Search

Sensorineural hearing loss can be caused by lesions to the inner ear during development. Understanding the events and signaling pathways that drive inner ear formation is crucial for determining the possible causes of congenital hearing loss. We have analyzed the innervation and expression of SOX2, JAGGED1, β-catenin (CTNNB1), and vitamin D receptor (VDR) in the inner ears of human conceptuses aged 5 to 10 weeks after fertilization (W) using immunohistochemistry. The prosensory domains of the human inner ear displayed SOX2 and JAGGED1 expression throughout the analyzed period, with SOX2 expression being more extensive in all the analyzed timepoints. Innervation of vestibular prosensory domains was present at 6 W and extensive at 10 W, while nerve fibers reached the base of the cochlear prosensory domain at 7-8 W. CTNNB1 and VDR expression was mostly membranous and present during all analyzed timepoints in the inner ear, being the strongest in the non-sensory epithelium. Their expression was stronger in the vestibular region compared to the cochlear duct. CTNNB1 and VDR expression displayed opposite expression trends during the analyzed period, but additional studies are needed to elucidate whether they interact during inner ear development.

Migratory foreign body appeared to be bird feather, caused peritonsillar and periparotid abscess in a nine-month-old infant. Patient presented painful, tender and fluctuating red neck mass on the left neck region II, and refusal of oral intake, with no fever. Azithromycin was introduced four days before presentation for suspected urinary tract infection. ENT examination revealed left peritonsillar abscess; ultrasound confirmed periparotid abscess, MSCT verified both diagnoses. Under general anaesthesia, we performed abscess incision, after pus drainage, small foreign body spontaneously came through the wound. After washing it with saline, it appeared like a bird feather. Subsequently, peritonsillar abscess was incised and drained. After 24-hour postoperative care on pediatric intensive care unit, the patient continued three-day parenteral antibiotic treatment on the otolaryngology department; it was discharged with a recommendation to continue seven days of oral antibiotic therapy. Suggested mechanism was ingestion of bird feather from stuffed bedding, that got trapped in the tonsillar crypt. Afterwards, it started to migrate through the neck tissue. Households with children younger than three years should not have feather stuffed clothes or beddings., Competing Interests: Declaration Competing of Interest None declared., (Copyright © 2020. Published by Elsevier B.V.)

Aim: We present the case of a 48-year-old male patient who underwent surgery for a recurrent metastatic parathyroid gland carcinoma in the patient's right paratracheal space of the neck. The patient had undergone surgery for lower right parathyroid gland carcinoma 28 months earlier., Results: The metastases were resected en bloc with an ipsilateral central neck dissection and with the removal of the enlarged lower left parathyroid gland. After exploration of the remnant parathyroid glands we noticed that lower left parathyroid gland was macroscopically enlarged so we decided to remove it to prevent possible hypercalcemia in future and to also prevent possible recurrence of cancer or development of a new primary, considering the identical embryological origin of the lower parathyroid glands and possibility of synchronous, multiple tumors, which generally follow the same embryological origin if they occur. The patient was also treated with radiation therapy after the surgery., Conclusion: With the present surgical approach to recurrent metastatic parathyroid gland carcinoma, we aimed to prevent the recurrence of cancer or development of new primary and prevent or delay hypercalcemia in the future with all severe adverse metabolic states associated with high serum calcium levels.

The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants' cristae was further used here to identify a profile of genes specific to the lacking cell type. Microarrays followed by a detailed consultation of web-accessible mouse databases allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have associated inner ear abnormalities. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X-linked deafness in humans. Our current study suggests an epigenetic role that mechanical, and potentially other, stimuli originating from muscle, play in organogenesis, and offers an approach to finding novel genes responsible for altered inner ear phenotypes.

