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Pelvic lymph node dissection (PLND) is the most accurate procedure for lymph node (LN) staging in prostate cancer (PCa) patients. LN sectioning and hematoxylin and eosin (H&E) staining of at least one slice remains the gold standard for LN evaluation, potentially leading to misdetection of small metastatic focus. Entire LN analysis is possible with One-Step Nucleic Acid Amplification (OSNA) by detecting cytokeratin 19 (CK19) mRNA as a surrogate for LN invasion. This study aimed to compare postoperative performance of OSNA pooling with conventional H&E staining for pathological LN detection in PCa patients. POPCORN was an observational, prospective, and multicenter study of patients with PCa who underwent PLND. Dissected LNs were analyzed by both methods. This study included 2503 LNs from 131 patients, showing no statistically significant differences in pathological LN detection. Concordance between methods was high (93.9%), as were specificity (96.6%) and negative predictive value (96.6%) of OSNA pooling. The measure of agreement (Cohen's Kappa [κ]) was 0.70. Only eight (6.1%) discordances were observed, including four misdetections from each method. Results showed a high concordance between OSNA pooling and H&E staining, suggesting that OSNA pooling may be a good alternative to H&E staining to detect LN metastases in PCa patients.

In general, mercury (Hg) undergoes biomagnification in aquatic systems. The absence of Hg biomagnification in a certain aquatic environment constitutes an exceptional finding and this seems to be the case for Sepetiba Bay, in Rio de Janeiro state (RJ), Brazil. There are three distinct ecological populations of Guiana dolphins in the Sepetiba Bay (SB)-Ilha Grande Bay (IGB) Complex, inhabiting: (1) the inner part of SB; (2) SB entrance; and (3) IGB. In addition, there are two other delphinid species, rough-toothed dolphin and Atlantic spotted dolphin, that feed on the SB-IGB Complex. Considering the widely employed use of cetaceans as sentinels of environmental contamination by bioaccumulative toxicants, we have biopsy sampled individuals of the abovementioned ecological populations/species for measuring skin Hg concentrations. Two Bryde's whales and one humpback whale were biopsied in the SB-IGB Complex as well. Skin Hg concentrations [μg g -1 dry weight (dw)] of Guiana dolphins were the highest in IGB, followed by SB entrance and the inner part of SB (0.99-5.47; 0.09-6.00; 0.08-2.22). Considering all species investigated in the present study, skin Hg concentrations were found in the following order: humpback whale < Bryde's whale < Guiana dolphins from SB inner part < Guiana dolphins from SB entrance < Guiana dolphins IGB = Atlantic spotted dolphins < rough-toothed dolphins. The skin Hg concentrations found in Guiana dolphins from the inner part of Sepetiba Bay (0.08-2.22) and rough-toothed dolphins from the SB-IGB Complex (1.26-20.0) are among the lowest and highest ever reported for dolphins worldwide, respectively., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Studies on the occurrence of POPs and other persistent compounds in pristine areas are extremely valuable, as they offer insights on the long-range transportation of POPs and the occurrence of natural compound producers' areas. In this regard, this study aimed to report data of both anthropogenic (polychlorinated biphenyls, PCBs, and polybrominated diphenyl ethers, PBDEs) and natural (methoxylated PBDEs, MeO-BDEs) compounds in tissues of the black triggerfish, Melichthys niger (Tetraodontiformes, Balistidae), specimens (n = 30) sampled in 2018 during a scientific expedition conducted at Trindade Island. Concentrations of ∑ 28 PCBs ranged from 73 to 1052 ng g -1 lw in liver, 334 to 1981 ng g -1 lw in gonads, and 20 to 257 ng g -1 lw in muscle, with the predominance of PCB-180 in liver and PCB-52 in gonad and muscle. Concentrations of ∑ 7 PBDEs ranged from -1 lw in liver, -1 lw in muscle, and they were < LOD in gonads. The BDE-47 was the most representative congener detected in liver and muscle. Mean concentrations of ∑ 8 MeO-BDEs were 270 ng g -1 lw, 442 ng g -1 lw, and 70 ng g -1 lw in liver, gonad, and muscle, respectively. The 2-MeO-BDE-68 was the most representative congener among MeO-BDEs. The mobilization of lower chlorinated PCBs from liver to other tissues, with possible retention of higher chlorinated PCBs in liver, can be a factor of concern considering the chronic exposure of those fish. PBDEs and MeO-BDEs in fish from remote environments were reported in a low number of studies worldwide. Considering that remote sites face environmental pollution either directly by anthropogenic influence or by long-range transportation, more studies on the occurrence of persistent compounds in these environments are paramount, and it is fundamental to understand the dispersion and accumulation of POPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The mechanisms underlying the formation of complex structures such as during the outgrowth of the cochlear duct are still poorly understood., Results: We have analyzed the morphological and molecular changes associated with cochlear development in mouse mutants for the transcription factor Meis2, which show defective coiling of the cochlea. These morphological abnormalities were accompanied by the formation of ectopic and extra rows of sensory hair cells. Gene profiling of otic vesicles from Meis2 mutants revealed a dysregulation of genes that are potentially involved in Sonic hedgehog (Shh)-mediated patterning of the cochlear duct. Like in Shh mutants, Meis2 defective mice showed a loss of genes that are expressed in the apical part of the cochlear duct., Conclusions: Taken together, these data reveal that the loss of Meis2 leads to a phenotype that resembles Shh mutants, suggesting that Meis2 is instrumental for cochlear Shh signaling. The modulation of the same subset of genes provides an interesting insight into which Shh responsive genes are essential for outgrowth and patterning of the cochlear duct., (© 2024 American Association for Anatomy.)

Background: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g -1 ) and submitted to three culinary treatments (roasting, steaming and grilling)., Results: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion., Conclusion: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

A 9-year-old boy diagnosed with acute myeloblastic leukemia and undergoing chemotherapy, was admitted with febrile neutropenia. During his admission, several violaceous plaques appeared on the upper extremities and anterior left hemithorax, which worsened and acquired a necrotic center. We performed a biopsy and histology showed a cutaneous infarction at the dermoepidermal and subcutaneous level. We observed abundant wide hyphae with right-angled branching and a culture isolated Rhizopus oryzae. A plastic surgery consultant performed a surgical debridement of the lesions and treatment was started with intravenous amphotericin B. The patient did well on treatment and after almost a month of hospitalization, he was discharged with oral posaconazole. Mucormycosis is an opportunistic fungal infection associated with immunosuppression, particularly involving prematurity and hematological diseases in the pediatric age group. Multiple lesions, as in our case, are infrequent. The clinical presentation is variable. Direct smear or histological observation is the quickest diagnostic technique whereas culture is the most definitive. The combination of surgical debridement and amphotericin B is the treatment with the highest survival rates.

