Exploring perceptions of factors aiding the development of critical thinking in adult dysphagia: A study among fourth-year speech-language pathology students.

BACKGROUND: The assessment and management of adult dysphagia in South Africa is complex as appropriate intervention requires a balance of theoretical knowledge and critical thinking to ensure service delivery is appropriate within a resource-constrained health care system. Critical thinking involves the skilful evaluation of information to make informed decisions for effective assessment and intervention. It is imperative for Speech-Language Pathologists (SLPs) to cultivate these skills from an early stage in their careers. This study therefore aims to investigate the factors perceived to enhance critical thinking to shed light on how students transition theory into clinical decision-making. This is vital to inform future practice in the realm of dysphagia and to enhance Speech Therapy education. METHODS: A qualitative research design was utilised to identify what facilitators assist SLP students to develop critical thinking skills in adult dysphagia. Data were gathered from students across three universities. Fifteen participants answered a self-developed online survey, and of those, four participated in a follow-up focus group. The data were analysed using a top-down approach and reflexive thematic analysis. RESULTS AND DISCUSSION: The results revealed that viewing videos on instrumental assessment measures, case studies and peer learning were perceived to expand critical thinking theoretically. Similarly, critical thinking was best supported in clinical contexts, which provided opportunities to observe expert clinicians at the bedside, obtain individual feedback and access supervision. CONCLUSION: The findings yielded recommendations for clinical educators involved in dysphagia training. This is necessary to better prepare SLP students to provide contextually relevant and responsive dysphagia services.

Prolegomena to any future philosophy of behavior analysis as a science.

This tribute to Howard Rachlin speculates about scholarly work that might have been. It explores how behavioral data might bear on philosophical issues, with examples that might be called case studies in experimental philosophy. In 1964, an issue of the Proceedings of the American Philosophical Society served a similar function. It was entitled "Psychology: A Behavioral Interpretation"; the papers included "Will," "Experience," "Appetite," "Humors," "Anxiety," and "Man." This presentation imagines what a contemporary project devoted to philosophical and behavior analytic perspectives on the topics of causation, freedom and volition, good and evil, time, words, and mind might have looked like. Along the way it notes how the project would have benefitted from Howard Rachlin's seminal contributions to both behavior analysis and philosophy. If ever such a project comes to pass, it will inevitably bear the stamp of his contributions.

Faustian bargains: Short-term and long-term contingencies in phylogeny, ontogeny, and sociogeny.

Rachlin's interpretations of self-control depend on the short-term versus the long-term consequences of behavior. Sometimes these effects support each other (typing an abstract produces a written product now and is later read by others). Sometimes they conflict (procrastination now is incompatible with finishing the abstract by deadline). We usually reserve the language of self-control for human cases where long-term consequences are chosen over short-term ones. Rachlin made this distinction salient in ontogeny, but it also applies to selection in phylogeny (Darwinian evolution) and sociogeny (behavior passed from one organism to another). Our account examines relations between short-term and long-term consequences at each level of selection. For example, sexual selection has adaptive, short-term mating consequences but may drive species to extreme specializations that jeopardize long-term survival. In sociogeny, as in the Tragedy of the Commons, group members may get immediate economic benefits from exploiting resources but exhaust those resources over the long term. Whatever the level, when short-term and long-term consequences have opposing effects, adaptive behavior may depend on whether temporally extended contingencies exert more control than more immediate benefits.

Tactical contingencies in the experimental analysis of reinforcement and operant classes.

In his "Tactics of Scientific Research" (1960), his work on avoidance, his discovery of equivalence classes and his cautions on applications of coercion, Murray Sidman created high standards for behavior analytic research. I illustrate his influence in the context of three examples he might have characterized as pilot studies. Each examined trial N+1 response probabilities depending on whether trial N responding had produced a reinforcer. Differentially reinforced interresponse times, keys pecked in arbitrary matching, and two-key response sequences provided no robust evidence that reinforcing some response property on trial N raises the probability of responding with that property on trial N+1. These negative findings shed light on the nature of operant classes and on the relation of reinforcers to the responses that produced them. Through selection, reinforcers create operant classes and engender variations of the responses within those classes; operant classes are held together by common contingencies. Sidman extended our understanding of operant classes by expanding them to include equivalence relations.

R106C TFG variant causes infantile neuroaxonal dystrophy "plus" syndrome.