Objective: The objective of this study was to evaluate the excitability of contralateral and ipsilateral corticobulbar pathways, using the methodologies of navigated transcranial magnetic stimulation (nTMS) and transcranial electrical stimulation (TES)., Methods: In 11 healthy subjects, the primary motor cortex (M1) for laryngeal muscles was mapped with nTMS in both hemispheres and the corticobulbar motor evoked potentials (CoMEPs) were recorded from the right cricothyroid muscle. In 15 patients undergoing left craniotomy, CoMEPs were obtained from cricothyroid muscles bilaterally, using TES over C3/Cz and C4/Cz., Results: In five out of 11 healthy subjects, both contralateral and ipsilateral CoMEPs were recorded from the right cricothyroid muscle. In eight out of 15 patients, contralateral and ipsilateral CoMEPs were elicited with TES over C3/Cz, while in five out of 15 patients contralateral and ipsilateral CoMEPs were elicited with TES over C4/Cz. Contralateral CoMEP amplitude responses were significantly larger compared to ipsilateral CoMEP amplitudes in both groups., Conclusion: We obtained significantly larger amplitude responses of contralateral CoMEPs from cricothyroid muscles compared to ipsilateral CoMEP amplitude using nTMS in healthy subjects and TES in patients. This confirms the bilateral nature of corticobulbar pathway projections for laryngeal muscles, with contralateral domination., Significance: These findings will influence recording of CoMEPs during preoperative and intraoperative mapping of M1 for laryngeal muscle representation, and they facilitate the pathophysiologic research of motor speech disorders., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Hypothesis: Spatiotemporal interplay of factors controlling proliferation, differentiation and apoptosis within the developing human inner ear is essential for labyrinth morphogenesis and development of vestibular and cochlear functions., Background: Studies on the early human inner ear development are scarce and insufficient., Methods: The immunolocalization of Ki-67, Bcl-2, caspase-3, and IGF-1 was analyzed in 6 human inner ears, 5 to 10 gestational weeks old. Statistical data were analyzed using the Kruskal-Wallis test., Results: During the analyzed period, the otocyst has transformed into cochlear duct and saccule ventrally and semicircular canals and utricle dorsally. Initial differentiation of sensorineural fields characterized organ of Corti, maculae, and cristae ampullares. Intense (50%) and evenly distributed proliferation Ki-67 in the otocyst decreased to 24% to 30% and became spatially restricted within the membranous labyrinth epithelium. Simultaneously, expression of antiapoptotic Bcl-2 protein increased in sensorineural fields of organ of Corti, macula, and crista ampullaris. Throughout the investigated period, apoptotic caspase-3 positive cells were mainly distributed at the luminal and basal surfaces of labyrinth epithelium. An inhibitor of apoptosis IGF-1 co-expressed with Bcl-2 and increased in the sensorineural fields with advancing development., Conclusion: The described expression pattern indicates roles for cell proliferation in the growth of the inner ear and Bcl-2 in differentiation of sensorineural fields and protection from apoptosis. Both IGF-1-and caspase-3-mediated apoptosis seem to contribute to proper morphogenesis, differentiation, and innervations of sensorineural fields within the cochlea, semicircular canals, saccule, and utricle. Alterations in spatiotemporal interplay of investigated factors might lead to disturbances of vestibular and cochlear function.

Background: Factor V Leiden has been described as a common genetic risk factor for venous thromboembolism. The geographic distribution of this abnormality varies greatly, being high in Europe and almost absent in Asia and Africa. Particularly high prevalence is observed in some Mediterranean countries, which suggests the Mediterranean origin of this mutation. Similarly, prevalence of silent mutation 1311 of the G6PD gene seems to be higher among Mediterranean populations. Since the Dalmatian population (of south Croatia) geographically belongs to the Mediterranean populations we analyzed the prevalence of FV-Leiden and silent mutation 1311 in this region. Furthermore, because the coincidence of G6PD deficiency and venous thromboembolism was described earlier, we tested a possible association of FV-Leiden and G6PD deficiency., Methods: One hundred sixty-eight healthy blood donors and 55 G6PD deficient individuals originating from the Dalmatian region were tested for the presence of FV-Leiden mutation and silent mutation 1311., Results: Prevalence of FV-Leiden among blood donors was 2.4%, while among G6PD deficient individuals it was significantly higher, 11% (p=0.011). Prevalence of silent mutation 1311 among blood donors and G6PD deficient individuals was 21 and 15%, respectively., Conclusions: Observed allele frequencies among individuals originating from the Dalmatian region is similar to the neighboring European and Mediterranean populations. Interestingly, our results indicate the association of the FV-Leiden and G6PD deficiency and warrant further studies.

The spatial and temporal distribution as well as ultrastructural and biochemical characteristics of apoptotic and mitotic cells during human eye development were investigated in 14 human conceptuses of 4-9 postovulatory weeks, using electron and light microscopy. In the 5th developmental week, apoptotic and mitotic cells were found in the neuroepithelium of the optic cup and stalk, being the most numerous at the borderline between the two layers of the optic cup, and at the place of transition of the optic cup into stalk. They were also found at the region of detachment of the lens pit from the surface ectoderm. In the later developmental stages (the 6th-the 9th week), apoptotic and mitotic cells were observed in the neural retina and the anterior lens epithelium. Throughout all stages examined, mitotic cells were found exclusively adjacent to the lumen either of the intraretinal space or the optic stalk ventricle, or were restricted to the superficial epithelial layer of the lens primordium. Unlike mitotic cells, apoptotic cells occurred throughout the whole width both of the neuroepithelium and the surface epithelium. Ultrastructurally, apoptotic cells were characterised by round- or crescent-shaped condensations of chromatin near the nuclear membrane, while in the more advanced stages of apoptosis by apoptotic bodies. The distribution of caspase-3-positive cells coincided with the location of apoptotic cells described by morphological techniques indicating that the caspase-3-dependent apoptotic pathway operates during the all stages of human eye development. The location of cells positive for anti-apoptotic bcl-2 protein was in accordance with the regions of eye with high mitotic activity, confirming the role of bcl-2 in protecting cells from apoptosis. In the earliest stage of eye development, apoptosis and mitosis might be associated with the sculpturing of the walls of optic cup and stalk, while high mitotic activity along the intraretinal space and optic stalk ventricle indicates its role in the gradual luminal closure. These processes also participate in the detachment of the lens pit epithelium from the surface ectoderm as well as in further closure of the lens vesicle. Later on, both processes seem to be involved in the neural retina differentiation, lens morphogenesis and secondary lens fibre differentiation.