Background: We hypothesized that, as posterior malleolar ankle fractures usually present one or two main fragments, the buttress plating principle can be successfully achieved either with conventional nonlocking or anatomic locking posterior tibia plates, and no clinical differences should be found. The aim of this study was to evaluate the outcomes of posterior malleolar ankle (PM) fractures treated with conventional nonlocking (CNP) or anatomic locking plates (ALP), and also to compare both constructs in terms of crude costs., Methods: A retrospective cohort study was designed. CNP was used in 22 patients and ALP was used in 11 patients. American Orthopedic Foot and Ankle Society (AOFAS) score was registered at four weeks, 3-6 months, 12 and 24 months to assess all patients' functional status. The primary outcome was ankle and hindfoot AOFAS score at 12 months follow-up visit. All complications, radiographic evaluation and implant construct costs were also registered and compared. The average follow-up was 25.4 (range, 12-42) months., Results: No significant difference was observed between both cohorts, in terms of AOFAS score and complication rate (P > .05). We found that ALP construct is 17 times more expensive than CNP construct in our institution (P < .001)., Conclusion: Anatomic locking posterior tibial plates may be an interesting device when poor bone quality is present or when a true multifragmentary pilon fracture is faced. Anatomic locking posterior tibia plate should not become a regular implant for any PM fracture since equivalent clinical and radiological results were obtained in our study using CNP with a significant reduced cost., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Persistent organic pollutants (POPs) were analyzed in 136 blubber samples of Franciscana dolphins from Brazil (Pontoporia blainvillei), which is the most threatened dolphin in the Southwestern Atlantic. The dolphins were caught by the fishery fleet and collected from 2000 to 2018 in three regions of São Paulo state: northern São Paulo (SPN), central São Paulo (SPC), and southern São Paulo (SPS). The POPs analyzed in this study were polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDTs), Mirex, hexachlorobenzene (HCB), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and polybrominated diphenyl ethers (PBDEs). The concentrations ranged from 36 to 7200 ng g -1 lipid weight (lw) and 113-42200 ng g -1 lw for predominant compounds DDTs and PCBs, respectively. Similar profiles of PCB congeners were observed with a predominance of hexachlorinated compounds, representing approximately 50% of the total PCB amount; the highest PCB concentrations were observed from Baixada Santista (SPC) proximate to a highly urbanized and industrial coastal area. Significant differences were observed between the sexes and maturity of dolphins, mainly for PCBs, DDTs, and Mirex. In general, POPs other than HCB in Franciscana dolphins showed downward temporal trends, matching the regulatory periods for restricting and/or banning these compounds. Although POP concentrations are declining, PCB levels remain high in small dolphins, suggesting adverse health effects on Franciscanas. As organic contaminants are one of the numerous threats Franciscanas have been vulnerable to along the Brazilian coast, we recommend monitoring POPs levels every five years to check for declining (or stabilizing) trends., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Accumulation of pesticides has a harmful impact on the environment and human health. The main goal of this work was to develop a method to determine and quantify the residues of thirteen pesticides in edible fish and bivalves such as parati ( Mugil curema ), seabass ( Centropomus ssp.), mullet ( Mugil brasiliensis ), clams ( Anomalocardia brasiliana ) and mussel ( Mytilus galloprovincialis ) collected from Sepetiba Bay and Parnaiba River Delta (Brazil) between 2019 and 2020. Matrix solid-phase dispersion (MSPD) was used for extraction and quantification through gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). The method was validated (linearity, accuracy and precision) for fatty fish ( Salmo salar ), lean fish ( Mugil curema ) and bivalves ( Mytilus edulis ). The survey found linear correlation coefficients (r) equal to or greater than 0.9 for almost all analytes. The relative standard deviations (RSD) of five replicates were less than 20% for almost all analytes at different concentrations in lean fish, fatty fish and bivalves. Most analytes showed satisfactory accuracy. Alachlor herbicide was found in samples of seabass, mussels, clams and parati with levels ranging between 0.55 to 420.39 μg kg -1 dw. Ethion was found in parati (maximum 211.22 μg kg -1 dw), mussels (15.1 μg kg -1 dw) and clams (maximum 44.50 μg kg -1 dw). Alachlor was found in clams (maximum 93.1 μg kg -1 dw), and bifenthrin was found in parati (maximum 43.4 μg kg -1 dw) and clams (maximum 42.21 μg kg -1 dw). The validated method was satisfactory for the determination of eleven pesticides in the fatty fish matrix, and thirteen pesticides in the samples of lean fish and bivalves. The presence of alachlor, ethion and bifenthrin stands out.

Hearing loss is the most prevalent sensorineural impairment in humans. Yet despite very active research, no effective therapy other than the cochlear implant has reached the clinic. Main reasons for this failure are the multifactorial nature of the disorder, its heterogeneity, and a late onset that hinders the identification of etiological factors. Another problem is the lack of human samples such that practically all the work has been conducted on animals. Although highly valuable data have been obtained from such models, there is the risk that inter-species differences exist that may compromise the relevance of the gathered data. Human-based models are therefore direly needed. The irruption of human induced pluripotent stem cell technologies in the field of hearing research offers the possibility to generate an array of otic cell models of human origin; these may enable the identification of guiding signalling cues during inner ear development and of the mechanisms that lead from genetic alterations to pathology. These models will also be extremely valuable when conducting ototoxicity analyses and when exploring new avenues towards regeneration in the inner ear. This review summarises some of the work that has already been conducted with these cells and contemplates future possibilities.

