HIPK2 in cancer biology and therapy: Recent findings and future perspectives

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates and regulates a plethora of transcriptional regulators and chromatin modifiers. The heterogeneity of its interactome allows HIPK2 to modulate several cellular processes and signaling pathways, ultimately regulating cell fate and proliferation. Because of its p53-dependent pro-apoptotic activity and its downregulation in many tumor types, HIPK2 is traditionally considered a bone fide tumor suppressor gene. However, recent findings revealed that the role of HIPK2 in the pathogenesis of cancer is much more complex, ranging from tumor suppressive to oncogenic, strongly depending on the cellular context. Here, we review the very recent data emerged in the last years about the involvement of HIPK2 in cancer biology and therapy, highlighting the various alterations of this kinase (downregulation, upregulation, mutations and/or delocalization) in dependence on the cancer types. In addition, we discuss the recent advancement in the understanding the tumor suppressive and oncogenic functions of HIPK2, its role in establishing the response to cancer therapies, and its regulation by cancer-associated microRNAs. All these data strengthen the idea that HIPK2 is a key player in many types of cancer; therefore, it could represent an important prognostic marker, a factor to predict therapy response, and even a therapeutic target itself

3-morpholino-7-[N-methyl-N-(4′-carboxyphenyl)amino]phenothiazinium chloride

The synthesis of 3-morpholino-7-[N-methyl-N-(4′-carboxyphenyl)amino]phenothiazinium chloride is reported here. Interestingly, non-symmetric phenothiazinium salt is functionalized with a carboxylic acid group that allows the easy and stable anchoring on metal oxides. In addition, the morpholine unit reduces the dye aggregation tendency; thus, improving its potential applications in the biomedical and photo-electrocatalytic field

A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications

Patient-reported outcome measures in drugs for neurological conditions approved by European Medicines Agency 2017-2022

BackgroundRegulatory agencies have been responsive to public demand for inclusion of the patient experience in evaluating and approving therapies. Over the years, patient-reported outcome measures (PROMs) have become increasingly prevalent in clinical trial protocols; however, their influence on regulators, payers, clinicians, and patients' decision-making is not always clear. We recently conducted a cross-sectional study aimed at investigating the use of PROMs in new regulatory approvals of drugs for neurological conditions between 2017 and 2022 in Europe.MethodsWe reviewed European Public Assessment Reports (EPARs) and recorded on a predefined data extraction form whether they considered PROMs, their characteristics (e.g., primary/secondary endpoint, generic/specific instrument) and other relevant information (e.g., therapeutic area, generic/biosimilar, orphan status). Results were tabulated and summarized by means of descriptive statistics.ResultsOf the 500 EPARs related to authorized medicines between January 2017 and December 2022, 42 (8%) concerned neurological indications. Among the EPARs of these products, 24 (57%) reported any use of PROMs, typically considered as secondary (38%) endpoints. In total, 100 PROMs were identified, of which the most common were the EQ-5D (9%), the SF-36 (6%), or its shorter adaptation SF-12, the PedsQL (4%).ConclusionsCompared to other disease areas, neurology is one where the use of patient-reported outcomes evidence is inherently part of the clinical evaluation and for which core outcome sets exist. Better harmonization of the instruments recommended for use would facilitate the consideration of PROMs at all stages in the drug development process

Carcinoma sieroso papillare del peritoneo in paziente già operata di carcinoma mammario. Caso clinico

Il carcinoma sieroso papillare del peritoneo (PPSC) è un tumore raro che si riscontra più frequentemente nel sesso femminile. L?età media al momento della diagnosi è di 56 anni. Si diffonde coinvolgendo il peritoneo, la superficie delle ovaie e la pelvi. L?istologia è indistinguibile dall?analogo tumore ovarico, cioè il carcinoma sieroso papillare (PSCO). L?istogenesi del PPSC è probabilmente correlata all?epitelio celomatico embrionale. Sintomi e segni clinici tipici sono distensione addominale, costipazione, nausea, vomito, riduzione dell?appetito, malessere generale e perdita di peso. La chirurgia citoriduttiva, in aggiunta alla chemioterapia con cisplatino e ad altre terapie come l?immunoterapia e la radioterapia, aumenta la sopravvivenza dei pazienti affetti da PPSC. Viene descritto il caso di una paziente di 51 anni, già operata di carcinoma mammario, nella quale si manifestavano alcuni dei segni e sintomi descritti. L?intervento chirurgico dimostrò le localizzazioni sierose caratteristiche. Si fece una larga exeresi ma la malata morì 14 mesi dopo per la fatale progressione della malattia. English version The peritoneal papillary serous carcinoma (PPSC) is a rare tumor more frequently revealed in female. The onset mean age is 56 years. It implicate peritoneum, ovary?s surface and pelvis. The histology of this disease is similar to papillary serous carcinoma ovary (PSCO). The PPSC histogenesis is probably correlated to coelomatic embryonal epithelium. Clinical characteristics are abdominal swelling, constipation, nausea, emesis, inappetence, feel unwell, lose weight. The cytoreductive surgery and the cisplatinum chemotherapy, and other treatments like immunotherapy and radiotherapy, increase the PSCP patient survival. A case of a 51 years old patient with previous surgery for breast cancer is here described. She show some of the yet described clinical findings. At the surgery we found the typically serous peritoneal localizations. We performed a debulking, and the patient died 14 months after the operation due to the disease progression

