Πέμπτη 13 Ιανουαρίου 2022

Exposure to aluminium chloride during the peripuberal period induces prostate damage in male rats

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Via histochem

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Acta Histochem. 2022 Jan 9;124(1):151843. doi: 10.1016/j.acthis.2022.151843. Online ahead of print.

ABSTRACT

Aluminium (Al) is an important metal, but it can be toxic including for prostate tissue. This study aimed to evaluate whether exposure to aluminium chloride (AlCl3) during the peripubertal period affects ventral prostate development in rats. Male Wistar rats (30 days old) were distributed into three experimental groups: control (sterile 0.9% saline solution), AL7 (7 m g AlCl3/kg) and AL34 (34 mg AlCl3/kg). Animals were treated intraperitoneally from postnatal day (PND) 36-66 (peripubertal period). At PND67, the animals were anaesthetized and euthanized. Blood was collected for testosterone levels. The ventral prostate (VP) was removed, weighed and processed for histochemistry and immunohistochemistry to detect androgen (AR) and Ki67. Stereological and histopathological analyses, mast cell counts, and determinations of myeloperoxidase (MPO) and N-acetyl glycosidase (NAG) activity and IL-6 levels were performed. The AL34 group presented a reduction in body weight and increase in MPO activity compared to the other groups. In both the AL7 and AL34 groups, there was reorganization of the prostatic tissue compartments. There was no significant difference in prostate weight, number of granulated or degranulated mast cells, or testosterone levels. In conclusion, the exposure to aluminium chloride during the peripubertal period impairs the prostatic devel opment.

PMID:35021147 | DOI:10.1016/j.acthis.2022.151843

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Association of Performance on Dichotic Auditory Tests With Risk for Incident Dementia and Alzheimer Dementia

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This cohort study examines associations between signal sen sitivity, central auditory processing, and dementia and Alzheimer dementia risk.
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Postoperative respiratory adverse events in children after endoscopic laryngeal cleft repair

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Eur Arch Otorhinolaryngol. 2022 Jan 13. doi: 10.1007/s00405-021-07250-1. Online ahead of print.

ABSTRACT

PURPOSE: Due to the serious nature of respiratory adverse events, understanding their incidence can help in decisions regarding safe postoperative disposition. There have been no studies, however, evaluating the risk of postoperative respiratory adverse events (PRAEs) in children undergoing endoscopic laryngeal cleft (LC) repair, which is the primary objective of this study.

METHODS: We conducted a retrospective chart review of all patients who underwent LC repair at a large tertiary children's hospital from 2015 to 2020. PRAEs were defined as having at least one of the following: remained intubated, required reintubation, required positive pressure ventilation, required high flow O2 nasal cannula, or required more than one dose of racemic epinephrine. Univariate analyses compared demographic, preoperative character istics, and intraoperative characteristics between those with and without a PRAE.

RESULTS: Overall, 8/26 (31%) patients had a PRAE and there were no differences between patients who did and did not have a PRAE and most comorbidities. Younger age (p = 0.03), being male (p = 0.07), and being admitted preoperatively (p = 0.07) were potentially associated with PRAEs. Need for intraoperative intubation for any reason or duration was associated with increased incidence of PRAEs (p = 0.02).

CONCLUSION: The overall 31% incidence of postoperative respiratory adverse events reaffirms the appropriateness of PICU disposition for a large proportion of children undergoing endoscopic LC repair. Further studies with increased sample sizes are needed to tease apart patient or procedure-specific factors that significantly increase the risk of respiratory adverse events to have more definitive evidence regarding safe postoperative disposition.

PMID:35024957 | DOI:10.1007/s00405-021-07250-1

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Lenvatinib Plus Anti-PD-1 Combination Therapy for Advanced Cancers: Defining Mechanisms of Resistance in an Inducible Transgenic Model of Thyroid Cancer

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Thyroid, Ahead of Print.
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Τετάρτη 12 Ιανουαρίου 2022

Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India

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World J Nucl Med. 2021 Nov 1;20(4):361-368. doi: 10.4103/wjnm.wjnm_143_20. eCollection 2021 Oct-Dec.

