We report the case of a 42-year-old male patient with acute onset of asymmetrical polyarthritis of the medium and large joints as well as fever and elevated serological inflammation markers. The symptoms began shortly after initiation of thiamazole treatment for newly diagnosed Graves' disease. Antithyroid arthritis syndrome (AAS) is a rare but serious adverse side effect of antithyroid treatment with thioamides such as thiamazole. Clinically, AAS may present with myalgia, arthralgia, fever, exanthema and polyarthritis. In the case of suspected AAS, when possible the thionamide medication should be rapidly discontinued or modified in consultation with the endocrinologist. In some cases anti-inflammatory therapy with NSAID or corticosteroids may be required for symptom control.

The creases of the palm have been of interest for clinicians, anthropologists, and palmists for hundreds of years, but the variations in them have only been studied during the past 50 years. The simian crease, aptly named for its resemblance to the palmar creases of nonhuman simian primates, has received recognition clinically and anthropologically owing to its abnormal appearance and confounding cytogenetic etiology. Given the rarity of these palmar creases but also their usefulness in diagnosing congenital disorders, discussion of cases of those disorders could provide clinicians with further helpful diagnostic knowledge. This review of the literature focuses on the history, embryology, genetic and hereditary origins, and clinical significance of simian creases for the benefit of the diagnosing clinician. Clin. Anat. 32:1042-1047, 2019. © 2019 Wiley Periodicals, Inc.

There is conclusive evidence to demonstrate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) in human development and growth, vision, and cell membrane fluidity (membrane order). N-3 PUFA also contribute to human health maintenance through correction of arrhythmias, inhibition of platelet aggregation and prolongation of clotting time, lowering blood pressure, lowering serum triglycerides and plasma homocysteine, being antiinflammatory and immunomodulatory, being cardio-protective, increasing insulin sensitivity in Asians, and decreasing the risk of breast and colorectal cancers. This understanding of a wide spectrum of biological effects attributable to n-3 PUFA has been unsettled by a systematic review of randomized clinical intervention trials (RCTs) which has reported that n-3 PUFA have negligible or no effect on all-cause or cardiovascular mortality. Here, possible reasons for the inconsistencies in regard to n-3 PUFA and cardiovascular diseases, along with the implications for their broader biology, are considered.

A previous review of alternative treatments (Tx) of ADHD--those other than psychoactive medication and behavioral/psychosocial Tx--was supplemented with an additional literature search focused on adults with ADHD. Twenty-four alternative Tx were identified, ranging in scientific documentation from discrediting controlled studies through mere hypotheses to positive controlled double-blind clinical trials. Many of them are applicable only to a specific subgroup. Although oligoantigenic (few-foods) diets have convincing double-blind evidence of efficacy for a properly selected subgroup of children, they do not appear promising for adults. Enzyme-potentiated desensitization, relaxation/EMG biofeedback, and deleading also have controlled evidence of efficacy. Iron supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback, massage, meditation, mirror feedback, channel-specific perceptual training, and vestibular stimulation all have promising prospective pilot data, many of these tests reasonably controlled. Single-vitamin megadosage has some intriguing pilot trial data. Zinc supplementation is hypothetically supported by systematic case-control data, but no systematic clinical trial. Laser acupuncture has promising unpublished pilot data and may be more applicable to adults than children. Essential fatty acid supplementation has promising systematic case-control data, but clinical trials are equivocal. RDA vitamin supplementation, non-Chinese herbals, homeopathic remedies, and antifungal therapy have no systematic data in ADHD. Megadose multivitamin combinations are probably ineffective for most patients and are possibly dangerous. Simple sugar restriction seems ineffective. Amino acid supplementation is mildly effective in the short term, but not beyond 2-3 months. Thyroid treatment is effective in the presence of documented thyroid abnormality. Some alternative Tx of ADHD are effective or probably effective, but mainly for certain patients. In some cases, they are the Tx of choice, and initial evaluation should consider the relevant etiologies. A few have failed to prove effective in controlled trials. Most need research to determine whether they are effective and/or to define the applicable subgroup. Some of them, although not safer than standard Tx, may be preferable for an etiologic subgroup.

Due to the outbreak of the COVID-19 pandemic, in recent months we have experienced deep changes in our daily and professional lives. In the context of pandemic containment, routine rheumatological procedures have changed in many areas. To guarantee sufficient protection against the infection for patients and staff, telemedicine (especially telephone and video consultation) has increasingly been used. Due to the Digital Healthcare Act (DiGAV), whereby patients will have a legal claim to specific digital health applications in Germany, medical apps and wearables will offer new opportunities for telemedical monitoring. This article provides an overview of telemedical care options in the field of rheumatology. Furthermore, opportunities and limitations of telemedicine in rheumatology are reviewed.

