The thyroid is an endocrine gland in all vertebrates that develops from the ventral floor of the anterior pharyngeal endoderm. Unravelling the molecular mechanisms of thyroid development helps to understand congenital hypothyroidism caused by the absence or reduction of this gland in newborn humans. Severely reduced or absent thyroid-specific developmental genes concomitant with the complete loss of the functional gland in the zebrafish hands off (han, hand2) mutant reveals the han gene as playing a novel, crucial role in thyroid development. han-expressing tissues surround the thyroid primordium throughout development. Fate mapping reveals that, even before the onset of thyroid-specific developmental gene expression, thyroid precursor cells are in close contact with han-expressing cardiac lateral plate mesoderm. Grafting experiments show that han is required in surrounding tissue, and not in a cell-autonomous manner, for thyroid development. Loss of han expression in the branchial arches and arch-associated cells after morpholino knock-down of upstream regulator genes does not impair thyroid development, indicating that other han-expressing structures, most probably cardiac mesoderm, are responsible for the thyroid defects in han mutants. The zebrafish ace (fgf8) mutant has similar thyroid defects as han mutants, and chemical suppression of fibroblast growth factor (FGF) signalling confirms that this pathway is required for thyroid development. FGF-soaked beads can restore thyroid development in han mutants, showing that FGFs act downstream of or in parallel to han. These data suggest that loss of FGF-expressing tissue in han mutants is responsible for the thyroid defects.

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Objectives Non‐treponemal serological tests are used to monitor treatment response during syphilis infection. Syphilis‐ and HIV‐coinfected patients may experience incomplete resolution in non‐treponemal titres, which is referred to as the serofast state. The goal of this study was to evaluate risk factors for serofast state in HIV‐infected patients. Methods From November 2015 to June 2018, 1530 HIV‐positive patients were tested for syphilis using a Treponema pallidum particle agglutination (TPPA) assay. Among TPPA‐positive patients, medical records were reviewed for early syphilis infection. Serofast state was defined as a less than four‐fold decrease in non‐treponemal antibody titres during a 6‐month follow‐up period in the absence of symptoms of syphilis. Baseline characteristics were tested as predictive factors of serological response. Results In all, 515 patients (33.7%) tested positive in TPPA assays, and in 163 patients at least one previous syphilis infection was documented. A total of 61 out of 163 patients (37.4%) were in a serofast state. A history of previous syphilis infection (61 vs. 43%; P = 0.04) was more common in serofast patients than in patients with serological cure after 6 months. Non‐treponemal titres ≥ 1:32 before therapy (47 vs. 25%; P = 0.005) and adjunctive corticosteroids to prevent the Jarisch–Herxheimer reaction (35% vs 15%; P = 0.006) were associated with serological cure after 6 months, but corticosteroid therapy had no influence at 12 months. The intensity of syphilis treatment did not affect serological cure. Conclusion Corticosteroids for prevention of the Jarisch–Herxheimer reaction were associated with earlier serological cure. Although serological response is the accredited surrogate method to monitor syphilis treatment, the biological significance of the serofast state remains unclear.