Current practices of identifying and treating small indolent thyroid cancers constitute an important but in some ways unusual form of overdiagnosis. Overdiagnosis refers to diagnoses that generally harm rather than benefit patients, primarily because the diagnosed condition is not a harmful form of disease. Patients who are overdiagnosed with thyroid cancer are harmed by the psycho-social impact of a cancer diagnosis, as well as treatment interventions such partial or total thyroidectomy, lifelong thyroid replacement hormone, monitoring, surgical complications (...) and other side effects. These harms seem to outweigh any putative benefit of knowing about a cancer that would not have caused problems if left undiscovered. In addition to harms to patients, thyroid cancer overdiagnosis leads to significant opportunity costs at a societal level, due to costs of diagnosis and treatment. Unlike many other overdiagnosed cancers, accurate risk stratification is possible with thyroid cancer. At the individual patient level, use of this risk information might support informed choice and/or shared decision-making, as mandated by clinical ethics frameworks. And this approach might, to some extent, help to reduce rates of diagnosis and intervention. In practice, however, it is unlikely to stem the rising incidence and associated harms and costs of overdiagnosed thyroid cancer, especially in situations where health professionals have conflicts of interest. We argue in this article that thyroid cancer overdiagnosis may be usefully understood as a public health problem, and that some public health approaches will be readily justifiable and are more likely to be effective in minimising its harms. (shrink)

The evolutionary origins of several vertebrate organs are still controversial. The thyroid is classically thought to derive directly from the endostyle (a pharyngeal organ found in urochordates, cephalochordates and lampreys). Several molecular and biochemical lines of evidence agree with this scenario. However, a recent paper,1 describing the expression of a FoxE ortholog in amphioxus, suggests that some molecular pathways might actually have been recruited from an adjacent region of the pharynx. Although additional data from urochordates and lamprey are needed (...) to confirm this hypothesis; these results propose an interesting new scenario for thyroid evolution that involved the reorganisation of genetical and morphological features in the pharyngeal endoderm in order to give rise to a entirely new organ. They also give an indication that the ancestral role of the FoxE gene family was probably limited to the differentiation of part of the pharynx. BioEssays 24:696–699, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Emotion-processing impairment represents a risk factor for the development of somatic illness, affecting negatively both health-related quality of life and disease management in several chronic diseases. The present pilot study aims at investigating the associations between alexithymia and depression, anxiety, and HRQoL in patients with Hashimoto’s thyroiditis ; examining the association between these three psychological conditions together with HRQoL, and thyroid autoantibodies status as well as thyroid echotexture in patients with HT; and comparing the intensity of all these (...) clinical psychological features in patients with HT versus controls. Twenty-one patients with serologically or ultrasonographically verified HT and 16 controls with non-toxic goiter or postsurgical hypothyroidism were recruited for this study. Serum thyrotropin and free thyroxine, as well as thyroid autoantibodies, were assayed. Alexithymia, depression, anxiety, and HRQoL were assessed with Toronto Alexithymia Scale; Beck Depression Inventory, second edition; Hamilton Anxiety Rating Scale; and Health Survey Short-Form 36, respectively. A negative relationship between the difficulty to describe feelings and the cognitive component of depression was found. Besides, patients with seronegative HT had lower somatic anxiety than patients with HT who tested positive. Besides, no statistically significant difference was found between patients with HT and controls with regard to somatic anxiety. The present study suggests the relevance of alexithymia in patients suffering from HT, which may be intertwined with a possible state of underreported depression that is mainly expressed through physical complaints. Promoting the capability to describe and communicate feelings could contribute to psychological elaboration and coping with the disease and, consequently, to the improvement of self-management and perceived HRQoL. (shrink)

Skeletal myoblasts have their origin early in embryogenesis within specific somites. Determined myoblasts are committed to a myogenic fate; however, they only differentiate and express a muscle‐specific phenotype after they have received the appropriate environmental signals. Once proliferating myoblasts enter the differentiation programme they withdraw from the cell cycle and form post‐mitotic multinucleated myofibres (myogenesis); this transformation is accompanied by muscle‐specific gene expression. Muscle development is associated with complex and diverse protein isoform transitions, generated by differential gene expression and mRNA (...) splicing. The myofibres are in a state of dynamic adaptation in response to hormones, mechanical activity and motor innervation, which modulate differential gene expression and splicing during this functional acclimatisation. This review will focus on the profound effects of thyroid hormone on skeletal muscle, which produce alterations in gene and isoform expression, biochemical properties and morphological features that precipitate in modified contractile/mechanical characteristics. Insight into the molecular events that control these events was provided by the recent characterisation of the MyoD gene family, which encodes helix‐loop‐helix proteins; these activate muscle‐specific transcription and serve as targets for a variety of physiological stimuli. The current hypothesis on hormonal regulation of myogenesis is that thyroid hormones (1) directly regulate the myoD and contractile protein gene families, and (2) induce thyroid hormone receptor‐transcription factor interactions critical to gene expression. (shrink)

Amphibian metamorphosis is a post‐embryonic process that systematically transforms different tissues in a tadpole. Thyroid hormone plays a causative role in this complex process by inducing a cascade of gene regulation. While natural metamorphosis does not occur until endogenous thyroid hormone has been synthesized, tadpoles are competent to respond to exogenous thyroid hormone shortly after hatching. In addition, even though the metamorphic transitions of individual organs are all controlled by thyroid hormone, each occurs at distinct developmental (...) stages. Recent molecular studies suggest that this competence of premetamorphic tadpoles to respond to the hormone and the developmental stage‐dependent regulation of tissue‐specific transformations are determined in part by the levels of thyroid hormone receptors and the concentrations of cellular free thyroid hormone. In addition, at least two genes, encoding a cytosolic thyroid hormone binding protein and a 5‐deiodinase, respectively, are likely to be critical players in regulating cellular free thyroid hormone concentrations. This review discusses how all of these molecuar components coordinate to induce amphibian metamorphosis in a correct spatial and temporal manner. These studies provde us with general clues as to how and why tissues become competent to respond to hormonal signals. (shrink)

