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Three lipid-dependent Malassezia isolates (here named 114A, 114B and 114C) recovered from a dog with skin lesions were phenotypically and genotypically characterized. All presented ovoid cells and buds formed on a narrow base. Most of the results from physiological tests were consistent with those of Malassezia furfur. The phylogenetic analysis of ITS-1 and LSU nucleotide sequences was concordant in placing all three clinical Malassezia isolates close to M. furfur. However, the phylogenetic data on the chs-2 sequence revealed that clinical isolate 114A is distinct from M. furfur and was closely affiliated to the sequence of M. pachydermatis with high nodal support. In particular, lipid-dependent isolates 114A displayed chs-2 sequences similar (100%) to that of the non-lipid dependent species Malassezia pachydermatis. The presence of the genetic and physiological polymorphisms detected in these three isolates of M. furfur could have resulted from a process of adaptation of this anthropophilic species to a new host. [ABSTRACT FROM AUTHOR]

The article investigates the case of a 20-month old female who was treated for Wilms tumor stage I. The patient underwent left nephrectomy and chemotherapy according to national chemotherapy protocol of Wilms tumor in children and subsequently given acetaminophen for an ulcerative lesion on the forearm. After 29 days of acetaminophen treatment, the patient suffered acute liver failure (ALF) and lapsed to comatose status upon admission to the pediatric intensive care unit (PICU). After spontaneous recovery, it was concluded that prolonged use of acetaminophen combined with other liver-metabolized drugs can lead to potential risk of ALF.

Background: SMYD3 has been found implicated in cancer progression. Its overexpression correlates with cancer growth and invasion, especially in gastrointestinal tumors. SMYD3 transactivates multiple oncogenic mechanisms, favoring cancer development. Moreover, it was recently shown that SMYD3 is required for DNA restoration by promoting homologous recombination (HR) repair., Methods: In cellulo and in vivo models were employed to investigate the role of SMYD3 in cancer chemoresistance. Analyses of SMYD3-KO cells, drug-resistant cancer cell lines, patients' residual gastric or rectal tumors that were resected after neoadjuvant therapy and mice models were performed. In addition, the novel SMYD3 covalent inhibitor EM127 was used to evaluate the impact of manipulating SMYD3 activity on the sensitization of cancer cell lines, tumorspheres and cancer murine models to chemotherapeutics (CHTs)., Results: Here we report that SMYD3 mediates cancer cell sensitivity to CHTs. Indeed, cancer cells lacking SMYD3 functions showed increased responsiveness to CHTs, while restoring its expression promoted chemoresistance. Specifically, SMYD3 is essential for the repair of CHT-induced double-strand breaks as it methylates the upstream sensor ATM and allows HR cascade propagation through CHK2 and p53 phosphorylation, thereby promoting cancer cell survival. SMYD3 inhibition with the novel compound EM127 showed a synergistic effect with CHTs in colorectal, gastric, and breast cancer cells, tumorspheres, and preclinical colorectal cancer models., Conclusions: Overall, our results show that targeting SMYD3 may be an effective therapeutic strategy to overcome chemoresistance., (© 2024. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic individuals are not achievable due to its relatively low incidence, pancreatic cancer surveillance programs are recommended for patients with germline causative variants in PDAC susceptibility genes or a strong family history. In this study, we sought to determine the prevalence and significance of germline alterations in major genes ( ATM , BRCA1 , BRCA2 , CDKN2A , EPCAM , MLH1 , MSH2 , MSH6 , PALB2 , PMS2 , STK11 , TP53 ) involved in PDAC susceptibility. We performed a systematic review of PubMed publications reporting germline variants identified in these genes in PDAC patients. Overall, the retrieved articles included 1493 PDAC patients. A high proportion of these patients ( n = 1225/1493, 82%) were found to harbor alterations in genes ( ATM , BRCA1 , BRCA2 , PALB2 ) involved in the homologous recombination repair (HRR) pathway. Specifically, the remaining PDAC patients were reported to carry alterations in genes playing a role in other cancer pathways ( CDKN2A , STK11 , TP53 ; n = 181/1493, 12.1%) or in the mismatch repair (MMR) pathway ( MLH1 , MSH2 , MSH6 , PMS2 ; n = 87/1493, 5.8%). Our findings highlight the importance of germline genetic characterization in PDAC patients for better personalized targeted therapies, clinical management, and surveillance.

Cells respond to DNA damage by activating a complex array of signaling networks, which include the AMPK and mTOR pathways. After DNA double-strand breakage, ATM, a core component of the DNA repair system, activates the AMPK-TSC2 pathway, leading to the inhibition of the mTOR cascade. Recently, we showed that both AMPK and mTOR interact with SMYD3, a methyltransferase involved in DNA damage response. In this study, through extensive molecular characterization of gastrointestinal and breast cancer cells, we found that SMYD3 is part of a multiprotein complex that is involved in DNA damage response and also comprises AMPK and mTOR. In particular, upon exposure to the double-strand break-inducing agent neocarzinostatin, SMYD3 pharmacological inhibition suppressed AMPK cascade activation and thereby promoted the mTOR pathway, which reveals the central role played by SMYD3 in the modulation of AMPK-mTOR signaling balance during cancer cell response to DNA double-strand breaks. Moreover, we found that SMYD3 can methylate AMPK at the evolutionarily conserved residues Lys411 and Lys424. Overall, our data revealed that SMYD3 can act as a bridge between the AMPK and mTOR pathways upon neocarzinostatin-induced DNA damage in gastrointestinal and breast cancer cells.