TFG (tropomyosin-receptor kinase fused gene) encodes an essential protein in the regulation of vesicular trafficking between endoplasmic reticulum and Golgi apparatus. The homozygous variant c.316C > T within TFG has been previously associated with a complicated hereditary spastic paraplegia (HSP) phenotype in two unrelated Indian families. Here, we describe the first Italian family with two affected siblings harboring the same variant, who in childhood were classified as infantile neuroaxonal dystrophy (INAD) based on clinical and neuropathological findings. Twenty years after the first diagnosis, exome sequencing was instrumental to identify the genetic cause of this disorder and clinical follow-up of patients allowed us to reconstruct the natural history of this clinical entity. Investigations on patient's fibroblasts demonstrate the presence of altered mitochondrial network and inner membrane potential, associated with metabolic impairment. Our study highlights phenotypic heterogeneity characterizing individuals carrying the same pathogenic variant in TFG and provides an insight on tight connection linking mitochondrial efficiency and neuronal health to vesicular trafficking.

PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.

Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.

A quantitative analysis of the behavior maintained by delayed reinforcers.

Random-interval reinforcement was arranged for a sequence of pigeon first-key pecks followed by second-key pecks. First-key pecks, separated from reinforcers by delays that included number of second-key pecks and time, decreased in rate as delays increased. Delay functions, or gradients, were obtained in one experiment with reinforced sequences consisting of M first-key pecks followed by N second-key pecks (M + N = 16), in a second where required first-key pecks were held constant (M = 8), and in a third where minimum delay between most recent first-key pecks and reinforcers varied. In each, gradients were equally well fitted by exponential, hyperbolic and logarithmic functions. Performances were insensitive to reinforcer duration and functions were consistent across varied random-interval values. In one more experiment, time and number delays were independently varied using differential reinforcement of rate of second-key pecks. Delay gradients depended primarily on time rather than on number of second-key pecks. Thus, reinforcers have effects based on earlier responses, not just the ones that produced them, with the contribution of each response weighted by the time separating it from the reinforcer rather than by intervening behavior. Situations where unwanted responses (e.g., errors) often precede reinforced corrects can maintain them unless designed to avoid such effects of delay.

Selective inhibitors of aurora kinases inhibit proliferation, reduce cell viability and impair cell cycle progression in papillary thyroid carcinoma cells.

The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC50 comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC.

Metachronous elastofibromas.

Elastofibroma Dorsi (EFD) is a rare pseudo-tumor characterized by the overgrowth of elastic fibers mixed to adipose and connective tissues typically growing in the subscapular region. This can be bilateral but only rarely synchronous affecting different anatomical sites at the same time. Hereby we present a case of a 42-year-old male patient found with three different metachronous elastofibromas: bilateral EFD and a further third localization by the right elbow. The two EFs in the subscapular region were resected. After surgery pain reoccurred on the right side. This required the implantation of a spinal electro-stimulator. The elbow lesion was not excised as it was asymptomatic.

Environments organize the verbal brain.

FOXP2 expression in the evolution of language derives from its role in allowing vocal articulation that is sensitive to its consequences. The discrete verbal discourse it allows must have evolved recently relative to affective features of vocal behavior such as tone of voice. Because all organ systems must have evolved in the service of behavior, attention is given to ways in which environments may have driven brain organization.

The dual Aurora kinase inhibitor ZM447439 prevents anaplastic thyroid cancer cell growth and tumorigenicity.

The anaplastic thyroid cancer (ATC) is among the most aggressive human tumors which fail to respond to all the currently available therapeutic approaches. As a consequence most patients die within a few months from diagnosis. In the present preclinical study, the effects of the ZM447439, a functional inhibitor of Aurora kinases, on the growth and tumorigenicity of a panel of ATC derived cell lines (CAL-62, 8305C, 8505C and BHT-101) were evaluated. The treatment of the different ATC cells with ZM447439 inhibited proliferation in a time- and dose-dependent manner, with IC50 comprised between 0.5 mM and 5 mM. Moreover, the drug remarkably impaired the formation of colonies in soft agar of all the cell lines. Consistently with Aurora inhibition, immunofluorescence and immunoblotting experiments demonstrated that Aurora auto-phosphorylation following drug treatment was completely abrogated, and treated cells were characterized by the presence of multiple spindles with short microtubules. In the same experiments we observed the loss of histone H3 phosphorylation on Ser10, specifically due to Aurora-B, after ZM447439 treatment. Time-lapse videomicroscopy and flow cytometric analysis demonstrated that in presence of ZM447439 the cells were able to enter mitosis but not to complete it, becoming polyploid. Almost all the ATC cell lines studied showed increased apoptosis after only 48 h of treatment. In conclusion, our data demonstrate that ZM447439 is effective in reducing cell growth and tumorigenicity of different ATC derived cell lines, and further investigations are needed to exploit its potential therapeutic value for ATC treatment.