In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine (L-T4) is aimed to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than (...) preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective. (shrink)

ObjectiveWe aim to investigate the feasibility of using diffusion tensor imaging to evaluate changes in extraocular muscles and lacrimal gland in patients with thyroid-associated ophthalmopathy and to evaluate disease severity.Materials and MethodsA total of 74 participants, including 17 healthy controls, 22 patients with mild TAO, and 35 patients with moderate-severe TAO, underwent 3-Tesla DTI to measure fractional anisotropy and mean diffusivity of the EOMs and LG. Ophthalmological examinations, including visual acuity, exophthalmos, intraocular pressure, and fundoscopy, were performed. FA and (...) MD values were compared among patients with different disease severity. Multiple linear regression was adopted to predict the impact of clinical variables on DTI parameters of orbital soft tissue.ResultsTAO patients’ EOMs and LG showed significantly lower FA values and higher MD compared to HCs’. Moderate-severe TAO patients’ EOMs and LG had dramatically lower FA and higher MD compared with HCs. In addition, only the DTI parameters of the medial rectus were considerably different between mild and moderate-severe TAO patients. Multiple linear regression showed that disease severity had a significant impact on the DTI parameters of orbital soft tissue.ConclusionDTI is a useful tool for detecting microstructural changes in TAO patients’ orbital soft tissue. DTI findings, especially medial rectus DTI parameters, can help to indicate the disease severity in TAO patients. (shrink)

Alpha‐fetoprotein (AFP)AFP, alpha‐fetoprotein; T3R, thyroid hormone (triiodothyronine) receptor; RAR, retionic acid receptor; erbA, putative thyroid hormone receptor proto‐oncogene products; VDR, vitamin D receptor; MR, mineralocorticoid receptor; GR, glucocorticoid receptor; PR, progesterone receptor; AR, androgen receptor; HRE, hormone response element on DNA; RXR, retionic‐X‐receptor; RAP, receptor auxiliary (accessory) proteins; E, estrogen. is a tumor‐associated fetal marker, associated both with tumor growth and with birth defects. AFP, whose precise function is unknown, has been classified as belonging to a protein superfamily (...) together with albumin and vitamin D‐binding (Gc) protein. AFP has been shown to bind various ligands in vitro including fatty acids, estrogens, thyroid hormones and retinoic acids. The steroid/thyroid nuclear receptor superfamily of proteins has recently become a major focus of biomedical investigation regarding regulation of gene expression. These receptors are thought to bind to DNA‐hormone response elements (HRE) that affect growth, development, differentiation, reproduction and homeostasis. The HREs are known to share DNA sequences with the various members of the nuclear receptor superfamily. In the present report, the possibility of a leucine‐zipper dimerization (heptad) motif in the carboxy‐terminal third domain of both rodent and human AFP is postulated. The presence of nine such hydrophobic repeats in the third domain of the AFP molecule mimics the heptad dimerization repeats found in the retinoic acid, thyroid, e‐erbA and other members of the nuclear receptor superfamily. Computer analysis revealed that the most conservative matching occurred between AFP and the retinoic acid class of receptors. However, other superfamily members displayed 40–60% homology with 5 of 9 AFP heptads. These findings could provide a possible mechanism for explaining the growth‐regulatory properties (both inhibition and enhancement) that have been ascribed to AFP in the last decade. (shrink)

BackgroundDiagnosis and treatment of differentiated thyroid carcinomas cause anxiety and depression. Additionally, these patients suffer hormonal alterations that are associated with psychological symptoms. This study aims to evaluate the effectiveness of a psycho-oncological intervention based on counseling to reduce anxiety and depression related to the treatment in patients with DTC.MethodsA non-randomized controlled study, with two groups [experimental group, n = 37, and control group, n = 38] and baseline and posttreatment measures, was designed. Patients in the EG received a (...) psycho-oncological intervention based on counseling in addition to the standard treatment. The independent variable was the assigned group and the dependent one was the evolution of anxiety and depression, which were analyzed separately, and both were evaluated using the Hospital Anxiety and Depression Scale. Other relevant covariables related to the quality of life were also analyzed using Short Form-36 Health Survey and Psychological General Wellbeing Index scales.ResultsThe difference of the posttreatment-baseline variation showed a statistically significant reduction in anxiety and depression in the EG in relation to the CG. The mean of the Psychological General Wellbeing Index scales score increased significantly in the EG and decreased significantly in the CG. All the baseline and the posttreatment scores of the variables evaluated showed a statistically significant improvement in the EG vs. the CG.ConclusionThis study demonstrates significant benefits of psycho-oncological intervention based on counseling in anxiety, depression, QoL, and wellbeing of the patient with differentiated thyroid carcinomas. (shrink)

PurposeThyroid-associated ophthalmopathy is a vision threatening autoimmune and inflammatory orbital disease, and has been reported to be associated with a wide range of structural and functional abnormalities of bilateral hemispheres. However, whether the interhemisphere functional connectivity of TAO patients is altered still remain unclear. A new technique called voxel-mirrored homotopic connectivity combined with support vector machine method was used in the present study to explore interhemispheric homotopic functional connectivity alterations in patients with TAO.MethodsA total of 21 TAO patients and 21 (...) wellmatched healthy controls, respectively, underwent functional magnetic resonance imaging scanning in the resting state. We evaluated alterations in the resting state functional connectivity between hemispheres by applying VMHC method and then selected these abnormal brain regions as seed areas for subsequent study using FC method. Furthermore, the observed changes of regions in the VMHC analysis were chosen as classification features to differentiate patients with TAO from HCs through support vector machine method.ResultsThe results showed that compared with HCs, TAO patients showed significantly lower VMHC values in the bilateral postcentral gyrus, lingual gyrus, calcarine, middle temporal gyrus, middle occipital gyrus and angular. Moreover, significantly decreased FC values were found between the right postcentral gyrus/lingual gyrus/calcarine and left lingual gyrus/cuneus/superior occipital gyrus, left postcentral gyrus/lingual gyrus/calcarine and right lingual gyrus/ middle temporal gyrus, right middle temporal gyrus and left cerebellum-8/lingual gyrus/middle occipital gyrus/supplementary motor area, left middle temporal gyrus and right middle occipital gyrus, right middle occipital gyrus/angular and left middle temporal pole. The SVM classification model achieved good performance in differentiating TAO patients from HCs.ConclusionThe present study revealed that the altered interhemisphere interaction and integration of information involved in cognitive and visual information processing pathways including the postcentral gyrus, cuneus, cerebellum, angular, widespread visual cortex and temporal cortex in patients with TAO relative to HC group. VMHC variability had potential value for accurately and specifically distinguishing patients with TAO from HCs. The new findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO. (shrink)