ABSTRACT

Management of differentiated thyroid carcinoma (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (TENIS) and negative neck ultrasound scan causes considerable diagnostic and therapeutic dilemma, especially in resource-poor settings. The aim of this study was to evaluate clinicopathological features and outcome of TENIS patients with negative n eck US attending a thyroid cancer clinic in India. From a DTC database of 722 containing 193 TENIS patients, subjects with negative neck US and negative Tg antibody (TgAb) were selected retrospectively and analyzed using appropriate statistical methods. The study group included 64 patients (male - 17, female - 47, mean age - 44.7 ± 12.8 years) with 54 papillary and 10 follicular thyroid carcinomas, American Thyroid Association (ATA) recurrence risk categorization (2009) - low - 16, intermediate - 28, and high - 2 0. Most of the patients became TENIS within 1 year of diagnosis with median Tg level of 6.5 ng/mL (1.2-996 ng/mL) and mean follow-up of 7.8 years. On follow-up, Tg dropped spontaneously in 27 patients, more among the low and intermediate-risk categories. For those with high or increasing Tg level, further imaging (fluorodeoxyglucose positron emission tomography/computed tomography) was done and 14 out of 18 were positive. Treatment included empiric radioactive iodine thera py-16, external beam radiation therapy (EBRT)-7, and lymph node dissection (LND)-10. A favorable outcome was seen in 36 patients and unfavorable in 28. Distant metastases were associated with unfavorable outcome and poor survival. Progression-free survival was significantly better in the Tg group of <10 at the time of TENIS (111 months) compared to the Tg group >10 (72 months). Tg level dropped spontaneously in nearly half the patients, especially if levels were <10 and more so among the low-risk category. Distant metastasis was predictive of unfavorable outcomes. Along with Tg level, the ATA risk category might help to predict clinical course and reduce unnecessary expensive imaging in resource-poor settings.

PMID:35018 151 | PMC:PMC8686749 | DOI:10.4103/wjnm.wjnm_143_20

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Calcitriol induces estrogen receptor alpha expression through direct transcriptional regulation and epigenetic modifications in estrogen receptor-negative breast cancer cells

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Am J Cancer Res. 2021 Dec 15;11(12):5951-5964. eCollection 2021.

ABSTRACT

Patients with estrogen receptor (ER) α-negative breast tumors have a poor prognosis and are not suitable for hormone therapy. Previously, we demonstrated that calcitriol, the active metabolite of vitamin D, induces ERα expression and re-establishes the response to antiestrogens in ER-negative breast cancer cells. However, the mechanisms involved in this process have not been elucidated. Therefore, the present study was undertaken to investigate the mechanisms implicated in the calcitriol-induced ERα expression in ER-negative breast cancer cells. Using EMSA and ChIP assays, we found that the calcitriol/vitamin D receptor (VDR)/retinoic X receptor (RXR) complex binds to putative vitamin D response elements (VDREs) in the ERα gene promoter region. In addition, we established by a fluorometric assay that calcitriol decreased DNA-methyltransferase and histone deac etylase activities. Flow cytometry and qPCR analyses showed that co-treatment of calcitriol with inhibitors of the histone deacetylase and DNA methyltransferase, and genistein significantly increased ERα expression, compared to that observed with the compounds alone. In conclusion, the calcitriol-dependent ERα induction in ER-negative breast cancer cells results from binding of the VDR-RXR complex to VDREs in the ERα gene promoter region, including the downregulation of enzymes with chromatin-remodeling activities. These results may bring forth novel mechanistic knowledge into the actions of calcitriol in ERα-negative breast cancer.

PMID:35018235 | PMC:PMC8727803

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Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring

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Thyroid, Ahead of Print.
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