterol in 15 asthmatics, using a rigidly controlled protocol. Appropriate serial physiologic measurements were made at regular intervals during the 90-day study. In all instances the day 1 bronchodilator response was significant, prompt, and sustained: at 1,3,4,8 and 12 wk the response was statistically the same as on day 1. It is concluded that, when the important variables are properly controlled, no evidence of tolerance to long-term therapy with fenoterol is demonstrable.


A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B.
Aglossia is a rare congenital malformation that often occurs as an isolated disorder or is observed in association with other congenital deformities, particularly limb defects. We present a unique case of a 7-year-old girl with aglossia, hypodactyli, rudimentary ears, retrognathic and V-shaped mandible. Her parental history revealed intrauterine exposure of medicines. The patient had problems in difficulty in eating, speech, taste sensation and hearing. The present case does not fit into Hall's classification of oromandibular limb hypogenesis syndrome (OLHS) which best describes hypoglossia and limb deformities. Therefore, the purpose of this article is to document the rare variant of OLHS which can be included in Hall's classification. How to cite this article: Kalaskar RR, Godhane A, Kalaskar A, Demble S. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B. Int J Clin Pediatr Dent 2016;9(1):78-81.


Diabetes mellitus in twins: a cooperative study in Japan. Committee on Diabetic Twins, Japan Diabetes Society.
In 1984, the Japan Diabetes Society organized a committee to collect data on diabetic twins in Japan. Within 3 years, through correspondence with Society members and hospitals, the Committee had contacted 87 pairs of twins, one or both of which had diabetes mellitus or glucose intolerance. Sixty-three pairs were monozygotic and 24 dizygotic. The probands, who had been diagnosed as diabetic or glucose-intolerant earlier, included 21 patients with insulin-dependent diabetes mellitus (IDDM), 56 with non-insulin-dependent diabetes (NIDDM), one with an unknown type of diabetes, and nine with glucose intolerance. Concordance between monozygotic twins was 45% for IDDM and 83% for NIDDM; between dizygotic twins, concordance was 0% (0/10) for IDDM and 40% (4/10) for NIDDM. Concordance was significantly greater in NIDDM than in IDDM, and in monozygotic than in dizygotic twins. Concordance was greater among twins in which one twin had developed diabetes after the age of 20 than among twins in which the age of onset had been earlier. There was no evidence that the period of discordance was shorter in the discordant pairs than in the concordant pairs. About 90% of the IDDM twin pairs lived together, against 20% of the NIDDM pairs, probably due to the later age of onset of NIDDM. The frequency of diabetes in family members other than the twins was higher in NIDDM than in IDDM regardless of concordance. In concordant pairs the presence or absence of various complications agreed in 68-97%; a few pairs were discordant for the severity of retinopathy, which may have resulted from differences in duration and hyperglycemic degree. A 75-g glucose tolerance test administered to the 'normal' discordant twins revealed borderline glucose intolerance in two of six IDDM co-twins and six of eight NIDDM co-twins. The early-phase insulin response was low in two of six IDDM co-twins and four of six NIDDM co-twins. These results are generally consistent with previous reports of diabetic twins in Western countries, reinforcing the importance of genetic factors in the pathogenesis of diabetes. Heredity has a particularly strong influence in NIDDM.


Metabolism of lysergic acid diethylamide (LSD): an update.
Lysergic acid diethylamide (LSD) is the most potent hallucinogen known and its pharmacological effect results from stimulation of central serotonin receptors (5-HT2). Since LSD is seen as physiologically safe compound with low toxicity, its use in therapeutics has been renewed during the last few years. This review aims to discuss LSD metabolism, by presenting all metabolites as well as clinical and toxicological relevance. LSD is rapidly and extensively metabolized into inactive metabolites; whose detection window is higher than parent compound. The metabolite 2-oxo-3-hydroxy LSD is the major human metabolite, which detection and quantification is important for clinical and forensic toxicology. Indeed, information about LSD pharmacokinetics in humans is limited and for this reason, more research studies are needed.


The treatment of colorectal carcinoma: standard chemotherapy and beyond.
Significant advances in the management of colorectal cancer patients have occurred within the past 5 years. New cytotoxic agents as well as novel targeted therapies have notably prolonged the survival of colorectal cancer patients with advanced disease. Some of these regimens have also been successfully applied to the adjuvant setting. Our improved scientific understanding of colorectal cancer will form the basis for further development of new methods to treat this common malignancy. The introduction of targeted therapeutics into the management of colorectal cancer is likely to extend the overall survival of patients further.


