Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges.

Diffuse intrinsic pontine glioma (DIPG), now referred to as diffuse midline glioma (DMG), is a highly aggressive pediatric cancer primarily affecting children aged 4 to 9 years old. Despite the research and clinical trials conducted to identify a possible treatment for DIPG, no effective drug is currently available. These tumors often affect deep midline brain structures in young children, suggesting a connection to early brain development's epigenetic regulation targets, possibly affecting neural progenitor functions and differentiation. The H3K27M mutation is a known DIPG trigger, but the exact mechanisms beyond epigenetic regulation remain unclear. After thoroughly examining the available literature, we found that over 85% of DIPG tumors contain a somatic missense mutation, K27M, in genes encoding histone H3.3 and H3.1, leading to abnormal gene expression that drives tumor growth and spread. This mutation impacts crucial brain development processes, including the epithelial-mesenchymal transition (EMT) pathway, and may explain differences between H3K27M and non-K27M pediatric gliomas. Effects on stem cells show increased proliferation and disrupted differentiation. The genomic organization of H3 gene family members in the developing brain has revealed variations in their expression patterns. All these observations suggest a need for global efforts to understand developmental origins and potential treatments.

HPV and Covid-19 Era: effects of nonpharmaceutical interventions on HPV transmission.

Human papillomavirus (HPV) is considered the commonest viral cause of sexually transmitted infections. The impact of social distance measures due to Covid-19 pandemic on HPV spread is unknown. Therefore, this study has analyzed the seven-year trend of HPV prevalence in all patients tested for HPV DNA at the Microbiology and Virology Unit at Bari Policlinico. Moreover, the HPV prevalence in 2020 has been compared with the previous year ones in order to evaluate the consequences of lockdown and social distancing measures on transmission risks. From 2013 to 2020, we retrospectively analyzed 64 anal swabs, 418 biopsies, 5925 cervical-vaginal swabs, 512 cervical swabs, 104 gland swabs, 154 oral swabs, 21 seminal fluids and 503 urethral swabs. HPV DNA detection was initially performed using nested-polymerase chain reaction (PCR) and subsequently multiplex real-time PCR assay. All statistical tests were carried out by the open-source environment R 4.0.3 (R Core Team). The data were analyzed according to yearly positivity rates, temporal trend and prevalence of HPV genotypes (HPV-6, HPV-11, HPV-16, HPV-18, high risk and low risk) by age category and sex. The number of patients increased steadily from 2016 to 2019 and then decreased in 2020. There were significant differences in prevalence between females and males for HPV-6 (6.16% in females Vs 30.80% in males), HPV-11 (0.82% Vs 7.16%) and HPV-16 (7.77% Vs 5.01%). The prevalence of HPV-6 and HPV-11 significantly increased in 2020 compared to 2013-2019 (15.72% Vs 8.52 and 3.18% Vs 1.44%). On the contrary, the overall prevalence of HPV DNA remained constant in 2020 (52.84% Vs 48.44%). Over time, the prevalence of HPV DNA (Coefficient=-0.020, p-value = 0.036) and particularly high-risk genotypes (Coefficient=-0.030, p-value = 0.005) decreased in females, while low-risk genotypes (Coefficient = 0.141, p-value= < 0.001) and the prevalence of HPV DNA increased in males (Coefficient = 0.068, p-value = 0.008). During the pandemic, the number of screened patients declined, although HPV prevalence compared to 2013-2019 remained constant or increased as in the case of low-risk genotypes. It can be assumed that the reduction of the screening coverage favored the emerging of the more symptomatic low-risk infections. In conclusion, nonpharmaceutical interventions due to Covid-19 pandemic did not reduce the risk of HPV infection but it likely caused a decrease in access to health services resulting in an increased risk of undiagnosed HPV.

To decrease the impact of Covid-19 pandemic on the general population, several measures of social distancing were worldwide implemented potentially affecting sexual behaviors.Evaluating the impact of the social distancing measures on the risk of sexually transmitted infections, the published studies reached contradictory results showing the absence of a common epidemiological trend.The overall prevalence of HPV and some of its genotypes among female and male patients did not decrease in 2020 compared to the years 2013­2019.The risk of the HPV infection was not affected by the social distancing measures.

Inflammation as Prognostic Hallmark of Clinical Outcome in Patients with SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to "F. Perinei" Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student's t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3+ and CD4+ CD8+ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19.