Percepção de risco sobre zoonoses em trabalhadores imigrantes e italianos no Noroeste da Itália

OBJETIVO: Analizar factores asociados a la baja percepción de riesgo de zoonosis e identificar los vacíos de conocimiento sobre la transmisión y prevención de zoonosis en trabajadores inmigrantes e italianos. MÉTODOS: Estudio transversal con 175 trabajadores de la industria agropecuaria y agroalimentaria en Piemonte, Italia. Los datos fueron obtenidos por medio de cuestionario semi-estructurado basado en estudio sobre conocimientos, actitudes y prácticas. Se calcularon proporciones y usó la prueba de Chi-cuadrado y odds ratio para estimar asociaciones. Se realizaron ocho entrevistas individuales con informantes clave en materia de inmigración y salud pública. RESULTADOS: Cerca de 47% de los trabajadores eran italianos y 53%, inmigrantes provenientes de Rumania, Marruecos, Albania, India, China, Argentina, Perú, Macedonia, Costa de Marfil, Ucrania y Colombia. Hubo diferencias significativas en la menor percepción del riesgo en el trabajo (p = 0,001). Se observó asociación entre falta de conocimientos correctos sobre zoonosis y ser inmigrante (OR=4,1; IC95% 1,7;9,8;p ≤ 0,01), trabajar en la industria pecuaria (OR = 2,9; IC95% 1,2;6,8;p = 0,01) y ser un trabajador no calificado (OR = 4,4; IC95% 1,2;15,4;p = 0,01). Otra fuerte asociación ocurrió entre ser inmigrante y tener empleo de baja calificación (OR = 6,7; IC95% 2,9;15,4;p ≤ 0,01). Se encontró mayor frecuencia de conductas de riesgo y menor nivel de conocimiento sobre zoonosis en el grupo de los inmigrantes asiáticos.OBJETIVO: To assess factors associated with a low risk perception of zoonoses and to identify the gaps in knowledge about transmission and prevention of zoonoses in immigrant and Italian workers. MÉTODOS: A cross-sectional study with 175 workers in the agro-livestock and agro-food industry in Piemonte, Italy, was carried out. Data were collected with a semi-structured questionnaire based on knowledge, attitudes and practices (KAP) survey. We calculated proportions and used chi-square tests and odds ratios to assess associations. Eight individual interviews with key informants on immigration and public health in Piemonte were carried out. RESULTADOS: Participants were 82 (47%) Italians and 93 (53%) immigrants. Immigrants were from Romania, Morocco, Albania, India, China, Argentina, Peru, Macedonia, Ivory Coast, Ukraine and Colombia. The study revealed significant differences in risk perception at work (p = 0.001). We found associations between "not having correct knowledge about zoonoses" and the following variables: i. "being immigrant" OR = 4.1 (95%CI 1.7;9.8 p ≤ 0.01); ii. "working in the livestock industry" OR = 2.9 (95%CI 1.2;15.4 p = 0.01); and iii. "being an unqualified worker" OR = 4.4 (95%CI 2.9;15.4 p ≤ 0.01). Another strong association was found between being immigrant and having a low job qualification OR = 6.7 (IC95% 2.9 - 15.4 p ≤ 0.01). Asian immigrants were the group with the highest frequency of risky behaviours and the lowest level of knowledge about zoonoses. CONCLUSÕES: Our results indicate that there were differences in risk perception of zoonoses between the groups participating in our study. These results suggest that immigrant status can be considered a risk factor for having lower risk perception and lower level of knowledge of zoonoses at work. There is a relationship between this specific knowledge of zoonoses and lack of training and instruction among migrant populations. Our results stress the need for developing education programs on zoonoses prevention among the immigrant population in Piemonte, Italy.OBJECTIVE: Analisar fatores associados à baixa percepção de risco de zoonoses e identificar as lacunas no conhecimento sobre a transmissão e prevenção de zoonoses em trabalhadores imigrantes e italianos. METHODS: Estudo transversal com 175 trabalhadores da indústria agropecuária e agroalimentar em Piemonte, Itália. Os dados foram obtidos por meio de questionário semiestruturado baseado em estudo sobre conhecimentos, atitudes e práticas. Foram calculadas proporções, com uso de teste qui-quadrado e odds ratio para estimar associações. Oito entrevistas individuais com informantes-chave em matéria de imigração e saúde pública foram realizadas. RESULTS: Cerca de 47% dos trabalhadores eram italianos e 53%, imigrantes, provenientes da Romênia, Marrocos, Albânia, Índia, China, Argentina, Peru, Macedônia, Costa do Marfim, Ucrânia e Colômbia. Houve diferenças significativas na menor percepção do risco no trabalho (p = 0,001). Observou-se associação entre falta de conhecimentos corretos sobre zoonoses e ser imigrante (OR = 4,1; IC95% 1,7;9,8; p ≤ 0,01), trabalhar na indústria pecuária (OR = 2,9; IC95% 1,2;6,8; p = 0,01) e ser um trabalhador não qualificado (OR = 4,4; IC95% 1,2;15,4; p = 0,01). Outra forte associação ocorreu entre ser imigrante e ter emprego de baixa qualificação (OR = 6,7; IC95% 2,9;15,4; p ≤ 0,01). Maior frequência de comportamentos de risco e menor nível de conhecimento sobre zoonoses foram encontrados no grupo dos imigrantes asiáticos. CONCLUSIONS: Foram observadas diferenças na percepção de risco de zoonoses entre os grupos participantes. O status de imigrante pode ser considerado fator de risco para ter baixa percepção de risco e menor nível de conhecimento das zoonoses no trabalho. Existe relação entre esse conhecimento específico de zoonoses e falta de formação e instrução entre as populações migrantes. É necessário desenvolver programas de educação sobre a prevenção de zoonoses entre a população imigrante

