Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive form of thyroid cancer (TC) characterized by an aggressive behavior and poor prognosis, resulting in patients' death within a year. Standard treatments, such as chemo and radiotherapy, as well as tyrosine kinase inhibitors, are ineffective for ATC treatment. Cancer immunotherapy is one of the most promising research area in oncology. The PD-1/PD-L1 axis is of particular interest, in light of promising data showing a restoration of host immunity against tumors, with the prospect of long-lasting remissions.
Methods
In this study, we evaluated PD-L1 expression in a large series of TCs (20 cases) showing a progressive dedifferentiation of the thyroid tumor from well differentiated TC to ATC, employing two different antibodies [R&D Systems and VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody]. We also tested the anti PD-L1 mAb in an in vivo animal model.
Results
We found that approximately 70–90% of ATC cases were positive for PD-L1 whereas normal thyroid and differentiated TC were negative. Moreover, all analyzed cases presented immunopositive staining in the endothelium of vessels within or in close proximity to the tumor, while normal thyroid vessels were negative. PD-L1 mAb was also effective in inhibiting ATC growth in an in vivo model.
Conclusions
These data suggest that immunotherapy may be a promising treatment specific for ATC suggesting the need to start with clinical TRIALs.
Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive form of thyroid cancer (TC) characterized by an aggressive behavior and poor prognosis, resulting in patients' death within a year. Standard treatments, such as chemo and radiotherapy, as well as tyrosine kinase inhibitors, are ineffective for ATC treatment. Cancer immunotherapy is one of the most promising research area in oncology. The PD-1/PD-L1 axis is of particular interest, in light of promising data showing a restoration of host immunity against tumors, with the prospect of long-lasting remissions.
Methods
In this study, we evaluated PD-L1 expression in a large series of TCs (20 cases) showing a progressive dedifferentiation of the thyroid tumor from well differentiated TC to ATC, employing two different antibodies [R&D Systems and VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody]. We also tested the anti PD-L1 mAb in an in vivo animal model.
Results
We found that approximately 70–90% of ATC cases were positive for PD-L1 whereas normal thyroid and differentiated TC were negative. Moreover, all analyzed cases presented immunopositive staining in the endothelium of vessels within or in close proximity to the tumor, while normal thyroid vessels were negative. PD-L1 mAb was also effective in inhibiting ATC growth in an in vivo model.
Conclusions
These data suggest that immunotherapy may be a promising treatment specific for ATC suggesting the need to start with clinical TRIALs.
The group 5 LEA (late embryogenesis abundant) proteins are an atypical LEA protein group, which is associated with resistance to multiple stresses. In this study, OsLea14-A gene was isolated from Oryza sativa L., which encodes a 5C LEA protein with 151 amino acids. The qPCR analysis showed that OsLea14-A expressed in all tissues and organs at all times. The expression of OsLea14-A in the panicles of plumping stage were dramatically increased. The heterologous expression of OsLea14-A in Escherichia coli improved its growth performance under salinity, desiccation, high temperature, and freeze-thaw stresses. The purified OsLea14-A protein can protect LDH activity from freeze-thaw-, heat-, and desiccation-induced inactivation. The overexpression of OsLea14-A in rice improved tolerance to dehydration, high salinity, CuSO4, and HgCl2, but excluding K2Cr2O7. The analysis of metal contents showed that the accumulation of OsLea14-A protein in transgenic rice could increase the accumulation of Hg, but could not increase the accumulation of Na, Cr, and Cu after HgCl2, NaCl, K2Cr2O7, and CuSO4 treatment, respectively. These results suggested that OsLea14-A conferred multiple stress tolerance and Hg accumulation, which made it a possible gene in genetic improvement for plants to acclimatize itself to multiple stresses and remediate Hg-contaminated soil.
The Volkswagen scandal has promoted experimental campaigns worldwide aimed to assess the real exhaust emissions of in-use vehicles. Attention has been paid to diesel vehicle NOx emissions that are much higher than legislative type-approval limits. This paper analysed exhaust emissions of a fleet of ten Euro 5 diesel vehicles. NOx emissions were measured during laboratory and track testing. In both cases, the type-approval test was carried out with cold and warm starts. Moreover, in the laboratory, a modified type-approval test and a real urban driving cycle were executed in order to characterise emissions in multiple operating conditions, outside of the homologation boundaries. The testing environment did not influence the emissions behaviour of the tested vehicles. Track and laboratory results, in fact, were comparable when ambient conditions were comparable. The parameter which played the main role in terms of NOx emissions is the ambient temperature, fixed at 23 °C in laboratory and not controlled on the track. Above 28 °C, NOx emissions were much higher than the approval limit (almost 600 mg/km). Moreover, warm driving cycles always introduced higher NOx emissions than cold ones, because of the partial use and/or deactivation of the EGR circuit (one of effective measures to reduce NOx formation). The ratio between warm and cold emissions ranged from 2 to 5. The engine parameter which helped explain the relationship between NOx emissions and thermal engine status was the intake air temperature. For intake air temperatures below 40 °C, NOx emissions were lower than 0.2 g/km. Above 40 °C, they suddenly increased up to almost 0.6 g/km. Another issue highlighted by the experimental results was that dynamic real driving caused the highest NOx emissions (almost 1 g/km).
