Constructing a Comprehensive Nanopattern Library through Morphological Transitions of Block Copolymer Surface Micelles via Direct Solvent Immersion.

This study establishes a comprehensive library of nanopatterns achievable by a single block copolymer (BCP), ranging from spheres to complex structures like split micelles, flower-like clusters, toroids, disordered micelle arrays, and unspecified unique shapes. The ordinary nanostructures of polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) surface micelles deposited on a SiOx surface undergo a unique morphology transformation when immersed directly in solvents. Investigating parameters such as immersion solvents, BCP molecular weight, substrate interactions, and temperature, this work reveals the influence of these parameters on the thermodynamics and kinetics governing the morphology transformation. Additionally, the practical application of BCP nanopattern templates for fabricating metal nanostructures through direct solvent immersion of surface micelles is demonstrated. This approach offers an efficient and effective method for producing diverse nanostructures, with the potential to be employed in nanolithography, catalysts, electronics, membranes, plasmonics, and photonics.

Sodium thiosulfate does not protect ovarian reserve from cisplatin-induced gonadotoxicity†.

Cisplatin, a platinum-containing alkylating agent, is used in the treatment of various tumors owing to its potent antitumor activity. However, it causes permanent and adverse effects, particularly hearing loss and depletion of ovarian reserve. Until recently, there were no clinically available protective agents to mitigate the adverse side effects of cisplatin-induced cytotoxicity. In 2022, sodium thiosulfate (STS) was approved by the Food and Drug Administration for mitigating hearing loss in children and adolescents undergoing cisplatin treatment. Consequently, our investigation aimed to determine if STS could protect ovarian reserve against cisplatin-induced gonadotoxicity. In an ex vivo culture, the cisplatin-only group exhibited a loss of primordial follicles, while post-STS administration after cisplatin exposure effectively protected primordial follicles. However, when post-STS was administrated either 6 or 4 h after cisplatin exposure, it did not confer protection against cisplatin-induced gonadotoxicity in postnatal day 7 or adolescent mouse models. Immunofluorescence assays using γH2AX and cPARP revealed that oocytes within primordial follicles exhibited DNA damage after cisplatin exposure, irrespective of post-STS administration. This underscores the rapid and heightened sensitivity of oocytes to gonadotoxicity. In addition, oocytes demonstrated an increased expression of pCHK2 rather than pERK, suggesting that the pathway leading to oocyte death differs from the pathway observed in the inner ear cell death following cisplatin exposure. These results imply that while the administration of STS after cisplatin is highly beneficial in preventing hearing loss, it does not confer a protective effect on the ovaries in mouse models.

Metabolic characteristics of granulosa cell tumor: role of PPARγ signaling†.

Granulosa cell tumors are relatively rare, posing challenges for comprehension and therapeutic development due to limited cases and preclinical models. Metabolic reprogramming, a hallmark of cancer, manifests in granulosa cell tumors with notable lipid accumulation and increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), a key lipid metabolism regulator. The roles of these features, however, remain unclear. In our previous work, we established a granulosa cell tumor model in mice by introducing a constitutively active Pik3ca mutant in oocytes, enabling the study of predictable tumor patterns from postnatal day 50. In this study, we characterized metabolic alterations during tumorigenesis (postnatal day 8 to day 50) and tumor growth (day 50 to day 65) in this model and explored the impact of PPARγ antagonism on human granulosa cell tumor proliferation. The tumor exhibited significant lipid accumulation, with PPARγ and the proliferation marker Ki67 co-localizing at postnatal day 65. Transcriptome analysis demonstrates that pathways for lipid metabolism and mitochondrial oxidation are promoted during tumorigenesis and tumor growth, respectively. Overlappingly upregulated genes during tumorigenesis and tumor growth are associated with lipid metabolism pathways. Correspondingly, mouse granulosa cell tumor shows overexpression of peroxisome proliferator-activated receptor gamma and DGAT2 proteins at postnatal day 65. Furthermore, GW9662 reduces the proliferation of KGN human granulosa cell tumor cells and decreases the phosphorylation of AKT and SMAD3. Our findings identify metabolic abnormalities in ooPIK3CA* granulosa cell tumor model and suggest peroxisome proliferator-activated receptor gamma as a potential driver for primary granulosa cell tumor growth.