We propose a biochemical mechanism for celiac disease and non‐celiac gluten sensitivity that may rationalize many of the extradigestive disorders not explained by the current immunogenetic model. Our hypothesis is based on the homology between the 33‐mer gliadin peptide and a component of the NMDA glutamate receptor ion channel – the human GRINA protein – using BLASTP software. Based on this homology the 33‐mer may act as a natural antagonist interfering with the normal interactions of GRINA and its partners. The (...) theory is supported by numerous independent data from the literature, and provides a mechanistic link with otherwise unrelated disorders, such as cleft lip and palate, thyroid dysfunction, restless legs syndrome, depression, ataxia, hearing loss, fibromyalgia, dermatitis herpetiformis, schizophrenia, toxoplasmosis, anemia, osteopenia, Fabry disease, Barret's adenocarcinoma, neuroblastoma, urinary incontinence, recurrent miscarriage, cardiac anomalies, reduced risk of breast cancer, stiff person syndrome, etc. The hypothesis also anticipates better animal models, and has the potential to open new avenues of research. (shrink)

The widespread adoption of radioisotopes as tools in biomedical research and therapy became one of the major consequences of the "physicists' war" for postwar life science. Scientists in the Manhattan Project, as part of their efforts to advocate for civilian uses of atomic energy after the war, proposed using infrastructure from the wartime bomb project to develop a government-run radioisotope distribution program. After the Atomic Energy Bill was passed and before the Atomic Energy Commission was formally established, the Manhattan Project (...) began shipping isotopes from Oak Ridge. Scientists and physicians put these reactor-produced isotopes to many of the same uses that had been pioneered with cyclotron-generated radioisotopes in the 1930s and early 1940s. The majority of early AEC shipments were radioiodine and radiophosphorus, employed to evaluate thyroid function, diagnose medical disorders, and irradiate tumors. Both researchers and politicians lauded radioisotopes publicly for their potential in curing diseases, particularly cancer. However, isotopes proved less successful than anticipated in treating cancer and more successful in medical diagnostics. On the research side, reactor-generated radioisotopes equipped biologists with new tools to trace molecular transformations from metabolic pathways to ecosystems. The U.S. government's production and promotion of isotopes stimulated their consumption by scientists and physicians, such that in the postwar period isotopes became routine elements of laboratory and clinical use. In the early postwar years, radioisotopes signified the government's commitment to harness the atom for peace, particularly through contributions to biology, medicine, and agriculture. (shrink)

Overdiagnosis refers to diagnosis that does not benefit patients because the diagnosed condition is not a harmful disease in those individuals. Overdiagnosis has been identified as a problem in cancer screening, diseases such as chronic kidney disease and diabetes, and a range of mental illnesses including depression and attention deficit hyperactivity disorder. In this paper, we describe overdiagnosis, investigate reasons why it occurs, and propose two different types. Misclassification overdiagnosis arises because the diagnostic threshold for the disease in question has (...) been set at a level where many people without harmful disease are nonetheless diagnosed. We illustrate misclassification overdiagnosis using the example of chronic kidney disease. Misclassification occurs in diseases diagnosed using biomarkers or based on patient reported phenomena. Maldetection overdiagnosis arises because, at the time the diagnosis is made and despite the presence of a 'gold standard' diagnostic test, it is not possible to discriminate between harmful and non-harmful cases of the index disease. We illustrate maldetection overdiagnosis using the example of thyroid cancer. While there is some overlap between misclassification and maldetection overdiagnosis, this conceptual analysis helps to clarify the phenomenon of overdiagnosis and is a necessary first step in developing strategies to address the problem. (shrink)

Cooption and modularity are informative concepts in evolutionary developmental biology. Genes function within complex networks that act as modules in development. These modules can then be coopted in various functional and evolutionary contexts. Hormonal signaling, the main focus of this review, has a modular character. By regulating the activities of genes, proteins and other cellular molecules, a hormonal signal can have major effects on physiological and ontogenetic processes within and across tissues over a wide spatial and temporal scale. Because of (...) this property, we argue that hormones are frequently involved in the coordination of life history transitions (LHTs) and their evolution (LHE). Finally, we promote the usefulness of a comparative, non-model system approach towards understanding how hormones function and guide development and evolution, highlighting thyroid hormone function in echinoids as an example. BioEssays 27:64–75, 2005. © 2004 Wiley Periodicals, Inc. (shrink)

Amal is a 27-year-old woman who has recently been diagnosed with a rare and aggressive type of thyroid cancer.1 She is also 12 weeks into her third pregnancy. Since her diagnosis, Amal and her husband have met with her oncologist multiple times to discuss several treatment options. Amal's oncologist recommends surgical resection of the tumor and radioactive iodine therapy, but that would require termination of the pregnancy, as iodine is contraindicated for pregnant women. Alternatively, Amal may elect to postpone (...) treatment until after her delivery; however, that could result in the growth and spread of the tumor. The oncologist encourages Amal and her husband to take some time to decide. They make plans to meet... (shrink)