Autistic-undisciplined thinking in the practice of medical trichology
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Ralph Michel Trueb, Hudson Dutra, Maria Fernanda Reis Gavazzoni Dias DOI:10.4103/ijt.ijt_79_18
Medical trichology is the branch of dermatology that deals with the scientific study of the hair and scalp in health and disease. As any discipline, the practice of medical trichology is not immune to malpractice, either deliberately or carelessly. In his publication "Autistic Undisciplined Thinking in Medicine and How to Overcome It," Swiss psychiatrist Eugen Bleuler describes yet another form of malpractice in medicine reflecting autistic-undisciplined thinking. Autism is not limited to psychopathology, but inherent to the thinking of man throughout history in his drive for knowledge, with thousands of theories lacking any basis in reality. Bleuler recognized the drive character of autistic thinking and how it leads to conclusions that are unshakable because they are determined by, and fulfill, emotional needs, rather than rational argumentation. Even with correct questions, the complexity and incalculability of some problems are often so great that it cannot do justice to realistic thinking and the boundaries between inadequately substantiated hypothesis and autistic sham explanation disappear. Statistics, careful research design, and the attempt to impose stringent methods on our thinking are to be commended. The habituation of the public to useless medicine, to misconceptions, is not hygiene, but negligent endangerment. It has created an industry that largely lives on the autistic thinking of patients and doctors and because it is prosperous, makes propaganda among lay people as well as among doctors that necessarily leads to abuses. This article aims at exposing the most prevalent among abuses in trichological practice due to autistic-undisciplined thinking, specifically: iron supplementation, antiandrogenic treatment, and individualized cell-based therapy in female androgenetic alopecia, treatment of folliculitis decalvans with retinoids, and the value of nutritional therapies.
Light microscopic morphology of indigenous Ghanaian African hair from scalp, eyebrow, axilla, and pubic regions
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Yusra Kalmoni, Frederick Kwaku Addai, Saviour Kweku Adjenti, Kevin Kofi Adutwum-Ofosu, John Ahenkorah, Bismarck Afedo Hottor, Richard Michael Blay DOI:10.4103/ijt.ijt_70_18
Context: Relatively scanty literature on autochthonic African Negroid hair morphology provokes research interest for anthropological, forensic, and cosmetic purposes. Aims: This study aimed to contribute basic morphological information on Ghanaian African hairs. Settings and Design: The study was done in selected second-cycle schools in Accra, Ghana, using convenient sampling. Subjects and Methods: Hairs were obtained by pluck method, from 30 males and 30 females aged 15–20 years. Ghanaian African autochthony was established if individuals had two generations of indigenous Ghanaian parentage. Scalp, eyebrow, axilla, and pubic hairs were image captured using a digital light microscope eyepiece connected to a computer. Diameters of hair strands were measured; types of the medulla and the form and shape of the hair roots were studied. Statistical Analysis Used: ANOVA test (SPSS Version 17.0) was used to compare the means of quantitative hair features among the sexes and the four regions of the body studied. Results: Pubic hair shaft was thickest (respective male and female diameters were 100.21 μm, 88.40 μm) and eyebrow hair was thinnest (53.97 and 46.69-μm diameters in males and females, respectively). Axillary and scalp hairs were the closest in diameters with 76.21 and 72.02 μm, respectively, in males and 73.07 and 71.15 μm, respectively, in females. Continuous type medulla was predominant in all hairs, with a trend of percentage occurrence in descending order from the pubic, axilla, eyebrow, and scalp in both sexes. Conclusions: Bodily regional differences in diameter of hair shaft and medullary presence were affirmed.
