Predictive Factors for Skip Lymph Node Metastasis and Their Implication on Recurrence in Papillary Thyroid Carcinoma

Skip lymph node (LN) metastases in papillary thyroid carcinoma (PTC) belong to N1b classification in the absence of central neck LN involvement. This study aimed to evaluate the predictive factors of skip metastases and their impact on recurrence in PTC patients with pN1b. A total of 334 PTC patients who underwent total thyroidectomy with LN dissection (central and lateral neck compartment) followed by radioactive iodine ablation were included. Patients with skip metastases tended to have a small primary tumor (≤1 cm) and single lateral neck level involvement. Tumor size ≤ 1 cm was an important predictive factor for skip metastases. Univariate analysis for recurrence showed that patients with a central LN ratio > 0.68, lateral LN ratio > 0.21, and stimulated thyroglobulin (Tg) levels > 7.3 ng/mL had shorter RFS (recurrence-free survival). The stimulated Tg level was associated with shorter RFS on multivariate analysis (>7.3 vs. ≤7.3 ng/mL; hazard ratio, 4.226; 95% confidence interval, 2.226−8.022; p < 0.001). Although patients with skip metastases tended to have a small primary tumor and lower burden of lateral neck LN involvement, there was no association between skip metastases and RFS in PTC with pN1b. Stimulated Tg level was a strong predictor of recurrence.

Transpupillary laser thermotherapy of retinoblastoma

Introduction. Despite the fact that transpupillary thermotherapy (TTT) is one of the main local methods of small retinoblastoma (RB) destruction, only a few studies have been published on the use of this method, and they are devoted only to certain aspects of the application of TTT.Purpose of the study – to evaluate the effectiveness of TTT in the treatment of children with RB.Material and methods. In the period from 2011 to 2020, 177 children (224 eyes, 1156 tumors) with RB were treated by TTT. Of these, 99 (56 %) patients were boys, 78 (44 %) – girls. The mean age at the time of treatment was 16.8 months (from 0 to 86 months). Bilateral RB was observed in 128 (72.3 %) patients, monolateral – in 49 (27.7 %). In 51 (28.8 %) cases, TTT was performed on an only eye. TTT was performed on eyes that had RB of groups A (n = 43; 19 %), B (n = 81; 36 %), C (n = 31; 14 %), D (n = 63; 28 %), E (n = 6; 3 %). In total, 1156 tumors were treated by TTT. 488 (42 %) tumors were localized post-equatorially (of which 27 were located juxtapapillary, 23 – in the macular zone, 22 – paramacular). 668 (58 %) foci had pre-equatorial localization (on the middle and far periphery of the fundus). The number of foci in one eye varied from 1 to 48 (mean – 5). The mean tumor thickness was 1.1 mm (from 0.2 to 4.5), the mean base diameter was 2.2 mm (from 0.3 to 13.4). TTT was performed using a diode laser with the following parameters: wavelength – 810 nm, spot diameter – 1200 microns, power from 200 to 800 mW (mean – 350 mW), exposure-from 3 to 15 s in the application mode, and continuous in the scanning mode.Results. Complete tumor regression after TTT was achieved in 92 % of cases (1064 tumors). Incomplete regression of the tumor with stabilization was achieved in 0.7 % (8 tumors). The average number of TTT sessions to achieve full regression was 1.7 (from 1 to 10). Complete tumor regression after 1 TTT session was achieved in 54 % of cases (622 tumors), after 2 sessions – in 11 % (132 tumors), after 3 sessions – in 7 % (85 tumors), after 4 or more sessions– in 19 % (225 tumors). In 7 % of cases (82 tumors), due to the progression of the tumor, other treatment methods (brachytherapy, cryotherapy, stereotactic radiosurgery) were applied. 209 (93 %) eyes were preserved. 15 (7 %) eyes were enucleated due to continued tumor growth, total retinal detachment, vitreous hemorrhage, or subatrophy of the eyeball. The mean follow-up after TTT was 35.5 months (from 3 to 112 months).Conclusion. TTT is a highly effective method of RB treatment and can be used for destruction of small primary foci of both post-equatorial and pre-equatorial localization, residual tumors after inefficiency of other local methods. TTT is also effective in the treatment of large cavitary tumors located in functionally significant areas of the retina.