Social media services, such as Twitter, offer great potential for a better understanding of rheumatic and musculoskeletal disorders (RMDs) and improved care in the field of rheumatology. This study examined the content and stakeholders associated with the Twitter hashtag #Covid4Rheum during the COVID-19 pandemic. The content analysis shows that Twitter connects stakeholders of the rheumatology community on a global level, reaching millions of users. Specifically, the use of hashtags on Twitter assists digital crowdsourcing projects and scientific collaboration, as exemplified by the COVID-19 Global Rheumatology Alliance registry. Moreover, Twitter facilitates the distribution of scientific content, such as guidelines or publications. Finally, digital data mining enables the identification of hot topics within the field of rheumatology.

As the medical community is increasingly offering transplantation to patients with increasing comorbidity burdens, the number of simultaneous heart-kidney (SHK) transplants is rising in the United States. How to determine eligibility for SHK transplant versus heart transplant alone is unknown. In this review, we situate this problem in the broader picture of organ shortage. We critically appraise available literature on outcomes in SHK versus heart transplant alone. We posit staged kidney-after-heart transplantation as a plausible alternative to SHK transplantation and review the pros and cons. Drawing lessons from the field of simultaneous liver-kidney transplant, we argue for an analogous policy for SHK transplant with standardized minimal eligibility criteria and a modified Safety Net provision. The new policy will serve as a starting point for comparing simultaneous versus staged approaches and refining the medical eligibility criteria for SHK.

Auricular chondritis frequently occurs in relapsing polychondritis. In addition to the primary form of the disease up to 30% of cases of chondritis can be secondary, e.g. due to autoimmune diseases. We describe the case of a 62-year-old male patient with auricular chondritis as the first symptom of granulomatosis with polyangiitis. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis should always be considered in the differential diagnostics of relapsing polychondritis and antibody testing should be performed accordingly.

The increasing use of smartphones is accompanied by a significant increase in the use of mobile applications (apps). Chronically ill patients could permanently profit from this development.This development is fuelled by the Digital Healthcare Act (DVG), whereby patients have a legal claim to certain apps, so-called digital health applications (DiGAs), which are reimbursed by the statutory health insurance companies. Especially in the field of rheumatology, there are various opportunities to implement apps in the management of chronic diseases and their comorbidities. Furthermore, rheumatic patients and rheumatologists are becoming interested in apps and are willing to use them in the daily routine. This article tries to shed light on the chances and risks of apps and gives a first insight into the digital landscape of rheumatology apps in Germany.

Loss of Forkhead box P1 (FOXP1) protein expression confers a poor prognosis in sporadic and familial breast cancer patients, and the FOXP1 gene maps to a tumor suppressor locus at chromosome 3p14. Although correlation studies have indicated that FOXP1 has a role in tumor suppression, determination of the regulatory mechanism of FOXP1 is required to establish its function in breast cancer. It has previously been identified that FOXP1 is regulated by estrogen in breast cancer and that treatment with bisphenol A is effective for regulating the transformation of the normal human breast epithelial cell line, MCF-10F. In addition, FOXO-regulated activation of FOXP1 inhibits the apoptosis of MCF-10F cells following tamoxifen and Akt inhibitor VIII administration. The present study indicates that FOXP1 regulation occurs via a PI3K/Akt/p70S6 kinase (p70S6K) signaling pathway. Following treatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt, MCF7 and MDA-MB-231 breast cancer cells demonstrated decreased FOXP1 protein expression levels; this result was also observed in the small interfering (si)RNA silencing of Akt. By contrast, overexpression of Akt resulted in increased FOXP1 protein expression levels in the MDA-MB-231 cells compared with the control cell lysates. Furthermore, treatment with rapamycin, a specific inhibitor of the mammalian target of rapamycin/p70S6K cascade, resulted in decreased FOXP1 expression in the MCF7 cells, but not in the MDA-MB-231 cells, which were resistant to rapamycin-induced inhibition. In addition, silencing of p70S6K using siRNA produced a marked decrease in FOXP1 expression. These data indicate that FOXP1 protein expression is regulated by a PI3K/Akt/p70S6K signaling cascade in breast cancer.

Studies in hamsters, mice and rats have demonstrated that estradiol (E2), its interconvertible metabolite estrone (E1) and their catechol metabolites, in particular 4-hydroxy E2/E1, are carcinogenic in the kidney, uterus and mammary gland. Observational studies and clinical trials consistently show that sustained exposure to E2/E1 is associated with the development of sporadic breast cancer. The weight of evidence supports the contribution of two complementary pathways in the initiation, promotion and progression of breast cancer. One pathway involves activation of nuclear and cytoplasmic signaling pathways through the binding of estrogen to nuclear and membrane-bound estrogen receptors leading to increased cell proliferation. The other pathway involves the oxidative metabolism of E2/E1 to catechols and then reactive quinones that can contribute to oxidative DNA damage and form specific, mutagenic depurinating adducts with adenine and guanine which then in turn can serve as biomarkers for the occurrence of these processes. Both pathways can serve as portals to preventive intervention. Antiestrogens are used clinically to block receptor-mediated signaling to block tumor growth. Various chemopreventive agents such as sulforaphane (SFN) and resveratrol have been shown in cell culture to block oxidative metabolism of E2/E1 and thus prevent DNA damage. Pretreatment of MCF-7 and MCF-10F cells with and inhibitor of catechol-O-methyltransferase (COMT) followed by treatment with E2 or 4-OH E2 caused increased oxidative DNA damage (8-oxo-dG) and depurinating DNA adducts showing the importance of E2-catechol O-methylation by COMT as a protective pathway. E2 treatment of MCF-10A cells with E2 or 4-OH E2 caused an increase in E2-adenine and guanine adducts. Treatment with sulforaphane increased