Currently, the presence of endocrine disrupting chemicals (EDCs) in the marine environment pose а potential risk to both wildlife and human health. The occurrence of EDCs in seafood depends of several factors such as source and amounts of EDCs that reach the aquatic environment, physicochemical features of EDCs, and its accumulation in trophic chain. This review highlights the occurrence and distribution of EDCs along the seafood in the last 6 years. The following EDCs were included in this review: brominated flame retardants (PBDEs, PBBs, HBCDDs, TBBPA, and novel flame retardants); pharmaceuticals (paracetamol, ibuprofen, diclofenac, carbamazepine), bisphenols, hormones, personal care products (Musk and UV Filters), and pesticides (organochlorides, organophosphates, and pyrethroids). Some of them were found above the threshold that may cause negative effects on human, animal, and environmental health. More control in some countries, as well as new legislation and inspection over the purchase, sale, use, and production of these compounds, are urgently needed. This review provides data to support risk assessment and raises critical gaps to stimulate and improve future research., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pharmaceuticals (PhACs) are considered emerging contaminants with potential accumulation in aquatic organisms. Thus, seafood consumption may cause long-term effects and health risk for consumers. In the present study, the occurrence of PhACs in seafood from two Brazilian coastal areas, Sepetiba Bay (n = 43) and Parnaiba Delta River (n = 48), was determined for the first time, and their potential risk for human health was assessed. An eco-friendly multi-analytes method was used, after being validated for the different types of matrices (mussels, fatty and lean fish). All compounds under study were detected at least in four seafood species, including chloramphenicol, an antibiotic prohibited in animal foods. Most PhACs had mean concentrations below limit of quantification. Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs), as well as simvastatin and carbamazepine were the main PhACs bioaccumulated in edible parts of seafood species from Brazil. The high trophic level carnivorous species, snook, was the most contaminated by NSAIDs, while bivalves were the seafood more contaminated by lipid regulators. The profile of contamination did not vary among different types of matrix, except in relation to carbamazepine and ketoprofen. These PhACs were more abundant in species from Sepetiba Bay, an area highly impacted by human influence. The estimated daily exposure for Brazilian population that consumes the studied species was up to 20.3 ng/kg bw/day via carib pointed-venus and 25.7 ng/kg bw/day via snooks, lower than acceptable daily intake. Thus, consumption of seafood species from Sepetiba Bay and Parnaiba Delta River seems to be safe to the population in what concerns the PhACs studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The current COVID-19 outbreak has highlighted the need for the development of new vaccines and drugs to combat Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Recently, various drugs have been proposed as potentially effective against COVID-19, such as remdesivir, infliximab and imatinib. Natural plants have been used as an alternative source of drugs for thousands of years, and some of them are effective for the treatment of various viral diseases. Emodin (1,3,8-trihydroxy-6-methylanthracene-9,10-dione) is a biologically active anthraquinone with antiviral activity that is found in various plants. We studied the selectivity of electrophilic aromatic substitution reactions on an emodin core (halogenation, nitration and sulfonation), which resulted in a library of emodin derivatives. The main aim of this work was to carry out an initial evaluation of the potential to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines. We have prepared emodin derivatives which displayed significant anti-HCoV-NL63 activity. We observed that halogenation of emodin can improve its antiviral activity. The most active compound in this study was the iodinated emodin analogue E&#95;3I, whose anti-HCoV-NL63 activity was comparable to that of remdesivir. Evaluation of the emodin analogues also revealed some unwanted toxicity to Vero cells. Since new synthetic routes are now available that allow modification of the emodin structure, it is reasonable to expect that analogues with significantly improved anti-HCoV-NL63 activity and lowered toxicity may thus be generated.

Especially added on many industrial and domestic products as flame retardants (FRs), polybrominated diphenyl ethers (PBDEs) are among the chemicals of high environmental concern because of their potential harmfulness for environmental and human health. Seafood consumption is considered the main source of PBDEs and their methoxylated congeners (MeO-BDEs) for humans. The present study aims to investigate the seasonal occurrence of six PBDEs and eight MeO-BDEs congeners using Douro river biota (different trophic levels) as sentinels, as well as to evaluate the human exposure risk to PBDEs through seafood consumption. Biota samples (n = 273) were collected from one of the most important Portuguese estuaries in the north-western coast of Portugal at four different seasons (2019-2020). The analyses were performed by an environmental-friendly extraction procedure followed by Gas Chromatography coupled to a triple quadrupole detector (GC-MS/MS). PBDEs were detected in all seafood samples analysed, with means ranging from 0.02 ng g -1 ww (flounder in autumn) to 3.75 ng g -1 ww (mussel in winter). Levels of lower-brominated PBDE congeners were significantly higher than higher-brominated ones in all seasons (p < 0.01). MeO-BDEs ranged from 0.001 ng g -1 ww (grey mullet in summer) to 5.66 ng g -1 ww (green crab in spring). Crabs and mussels presented the highest means of PBDEs and MeO-BDEs. Regarding the health risk assessment of the studied PBDE congeners (47, 99, and 153), consumption of Douro river fish is not a case of concern for consumers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polybrominated diphenyl ethers (PBDEs) and their methoxylated analogues (MeO-BDEs) are widely distributed in the environment. The main concern about the presence of PBDEs and MeO-BDEs in fish is due to their potential endocrine disruption effects in the specimens, and their potential risk to the health of human consumers. Considering these concerns, the goal of this study was to investigate the occurrence of PBDEs and MeO-BDEs in muscle tissues of blue shark (BSH), Prionace glauca, and yellowfin tuna (YFT), Thunnus albacares, caught in the Equatorial Atlantic Ocean (EAO), North-eastern Brazilian waters, and to evaluate the potential risk of human exposure by consumption. Muscle tissues of YFT and BSH were extracted using a Soxhlet apparatus and an Accelerated Solvent Extractor (ASE), respectively. PBDEs and MeO-BDEs were analysed by GC-NCI-MS. Concentrations of PBDEs ranged from not detected (nd) to 10 ng g -1 lipid weight (lw) in YFT muscle samples, while PBDE levels in BSH muscle samples ranged from -1 lw. Regarding MeO-BDEs, the concentration ranged from 55 to 578 ng g -1 lw and from -1 lw in YFT and BSH muscle samples, respectively. MeO-BDE congeners contribution in both YFT and BSH indicated a predominance of 2'-MeO-BDE-68, which is associated to the sponges or sponge-microbiota metabolites. ∑PBDE were statistically similar between YFT and BSH, as well as observed for ∑MeO-BDE. PBDEs and MeO-BDEs in YFT and BSH represent a low potential risk of human exposure through the consumption of edible tissues. Further studies are necessary for a complete assessment of human safety and species conservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Meis genes have been shown to control essential processes during development of the central and peripheral nervous system. Here we have explored the roles of the Meis2 gene during vertebrate inner ear induction and the formation of the cochlea. Meis2 is expressed in several tissues required for inner ear induction and in non-sensory tissue of the cochlear duct. Global inactivation of Meis2 in the mouse leads to a severely reduced size of the otic vesicle. Tissue-specific knock outs of Meis2 reveal that its expression in the hindbrain is essential for otic vesicle formation. Inactivation of Meis2 in the inner ear itself leads to an aberrant coiling of the cochlear duct. By analyzing transcriptomes obtained from Meis2 mutants and ChIPseq analysis of an otic cell line, we define candidate target genes for Meis2 which may be directly or indirectly involved in cochlear morphogenesis. Taken together, these data show that Meis2 is essential for inner ear formation and provide an entry point to unveil the network underlying proper coiling of the cochlear duct., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Durán Alonso, Vendrell, López-Hernández, Alonso, Martin, Giráldez, Carramolino, Giovinazzo, Vázquez, Torres and Schimmang.)