During the 1890s, animal development became associated with glandular activity, with profound implications for pediatric nosology and treatment. The significance of this endocrinological turn of developmental physiology and pathophysiology in part hinges on an often-overlooked continuity with ubiquitous early modern medical thought concerning semen as a recrementitious (reabsorbed) nutrient or stimulant. Mid-19th-century interests in adult sexual physiology were increasingly nerve-centered and antihumoral. Scattered empirical, particularly veterinarian, interests in gonadal developmental functions failed to moderate these explanatory trends. While Brown-Séquard’s rejuvenation experiments (...) still offered no clear starting point for a developmental endocrinology, in 1892 Gaston Variot and Paul Bezançon more explicitly deduced a testicular developmental endocrinological function from various observations on testicular ectopy and a local form of animal “demi-castration.” Ensuing interest in the thyroid, the thymus and in the testicles led to various working conceptions of their respective and putatively reciprocal developmental properties, including the idea of a thyroid–testis axis. From 1896, the pubertal affliction of chlorosis became the subject of multiple opotherapeutic approaches, providing an experimental basis for theories of ovarian internal secretion. Polyglandular therapy, piloted for divergent developmental conditions, remained routine until the 1930s despite the biological inefficacy of many endocrine products. (shrink)

The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which (...) it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g. enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional, and psychological health.Also watch the Video Abstract. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:From Impatience to EmpathyStephanie Pierce and Kavita Shah AroraWe gave J.H. a label the first time we met her, as many often do—“Uncooperative.” She was a patient with autism and intellectual delay who had presented to the emergency department (ED) with vaginal bleeding. After receiving the gynecology consult request from the emergency medicine physicians, we were already mentally formulating our recommendations based on the information they told us over (...) the phone. “Does not cooperate with exam,” “no acute surgical intervention is currently warranted,” and “recommend outpatient follow–up.”When we arrived in her room, she was sitting in the hospital bed surrounded by a protective shield of caregivers from her group home. We introduced ourselves as the gynecology team but it was obvious that J.H. could not communicate verbally. Upon speaking with her caregivers we learned that she had Cowden syndrome, a genetic disease that confers significantly increased risks for several types of cancer including endometrial, thyroid, and breast cancers. J.H. had also been having heavy vaginal bleeding, which was difficult for her caregivers to manage, and this was the reason she was brought into the emergency department. After attempting to gain as much information as we could from the caregivers, we started to perform an abdominal exam, which made J.H. extremely agitated. We quickly stopped the exam and the caregivers helped to calm J.H. We remember our mixture of emotions—bewilderment at the agitation and commotion in the exam room full of people, frustration at not being able to complete our exam fully, and annoyance that this “difficult patient” was taking up our limited time between surgical cases. Thankfully, these knee–jerk reactions were quickly replaced by feelings of concern for the patient and the realization of how frightening an experience this must be for her—being in a strange place with white walls and unfamiliar people, unable to communicate her thoughts.J.H.’s mother, her surrogate decision–maker, was not at the hospital that day but the caregivers told us that she had expressed a strong desire for her daughter to have a prophylactic hysterectomy due to her lifetime risk for developing uterine cancer as well as a permanent solution to the bleeding concerns. What had initially started as a simple ED consult was now turning into a complex question. The ethical and legal dilemma was obvious—whether to perform a major surgery that would irreversibly sterilize a patient who could not consent on her own behalf in order to minimize the potential risk of cancer later in life. While medical management could improve the bleeding and potentially reduce the risk of cancer, frequent exams would be necessary [End Page 19] to ensure that the medication was working and that premalignant changes were not occurring in J.H.’s uterus. However, based on our experience in the emergency department, J.H. would need anesthesia for such exams and it was doubtful the medications would completely normalize her elevated risk of uterine malignancy. We knew that in order to address this question, we would need to see J.H. again along with her mother to have a frank discussion about the risks and benefits of such a decision, and so we made plans to see her in our outpatient clinic.Several days later, J.H., her mother, and the group home caregivers arrived in the office. Anticipating a complex discussion, we had requested a representative from the hospital ethics committee to join us at the visit. We didn’t know what to expect meeting J.H.’s mother for the first time but as we sat in the room talking, it was obvious that she was truly trying to act in her daughter’s best interest. Similarly, it was touching to watch the faces of the caregivers from the group home as they nodded in solidarity with J.H.’s mother, also clearly wanting what was best for her and supporting her mother in this difficult decision. J.H., meanwhile, seemed content to sit silently with us during the discussion, surrounded as she was by people who cared deeply for her well–being.After extensive partnership with the ethics consultants... (shrink)

E4BP4, a mammalian basic leucine zipper (bZIP) transcription factor, was first identified through its ability to bind and repress viral promoter sequences. Subsequently, E4BP4 and homologues in other species have been implicated in a diverse range of processes including commitment to cell survival versus apoptosis, the anti‐inflammatory response and, most recently, in the mammalian circadian oscillatory mechanism. In some of these cases at least, E4BP4 appears to act antagonistically with members of the related PAR family of transcription factors with which (...) it shares DNA‐binding specificity. This diversity of function is mirrored by the regulatory pathways impinging on E4BP4, which include regulation by ras via the lymphokine IL‐3 in murine B‐cells, by thyroid hormone during Xenopus tail resorption, by glucocorticoids in murine fibroblasts and by calcium in rat smooth muscle cells. This article will cover the unfolding role/s of and regulation of E4BP4, E4BP4‐like proteins and PAR factors in species as diverse as mouse and C. elegans. BioEssays 24:1023–1029, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

An extensive, and controversial, literature concluding that prolactin (PRL), growth hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid hormones are critical immunoregulatory factors has accumulated. However, recent studies of mice deficient in the production of these hormones or expression of their receptors indicate that there are only a few instances in which these hormones are required for lymphocyte development or antigen responsiveness. Instead, a case is made that their primary role is to counteract the effects of negative immunoregulatory factors, (...) such as glucocorticoids, which are produced when the organism is subjected to major stressors. The immunoprotective actions of PRL, GH, IGF-I, and/or thyroid hormones in these instances may ensure immune system homeostasis and reduce the susceptibility to stress-induced disease. These immuno-enhancing effects could be exploited clinically in instances where the immune system is depressed due to illness or various treatment regimens. BioEssays 23:288–294, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Multicellular organisms develop on a predictable schedule that depends on both cell‐intrinsic timers and sequential cell‐cell interactions mediated by extracellular signals. The interplay between intracellular timers and extracellular signals is well illustrated by the development of oligodendrocytes, the cells that make the myelin in the vertebrate central nervous system. An intrinsic timing mechanism operates in each oligodendrocyte precursor cell to limit the length of time the cell divides before terminally differentiating. This mechanism consists of two components, a timing component, which (...) depends on the mitogen platelet‐derived growth factor (PDGF) and measures elapsed time, and an effector component, which depends on thyroid hormone and stops cell division and initiates differentiation at the appropriate time. The cell‐cycle inhibitor p27/Kip1 accumulates in the precursor cells as they proliferate and is part of both components of the timer. It seems likely that similar timing mechanisms operate in other cell lineages. BioEssays 22:64–71, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 until 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed (...) in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies. (shrink)