HPV vaccine narratives on Twitter during the COVID-19 pandemic: a social network, thematic, and sentiment analysis.

INTRODUCTION: The COVID-19 pandemic has increased online interactions and the spread of misinformation. Some researchers anticipate benefits stemming from improved public awareness of the value of vaccines while others worry concerns around vaccine development and public health mandates may have damaged public trust. There is a need to understand whether the COVID-19 pandemic, vaccine development, and vaccine mandates have influenced HPV vaccine attitudes and sentiments to inform health communication strategies. METHODS: We collected 596,987 global English-language tweets from January 2019-May 2021 using Twitter's Academic Research Product track. We determined vaccine confident and hesitant networks discussing HPV immunization using social network analysis. Then, we used a neural network approach to natural language processing to measure narratives and sentiment pertaining to HPV immunization. RESULTS: Most of the tweets in the vaccine hesitant network were negative in tone (54.9%) and focused on safety concerns surrounding the HPV vaccine while most of the tweets in the vaccine confident network were neutral (51.6%) and emphasized the health benefits of vaccination. Growth in negative sentiment among the vaccine hesitant network corresponded with legislative efforts in the State of New York to mandate HPV vaccination for public school students in 2019 and the WHO declaration of COVID-19 as a Global Health Emergency in 2020. In the vaccine confident network, the number of tweets concerning the HPV vaccine decreased during the COVID-19 pandemic but in both vaccine hesitant and confident networks, the sentiments, and themes of tweets about HPV vaccine were unchanged. CONCLUSIONS: Although we did not observe a difference in narratives or sentiments surrounding the HPV vaccine during the COVID-19 pandemic, we observed a decreased focus on the HPV vaccine among vaccine confident groups. As routine vaccine catch-up programs restart, there is a need to invest in health communication online to raise awareness about the benefits and safety of the HPV vaccine.

Thyroid hormone triiodothyronine does not protect ovarian reserve from DNA damage induced by X-ray and cisplatin.

PURPOSE: Cancer therapy can induce premature ovarian insufficiency, necessitating methods for preserving fertility in female cancer patients. However, the only accepted clinical practice for doing so is cryopreservation of embryos, unfertilized ova, and ovarian tissue, despite potential options such as in vitro maturation of follicles. Therefore, considerable interest has arisen in fertoprotective agents, with research on rat ovarian granulosa cells suggesting that triiodothyronine (T3) regulates an anti-apoptosis mechanism that protects the ovarian reserve from paclitaxel-induced DNA damage. In this study, we used postnatal day 5 mouse ovary to confirm the existence of T3 thyroid hormone receptor (THR), as well as to investigate the potential protective effects of T3 against cisplatin- and X-ray-induced apoptosis. We also tested the potential anti-apoptotic effect of T3 in the breast cancer cell line MDA-MB-231. METHODS: We treated cultured mouse ovaries with varying concentration of T3 and 4 µM cisplatin and 0.2 Gy X-ray. Real-time PCR, histological analysis, immunoblot analysis, and immunofluorescence were performed to assess the potential anti-apoptotic effects of T3. RESULTS: We confirmed that THR alpha and beta are expressed in the mouse ovary. T3 (0.1, 1, 10, 100 nM, and 1 µM) does not protect ovarian reserve from cisplatin- or X-ray-induced apoptosis or DNA damage. Similarly, it does not protect mouse granulosa cells and MDA-MB-231 cells from cisplatin- or X-ray-induced apoptosis. CONCLUSION: Our findings suggest that T3 is ineffective as a fertoprotective agent, and its candidacy as a potential agent to preserve fertility should be reconsidered.

Processing method determines the long-term stability of particle dispersions in concentrated nanoparticle/polymer suspensions.