Glial-derived neurotrophic factor (GDNF) has been proposed as a potent neurotrophic factor with the potential to cure neurodegenerative diseases. In the cochlea, GDNF has been detected in auditory neurons and sensory receptor cells and its expression is upregulated upon trauma. Moreover, the application of GDNF in different animal models of deafness has shown its capacity to prevent hearing loss and promoted its future use in therapeutic trials in humans. In the present study we have examined the endogenous requirement of GDNF during auditory development in mice. Using a lacZ knockin allele we have confirmed the expression of GDNF in the cochlea including its sensory regions during development. Global inactivation of GDNF throughout the hearing system using a Foxg1-Cre line causes perinatal lethality but reveals no apparent defects during formation of the cochlea. Using TrkC-Cre and Atoh1-Cre lines, we were able to generate viable mutants lacking GDNF in auditory neurons or both auditory neurons and sensory hair cells. These mutants show normal frequency-dependent auditory thresholds. However, mechanoelectrical response properties of outer hair cells (OHCs) in TrkC-Cre GDNF mutants are altered at low thresholds. Furthermore, auditory brainstem wave analysis shows an abnormal increase of wave I. On the other hand, Atoh1-Cre GDNF mutants show normal OHC function but their auditory brainstem wave pattern is reduced at the levels of wave I, III and IV. These results show that GDNF expression during the development is required to maintain functional hearing at different levels of the auditory system., (© 2019 Wiley Periodicals, Inc.)

The presence of pyrethroid compounds in hepatic tissue of Guiana dolphins (Sotalia guianensis) is reported for the first time. Twelve pyrethroids were determined in 50 animals from eight locations of the Brazilian coast. The highest average concentration of total pyrethroids (∑PYR) was 1166 ng.g -1 lw, with values ranging from 148 to 5918 ng.g -1 lw, in Ilha Grande Bay, Rio de Janeiro State, while the Espírito Santo State had the highest median, 568 ng.g -1 lw. Permethrin was the predominant compound in most areas, contributing for 42% to 81% of the ∑PYR, whereas cypermethrin was the most abundant compound in Guanabara and Sepetiba bays (79% and 81%, respectively), both located in Rio de Janeiro State. Biological factors were not correlated with pyrethroids concentration. Tetramethrin and es/fenvalerate compounds were negatively correlated to the age, suggesting degradation/metabolization capacity in these animals that increases throughout life. Despite being metabolized and excreted, the wide use of these pollutants is reflected in relevant concentrations found in Guiana dolphins. This is the first study evaluating pyrethroids in a representative number of hepatic samples and covering >2600 km of coast. The overall lack of information on pyrethroids in cetaceans highlights the importance of understanding the profile and distribution of these pollutants in dolphins which exclusively inhabit the Southwestern Atlantic coast., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Disabling hearing loss is the most common sensorineural disability worldwide. It affects around 466 million people and its incidence is expected to rise to around 900 million people by 2050, according to World Health Organization estimates. Most cases of hearing impairment are due to the degeneration of hair cells (HCs) in the cochlea, mechano-receptors that transduce incoming sound information into electrical signals that are sent to the brain. Damage to these cells is mainly caused by exposure to aminoglycoside antibiotics and to some anti-cancer drugs such as cisplatin, loud sounds, age, infections and genetic mutations. Hearing deficits may also result from damage to the spiral ganglion neurons that innervate cochlear HCs. Differently from what is observed in avian and non-mammalian species, there is no regeneration of missing sensory cell types in the adult mammalian cochlea, what makes hearing loss an irreversible process. This review summarizes the research that has been conducted with the aim of developing cell-based strategies that lead to sensory cell replacement in the adult cochlea and, ultimately, to hearing restoration. Two main lines of research are discussed, one directed toward the transplantation of exogenous replacement cells into the damaged tissue, and another that aims at reactivating the regenerative potential of putative progenitor cells in the adult inner ear. Results from some of the studies that have been conducted are presented and the advantages and drawbacks of the various approaches discussed., Competing Interests: Conflict-of-interest statement: The author declares no conflict of interest for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Halogenated natural products (HNPs) are widespread compounds found at high concentrations in top predators such as seabirds. This paper reviews available data on methoxylated polybrominated diphenyl ethers (MeO-BDEs), heptachloro-1'-methyl-1,2'-bipyrrole (Q1) and 1,1'-dimethyl-2,2'-bipyrroles (HDBPs) in these animals. In all, 25 papers reported such HNPs in seabirds. White tailed sea eagle from Sweden was the seabird species with higher MeO-BDEs levels in eggs and blood, while in liver the European shag from Norway was the one. Regarding HDBPs, glaucous gull livers from North Water Polynya and Leach's storm petrel eggs from South Canada (NE Atlantic) showed the highest levels, while brown skua eggs presented the highest concentration of Q1. DBP-Br 4 Cl 2 and DBP-Br 6 were the most abundant HDBPs in seabirds, although only one study investigated DBP-Br 6 . Furthermore, 2'-MeO-BDE-68/6'-MeO-BDE-47 ratios were lower than one in mostly of the studies (91%). The main sources of methoxylated congeners found in seabirds might to be from sponges and/or associated organisms (bacteria). The scarcity of data in seabirds showed the gap in knowledge. Few studies were done especially in tropical areas and Southern Hemisphere and the most were conducted in the northwest part of the globe. This review arouses the need of knowledge about the distribution of these compounds in seabirds worldwide as well as it encourages toxicological studies to better understand the possible effects of HNPs on seabirds., (Copyright © 2020 Elsevier B.V. All rights reserved.)

BACKGROUND: Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain. METHODS: Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995-1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000-2009 (P2, increase in immigration), and 2010-2016 (P3, decrease in immigration). RESULTS: We included 29 TB cases among 1183 children aged <18 years (2.4%, 243/100 000 person-years). The proportion was stable in P1 and P2 (1.3%), but decreased in P3 (0.8%). The median age at TB diagnosis was 6.4 years (IQR 4-10.6); most children in P3 were aged >10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period ( P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%). CONCLUSION: In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced.