The interconnection of scientific studies and art represented by Leonardo Da Vinci’s portraiture accentuates his role in documenting and archiving dermatologic conditions. His anatomical dissections, sketches, and paintings, including portraits, were all a means to observe, portray, and understand the nuances of the human body. In two of his most discussed portraits, Ginevra de’ Benci and Elisabetta del Giocondo, the Mona Lisa, Leonardo’s execution of the exterior anatomy is so precise that he may have illustrated manifestations of disease that allow (...) contemporary researchers to theorize diagnoses of dermatologic as well as neurologic, endocrine and vascular conditions. These include hypochromic anemia, muscular disorders, xanthelasma, thyroid disease, lipoma, and frontal fibrosing alopecia. Leonardo’s extraordinary talent in recording his observations of shades and textures of skin and his ability to capture the nuances of subtle variations in the human body have produced a historical record that allows modern dermatology practitioners to make further observations not possible in his time. Here, dermatology and art intersect serving to document and explain the human condition, permanently archived in Leonardo’s masterpieces. (shrink)

The Brain Death Reconsidered – Is It a Tenable Concept? Since 1968 it has been recognized in the medical practice that irreversible coma connected with apnea can serve as a criterion of human death. This approach was first introduced in the so called Harvard Protocol. As a result of the work of this commission, the brain-based criteria of human death were quickly legally introduced in America and in most countries in the world. The only symptom on which death can be (...) pronounced is, according to this new definition, the absence of spontaneous brain function. However, the acceptance of the new definition of death did not eliminate the old one completely. In many states both old and new definitions of death are legally valid. Practically, in these countries the alternative definition of death functions alongside the old one and diagnosis of death can be based both on the cardiac/respiratory and brain symptoms. One of the few exceptions proved to be Japan. The law in this country does not provide a uniform answer to the question of what human death is. Instead, it allows people to choose between traditional death and brain death. The law states that if a person wants to be an organ donor after brain death has occurred, he or she must record that intention on a donor card or label beforehand. Those who object to brain death and transplantation do not need donor cards. They are considered to be alive until the heart stops beating. In this way the Japanese law respects the opinion of 20-40% of the society who do not believe in the brain death. The opinion of the same percentage of people in Western societies who oppose BD is ignored by their legal systems. Initially the concept of BD did not cause a lot of controversy but this situation changed in the nineties of the last century. Since then many authors have criticized the validity of the brain-based criteria of death. They maintain that it is impossible to declare the absence of all the functions of the whole brain on the basis of the clinical tests supposed to detect it. There may be present some level of consciousness in brain death (BD) patients and therefore, they may feel pain. It is significant that 27% of the members of the teams which perform the excision of the heart for transplantation think that they are killing a living person and that in many countries during this operation a normal general anesthesia is required because of the vivid reaction of the body of the patient. The opponents of the brain death theory stress that the accurate examination of the so-called brain dead persons shows the persistence of the functions of significant parts of their brains. There are EEG waves recorded in 20-40% of BD patients. Event related potentials (ERP) show the reaction to verbal and non-verbal stimuli and the hormone production by the brain tissue can be detected in many BD people. The proper treatment could not only significantly prolong lives of the BD patients, but around 60% of possible donors with the lowest result of 3 in Glasgow Coma Scale could be restored to normal life if their brain edema is properly treated. This treatment should be based on the therapeutic hypothermia connected with the application of the thyroid hormones, whose level is usually too low in the patients with the brain injury. There is a growing lack of consensus regarding the issue of brain death, especially among physicians. Some regard brain death as a biological one, some as the death of the person but not of the human body, and the rest, as a definition accepted by the society, which doesn’t require other legitimacy than the freely chosen criteria. The brain death concept is also criticized from the philosophical point of view. The strength of the brain death theory was based on the premise that the brain is the integrating center of the body. According to this argument, the death of the brain means that the organism ceases to exist for it is no longer a functioning whole. To this argument the opponents of the brain death concept say that this question is not a question a priori but an empirical one and that the empirical data validate the opposite opinion, which says that the bodies of brain dead patients are alive. Some widely known cases show that even the real death of the entire brain means the death of the body and, therefore, may not signify the death of a human person. The integration of the body is the function of the organism as a whole and not of a single organ, even if this organ is the brain. This point of view can be confirmed by the opinion of St. Thomas Aquinas who says that the soul is primarily and per se connected with the body as a whole as the proportionate perfectible and only secondarily with the parts of the body, according to their ordination to the whole. So, the death of any single organ does not preclude the union of the soul with the rest of the body as a living whole. Moreover, the terms such as “consciousness” and “person” should not be identified. The term such as “human living nonpersons”, proposed by some bioethicists and referring to the people without consciousness has not been accepted in the official documents concerning BD. Bodies of the BD people are alive, therefore, it is not right to use the term “brain death” to describe the state of these patients, but rather the term “brain failure” should be used. As the result, according to some authors, the dead donor rule should be abolished. The Catholic Church stresses the sacredness of the human life from the beginning to the end. Therefore She requires that there be no doubts that the donor in BD is really dead. Because of the lack of consensus among physicians, philosophers and theologians, the popes John Paul II and Benedict XVI decided to continue the scientific research and discussion concerning BD between the representatives of various disciplines. Keywords: brain death, brain edema, global ischemic penumbra, therapeutic hypothermia, consciousness, person, substantial form. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Nuclear Power after Fukushima 2011:Buddhist and Promethean PerspectivesGraham ParkesDuring 2010 many environmentalists previously opposed to nuclear power were deciding, in the face of anthropogenic climate change from burning fossil fuels, that the only way to prevent runaway global warming would be to build more nuclear power plants after all.1 There are risks involved—though fewer than with carbon-based sources of energy.2 When one compares the detrimental effects of nuclear power (...) with those of burning fossil fuel, it is clear that the human injury and death toll (not to mention environmental devastation) resulting from the former have been nothing compared to the damage caused by the extraction and consumption of fossil fuels, owing to mining accidents, oil spills, and so forth—not to mention the massive carbon dioxide emissions.On the other hand, the problem of how and where to store the growing amount of radioactive waste from nuclear power plants, which remains deadly for many thousands of years, has yet to be solved. Costly security measures have to be taken to guard against terrorist attacks and theft of materials usable for nuclear devices. When full safety features are included, nuclear power plants become ever more expensive to build, and the costs of insuring them against accidents are so prohibitive that governments have to subsidize them, which they are increasingly unwilling to do.Not long after the explosions and meltdowns at the Fukushima Daiichi nuclear power station in March 2011, two dismal world records were announced: in 2010 we discharged a record amount of carbon dioxide (more than 30 gigatons) into the atmosphere, mainly by burning fossil fuels, and, as a direct consequence, carbon dioxide levels in the atmosphere (as measured at the Earth Systems Research Laboratory in Hawai'i) reached a record level of 395 parts per million. These figures suggest that we are continuing to generate a rise in global average temperatures that is already destroying the livelihoods of millions and will soon jeopardize the lives of hundreds of millions more.As a consequence of the 2011 Fukushima disaster, Japan—long a leading promoter of nuclear power—has begun to enforce some widely neglected safety regulations and is seriously reconsidering its reliance on nuclear energy. China has put construction of [End Page 89] new power plants on hold. Other nations (such as Germany, Italy, Switzerland, Thailand, and Malaysia) have decided to phase out or cancel plans to build more nuclear power stations. Yet the primary motivations remain unclear, since people's attitudes toward the dangers of nuclear radiation are anything but rational—as evidenced by the mass departure of foreigners from Japan after the catastrophe at Fukushima, when health dangers beyond the vicinity of the power station were minimal.In Europe, the reaction to the Fukushima disaster has clearly been aggravated by memories of the catastrophe at Chernobyl in 1986. While Chernobyl was a more widely destructive event than Fukushima, releasing a much greater amount of radioactivity, its effects on human health continue to generate disagreement. According to the third report on the effects of the Chernobyl catastrophe issued by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), among the 134 plant staff and emergency workers who suffered acute radiation syndrome (ARS), the condition proved fatal for twenty-eight of them. By 2006 another nineteen ARS survivors died, although their deaths were not directly attributable to the effects of ionizing radiation. Although the report attributes "a substantial fraction" of the six thousand cases of thyroid cancer in people who were children at the time of the accident to their consumption of milk contaminated with iodine-131, only fifteen cases had proved fatal by 2005, some twenty years later.3 The death toll, then, was fewer than fifty.By contrast, a study by a group of scientists from Belarus, Russia, and the Ukraine, Chernobyl: Consequences of the Catastrophe for People and the Environment, estimates the number of deaths attributable to the meltdown at around 980,000—almost twenty thousand times greater than the estimate by the UN scientific committee.4 What are we to make of this vast discrepancy, especially since the UNSCEAR report "was prepared in close cooperation with... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:From Linguistic Bridge Builder to Aspiring PhysicianManuel PatiñoI have been formally working as a medical interpreter for 2.5 years, but I have been closing linguistic bridges for as long as I can remember. My parents are from Colombia, and they immigrated to Boston in the late nineties, where I was born some years later. As the oldest son born in the US, I grew up as the only fluent (...) English speaker at home. This meant that I was the first person my [End Page 161] parents would turn to for any help with the language—doing taxes, filling out legal paperwork, or emailing their bosses. They would also turn to me to learn more about and understand their chronic medical conditions outside of the hospital.I remember coming home from school one day in 8th grade to my dad asking me: "¿Manu, me ayudas a traducir estos resultados?" He was pondering his recent lumbar spine MRI report and asked me to help him translate and interpret the medical jargon, and I gladly agreed. However, my fourteen-year-old brain drew a blank when thinking about how to translate "herniated discs" and "pinched nerve." I turned and gave my dad a fragmented Spanish translation of the MRI report, to which he nodded for some portions, stared blankly for others, and finally thanked me with a warmness that could not mask his confusion. It pained me to know that I wasn't able to help my dad understand what had been causing him severe pain in the previous months.Growing up, experiences like these lit a fire under me and fueled my desire to pursue a career in medicine so I could one day give my parents the care they deserved. In college, I took my premedical coursework with the intention of taking a couple of years before medical school to work and save up money. I wasn't sure what I would do for my gap years until my mom took an online medical interpreting course during my junior year. At the time, she worked as a patient transporter, and decided to take this course to improve her English. Since I was doing remote schooling during the pandemic, I spent many hours at home helping her prepare for her weekly assessments. By learning about the medical and sociocultural skills that interpreters must have to effectively serve patients, I became interested in diving into the interpreting world myself. In particular, I was drawn to how crucial it is for interpreters to not only overcome linguistic barriers, but also to navigate social and cultural disconnects between Western medical practices and those of Latin America.Motivated to learn more, I took the same online course in Spring of 2021 and absolutely loved it. At several points, I thought to myself: "Why hadn't I thought about medical interpreting sooner?" For me, it was the perfect combination of all my interests: using my bilingualism on a daily basis, learning in a medical setting, and serving my local Hispanic communities. After finishing the course, I cold-emailed the Head of Interpreting at my university's local hospital to see if they had any perdiem positions available. Luckily, they did! After two months of interpreting exams, paperwork, and onboarding, I was given a shiny new badge that read: "Manuel Patiño, Interpreter I."I still remember my first appointment as an official interpreter. It was for a young man—let's call him Juan—looking to freeze his sperm in anticipation of radioactive treatment for thyroid cancer. I had arrived a couple of minutes late to the waiting room since it was my first time going to the radiology-oncology department. When I introduced myself to Juan, his face lit up as if we'd known each other for years. He expressed how uneasy he was feeling at the prospect of going through this appointment with his limited English, and thanked me many times for my presence. Though I don't remember the specifics of the appointment, I often think back to Juan's beaming face upon seeing me and the faith and trust he had in me to be his linguistic bridge... (shrink)