Since the degree of particle dispersion can determine the physical properties of polymer nanocomposites (PNCs), plenty of studies have focused on the intrinsic parameters of PNCs such as the concentration/size/chemistry of nanoparticles/polymers relevant to the particle microstructure. While the consideration of these parameters is based on PNCs being in their equilibrium states, PNCs can be kinetically trapped in a nonequilibrium state during the multiple steps of processing. In other words, processing conditions can contribute more significantly to particle dispersion and the properties of PNCs beyond the effects of the intrinsic parameters. Hence, a systematic understanding of the nonequilibrium behaviour of PNCs is required to achieve the desired properties. In this work, we prepared concentrated suspensions with two different preparation pathways. The two different pathways yield different polymer conformations particularly near the particle surface despite the same composition of particles/polymers as the systems are trapped in a nonequilibrium state. Accordingly, the particle microstructures are also greatly changed by the preparation pathway. We found that even in the presence of solvents, these preparation pathway-dependent nonequilibrium effects on particle microstructures persist after several months of aging and ultimately determine the long-term stability of the particle dispersion.

TNNC1 knockout reverses metastatic potential of ovarian cancer cells by inactivating epithelial-mesenchymal transition and suppressing F-actin polymerization.

Troponin C type 1 (TNNC1) is commonly overexpressed in ovarian cancer. However, the biological implications of TNNC1 overexpression on ovarian cancer malignization and its related mechanism remain unknown. To elucidate these implications, we knocked out the TNNC1 gene in TNNC1-overexpressing SKOV-3-13 ovarian cancer cells using CRISPR/Cas-9 technology and observed the changes in metastatic phenotypes and related molecular pathways. TNNC1-knockout (KO) cells showed significantly reduced proliferation and colony formation when compared with TNNC1 wild-type cells (P < 0.01). In TNNC1-KO cells, wound healing, migration, and invasive phenotypes decreased. Upon observation of upstream regulators of epithelial-mesenchymal transition (EMT), levels of phosphorylated AKT (Ser-473 and Thr-308) and GSK-3ß (inactive form) were found to be decreased in TNNC1-KO cells. Accordingly, SNAIL and SLUG expression decreased and were almost completely localized in the cytoplasm following TNNC1 silencing. Regarding downstream EMT markers, N-cadherin and vimentin expression decreased, but E-cadherin expression increased. Related matrix metalloproteinase and chemokine expression generally decreased. TNNC1 deficiency also suppressed F-actin polymerization. In conclusion, TNNC1 overexpression contributes to the metastatic behavior of ovarian cancer by perturbation of EMT and actin microfilaments. Our results provide a better understanding of the detailed molecular mechanism of ovarian cancer metastasis associated with TNNC1 overexpression.

Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation.

Chemotherapy directly or indirectly affects organs in a short-term or continuous manner. Endocrine organs are especially sensitive to cancer treatment, leading to concerns among patients regarding their quality of life afterward. Side effects to the ovary include damage to the ovarian reserve, resulting in follicle loss, endocrine hormone deficiency, and infertility. It has been previously demonstrated that continuous treatment with 2 mg/kg cisplatin for 15 days can activate primordial follicles, suggesting that the response in the oocytes of primordial follicles was dependent on cisplatin concentration and administration frequency. However, our results demonstrate that continuous treatment with 2 mg/kg cisplatin for 15 days leads to the same consequence as with the continuous treatment of 5 mg/kg cisplatin: the death of oocytes in primordial follicles without indication of activation. Moreover, animals co-injected with melatonin and cisplatin did not display any significant differences from those treated with cisplatin only contrary to the known results. 6-hydroxymelatonin, a metabolite of melatonin, could not prevent follicle destruction, implying that melatonin does not confer the protection of ovarian follicles, either directly or indirectly. Altogether, our data support that fertoprotectants against cisplatin must target molecules that control cell death pathways in the oocytes of primordial follicles.

The physical properties and anticariogenic effect of experimental resin cement containing ursolic acid.