Total thyroidectomy for Graves' disease treatment.

OBJECTIVES: Graves' disease (GD) is the most common cause of hyperthyroidism, and accounts worldwide for 60-80% of all cases. The diagnosis is based on clinical findings, and is confirmed by the presence of TRAB, suppression of TSH, and elevation of free thyroxin (free T4), and triiodinethyronin (free T3). GD can be treated by antithyroid drugs, radioactive iodine, or surgery. The aim of this study was to review retrospectively the surgical management, in terms of safety and efficacy, in 50 patients operated in the Department of Surgical Sciences since 2005 through 2010 and followed up at the Endocrinology Unit A of the Experimental Medicine Department. We assessed postoperative complications, which included the presence, persistence and development of ophthalmopathy, transient hypocalcemia, permanent hypoparathyroidism and recurrent laryngeal nerve palsy. MATERIALS AND METHODS: We analyzed data from 50 patients with GD who were eligible and underwent Total Thyroidectomy (TT). Thirty-nine patients underwent TT for recurrent hyperthyroidism after medical therapy and eleven patients for severe ophtalmopathy. The mean follow up was 41 months (range: 10-70). RESULTS: Eleven patients had ophtalmopathy before surgery. Four patients developed an ophtalmopathy after surgery. Eleven patients presented hypocalcemia, transient in ten patients and permanent in one patient. Five patients developed a transient disphony. Conclusions. Total thyroidectomy is a safe and radical procedure in Graves' disease treatment. Complications of TT are not different than subtotal thyroidectomy if it's performed by expert surgeons.

Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells.

BACKGROUND: Activins control the growth of several tumour types including thoracic malignancies. In the present study, we investigated their expression and function in malignant pleural mesothelioma (MPM). METHODS: The expression of activins and activin receptors was analysed by quantitative PCR in a panel of MPM cell lines. Activin A expression was further analysed by immunohistochemistry in MPM tissue specimens (N=53). Subsequently, MPM cells were treated with activin A, activin receptor inhibitors or activin-targeting siRNA and the impact on cell viability, proliferation, migration and signalling was assessed. RESULTS: Concomitant expression of activin subunits and receptors was found in all cell lines, and activin A was overexpressed in most cell lines compared with non-malignant mesothelial cells. Similarly, immunohistochemistry demonstrated intense staining of tumour cells for activin A in a subset of patients. Treatment with activin A induced SMAD2 phosphorylation and stimulated clonogenic growth of mesothelioma cells. In contrast, treatment with kinase inhibitors of activin receptors (SB-431542, A-8301) inhibited MPM cell viability, clonogenicity and migration. Silencing of activin A expression by siRNA oligonucleotides further confirmed these results and led to reduced cyclin D1/3 expression. CONCLUSION: Our study suggests that activin A contributes to the malignant phenotype of MPM cells via regulation of cyclin D and may represent a valuable candidate for therapeutic interference.

Diagnostic utility of thyroglobulin measurement in the fine needle aspirates from cervical lymph nodes: a case report.

Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC). However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its routine association with cytology is recommended. We here describe the case of a 20 yr old girl complaining of the recent appearance of palpable non-painful laterocervical nodes in the neck. Ultrasound examination revealed the presence of 3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg protein and mRNA were determined in the needle washout. The cytological analysis was not diagnostic for the two CLNs, while that of the thyroid nodule reported the presence of colloid and groups of thyrocytes with normal morphology. Both CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA, suggestive of metastatic DTC. Based on these findings, the FNAC analysis was performed on the second smaller thyroid nodule suggesting (Tir4) the presence of PTC. The patient was then subjected to total thyroidectomy with lymph nodes resection of the central and homolateral compartments. The histological diagnosis confirmed the presence of a PTC in the small nodule and metastatic lymph nodes. In conclusion, this case confirms that the cytological diagnosis of cystic lymph nodes is challenging, and that the measurement of Tg protein and/or mRNA in the needle washout may overcome this limitation.

The urokinase plasminogen activating system in thyroid cancer: clinical implications.