Management objectives at times create significant value conflicts that have so far been seldom studied. This article analyses the ethical issues created by the operational objectives of management for physicians who work in Spanish hospitals. These issues are as follows: 1) the current system places quantity above quality, which represents a predominantly economist management perspective; 2) the system is hierarchical, lacks participation and deprives clinicians of decision-making authority; 3) the objectives are focused on outdated activities in terms of the current reality of the healthcare system and should therefore be updated considering, for example, chronicity and the continuity of care. After analysing these issues, we created a proposal for developing management objectives based on prioritising quality care (which ultimately results in efficient management), developing objectives in a participatory and mixed manner (with group and individual objectives) and designing new objectives in keeping with the current reality of the healthcare system. Putting this proposal into practice is not complicated because the final goal of clinicians and management is to provide optimal health care., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Spread of antimicrobial resistance and shortage of novel antibiotics have led to an urgent need for new antibacterials. Although aminoglycoside antibiotics (AGs) are very potent anti-infectives, their use is largely restricted due to serious side-effects, mainly nephrotoxicity and ototoxicity. We evaluated the ototoxicity of various AGs selected from a larger set of AGs on the basis of their strong antibacterial activities against multidrug-resistant clinical isolates of the ESKAPE panel: gentamicin, gentamicin C1a, apramycin, paromomycin and neomycin. Following local round window application, dose-dependent effects of AGs on outer hair cell survival and compound action potentials showed gentamicin C1a and apramycin as the least toxic. Strikingly, although no changes were observed in compound action potential thresholds and outer hair cell survival following treatment with low concentrations of neomycin, gentamicin and paromomycin, the number of inner hair cell synaptic ribbons and the compound action potential amplitudes were reduced. This indication of hidden hearing loss was not observed with gentamicin C1a or apramycin at such concentrations. These findings identify the inner hair cells as the most vulnerable element to AG treatment, indicating that gentamicin C1a and apramycin are promising bases for the development of clinically useful antibiotics.

Eight PBDE congeners, three emerging brominated flame retardants, five dechloranes and eight MeO-PBDEs were monitored in tissues (muscular, adipose, brain) and fur of southern elephant seal and Antarctic fur seal of the South Shetland Islands, Antarctic Peninsula. Total PBDEs and total dechloranes concentrations ranged between n.d.-6 ng/g lw. While PBDEs were not detected in brain tissue, Dec 602 was found in brain tissue of both seal species indicating that dechloranes -with potential neurological toxicity- could cross the blood-brain barrier. Emerging brominated flame retardants were not detected in any sample and only two MeO-PBDEs, which are of natural origin, were found. The presence of the detected compounds in biota from the Antarctic evidences their long-range transportation, being of special interest the detection of emerging compounds such as dechloranes. This is the first time that these contaminants have been detected in marine mammals from the Antarctic. BDE-47 concentrations were lower than previously reported for the same species, suggesting a successful effect of the existing regulation and bans on PBDEs. CAPSULE ABSTRACT: Halogenated flame retardants were in tissues of Antarctic seals proving long-range transport. Dechloranes showed similar behaviour to PBDEs, additionally they crossed the BBB., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hearing loss is the most common sensorineural disorder, affecting over 5% of the population worldwide. Its most frequent cause is the loss of hair cells (HCs), the mechanosensory receptors of the cochlea. HCs transduce incoming sounds into electrical signals that activate auditory neurons, which in turn send this information to the brain. Although some spontaneous HC regeneration has been observed in neonatal mammals, the very small pool of putative progenitor cells that have been identified in the adult mammalian cochlea is not able to replace the damaged HCs, making any hearing impairment permanent. To date, guided differentiation of human cells to HC-like cells has only been achieved using either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs). However, use of such cell types suffers from a number of important disadvantages, such as the risk of tumourigenicity if transplanted into the host´s tissue. We have obtained cells expressing hair cell markers from cultures of human fibroblasts by overexpression of GFI1, Pou4f3 and ATOH1 (GPA), three genes that are known to play a critical role in the development of HCs. Immunocytochemical, qPCR and RNAseq analyses demonstrate the expression of genes typically expressed by HCs in the transdifferentiated cells. Our protocol represents a much faster approach than the methods applied to ESCs and iPSCs and validates the combination of GPA as a set of genes whose activation leads to the direct conversion of human somatic cells towards the hair cell lineage. Our observations are expected to contribute to the development of future therapies aimed at the regeneration of the auditory organ and the restoration of hearing., Competing Interests: The authors have declared that no competing interests exist.

UV filters (UV-Fs) constitute a heterogeneous group of chemicals used as protection against the effects of UV radiation, widely used in all sort of goods and ubiquitous in the environment. The presence of these chemicals in fish is a matter of concern, because many UV-Fs display hormonal activity. In this study, muscle, gills, and liver from 11 Mugil liza individuals from the highly urbanized Guanabara Bay (Rio de Janeiro, Brazil) were analysed in order to detect eight UV-Fs and metabolites (4-dihydroxybenzophenone [BP1] (2-hydroxy-4-methoxybenzophenone [BP3], 4-methylbenzylidiene camphor [4MBC], ethylhexyl methoxycinnamate [EHMC], ethylhexyl dimethyl p-aminobenzoic acid [ODPABA], octocrylene [OC], 4-hydroxybenzophenone [4HB], and 4,4'-dihydroxybenzophenone [4DHB]) using liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results showed that both target UV-Fs and metabolites were ubiquitous in the analysed tissues. Lower concentrations were observed in muscle and gills (3.07-31.6ngg -1 dry weight (dw)), whereas in liver significant amounts of metabolites (5.47-451ngg -1 dw) were present. With the concentrations determined in the fish, an estimation of the daily intake revealed that consumption of muscle in the diet represent from 0.3 to 15.2ng UV-Fs (kg body weight -1 ) d -1 , higher than those reported in fish for selected persistent organic pollutants (POPs)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The sphenoid sinus is the most inaccessible part of the face, being inside the sphenoid bone and closely related to numerous vital neural and vascular structures. The objective of this study was to analyze and evaluate the variation of anatomy and the volume of the sphenoid sinus using helical computed tomography and medical imaging software., Materials and Methods: A total of 47 helical CT scans of sinuses of male and female individuals aged 18-86 years were selected. The images were formatted using ITK-SNAP software, consisting of three steps: (1) segmentation; (2) volumetric analysis and (3) 3D reconstruction. The sphenoid sinuses were also classified according to Hammer, i.e., in conchal, pre-sellar, sellar and post-sellar types. A single investigator, who is specialist in dental radiology and was trained and calibrated, performed the volume and image analysis. After 15 days, the segmentations were repeated., Results: The Dunn's multiple comparison test revealed significant differences in the volume rankings between the right and left sides (P = 0.0002), with the post-sellar type presenting the greatest volume on the right side compared to pre-sellar and sellar types. In the left sphenoid sinuses, the post-sellar type showed the greatest volume. The Lin's correlation coefficient showed excellent reproducibility values., Conclusions: According to the applied methodology, it was found that the volume of the sphenoid sinus was influenced by neither age nor gender (P > 0.005). There was difference in the volumes of sphenoid sinus on the right and left sides and in the anatomical classification.