The aim was to evaluate the physical properties and anti-bacterial activity of resin cement containing ursolic acid (UA) and determine the optimal concentration of UA. Five types of experimental resin cement were prepared according to UA concentration (0, 0.1, 0.5, 1.0, and 2.0 wt%). Flexural strength, film thickness and in vitro cytotoxicity were measured to confirm whether the resin was appropriate under International Organization for Standardization (ISO) criteria. Fifty extracted human molars were prepared, and indirect resin inlays were cemented with experimental resins. Acid-resistant nail varnish was applied, except for the 2-mm area around the restoration. Artificial caries were induced for 6 days through Streptococcus (S.) mutans (ATCC25175). Quantitative light-induced fluorescence (QLF) was used to evaluate the caries progression. One-way analysis of variance (ANOVA) followed by the Dunnett correction were used to statistically analyze the data. In all groups, the physical property of flexural strength, film thickness, and cytotoxicity were satisfied for ISO criteria (p > 0.05). On ∆F (-%) and ∆Q (-%⋅Px) values as QLF parameters, there was a tendency of being lower in groups of resin cement containing higher concentration of UA. Resin cement containing UA of greater than or equal to 0.5% significantly inhibited caries in the area around restoration (p < 0.05). There was no difference between the groups containing UA of greater than or equal to 0.5%. Resin cement containing 0.5% or more UA showed anti-carious effect in the limited range of 2% and satisfied the ISO criteria for flexural strength, film thickness and cytotoxicity.

The Role of Mutant p63 in Female Fertility.

The transcription factor p63, one of the p53 family members, plays an essential role in regulating maternal reproduction and genomic integrity as well as epidermal development. TP63 (human)/Trp63 (mouse) produces multiple isoforms: TAp63 and ΔNp63, which possess a different N-terminus depending on two different promoters, and p63a, p63b, p63g, p63δ, and p63ε as products of alternative splicing at the C-terminus. TAp63 expression turns on in the nuclei of primordial germ cells in females and is maintained mainly in the oocyte nuclei of immature follicles. It has been established that TAp63 is the genomic guardian in oocytes of the female ovaries and plays a central role in determining the oocyte fate upon oocyte damage. Lately, there is increasing evidence that TP63 mutations are connected with female infertility, including isolated premature ovarian insufficiency (POI) and syndromic POI. Here, we review the biological functions of p63 in females and discuss the consequences of p63 mutations, which result in infertility in human patients.

Comparison of volume-controlled, pressure-controlled, and pressure-controlled volume-guaranteed ventilation during robot-assisted laparoscopic gynecologic surgery in the Trendelenburg position.

Background: Pressure-controlled ventilation volume-guaranteed (PCV-VG) is being increasingly used for ventilation during general anesthesia. Carbon dioxide (CO2) pneumoperitoneum in the Trendelenburg position is routinely used during robot-assisted laparoscopic gynecologic surgery. Here, we hypothesized that PCV-VG would reduce peak inspiratory pressure (Ppeak), compared to volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV). Methods: In total, 60 patients were enrolled in this study and randomly assigned to receive VCV, PCV, or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 minutes after the induction of anesthesia (T0), 30 and 60 minutes after CO2 pneumoperitoneum and Trendelenburg positioning (T1 and T2, respectively), and 15 minutes after placement in the supine position at the end of anesthesia (T3). Results: The Ppeak was higher in the VCV group than in the PCV and PCV-VG groups (p=0.011). Mean inspiratory pressure (Pmean) was higher in the PCV and PCV-VG groups than in the VCV group (p<0.001). Dynamic lung compliance (Cdyn) was lower in the VCV group than in the PCV and PCV-VG groups (p=0.001). Conclusion: Compared to VCV, PCV and PCV-VG provided lower Ppeak, higher Pmean, and improved Cdyn, without significant differences in hemodynamic variables or arterial blood gas results during robot-assisted laparoscopic gynecologic surgery with Trendelenburg position.

Growth and Bone Mineral Density Changes in Ovariectomized Rats Treated with Estrogen Receptor Alpha or Beta Agonists.