Introduction: Hair casts have been reported in a variety of hair and scalp disorders. Trichoscopy allows a quick and noninvasive method for the evaluation of hair and scalp disorders in high magnification. However, the study of hair casts seen in trichoscopy is lacking. Objective: The main objective is to study the occurrence and patterns of tubular hair cast (THC) in different hair and scalp disorders. Patients and Methods: The patients with hair and scalp disorders presenting at the dermatology department of our hospital were evaluated using trichoscopy. Cases of primary parakeratotic disorders and behavioral disorders were excluded. After a detailed history and evaluation of the hair and scalp, histopathology, light microscopic examination, potassium hydroxide examination, and fungal culture were done when necessary. Results: THC was seen in total 21 cases of seven different hair and scalp disorders. Of these, the majority of cases were of discoid lupus erythematosus (DLE) (5/21) and maximum frequency of THCs within a disorder was seen in cases of pemphigus foliaceus (PF) (50%). Proximal casts occurred in 90.47% of cases. Single cast involving two shafts was seen in a case of PF, and two casts within a single shaft were seen in two cases of DLE and one case of alopecia areata. Conclusions: THCs in trichoscopy can be seen in various hair and scalp disorders and their study may help during the diagnosis of those disorders when combined with other trichoscopic features.
Research on the balance of thiol-disulfide in blood serum in women with telogen effluvium
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Ayşe Akbas, Fadime Kılınç, Sertaç Sener, Akta Akınş, Cemile Bıçer, Orhan Şen DOI:10.4103/ijt.ijt_78_17
Backgrounds: Telogen effluvium (TE) is the most common reason for hair loss in humans. Although the exact etiopathogenesis of TE has not been revealed clearly and completely, multifactorial etiologies are to be blamed. In recent years, since oxidative stress (OS) has been shown to play an important role in the etiopathogenesis of so many diseases, the effects of OS on several skin diseases are researched and analyzed. Thiols are antioxidant components that include sulfur group, and the balance of thiol-disulfide has an important role in the formation and prevention of OS. This balance is destroyed in many diseases and its effect on TE is not clearly understood yet. Objectives: In this study, we aimed to search the thiol–disulfide balance that could reveal OS in patients with TE. Materials and Methods: Fifty-two patients with TE and control group of 46 persons were included in the study. Native thiol, disulfide, and total thiol levels were evaluated by a new, automatic spectrophotometric method. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol rates were calculated. Results: There was no statistical difference between TE patients and control group in terms of native thiol, disulfide, and total thiol levels. Thiol–disulfide balance was fixed and not affected in TE patients.
Serum interleukin-15 is a marker of alopecia areata severity
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Adel Ali Ebrahim, Rehab Mohammed Salem, Asmaa Adel El Fallah, Esraa Taha Younis DOI:10.4103/ijt.ijt_80_18
Background: Interleukin-15 (IL-15) is a cytokine that is involved in many inflammatory and autoimmune diseases. Although alopecia areata (AA) is an autoimmune disease, serum levels of IL-15 have not been studied well in AA patients. Aim of the Work: We aims at evaluating the serum levels of IL-15 in active AA. Subject and Methods:This case-control study included 40 AA patients and 40 apparently healthy matched controls. Written informed consents were obtained from all the participants. The scalp was examined to assess sites, number, and size of alopecia patches, and the severity of AA lesions was assessed using the Severity of Alopecia Tool score (SALT score) which determine the percentage of hair loss in the scalp. The body was carefully examined to detect any alopecia patches in any hairy area. Nail examination was carried out to detect any nail involvement. Serum IL-15 levels were measured using an ELISA kits. Results: Serum levels of IL-15 in patients were significantly higher than those in the control group (P < 0.001). Serum levels in alopecia totalis were significantly higher than those with one or two patches, and serum levels in patients with both scalp and body involvement were significantly elevated than the levels of patients with either scalp or body involvement. There was a statistically significant positive correlation between SALT score and serum levels of IL-15 (P < 0.001). Conclusion: Serum IL-15 may be a marker of AA severity.
Luisa Groba Bandeira, Maria Cláudia Alves Luce, Bruno De Castro E Souza, Priscila Kakizaki, Neusa Yuriko Sakai Valente DOI:10.4103/ijt.ijt_16_18
We report a case of trigeminal trophic syndrome (TTS) on the scalp of a 69-year-old woman. Initially, the diagnosis of pityriasis amiantacea was considered. The review of pathological antecedents and knowledge of TTS were fundamental for the diagnosis of this illness. We performed a brief review on TTS and differential diagnoses.
Nerve sheath myxoma, a superficial myxoid tumor, was first described in 1969 by Harkin and Reed. Tumor has cytological and histological resemblance with neurothekeoma, another cutaneous myxoid lesion. Nerve sheath myxoma affects individuals of all age groups and equal predilection for both genders with most favored sites being the fingers and knee. Here, we present a case report of nerve sheath myxoma of the scalp, diagnosed and confirmed with histopathology and immunohistochemistry.
Woolly hair nevus is a rare non hereditary disorder of scalp characterized by curling and kinking of hair. It can present in childhood or adolescent age. Dermoscopy is a useful noninvasive technique to help in the diagnosis of wolly hair nevus. We report a case of woolly hair nevus associated with linear epidermal nevus.