Aim: Compound odontoma has been reported to be the most common of all odontogenic neoplasms and tumor- like lesions. Only rarely the treatment of this lesion in association with an impacted tooth has been reported., Case Report: A compound odontoma in a 10-year-old girl, associated with an impacted permanent incisor is described, focusing on the diagnosis and the importance of early treatment of this lesion. The patient underwent surgical excision of the lesion and it was decided to wait for the spontaneous eruption of the impacted tooth. After 6 months no eruption was observed and thus the orthodontic treatment was deemed necessary. At the one-year follow-up, the tooth was brought into the maxillary arch.

The life cycles of filarioids of dogs presenting dermal microfilariae have been little studied. Following the recent retrieval of dermal microfilariae identified as Cercopithifilaria sp. in a dog from Sicily (Italy), this study was designed to assess the role of the brown dog tick Rhipicephalus sanguineus as an intermediate host of this filarial species. An experimental tick infestation was performed on an infected dog using 300 nymphs of R. sanguineus. Engorged nymphs were collected and examined by both microscopic dissection and molecular analysis at five time points (i.e., the same day of tick detachment and 10, 20, 30 and 50 days post-detachment) to detect the presence and developmental stage of filariae in the ticks. A total of 270 engorged nymphs were collected from the dog and developing filarioid larvae detected in 10 (5%) out of 200 ticks dissected. Infective third-stage larvae were observed in 4 (2%) of the all dissected ticks, 30 days post-detachment. Twelve (6.6%) out of 181 samples molecularly tested were positive for Cercopithifilaria sp. This study demonstrates that nymphs of R. sanguineus feeding on a dog naturally infected by Cercopithifilaria sp. can ingest microfilariae, which develop up to the third infective stage thus suggesting that this tick species might act as an intermediate host of this little known canine filarioid., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Self-stereotyping is a process by which people belonging to a stigmatized social group tend to describe themselves more with stereotypical traits as compared with traits irrelevant to the ingroup stereotype. The present work analyzes why especially members of low-status groups are more inclined to self-stereotype compared to members of high-status groups. We tested the hypothesis that belonging to a low-, rather than a high-status group, makes low-status members feel more threatened and motivates them to protect their self-perception by increasing their similarity with the ingroup. Specifically, we investigated the effects of an experimental manipulation that was conceived to either threaten or protect the natural group membership of participants from either a low- or a high-status group on the level of self-stereotyping. The findings supported the idea that only low-status group members protected themselves when their group identity was threatened through increased self-stereotyping.

Acetaminophen is considered as a safe analgesic and antipyretic drug in paediatric age. The main problem in the use of acetaminophen is acute liver failure after an overdose or an acute intoxication. We report a case of fulminant liver failure and spontaneous recovery in a patient treated with a prolonged course of acetaminophen at recommended dosages.

Carnitine palmityl-transferase (CPT) II deficiency is a rare disorder of the fatty acid beta-oxidation cycle. CPT II deficiency can be associated with rhabdomyolysis in particular conditions that increase the requirement for fatty acid oxidation, such as low-carbohydrate and high-fat diet, fasting, exposure to excessive cold, lack of sleep and prolonged exercise. The best known CPT II deficiency is the muscular form with episodic muscle necrosis and paroxysmal myoglobinuria after prolonged exercise. We report a case of a four-year-old male child, who, after one day of hyperthermia and fasting, developed a massive rhabdomyolysis beginning with acute respiratory failure and later complicated by acute renal failure. Appropriate management in Pediatric Intensive Care Unit (PICU) (mechanical ventilatory support, fluid supply combined with mannitol and bicarbonate infusions, administration of acetaminophen and antibiotics, and continuous venovenous haemofiltration) brought about complete resolution with an excellent outcome. Biochemical investigation of muscle biopsy and genetic analysis showed a deficiency of CPT II. The onset of CPT II deficiency with respiratory failure is extremely rare, but a correct and early diagnosis of rhabdomyolysis is the key to successful treatment. A metabolic myopathy such as CPT II deficiency should be suspected in children affected by rhabdomyolysis if trauma, crash, infections, drugs or extreme exertion can be excluded.

Little precise information is available on the systematics, genetics, ecology and epidemiology of yeasts of the genus Malassezia from different animal species. In the present study, one hundred and four isolates of Malassezia (lipid dependent or non-lipid dependent) from dogs were characterized by their chitin synthase 2 gene (CHS2), and the large subunit (LSU) and the first internal transcribed spacer (ITS-1) of nuclear ribosomal DNA sequences, and compared genetically with well-defined reference strains of Malassezia pachydermatis and heterologous species, including Malassezia furfur and Candida albicans. For each locus examined, three main sequence types (i.e. A, B and C) represented all of the 104 isolates, which were designated as genotypes A, B and C, respectively. A fourth, minor sequence type was also defined for the ITS-1. The nucleotide differences among genotypes was consistent with the magnitudes of intraspecific variability reported in previous studies. The genetic analysis of the sequence data sets (for individual loci) showed that all Malassezia genotypes clustered (with moderate to strong support) with the reference sequences of M. pachydermatis to the exclusion of the outgroups M. furfur and C. albicans. The present study reveals that multiple genetic variants of M. pachydermatis occur on dogs. The multilocus approach employed herein provides a foundation for future investigations of M. pachydermatis from other animals and humans, and their ecology and epidemiology.