BACKGROUND: Estrogen controls the pubertal growth spurt, growth plate closure, and accretion of bone mineral density (BMD) of long bones after biding estrogen receptor (ER). There are two subtypes of ER, ERα and ERß. If each ER subtype has different effects, we may control those actions by manipulating the estrogen binding intensity to each ER subtype and increase the final adult height without markedly reducing BMD or impairing reproductive functions. The purpose of our study was to compare these effects of ERα and ERß on long bones in ovariectomized rats. METHODS: Thirty female rats were ovariectomized and randomly divided into 3 groups. The control, propylpyrazole triol (PPT), and 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) groups were subcutaneously injected for 5 weeks with sesame oil, PPT as an ERα agonist, and DPN as an ERß agonist, respectively. The crown-lump length and body weight were measured weekly. BMD, serum levels of growth hormone (GH) and estradiol were checked before and after 5 weeks of injections. Pituitary GH1 expression levels were determined with quantitative real-time polymerase chain reaction, the proximal tibias were dissected, decalcified and stained with hematoxylin-eosin, and the thicknesses of epiphyseal plates including proliferative and hypertrophic zones were measured in 20-evenly divided sites after 5 weeks of injections. Comparisons for auxological data, serum hormone and pituitary GH1 expression levels, BMD, and epiphyseal plate thicknesses among 3 groups before and after injections were conducted. RESULTS: There was no significant difference in body lengths among 3 groups. The body weights were significantly lower, but, serum GH, pituitary GH1 expression levels, and BMDs were higher in PPT group than the other 2 groups after 5 weeks of injections. There was no significant difference in the thicknesses of the total epiphyseal plate, proliferative, and hypertrophic zone among 3 groups. CONCLUSION: ERα is more involved in pituitary GH secretion and bone mineral deposition than ERß. Weight gain might be prevented with the ERα agonist.

Initial Solvent-Driven Nonequilibrium Effect on Structure, Properties, and Dynamics of Polymer Nanocomposites.

Unusual structures and dynamic properties found in polymer nanocomposites (PNCs) are often attributed to immobilized (adsorbed) polymers at nanoparticle-polymer interfaces, which are responsible for reducing the intrinsic incompatibility between nanoparticles and polymers in PNCs. Although tremendous effort has been made to characterize the presence of immobilized polymers, a systematic understanding of the structure and dynamics under different processing conditions is still lacking. Here, we report that the initial dispersing solvent, which is not present after producing PNCs, drives these nonequilibrium effects on polymer chain dynamics at interfaces. Employing extensive small-angle scattering, proton NMR spectroscopy, and rheometry experiments, we found that the thickness of the immobilized layer can be dependent on the initial solvent, changing the structure and the properties of the PNC significantly. In addition, we show that the outcome of the initial solvent effect becomes more effective at particle volume fractions where the immobile layers begin to interact.

Controlled Segmentation of Metal Nanowire Array by Block Copolymer Lithography and Reversible Ion Loading.

Spatial arrangement of 1D nanomaterials may offer enormous opportunities for advanced electronics and photonics. Moreover, morphological complexity and chemical diversity in the nanoscale components may lead to unique properties that are hardly anticipated in randomly distributed homogeneous nanostructures. Here, controlled chemical segmentation of metal nanowire arrays using block copolymer lithography and subsequent reversible metal ion loading are demonstrated. To impose chemical heterogeneity in the nanowires generated by block copolymer lithography, reversible ion loading method highly specific for one particular polymer block is introduced. Reversibility of the metal ion loading enables area-selective localized replacement of metal ions in the self-assembled patterns and creates segmented metal nanowire arrays with different metallic components. Further integration of this method with shear aligning process produces high aligned segmented metal nanowire array with desired local chemical compositions.

HPV-independent Differentiated Vulvar Intraepithelial Neoplasia (dVIN) is Associated With an Aggressive Clinical Course.