To catalog the diversity and abundance of halogenated organic compounds (HOCs) accumulating in high trophic marine species from the southwestern Atlantic Ocean, tissue from bottlenose dolphins (Tursiops truncatus) stranded or incidentally captured along the coast of Rio de Janeiro, Brazil, were analyzed by a nontargeted approach based on GC×GC/TOF-MS. A total of 158 individual HOCs from 32 different structural classes were detected in the blubber of 4 adult male T. truncatus. Nearly 90% of the detected compounds are not routinely monitored in the environment. DDT-related and mirex/dechlorane-related compounds were the most abundant classes of anthropogenic origin. Methoxy-brominated diphenyl ethers (MeO-BDEs) and chlorinated methyl- and dimethyl bipyrroles (MBPs and DMBPs) were the most abundant natural products. Reported for the first time in southwestern Atlantic cetaceans and in contrast to North American marine mammals, chlorinated MBPs and DMBPs were more abundant than their brominated and/or mixed halogenated counterparts. HOC profiles in coastal T. truncatus from Brazil and California revealed a distinct difference, with a higher abundance of MeO-BDEs, mirex/dechloranes and chlorinated bipyrroles in the Brazilian dolphins. Thirty-six percent of the detected HOCs had an unknown structure. These results suggest broad geographical differences in the patterns of bioaccumulative chemicals found in the marine environment and indicate the need to develop more complete catalogs of HOCs from various marine environments.

The factors that influence decision making in severe aortic stenosis (AS) are unknown. Our aim was to assess, in patients with severe AS, the determinants of management and prognosis in a multicenter registry that enrolled all consecutive adults with severe AS during a 1-month period. One-year follow-up was obtained in all patients and included vital status and aortic valve intervention (aortic valve replacement [AVR] and transcatheter aortic valve implantation [TAVI]). A total of 726 patients were included, mean age was 77.3 ± 10.6 years, and 377 were women (51.8%). The most common management was conservative therapy in 468 (64.5%) followed by AVR in 199 (27.4%) and TAVI in 59 (8.1%). The strongest association with aortic valve intervention was patient management in a tertiary hospital with cardiac surgery (odds ratio 2.7, 95% confidence interval 1.8 to 4.1, p <0.001). The 2 main reasons to choose conservative management were the absence of significant symptoms (136% to 29.1%) and the presence of co-morbidity (128% to 27.4%). During 1-year follow-up, 132 patients died (18.2%). The main causes of death were heart failure (60% to 45.5%) and noncardiac diseases (46% to 34.9%). One-year survival for patients treated conservatively, with TAVI, and with AVR was 76.3%, 94.9%, and 92.5%, respectively, p <0.001. One-year survival of patients treated conservatively in the absence of significant symptoms was 97.1%. In conclusion, most patients with severe AS are treated conservatively. The outcome in asymptomatic patients managed conservatively was acceptable. Management in tertiary hospitals is associated with valve intervention. One-year survival was similar with both interventional strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study aimed at evaluating the validity of cone-beam computed tomography (CBCT) for assessing mandibular bone quality using the Klemetti classification. The morphology of the endosteal mandibular cortex of 30 (60 hemi-mandibles) postmenopausal women between the ages of 45 and 80 years was evaluated based on the Klemetti classification in panoramic radiographs used as reference images. Afterwards, panoramic reconstruction and cross-sectional slices of CBCT examinations of these patients were analyzed and categorized according to the same classification. All the images were assessed by two oral radiologists. The McNemar-Bowker test compared the agreement between the CBCT images and the reference images. No differences were found between the diagnostic results based on panoramic radiography and panoramic reconstruction. However, the mean scores for the cross-sectional evaluation were higher, and the results, statistically different from the others. Based on the disagreement found between the panoramic radiographs and the CBCT cross-sectional slices, the Klemetti classification is not an adequate means of assessing bone quality with CBCT. On the other hand, the higher values found for the cross-sectional slices could be associated with better visibility on the CBCT images.

Pyrethroids (PYR) and UV filters (UVF) were investigated in tissues of paired mother-fetus dolphins from Brazilian coast in order to investigate the possibility of maternal transfer of these emerging contaminants. Comparison of PYR and UVF concentrations in maternal and fetal blubber revealed Franciscana transferred efficiently both contaminants to fetuses (F/M > 1) and Guiana dolphin transferred efficiently PYR to fetuses (F/M > 1) different than UVF (F/M < 1). PYR and UVF concentrations in fetuses were the highest-ever reported in biota (up to 6640 and 11,530 ng/g lw, respectively). Muscle was the organ with the highest PYR and UVF concentrations (p < 0.001), suggesting that these two classes of emerging contaminants may have more affinity for proteins than for lipids. The high PYR and UVF concentrations found in fetuses demonstrate these compounds are efficiently transferred through placenta. This study is the first to report maternal transfer of pyrethroids and UV filters in marine mammals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Current optical reflectometric techniques used to characterize optical fibers have to trade-off longitudinal range with spatial resolution and therefore struggle to provide simultaneously wide dynamic range (>20dB) and high resolution (<10cm). In this work, we develop and present a technique we refer to as Optical Side Scattering Radiometry (OSSR) capable of resolving discrete and distributed scattering properties of fibers along their length with up to 60dB dynamic range and 5cm spatial resolution. Our setup is first validated on a standard single mode telecoms fiber. Then we apply it to a record-length 11km hollow core photonic band-gap fiber (HC-PBGF) the characterization requirements of which lie far beyond the capability of standard optical reflectometric instruments. We next demonstrate use of the technique to investigate and explain the unusually high loss observed in another HC-PBGF and finally demonstrate its flexibility by measuring a HC-PBGF operating at a wavelength of 2µm. In all of these examples, good agreement between the OSSR measurements and other well-established (but more limited) characterization methods, i.e. cutback loss and OTDR, was obtained.

Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the cochlea and to control correct patterning of the organ of Corti. We show here that the Otx2 gene, a mammalian ortholog of the Drosophila orthodenticle homeobox gene, is a crucial target of N-myc during inner ear development. Otx2 expression is lost in N-myc mouse mutants, and N-myc misexpression in the chick inner ear leads to ectopic expression of Otx2. Furthermore, Otx2 enhancer activity is increased by N-myc misexpression, indicating that N-myc may directly regulate Otx2. Inactivation of Otx2 in the mouse inner ear leads to ectopic expression of prosensory markers in non-sensory regions of the cochlear duct. Upon further differentiation, these domains give rise to an ectopic organ of Corti, together with the re-specification of non-sensory areas into sensory epithelia, and the loss of Reissner's membrane. Therefore, the Otx2-positive domain of the cochlear duct shows a striking competence to develop into a mirror-image copy of the organ of Corti. Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea., (© 2015. Published by The Company of Biologists Ltd.)

Dental implant and chin osteotomy are executed on the mandible body and the mental nerve is an important anatomical limit. The aim of this research was to know the position of the mental nerve loop comparing result in panoramic radiography and cone beam computed tomography. We analyzed 94 hemimandibles and the patient sample comprised female and male subjects of ages ranging from 18 to 52 years (mean age, 35 years) selected randomly from the database of patients at the Division of Oral Radiology at Piracicaba Dental School State University of Campinas; the anterior loop (AL) of the mental nerve was evaluated regarding the presence or absence, which was classified as rectilinear or curvilinear and measurement of its length was obtained. The observations were made in the digital panoramic radiography (PR) and the cone beam computed tomography (CBCT) according to a routine technique. The frequencies of the AL identified through PR and CBCT were different: in PR the loop was identified in 42.6% of cases, and only 12.8% were bilateral. In contrast, the AL was detected in 29.8% of the samples using CBCT, with 6.4% being bilateral; Statistical comparison between PR and CBCT showed that the PR led to false-positive diagnosis of the AL in this sample. According to the results of this study, the frequency of AL is low. Thus, it can be assumed that it is not a common condition in this population.

Objective: The aim was to evaluate the relationship between orofacial function, dentofacial morphology, and bite force in young subjects., Subjects and Methods: Three hundred and sixteen subjects were divided according to dentition stage (early, intermediate, and late mixed and permanent dentition). Orofacial function was screened using the Nordic Orofacial Test-Screening (NOT-S). Orthodontic treatment need, bite force, lateral and frontal craniofacial dimensions and presence of sleep bruxism were also assessed. The results were submitted to descriptive statistics, normality and correlation tests, analysis of variance, and multiple linear regression to test the relationship between NOT-S scores and the studied independent variables., Results: The variance of NOT-S scores between groups was not significant. The evaluation of the variables that significantly contributed to NOT-S scores variation showed that age and presence of bruxism related to higher NOT-S total scores, while the increase in overbite measurement and presence of closed lip posture related to lower scores. Bite force did not show a significant relationship with scores of orofacial dysfunction. No significant correlations between craniofacial dimensions and NOT-S scores were observed., Conclusion: Age and sleep bruxism were related to higher NOT-S scores, while the increase in overbite measurement and closed lip posture contributed to lower scores of orofacial dysfunction., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This paper reviews the available data on brominated flame retardants, the polybrominated diphenyl ethers (PBDEs), as well as on the naturally-produced methoxylated polybrominated diphenyl ethers (MeO-PBDEs) in cetacean tissues around the world. Levels and possible sources of both compound classes are discussed. Odontocete cetaceans accumulate higher PBDE concentrations than mysticete species. PBDE contamination was higher in cetaceans from the Northern hemisphere, whereas MeO-PBDE levels were higher in animals from the Southern hemisphere. Southern resident killer whales from NE Pacific presented the highest levels reported in biota, followed by bottlenose dolphins from North Atlantic (U.K. and U.S. coast). Many species presented PBDE concentrations above threshold levels for health effects in odontocetes. Time trend studies indicate that PBDE concentrations in odontocetes from Japan, China, U.S. and Canada coastal zones have increased significantly over the past 30 years. Studies from U.K. waters and NE Atlantic showed a decrease and/or stability of PBDE levels in cetacean tissues in recent decades. The highest MeO-PBDE concentrations were found in dolphins from Tanzania (Indian Ocean), bottlenose dolphins from Queensland, Australia (SW Pacific), and odontocetes from coastal and continental shelf waters off southeastern Brazil (SW Atlantic). The upwelling phenomenon and the presence of coral reef complexes in these tropical oceans may explain the large amounts of the naturally-produced organobromines. Considering that these bioaccumulative chemicals have properties that could cause many deleterious effects in those animals, future studies are required to evaluate the potential ecotoxicological risks., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Blubber samples from three delphinid species (false killer whale, Guiana and rough-toothed dolphin), as well as liver samples from franciscana dolphins were analyzed for dioxins and related compounds (DRCs). Samples were collected from 35 cetaceans stranded or incidentally captured in a highly industrialized and urbanized area (Southeast and Southern Brazilian regions). Dioxin-like PCBs accounted for over 83% of the total TEQ for all cetaceans. Non-ortho coplanar PCBs, for franciscanas (82%), and mono-ortho PCBs (up to 80%), for delphinids, constituted the groups of highest contribution to total TEQ. Regarding franciscana dolphins, significant negative correlations were found between total length (TL) and three variables, ΣTEQ-DRCs, ΣTEQ-PCDF and ΣTEQ non-ortho PCB. An increasing efficiency of the detoxifying activity with the growth of the animal may be a plausible explanation for these findings. This hypothesis is reinforced by the significant negative correlation found between TL and PCB126/PCB169 concentration ratio. DRC concentrations (ng/g lipids) varied from 36 to 3006, for franciscana dolphins, as well as from 356 to 30,776, for delphinids. The sum of dioxin-like and indicator PCBs varied from 34,662 to 279,407 ng/g lipids, for Guiana dolphins from Rio de Janeiro state, which are among the highest PCB concentrations ever reported for cetaceans. The high concentrations found in our study raise concern not only on the conservation of Brazilian coastal cetaceans, but also on the possibility of human health problem due to consumption of fish from Brazilian estuaries., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Most current bioexposure assessments for UV filters focus on contaminants concentrations in fish from river and lake. To date there is not information available on the occurrence of UV filters in marine mammals. This is the first study to investigate the presence of sunscreen agents in tissue liver of Franciscana dolphin (Pontoporia blainvillei), a species under special measures for conservation. Fifty six liver tissue samples were taken from dead individuals accidentally caught or found stranded along the Brazilian coastal area (six states). The extensively used octocrylene (2-ethylhexyl-2-cyano-3,3-diphenyl-2-propenoate, OCT) was frequently found in the samples investigated (21 out of 56) at concentrations in the range 89-782 ng·g(-1) lipid weight. São Paulo was found to be the most polluted area (70% frequency of detection). Nevertheless, the highest concentration was observed in the dolphins from Rio Grande do Sul (42% frequency of detection within that area). These findings constitute the first data reported on the occurrence of UV filters in marine mammals worldwide.