Breast cancer is the second cause of cancer‑related deaths in woman and the incidence of the disease has increased worldwide, in part due to improvements in early detection. Several drugs with anticancer effects have been extracted from plants in the last 20 years, many of which are particularly effective against breast cancer cells. In particular, we have become interested in the ethanolic extract from Senecio graveolens (synonym of S. nutans), a plant commonly called Chachacoma, in an effort to isolate compounds that could demonstrate cytotoxic effects on breast cancer cells. Senecio (Asteraceae) is the largest gender in Chile comprising approximatly 200 species. These herbs inhabit areas over 3,500 meters above the sea level in the Andes Mountains. S. graveolens is commonly used by local communities for its medicinal properties, particularly its capacity to ameliorate high-altitude-associated sickness. The cytotoxic effect of the alcoholic extract from S. graveolens, as well as its most abundant compound 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone, were tested in the breast cancer cell lines ZR-75-1, MCF-7 and MDA-MB‑231, and non-tumorigenic MCF-10F cells. We show that the phytochemical extract was able to induce cytotoxicity in cancer cells but not in MCF-10F. Importantly, this effect was enhanced under hypoxic conditions. However, 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone, the main compound, did not by itself show an effective anticarcinogenic activity in comparison to the whole extract. Interestingly, the cytotoxic effect of the phytochemical extract was dependent on the basal MnSOD protein expression. Thus, cytotoxicity was increased when MnSOD levels were low, but resistance was evident when protein levels were high. Additionally, the crude extract seems to trigger cell death by a variety of processes, including autophagy, apoptosis and necrosis, in MCF-7 cells. In summary, S. graveolens extract possess anticancer activity displaying a specific cytotoxic effect on cancer cells, thus serving as a potential source of phytochemical compounds for cancer treatment.

The expression of CYP27B1 or vitamin D 1α-hydroxylase (1α-OHase) and CYP24A1 in specific tissues may act as the central part between 25-hydroxyvitamin D [25(OH)D] serum levels and the anticancer effects of1α,25-dihydroxyvitamin D [1α,25(OH)2D3],alternative splicing of these enzymes may affect their biological functions. Here, we describe the expression of CYP24A1 and its splicing variants detected in breast cells and tissues. Manifestation of CYP24A1 mRNA was measured by RT-PCR followed by western blot analysis for protein expression. In MCF-7 cells, the expression of CYP24A1 protein was reduced by about 57% compared to MCF-10F cells. Western blot analysis revealed a signal band at 56 kDa, with additional bands detected at 42 and 44 kDa. The expression of CYP24A1 mRNA was reduced by about 58% in breast cancer tissues. We found only one signal in the benign tissues at 56 kDa in western blot, whereas in malignant tissue, an additional band was detected at 40kDa. Our results suggest that alternative splicing of CYP24A1 may lead to a catalytically dysfunctional enzyme.

Long-term exposure to estrogens influences the development of breast cancer in women, but the precise mechanisms involved are not clearly defined. Our working hypothesis is that estrogen modulates this process by two separate processes. One involves the binding of estradiol to estrogen receptor (ER) alpha with stimulation of cell proliferation. Errors in DNA occurring during replication result in fixed mutations when not repaired. The other process results from the formation of genotoxic metabolites of estradiol, which can bind to DNA, cause depurination, and result in mutations. Our collaborative group, funded by a Department of Defense Center of Excellence grant, has examined this hypothesis using a variety of experimental methods. Estradiol and its catechol-estrogen metabolite 4-OH-estradiol causes mutations in cell culture systems and can transform benign MCF-10F cells, allowing them to cause tumors in SCID mice. We have demonstrated loss of heterozygosity and gains and losses of DNA segments by comparative genomic hybridization methodology. The depurinated estradiol-guanine and -adenine adducts are measurable in MCF-7 breast cancer cells in culture and in mouse mammary tissue. The double transgenic, alpha estrogen receptor knockout/Wnt-1 knockin mouse model allows us to dissect out the separate effects of ER-mediated and ER-independent actions of estradiol. Knock out of the ER alpha delays the onset of breast tumors in this model, demonstrating a role of receptor-mediated actions. Oophorectomy delays the onset of tumors and reduces overall incidence, providing evidence for an ER-independent effect. Taken together, these data suggest that both ER-dependent and genotoxic ER-independent effects of estradiol mediate breast cancer development.