Differentiated vulvar intrapeithelial neoplasia (dVIN) is an human papillomavirus (HPV)-independent precursor of squamous cell carcinoma (SCC), and the aim of this study was to better characterize its natural history. Cases of dVIN were identified from the pathology archives. Outcomes of patients with dVIN only, without associated invasive SCC, were compared with a cohort of patients with high-grade squamous intraepithelial lesion [HSIL(VIN3)]. Eighteen patients diagnosed with dVIN with adjacent invasive SCC (SCC/dVIN) and 7 patients with dVIN only, without invasive carcinoma, were identified. Mean age in both cohorts was 75 yr. All lesions but 1 were unifocal. In 35% of SCC/dVIN cases the surgical resection margins were positive for SCC, with 75% and 60% having margins positive for dVIN in the SCC/dVIN and dVIN-only cohorts, respectively. In total, 23/25 women with dVIN only or dVIN/SCC, for whom there was follow-up information, experienced either progression to or recurrence of invasive SCC, respectively, at a median of 1.1 yr, including all but 1 case of dVIN only, where the median time of progression to invasive SCC was 1.9 yr. A total of 22/25 women died of disease with a median overall survival of 3.4 yr. The outcome (i.e. progression to invasive carcinoma) of patients with dVIN only was significantly worse than that of a comparison group of 18 patients with HSIL(VIN3) (progression-free survival log-rank, P<0.001; disease-specific survival, P=0.04; overall survival, P=0.01). Six of 7 patients with dVIN only developed invasive carcinoma on follow-up, compared with 0 of 18 patients with HSIL(VIN3). The diagnosis of dVIN indicates the presence of a high-risk human papillomavirus-negative precursor of invasive SCC. These patients are likely to progress to invasive carcinoma over a relatively short period, at which point their prognosis is guarded.

Unfavorable Course of Subclinical Hypothyroidism in Children with Hashimoto's Thyroiditis Compared to Those with Isolated Non-Autoimmune Hyperthyrotropinemia.

Subclinical hypothyroidism (SCH) is a common problem in pediatric population, and the natural history of SCH varies depending on its etiology. Whether Hashimoto's thyroiditis (HT) negatively affects the natural course of SCH was investigated in pediatric patients without concomitant diseases. Predictors for levothyroxine medication were also evaluated. Medical records of 109 children with SCH (91 girls, 5?18 years) diagnosed between 2005 and 2014 were retrospectively reviewed. Patients were classified into HT (n = 37) and isolated non-autoimmune hyperthyrotropinemia (iso-NAHT, n = 72). During median 2 years of follow-up, only 10.1% of SCH patients eventually initiated levothyroxine, and HT patients showed a higher probability of requiring levothyroxine medication than iso-NAHT patients (21.6% vs. 4.2%). Underlying HT independently predicted deterioration of thyroid function, leading to levothyroxine medication (hazard ratios [HRs], 4.6 vs. iso-NAHT, P = 0.025). High titers of anti-thyroglobulin antibodies (TGAbs) predicted later medication in the HT group (HRs, 28.2 vs. normal TGAbs, P = 0.013). Most pediatric SCH showed benign and self-remitting courses. Underlying HT significantly increases the risk for levothyroxine medication, especially with high titers of TGAbs.

Meta-analysis method for discovering reliable biomarkers by integrating statistical and biological approaches: An application to liver toxicity.

Biomarkers that are identified from a single study often appear to be biologically irrelevant or false positives. Meta-analysis techniques allow integrating data from multiple studies that are related but independent in order to identify biomarkers across multiple conditions. However, existing biomarker meta-analysis methods tend to be sensitive to the dataset being analyzed. Here, we propose a meta-analysis method, iMeta, which integrates t-statistic and fold change ratio for improved robustness. For evaluation of predictive performance of the biomarkers identified by iMeta, we compare our method with other meta-analysis methods. As a result, iMeta outperforms the other methods in terms of sensitivity and specificity, and especially shows robustness to study variance increase; it consistently shows higher classification accuracy on diverse datasets, while the performance of the others is highly affected by the dataset being analyzed. Application of iMeta to 59 drug-induced liver injury studies identified three key biomarker genes: Zwint, Abcc3, and Ppp1r3b. Experimental evaluation using RT-PCR and qRT-PCR shows that their expressional changes in response to drug toxicity are concordant with the result of our method. iMeta is available at http://imeta.kaist.ac.kr/index.html.