The urokinase plasminogen activator (uPA) system (uPAS) comprises the uPA, its cell membrane receptor (uPAR) and two specific inhibitors, the plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2). The uPA converts the plasminogen in the serine protease plasmin, involved in a number of physiopathological processes requiring basement membrane (BM) or extracellular matrix (ECM) remodelling, including tumor progression and metastasis. The tumor-promoting role of PAS is not limited to the degradation of ECM and BM required for local diffusion and spread to distant sites of malignant cells, but widens to tumor cell proliferation, adhesion and migration, intravasation, growth at the metastatic site and neoangiogenesis. The relevance of uPAS in cancer progression has been confirmed by several studies which documented an increased expression of uPA, uPAR and PAI-1 in different human malignancies, and a positive correlation between the levels of one or more of them and a poor prognosis. For these reasons, the uPAS components have aroused considerable interest as suitable targets for anticancer therapy, and several pharmacological approaches aimed at inhibiting the uPA and/or uPAR expression or function in preclinical and clinical settings have been described. In the present manuscript, we will first glance at uPAS biological functions in human cancer progression and its clinical significance in terms of prognosis and therapy. We will then review the main findings regarding expression and function of uPAS components in thyroid cancer tissues along with the experimental and clinical evidence suggesting its potential value as molecular prognostic marker and therapeutic target in thyroid cancer patients.

Surgical strategies in patients with medullary thyroid carcinoma.

OBJECTIVES: Aim of the study was to identify, in 59 operated patients affected by medullary thyroid carcinoma (MTC), the recurrence rate, survival, mortality and incidences of surgically derived hypoparathyroidism and recurrent laryngeal nerve injury (RLNI). MATERIALS AND METHODS: Based on pre-surgical diagnosis of the 59 patients included in the study, 35 underwent total thyroidectomy with central neck dissection (Group A), 14 total thyroidectomy, central neck dissection and monolateral functional neck dissection (Group B) and 10 total thyroidectomy central neck dissection, bilateral functional neck dissection (Group C). Overall survival, recurrences, incidence of hypoparathyroidism and RLNI were evaluated. RESULTS: The survival and recurrences were not statistically different among the three Groups. In Group B there was major probability of re-operation (p=0.042). The mortality rate was clearly major in Group C (p=0.003) due to the stage of pathology. Group C showed a high number of hypoparatiroidism compared to Group B, and B compared to A. In Group A there was only one unexpected RLNI; in 5 cases, 3 in Group B and 2 in Group C, there were a necessity laringeal section due to nerve tumor involvement. CONCLUSIONS: From our data it appears clearly that disease outcome following the different surgical approaches is mainly determinated by the stage of the disease at diagnosis. However, the finding that patients in Group A and B showed a high rate of local-regional recurrences may suggest that homolateral lymphadenectomy in Group A patients and bilateral lymphadenectomy in Group B patients should be always performed.

Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines.

OBJECTIVES: Anaplastic thyroid carcinomas (ATC) are highly aggressive tumours unresponsive to any available radio- or chemotherapeutic protocol, with a median survival rate of 4-5 months from the time of diagnosis. We previously demonstrated that ATC are characterized by increased expression of the kinases Aurora-A, -B and -C, involved in the regulation of multiple steps of the mitotic phase. In this study, the in vitro effects of SNS-314 mesylate, a pan-inhibitor of the Aurora kinases, on growth and tumorigenicity of ATC cells were evaluated. MATERIALS AND METHODS: The effects of SNS-314 mesylate were assessed on the ATC derived cell lines CAL-62, 8305C, 8505C and BHT-101 by means of cell proliferation assay, immunofluorescence, cytofluorimetry, time lapse microscopy, and colony formation in soft agar. RESULTS: Treatment of the different ATC cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC(50) comprised between 2.6 nM and 26.6 nM. CAL-62 cells exposed for 24 h to SNS-314 mesylate 100 nM evidenced a significant augmentation of the apoptotic index. Time-lapse video-microscopy of CAL-62 cells showed that SNS-314 mesylate prevents the completion of mitosis leading to polyploidy. Western blot experiments demonstrated that the auto-phosphorylation of the Aurora kinases as well as histone H3 phosphorylation in CAL-62 treated cells was inhibited. Finally, the drug inhibited colony formation in soft agar of all cell lines. CONCLUSIONS: Our results demonstrated that SNS-314 mesylate is capable to efficiently reduce cell growth and tumorigenicity of different ATC derived cell lines suggesting its potential therapeutic value for ATC treatment.

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (β = 1.416, P = 0.039) and body mass index (β = 0.390, P < 0.001), and was also inversely associated with adiponectin (β = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation.

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (ß = 1.416, P = 0.039) and body mass index (ß = 0.390, P < 0.001), and was also inversely associated with adiponectin (ß = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.