Retinoids play an important role in development and differentiation(1,2). Their effect is mediated through nuclear receptors, RAR (α, β and γ) and RXR (α, β and γ),Abbreviations. RAR: retinoic acid receptor; RXR: retinoid X receptor; T3:thyroid hormone receptor; VD3R: vitamin D3 receptor; PPAR: peroxisome proliferator activated receptor; EcR ecdycsone receptor; USP, ultraspiracle; NGFI‐B: also referred to as nur77a; ELP: embryonal long terminal repeat‐binding protein; FTZ‐F1: positive regulator of the fushi tarazu gene in blastodermstage embryos of Drosophila melanogaster; GR: glucocorticoid (...) receptor; ER: estrogen receptor; RARE, retinoic acid response element; PR: progesterone receptor; DR+x: direct repeat with a spacing of x nucleotides; DBD: DNA‐binding domain; CRABP I and II: cellular retinoic acid binding protein type I and II, respectively; MoMLV: Moloney Murine Leukemia Virus; TBP: TATA‐binding protein; TAF: TBP associated factor. which are members of a distinct subclass (hereafter referred to as type II) of the nuclear receptor superfamily that includes the thyroid hormone receptor (T3R), the vitamin D3 receptor (VD3R) and the peroxisome proliferator activated receptor (PPAR). Type II receptors transactivate through binding sites composed of closely related half‐sites (consensus sequence AGG/T TCA) arranged as direct repeats and, with the possible exception of RXR, do not bind to their cognate binding sites as homodimers but require RXR for high affinity binding. RXR thus provides a link between biologically distinct ligand induced pathways and is a potential target for cross‐regulation. In addition, RAR can utilize alternative routes to enhance transcription initiation mediated through transcriptional co‐activators which are expressed in a cell‐type specific manner. (shrink)

In his World Culture and the Black Experience Professor Ali Mazrui states that “by being left behind scientifically African languages gradually became incapable either of coping with or stimulating new areas of reflection and analysis”. He agrees with Professor Mohammed Hyder of Nairobi that “if a serious attempt were made to develop a ‘technical limb’ to Swahili, this would indeed be possible” by the simple device of writing redioaktivu for radioactive and thairodi for thyroid and so forth. He thinks, (...) however, that “the majority of African languages have too few speakers to warrant a serious undertaking to convert them into scientific and technological languages.” In any case such an attempt “would be an extreme form of cultural autarchy”. (shrink)

The structural-parametric synthesis of neural networks of deep learning, in particular convolutional neural networks used in image processing, is considered. The classification of modern architectures of convolutional neural networks is given. It is shown that almost every convolutional neural network, depending on its topology, has unique blocks that determine its essential features, Residual block, Inception module, ResNeXt block. It is stated the problem of structural-parametric synthesis of convolutional neural networks, for the solution of which it is proposed to use a (...) genetic algorithm. The genetic algorithm is used to effectively overcome a large search space: on the one hand, to generate possible topologies of the convolutional neural network, namely the choice of specific blocks and their locations in the structure of the convolutional neural network, and on the other hand to solve the problem of structural-parametric synthesis of convolutional neural network of selected topology. The most significant parameters of the convolutional neural network are determined. An encoding method is proposed that allows to repre- sent each network structure in the form of a string of fixed length in binary format. After that, several standard genetic operations were identified, i.e. selection, mutation and crossover, which eliminate weak individuals of the previous generation and use them to generate competitive ones. An example of solving this problem is given, a database of patients with thyroid disease was used as a training sample. (shrink)

Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, (...) we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms—as discussed in the contemporary philosophy of science—may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched “flat”, i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams. (shrink)

More than 10,000 people have died in the Japanese tsunami, and the survivors are cold and hungry. But the media concentrate on nuclear radiation from which no one has died—and is unlikely to. Nuclear radiation at very high levels is dangerous, but the scale of concern that it evokes is misplaced. Nuclear technology cures countless cancer patients everyday—and a radiation dose given for radiotherapy in hospital is no different in principle to a similar dose received in the environment. What of (...) Three Mile Island? There were no known deaths there. And Chernobyl? The most recent UN report confirms the known death toll—28 fatalities among emergency workers plus 15 fatal cases of child thyroid cancer—which would have been avoided if iodine tablets had been taken. And in each case, the numbers are minute compared with the 3,800 people at Bhopal in 1984 who died as a result of a leak of chemicals from the Union Carbide pesticide plant. (shrink)

This full-color, user-friendly book features simple meridian exercises that combine breathing, movement, stretching, and focused attention to improve overall balance and flexibility. The book identifies specific meridian exercises to alleviate common ailments, including headaches, colds, and the flu, as well as more serious conditions, such as high blood pressure, diabetes, and thyroid disorders. Meridian exercise is a technique developed and perfected over the course of thousands of years in the Asian healing arts traditions. This book includes the following features: (...) Low-impact, time-efficient exercises that relieve stress, restore physical health, and rebalance the mind Step-by-step instructions with accompanying photos for dozens of exercises specifically designed for common symptoms Breathing and relaxation techniques to awaken innate healing power and. (shrink)