The role of teachers' socio-emotional competence in reducing burnout through increased work engagement

IntroductionResearch has highlighted the relevance of socio-emotional competence in buffering the harmful impacts of perceived stress on the psychological facets of the teaching profession. The purpose of this paper is to innovatively investigate the relationships between perceived stress, work engagement, and burnout in a single comprehensive model, when considering the potential role that socio-emotional competence plays in mitigating the adverse impact of perceived stress on burnout.MethodsA total of 276 Italian in-service teachers (mean age = 46.6 ± 9.9 years) completed quantitative self-report measures of perceived stress, socio-emotional competence, work engagement, and burnout. Data were analyzed by using a structural equation modeling (SEM) approach.ResultsAll fit indexes supported the model's full acceptance and suggested that teachers' socio-emotional competence reduced the effect of perceived stress on the risk of burnout by increasing their level of work engagement.DiscussionThe implications of the findings are discussed in terms of promoting interventions that target not only stress reduction but also foster teachers' socio-emotional competence in order to maintain a good level of work engagement and reduce the effect of stress on burnout

Pazopanib-Induced Heart Failure in a Metastatic Sarcoma Patient: between Reversible Side Effect and Efficacy

 Introduction: Pazopanib, a multi-target tyrosine-kinase inhibitor (TKI), is a relatively novel anticancer agent registered for advanced renal cell carcinoma recently emerged in the setting of advanced soft-tissue sarcoma (STS). In the early clinical trials pazopanib has been very marginally linked to left ventricular ejection fraction (LVEF) dysfunction as, on contrary, reported for other anti-angiogenesis TKIs, such as Sunitinib and Sorafenib. Presentation of Case: We here present a case of severe, but reversible, congestive cardiac failure in a 37-year old Caucasian man affected by soft-tissue sarcoma during an efficacious treatment with pazopanib. Conclusion: Cardiac damage from novel TKI treatments is still an underestimated phenomenon. In our patient, pazopanib was the only treatment ensuring stability of disease and its discontinuation meant disease progression. Post-approval monitoring of novel TKIs should be taken into account by clinicians including a careful monitoring of LVEF and all symptoms suggestive of cardiac dysfunction, in particular for drugs potentially capable to change the natural history of still uncurable cancer.

Listeria Monocytogenes in a Young Patient with Non Hodgkin's Lymphoma: Case Report

Listeria monocytogenes is an intracellular food-borne pathogen, widely distributed in the environment, which rarely causes clinical infection in healthy people, but may cause severe disease in immunocompromised patients. A case of listeriosis is certified in an immunocompromised patient, thus confirming this microorganism to be an opportunistic human pathogen