Pediatric Goiter: Can Thyroid Disorders Be Predicted at Diagnosis and in Follow-Up?

OBJECTIVE: To investigate the prevalence of thyroid dysfunction, autoimmune thyroid disease (AITD), and simple goiter at goiter diagnosis, and to analyze the natural course of simple goiter and predictors for progression to AITD and/or thyroid dysfunction. STUDY DESIGN: In total, 939 patients (770 females, 5.0-17.9 years) with goiter were reviewed retrospectively. Anthropometrics, pubertal status, goiter grade, and family history (FH) of thyroid disease were investigated. Simple goiter was defined as euthyroid goiter without pathologic cause, after excluding AITD and isolated nonautoimmune hyperthyrotropinemia (iso-NAHT). RESULTS: At diagnosis, 36.9% of children showed thyroid dysfunction and/or AITD (euthyroid AITD [9.9%], hyper- or hypothyroid AITD [18.4%], iso-NAHT [8.6%]). Risk for subsequent medication was higher in euthyroid AITD than simple goiter (20.4% vs 0.3%, P < .001). Hashimoto thyroiditis (HT) and iso-NAHT developed in 5.2% and 6.6% of patients initially diagnosed with simple goiter during the median 2.0-year follow-up. Compared with the persistent simple goiter group, the HT group had greater FH (54.8% vs 23.6%) and unchanged or increasing goiter size (89.3% vs 71.8%), and the iso-NAHT group had a higher proportion of patients within the upper tertile range of baseline thyrotropin levels (71.8% vs 24.9%) and unchanged or increasing goiter size (86.8% vs 71.8%; all P < .05). CONCLUSIONS: Thyroid disorders were detected in one-third of pediatric patients presenting with goiter. The higher risk for thyroid dysfunction needing medication in patients with euthyroid AITD emphasizes the importance of autoantibody evaluation at diagnosis. During simple goiter follow-up, progression to HT or iso-NAHT occurs, especially in patients with FH or persistent goiter.

Geography of follicle formation in the embryonic mouse ovary impacts activation pattern during the first wave of folliculogenesis.

During embryonic development, mouse female germ cells enter meiosis in an anterior-to-posterior wave believed to be driven by retinoic acid. It has been proposed that ovarian follicle formation and activation follow the same general wave of meiotic progression; however, the precise anatomic specification of these processes has not been delineated. Here, we created a mouse line using Mvh, Gdf9, and Zp3 promoters to drive distinct temporal expression of three fluorescent proteins in the oocytes and to identify where the first follicle cohort develops. The fluorescent profile revealed that the first growing follicles consistently appeared in a specific region of the ovary, the anterior-dorsal region, which led us to analyze if meiotic onset occurred earlier in the dorsal ovarian region. Surprisingly, in addition to the anterior-to-posterior wave, we observed an early meiotic entry in the ventral region of the ovary. This additional anatomic stratification of meiosis contrasts with the localization of the initial follicle formation and activation in the dorsal region of the ovary. Therefore, our study suggests that the specification of cortical and medullar areas in the ventral and dorsal regions on the ovary, rather than the onset of meiosis, impacts where the first follicle activation event occurs.

Large-area nanosquare arrays from shear-aligned block copolymer thin films.

While block copolymer lithography has been broadly applied as a bottom-up patterning technique, only a few nanopattern symmetries, such as hexagonally packed dots or parallel stripes, can be produced by spontaneous self-assembly of simple diblock copolymers; even a simple square packing has heretofore required more intricate macromolecular architectures or nanoscale substrate prepatterning. In this study, we demonstrate that square, rectangular, and rhombic arrays can be created via shear-alignment of distinct layers of cylinder-forming block copolymers, coupled with cross-linking of the layers using ultraviolet light. Furthermore, these block copolymer arrays can in turn be used as templates to fabricate dense, substrate-supported arrays of nanostructures comprising a wide variety of elements: deep (>50 nm) nanowells, nanoposts, and thin metal nanodots (3 nm thick, 35 nm pitch) are all demonstrated.