Mandible histology in Metoposaurus krasiejowensis (Temnospondyli, Stereospondyli) from the Upper Triassic of Poland

Recent studies that have systematically augmented our knowledge of dermal bones of the Late Triassic temnospondyl amphibian Metoposaurus krasiejowensis have mostly focused on shoulder girdle elements and the skull. So far, histological data on the mandible are still scant. For the present study, two mandibles have been examined, using 50 standard thin sections. Dermal bones of the mandible reveal a uniform diploë structure, with the external cortex consisting of moderately vascularised, parallel-fibred bone, as well as a distinct alternation of thick zones and thinner annuli. Dense bundles of well-mineralised Sharpey’s fibres are seen in the external cortex over the entire length of the mandible. The trabecular middle region is highly porous and well vascularised, showing small primary vascular canals and more numerous secondary osteons; irregular erosion spaces occur in large numbers as well. The thin and poorly vascular internal cortex consists of parallel-fibred bone. The articular is not a dermal bone in origin, having been formed of a thin layer of avascular cortex and a very extensive, trabecular middle region. In contrast to the dermal bones of the mandible, the articular developed from a cartilaginous precursor, as evidenced by numerous remains of calcified cartilage in the central parts of the bone. Histological variability is extremely high along the mandible, its anterior part being characterised by high compactness and biomechanically good resistance in contrast to the highly porous posterior parts. Distinct variations of bone thickness and degree of bone porosity in specific areas of the mandible, may be due to local differences in biomechanics during feeding. The microstructure of the mandible corroborates a previous study of the active and ambush predation strategy in metoposaurids.

Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance

An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft’s immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft’s microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance.

On Small Primary Modules

Let be a commutative ring with an identity and be a unitary -module. We say that a non-zero submodule of is primary if for each with en either or and an -module is a small primary if = for each proper submodule small in. We provided and demonstrated some of the characterizations and features of these types of submodules (modules).

ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus

Recent studies have shown that ZBTB20, a zinc-finger protein containing transcription factor, is highly expressed in small-diameter primary sensory neurons in mice, and modulates pain through regulating TRP channels. However, whether ZBTB20 regulates itch sensation has not been demonstrated. In this study, small-diameter primary sensory neuron-specific ZBTB20 knockout (PN-ZB20KO) mice were used to investigate the role of ZBTB20 in the regulation of itch sensation. First, both histamine-dependent and non-histamine-dependent itch behaviors induced by injection of histamine and chloroquine (CQ) into the cheek were significantly diminished in PN-ZB20KO mice. Second, double immunohistochemistry showed that ZBTB20 was mainly expressed in CGRP-labeled small peptidergic neurons and was expressed at low levels in IB4-labeled small non-peptidergic and NF200-labeled large neurons in the trigeminal ganglia (TG). ZBTB20 was also expressed in most TRPV1+ and TRPA1+ neurons and to a lesser extent in TRPM8+ neurons in the TG. Furthermore, cheek injection of histamine and CQ enhanced the mRNA expression of TRPV1 and TRPA1 but not TRPM8 in the TG. Moreover, TRPV1 and TRPA1 knockout (KO) mice exhibited attenuation of itch behavior induced by histamine and CQ, respectively. Finally, silencing endogenous ZBTB20 with recombinant lentivirus expressing a short hairpin RNA against ZBTB20 (LV-shZBTB20) in TG neurons attenuated histamine- and non-histamine-induced itch and downregulated TRP channels in the TG. Our study suggests that ZBTB20 plays an important role in mediating itch in small primary sensory neurons.