Concentrations of Dechlorane (Dec) 603 (0.75 ng/g lipid weight (lw); mean) and Dec 602 (0.38 ng/g lw; mean) were quantified in more than 95% of the franciscana (Pontoporia blainvillei) dolphin samples, whereas the frequency of detection decreased to 75% for Dechlorane Plus (DP) (1.53 ng/g lw, mean). The presence of Chlordene Plus (CP) was also observed (0.13 ng/g lw, mean) in half of the samples. On the contrary, Dec 604, decachloropentacyclooctadecadiene (aCl(10)DP), and undecachloropentacyclooctadecadiene (aCl(11)DP) concentrations were below the limit of quantifications in all cases. To the best of our knowledge, this is the first article reporting the presence of Dec 603, Dec 602, and CP in mammals. For comparative purposes, levels of Mirex, polybrominated diphenyl ethers (PBDEs), and decabromodiphenylethane (DBDPE) are also reported. Considering geographic distribution evaluation together with the strong positive correlations found between DP and PBDEs (r(s) = 0.63; p < 0.01), highly anthropogenic areas were identified as potential sources of these chemicals in this dolphin species. However, local sources for Dec 602, 603, Mirex, CP, and DBDPE were not found indicating that in this case historical use and/or atmospheric transport and deposition may play an important role in their fate.

Liver samples from 53 Franciscana dolphins along the Brazilian coast were analyzed for organobrominated compounds. Target substances included the following anthropogenic pollutants: polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), pentabromoethylbenzene (PBEB), hexabromobenzene (HBB), decabromodiphenylethane (DBDPE), as well as the naturally-generated methoxylated-PBDEs (MeO-PBDEs). PBDE concentrations ranged from 6 to 1797 ng/g lw (mean 166 ± 298 ng/g lw) and were similar to those observed in cetaceans from Northern Hemisphere. PBBs were found in all sampling locations (

Aim: Hearing loss is the most common sensory disorder in humans, its main cause being the loss of cochlear hair cells. We studied the potential of human mesenchymal stem cells (hMSCs) to differentiate towards hair cells and auditory neurons., Materials & Methods: hMSCs were first differentiated to neural progenitors and subsequently to hair cell- or auditory neuron-like cells using in vitro culture methods., Results: Differentiation of hMSCs to an intermediate neural progenitor stage was critical for obtaining inner ear sensory lineages. hMSCs generated hair cell-like cells only when neural progenitors derived from nonadherent hMSC cultures grown in serum-free medium were exposed to EGF and retinoic acid. Auditory neuron-like cells were obtained when treated with retinoic acid, and in the presence of defined growth factor combinations containing Sonic Hedgehog., Conclusion: The results show the potential of hMSCs to give rise to inner ear sensory cells.

The present study constitutes the first investigation to demonstrate pyrethroid bioaccumulation in marine mammals, despite the assumption that these insecticides are converted to non-toxic metabolites by hydrolysis in mammals. Twelve pyrethroids were determined in liver samples from 23 male franciscana dolphins from Brazil. The median concentration values for total pyrethroids were 7.04 and 68.4 ng/g lw in adults and calves, respectively. Permethrin was the predominant compound, contributing for 55% of the total pyrethroids. Results showed a distinct metabolic balance of pyrethroids through dolphin life. High loads are received at the beginning of their lives and, when they reach sexual maturity, these mammals seem to degrade/metabolize pyrethroids. Maternal transfer of these compounds was also evaluated through the analysis of breast milk and placenta samples. Pyrethroids were detected in both matrices, with values between 2.53-4.77 ng/g lw and 331-1812 ng/g lw, respectively. Therefore, for the first time, a study shows mother-to-calf transfer of pyrethroids by both gestational and lactation pathways in dolphins., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The objective of this study was to quantify the cortical bone thickness of the mandibular ramus to determine conditions related to sagittal split ramus osteotomy and placement of screws. The patient sample comprised 44 subjects of ages ranging from 46 to 52 years (mean age, 49 years). The cone-beam computed tomography was performed and realized 3 cuts in the third molar area (section A), 5 mm posterior (section B), and 5 mm posterior to the latter (section C). Measurement in the cortical areas of the superior and inferior levels related to mandibular canal and measurement related to the total width of the mandible was executed. Intraclass correlation coefficient with P < 0.05 was used. The result showed that the buccal and lingual cortical zone did not present statistical differences, and the minor value was 1.5 mm for each one. There were no differences in the superior and inferior cortical bone, and the total width of the mandible was between 15.9 and 8.5 mm in the anterior area, between 17.4 and 12.8 mm in the middle area, and between 18 and 8.8 mm in the posterior area. The distance superiorly to the mandibular canal presented a minimal SD with a mean of 8.5 mm in the anterior region, 10.6 mm for the middle region, and 12.5 mm in the posterior region. In conclusion, the cortical thickness of the mandibular ramus in the adult population is particularly strong and offers a good anchorage for screw insertion in sagittal split ramus osteotomy.

Aim: The association between bone quality and fracture risk in the mandibular angle with the presence of impacted/semi-impacted third molars and after their extraction is controversial. This study aimed to assess mandibular bone quality in digital radiographies of patients after extraction of impacted/semi-impacted lower third molars., Methods: A total of 130 sets of digital panoramic radiographies were selected and divided into the following three groups: Group 1 with 50 panoramic radiographies of patients with impacted/semi-impacted lower third molars, Group 2 with 30 panoramic radiographies of patients with lower third molar agenesis, and Group 3 with 50 panoramic radiographies of patients after extraction of impacted/semi-impacted lower third molars. The mandibular angular cortex was the anatomical structure used as parameter for bone quality assessment. ANOVA and Student's t test were applied for comparison between groups., Results: Mandibular angular cortical width was significantly lower when the third molar was present in both genders (P<0.05). Agenesis of the third molar in women was associated with lower thickness of the mandibular cortex when compared with patients who had their third molar extracted (P<0.05)., Conclusion: It can be concluded that the absence of impacted/semi-impacted lower third molars, was associated with a significant increase in cortical width.