Parasite facilitates plant species coexistence in a coastal wetland.
Outbreaks of infectious agents in natural ecosystems are on the rise. Understanding host-pathogen interactions and their impact on community composition may be central to the conservation of biological diversity. Infectious agents can convey both exploitive and facilitative effects that regulate host populations and community structure. Parasitic angiosperms are highly conspicuous in many plant communities, and they provide a tractable model for understanding parasite effects in multispecies communities. I examined host identity and variation in host infectivity of a holoparasitic vine (Cuscuta salina) within a California salt marsh. In a two-year parasite removal experiment, I measured the effect of C. salina on its most frequent host, a rare hemiparasite, and the plant community. C. salina clearly suppressed the dominant host, but rare plant fitness and plant species diversity were enhanced through indirect effects. Priority effects played a role in the strength of the outcome due to the timing of life history characteristics. The differential influence of parasites on the fecundity of multiple hosts can change population dynamics, benefit rare species, and alter community structure. The continuum of negative to positive consequences of parasitic interactions deserves more attention if we are to understand community dynamics and successfully restore tidal wetlands.


Bridging intimate partner violence and the human brain: a literature review.
Past studies mainly focused on the physical and structural brain injuries in women survivors with a history of intimate partner violence (IPV), but little attention has been given to the biological impact and cognitive dysfunction resulting from such psychological stress. In this article, we aim to establish the connection between IPV and the brain by reviewing current literature examining (1) the biological mechanisms linking IPV, stress, and the brain; (2) the functional and anatomical considerations of the brain in abused women; and (3) the abused women's behavioral responses to IPV, including fear, pain, and emotion regulation, by utilizing functional neuroimaging. The major significance of this study is in highlighting the need to advance beyond self-reports and to obtain scientific evidence of the neurological impact and cognitive dysfunction in abused women with a history of IPV, an area in which current literature remains at a descriptive level.


Altering the Multimodal Resonance in Ultrathin Silicon Ring for Tunable THz Biosensing.
A technique is implemented for altering the multimodal resonance generated in an ultrathin silicon ring resonator-based terahertz (THz) absorber. The absorber provides the dual-band resonance with the excitation of magnetic and electric dipole in the lower and upper band, respectively. The field of magnetic and electric dipoles is altered using a non-resonant graphene ring placed in the center of the generated dipolar arrangement and the tunability and perfect absorption is achieved. A circuit model is prepared using transmission line method and absorber operation is verified. The proposed absorber can be utilized as a biosensor for the detection of malaria virus and glucose percentage in water. The sensor offers highest sensitivity as 0.29 and 0.27 THz per thickness unit change and quality factor as 117.53 and 245 in the lower and upper band, respectively during the sensing of analyte thickness. Also, it offers the sensitivity as 0.20 and 0.10 THz per refractive index unit change and quality factor as 105.28 and 211.84 in the lower and upper band, respectively during refractive index sensing. Moreover, the structure remains insensitive to polarization angle of the incident electromagnetic wave.


Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine.
Acute lung injury (ALI) affects over 10% of patients hospitalised in critical care, with acute respiratory distress syndrome (ARDS) being the most severe form of ALI and having a mortality rate in the region of 40%. There has been slow but incremental progress in identification of biomarkers that contribute to the pathophysiology of ARDS, have utility in diagnosis and monitoring, and that are potential therapeutic targets (Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Thompson T, Ware LB, Matthay MA, Lancet Respir Med 2014, 2:611--620). However, a major issue is that ARDS is such a heterogeneous, multi-factorial, end-stage condition that the strategies for "lumping and splitting" are critical (Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX, Am J Respir Crit Care Med 2016, 194:147--155). Nevertheless, sequencing of the human genome, the availability of improved methods for analysis of transcription to mRNA (gene expression), and development of sensitive immunoassays has allowed the application of network biology to ARDS, with these biomarkers offering potential for personalised or precision medicine (Sweeney TE, Khatri P, Toward precision medicine Crit Care Med; 2017 45:934-939). Biomarker panels have potential applications in molecular phenotyping for identifying patients at risk of developing ARDS, diagnosis of ARDS, risk stratification and monitoring. Two subphenotypes of ARDS have been identified on the basis of blood biomarkers: hypo-inflammatory and hyper-inflammatory. The hyper-inflammatory subphenotype is associated with shock, metabolic acidosis and worst clinical outcomes. Biomarkers of particular interest have included interleukins (IL-6 and IL-8), interferon gamma (IFN-γ), surfactant proteins (SPD and SPB), von Willebrand factor antigen, angiopoietin 1/2 and plasminogen activator inhibitor-1 (PAI-1). In terms of gene expression (mRNA) in blood there have been found to be increases in neutrophil-related genes in sepsis-induced and influenza-induced ARDS, but whole blood expression does not give a robust diagnostic test for ARDS. Despite improvements in management of ARDS on the critical care unit, this complex disease continues to be a major life-threatening event. Clinical trials of β2-agonists, statins, surfactants and keratinocyte growth factor (KGF) have been disappointing. In addition, monoclonal antibodies (anti-TNF) and TNFR fusion protein have also been unconvincing. However, there have been major advances in methods of mechanical ventilation, a neuromuscular blocker (cisatracurium besilate) has shown some benefit, and stem cell therapy is being developed. In the future, by understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care (Seymour CW, Gomez H, Chang CH, Clermont G, Kellum JA, Kennedy J, Yende S, Angus DC, Crit Care 2017, 21:257).


Peptide-based investigation of the Escherichia coli RNA polymerase σ(70):core interface as target site.
The number of bacterial strains that are resistant against antibiotics increased dramatically during the past decades. This fact stresses the urgent need for the development of new antibacterial agents with novel modes of action targeting essential enzymes such as RNA polymerase (RNAP). Bacterial RNAP is a large multi-subunit complex consisting of a core enzyme (subunits: α(2)ββ'ω) and a dissociable sigma factor (σ(70); holo enzyme: α(2)ββ'ωσ(70)) that is responsible for promoter recognition and transcription initiation. The interface between core RNAP and σ(70) represents a promising binding site. Nevertheless, detailed studies investigating its druggability are rare. Compounds binding to this region could inhibit this protein-protein interaction and thus holo enzyme formation, resulting in inhibition of transcription initiation. Sixteen peptides covering different regions of the Escherichia coli σ(70):core interface were designed; some of them-all derived from σ(70) 2.2 region-led to a strong RNAP inhibition. Indeed, an ELISA-based experiment confirmed the most active peptide P07 to inhibit the σ(70):core interaction. Furthermore, an abortive transcription assay revealed that P07 impedes transcription initiation. In order to study the mechanism of action of P07 in more detail, molecular dynamics simulations and a rational amino acid replacement study were performed, leading to the conclusion that P07 binds to the coiled-coil region in β' and that its flexible N-terminus inhibits the enzyme by interaction with the β' lid-rudder-system (LRS). This work revisits the β' coiled-coil as a hot spot for the protein-protein interaction inhibition and expands it by introduction of the LRS as target site.


Temperature activated transient receptor potential ion channels from Antarctic fishes.
Antarctic notothenioid fishes (cryonotothenioids) live in waters that range between -1.86°C and an extreme maximum +4°C. Evidence suggests these fish sense temperature peripherally, but the molecular mechanism of temperature sensation in unknown. Previous work identified transient receptor potential (TRP) channels TRPA1b, TRPM4 and TRPV1a as the top candidates for temperature sensors. Here, cryonotothenioid TRPA1b and TRPV1a are characterized using Xenopus oocyte electrophysiology. TRPA1b and TRPV1a showed heat-evoked currents with Q10s of 11.1 ± 2.2 and 20.5 ± 2.4, respectively. Unexpectedly, heat activation occurred at a threshold of 22.9 ± 1.3°C for TRPA1b and 32.1 ± 0.6°C for TRPV1a. These fish have not experienced such temperatures for at least 15 Myr. Either (1) another molecular mechanism underlies temperature sensation, (2) these fishes do not sense temperatures below these thresholds despite having lethal limits as low as 5°C, or (3) native cellular conditions modify the TRP channels to function at relevant temperatures. The effects of osmolytes, pH, oxidation, phosphorylation, lipids and accessory proteins were tested. No conditions shifted the activity range of TRPV1a. Oxidation in combination with reduced cholesterol significantly dropped activation threshold of TRPA1b to 11.3 ± 2.3°C, it is hypothesized the effect may be due to lipid raft disruption.