The precocious induction in vivo and in culture of insect and amphibian metamorphosis by exogenous ecdysteroids and thyroid hormones, and its retardation or inhibition by juvenile hormone and prolactin, respectively, has allowed the analysis of such diverse processes of post‐embryonic development as morphogenesis, tissue remodelling, functional reorganization, and programmed cell death. Metamorphosis in vertebrates also shares many similarities with mammalian development in the late foetal and perinatal period. This review describes the regulation of expression of some of the ‘adult’ (...) gene products during metamorphosis in invertebrates and vertebrates. Recent studies on metamorphosis have revealed the important role played by auto‐induction of hormone receptor genes, based on which a model will be presented to explain the activation of ‘downstream’ genes which give rise to the adult phenotype. It will also be argued that metamorphosis is an ideal model for analyzing some of the major mechanisms governing post‐embryonic development. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Shame is Not an Effective Diet PlanJudith BrukThe stigma of being obese is so strong that it is assumed that anyone with the condition is (or should be) deeply ashamed. After all, it’s really easy to lose weight, right? Just cut out dessert and walk around the block three times a week. If you can’t even do that, then you are definitely a moral failure, have succumbed to Gluttony (...) and Sloth, and deserve to be shunned by society.The problem is that shame is not a very effective diet plan; quite the opposite. It’s no surprise that recent research shows that shame leads to depression that leads to isolation, which, in the morbidly obese, leads to a suicide rate twelve times that of healthy–weight people.Unfortunately, it is indeed true that many obese people feel a great deal of shame, even if we occasionally put on a façade of bravado or seeming shamelessness, e.g., the “large and in charge” sitcom staple trope. The bottom line is that our shame about our weight does keep us from engaging with other people, limits our willingness to participate in physical activities, and generally makes us reluctant to simply exist out in public. None of these are behaviors conducive to positive lifestyle changes.For years I engineered my life so I would only go out of my house when absolutely necessary: grocery shopping and the occasional meeting at work were pretty much it (I usually work from home). I went for years without going to a movie, shopping for clothes in a store, eating in a restaurant, gardening, or any of the other activities I once enjoyed. I was ashamed to be seen. And since I had tried and tried and tried and tried to lose weight for three decades and only ended up more overweight as the years went by, I finally, truly gave up. I convinced myself my psychological makeup was so flawed (or was missing whatever ingredient it was that made someone succeed at sustained weight loss) that I just hoped my inevitable heart attack would be instantaneously fatal. This thinking is irrational, or at least unhealthy. (I am an otherwise fairly smart person with an advanced degree and am professionally employed.) Yet, it is basically the path that both societal attitudes and medical treatment lead us down at this point in time.Here are a few examples that illustrate how the path to irrationality evolved for me.About twelve years ago, I decided to see a psychotherapist to get to the bottom of my subconscious psychological issue that was keeping me overweight. This therapist suggested I see a nutritionist who gave me a list of detailed thyroid tests to take to my doctor so she could order the labs and we could get a full profile of how my thyroid was functioning. Upon presenting the list to my doctor’s PA (my doctor was not available that day), she rolled her eyes, gave a very deep sigh and said to me, “Every fat woman wants to believe it’s because of her thyroid and it never, ever is.” I was so embarrassed for having even brought the subject up that in an effort to save face, I reacted to my shame by replying, “Yeah, I just assume my extreme lack of energy and excess weight is simply because I eat too much.” She said, “Right, so let’s not even bother running these tests.” It was at least ten years later that I finally had the thyroid panel run and found out it was very low functioning.After about a year of seeing that shrink, she declared me “cured” and sent me on my way, though I had not lost any weight. It was about this time I first began thinking that throwing in the towel [End Page 91] was a good option. That didn’t mean that I went out and ate pizza and ice cream every day. Not at all. In fact, given the fact that I had been vegetarian and general health–food freak beginning in my mid–twenties, I rarely had anything in the house that contained sugar... (shrink)

Keratins are a family of intermediate filaments that serve various crucial roles in skin physiology. For mammalian skin to function properly, and to produce epidermal and hair keratins that are optimally adapted for their environment, it is critical that keratin gene and protein expression are stringently controlled. Given that the skin is not only targeted by multiple hormones, but also constitutes a veritable peripheral endocrine organ, it is not surprizing that intracutaneous keratin expression is underlined by tight endocrine controls. These (...) controls encompass thyroid hormones, steroid hormones such as glucocorticoids (GCs), retinoic acid (RA) and vitamin D, and several neuroendocrine mediators. Here, we review why a better understanding of the endocrine controls of keratin expression is not only required for an improved insight into normal human skin and hair function, but may also open new therapeutic avenues in a wide range of skin and hair diseases. (shrink)

The world famous Eltroxin saga of 2009–2011, which ignited heated public debates in Europe, Canada, and Australia, reveals the problematic nature of standalone autonomy protection cases. Eltroxin is a life-sustaining thyroid hormone replacement medicine used by millions worldwide; it was reformulated in 2008, and around 10% of patients were badly affected. Poor communication and lack of professional information triggered public hysteria as a global wave of complaints about harmful side effects, including hair loss, weight gain, extreme fatigue, headaches, diarrhoea, (...) and heightened heart rates, flooded the media. Israeli Eltroxin users (around 250 thousand people) were similarly unaware. Following many media reports and ministerial regulations, a high-profile consumer class action was launched against Perrigo, the distributor. Ten years of court proceedings culminated in a compensation settlement of approximately US$ 14 million. This relatively low sum covered the injuries of those patients who were physically affected; compensation for standalone autonomy injuries to all patients (who were denied information about changes to their life-sustaining medicine) was refused. The monetary settlement and court decision were hugely disappointing to the class plaintiffs, and a negative signal was sent to the proponents of consumers' and patients' personal autonomy. However, the class action still marked a positive change in pharmaceutical protocols for relations between health authorities, commercial pharmacy entities, and patients/consumers as seen by the proactive communication around a subsequent Eltroxin reformulation in 2020 in Israel, Europe, and South Africa (Aspen Pharmacare, 2020).1 This paper highlights the vast potential value of consumer class action proceedings, and pharmaceutical consumer (patient) class actions in particular, for public welfare and private autonomy. The paper will explain leading Israeli case law related to consumer autonomy protection in tort law and will argue that this law still holds the unique protection of autonomy as a basic human right and accordingly recognises harm to autonomy as a viable form of damage. Additionally, it illustrates why and how consumer protection class actions are an important tool for protection of human rights in general and of patients' rights in particular. (shrink)