contact vulvitis due to pseudowintera colorata in a topical herbal medicament

Sir, Besides traditional topical and systemic pharmacological treatments for the therapy of vulvovaginal yeast and bacterial infections, numerous over-the-counter medicaments containing natural substances (e.g. tea tree oil, echinacea, sodium caprylate, propolis) are marketed. Patients often prefer alternative medicine and selfprescribe herbal-based products. We report here an unusual case of acute vulvitis that occurred in a young patient after prolonged topical use of an antifungal herbal preparation

Gender-related time course of sleep disturbances and psychological symptoms during the COVID-19 lockdown: a longitudinal study on the Italian population

Italy was the first western hotspot of the COVID-19 pandemic. In order to contain the spread of the virus, the Italian Government imposed home confinement to the entire population for almost two months. The present study is the first large-scale longitudinal report of the sleep and mental health changes during the prolonged lockdown due to the COVID-19 outbreak. We focused on the gendered vulnerability in a sample of the Italian population since cross-sectional research identified women to be more at-risk than men during this unprecedented situation. A total of 2701 individuals (mean age ± standard deviation, 32.37 ± 11.62; range, 18–82) participated in a web-based longitudinal survey consisting of two measurements. Participants were first-time recruited on social networks and via telephone messages through a snowball sampling and tested during the third week of the lockdown period. Subsequently, a follow-up evaluation was carried out during the seventh week of restraining measures. The survey assessed sleep quality, insomnia and depression symptoms, perceived stress, and anxiety, using the following questionnaires: the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, the Beck Depression Inventory-second edition, the 10-item Perceived Stress Scale, and the State-Anxiety Inventory. Female gender showed the worst condition for all the examined dimensions in both the assessments. Nevertheless, at the follow-up women reported a reduction in insomnia and depression severity symptoms, perceived stress, and anxiety. On the other hand, male participants showed a worsening of sleep quality, insomnia symptoms, and perceived stress. Consequently, the gender prevalence gap of clinical conditions such as insomnia and depression was largely reduced under lockdown. Our investigation pointed to a different time course of sleep and mental health between genders during the home confinement period. Women seemed to show greater long-term resilience during the lockdown. Meanwhile, the male gender emerges as the most vulnerable category to the extension of the restraining measures. Our results suggest that there is no “weaker gender” after a prolonged lockdown. Indeed, the Italian population transversely presented signs of psychological suffering and significant sleep disturbances after the protracted and stressful lockdown period due to the COVID-19 pandemic

IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Historically, senescence has been considered a safe program in response to multiple stresses in which cells undergo irreversible growth arrest. This process is characterized by morphological and metabolic changes, heterochromatin formation, and secretion of inflammatory components, known as senescence-associated secretory phenotype (SASP). However, recent reports demonstrated that anti-cancer therapy itself can stimulate a senescence response in tumor cells, the so-called therapy-induced senescence (TIS), which may represent a temporary bypass pathway that promotes drug resistance. In this context, several studies have shown that EGFR blockage, by TKIs or moAbs, promotes TIS by increasing IL-1 cytokine production, thus pushing cells into a "pseudo-senescent" state. Today, senotherapeutic agents are emerging as a potential strategy in cancer treatment thanks to their dual role in annihilating senescent cells and simultaneously preventing their awakening into a resistant and aggressive form. Here, we summarize classic and recent findings about the cellular processes driving senescence and SASP, and we provide a state-of-the-art of the anti-cancer strategies available so far that exploits the activation and/or blockade of senescence-based mechanisms

Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in patients with COVID-19

Conflicting evidence regarding the use of hydroxychloroquine (HCQ) and azithromycin for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection do exist. We performed a retrospective single-center cohort study including 377 consecutive patients admitted for pneumonia related to coronavirus disease 2019 (COVID-19). Of these, 297 were in combination treatment, 17 were on HCQ alone, and 63 did not receive either of these 2 drugs because of contraindications. The primary end point was in-hospital death. Mean age was 71.8 ± 13.4 years and 34.2% were women. We recorded 146 deaths: 35 in no treatment, 7 in HCQ treatment group, and 102 in HCQ + azithromycin treatment group (log rank test for Kaplan–Meier curve P < 0.001). At multivariable Cox proportional hazard regression analysis, age (hazard ratio (HR) 1.057, 95% confidence interval (CI) 1.035–1.079, P < 0.001), mechanical ventilation/continuous positive airway pressure (HR 2.726, 95% CI 1.823–4.074, P < 0.001), and C reactive protein above the median (HR 2.191, 95% CI 1.479–3.246, P < 0.001) were directly associated with death, whereas use of HCQ + azithromycin (vs. no treatment; HR 0.265, 95% CI 0.171–0.412, P < 0.001) was inversely associated. In this study, we found a reduced in-hospital mortality in patients treated with a combination of HCQ and azithromycin after adjustment for comorbidities. A large randomized trial is necessary to confirm these findings

Neuregulin 4 Boosts the Efficacy of Anti-ERBB2 Neutralizing Antibodies

ERBB4 is a tyrosine kinase receptor reported to exert both oncogenic and tumor suppressor activities. These paradoxical effects were suggested to stem from different ERBB4 homo-/hetero-dimers and/or isoforms. By stratifying breast cancer patients for clinical and molecular subtypes and ERBB4 mRNA abundance, we here report that higher ERBB4 levels correlate with longer relapse-free survival in breast cancer patients of HER2-enriched and luminal A molecular subtypes, proposing a cancer-protecting role for this receptor in these specific subgroups. We also observed that HER2-enriched breast cancers express intermediate ERBB4 mRNA levels compared to luminal and triple-negative/basal-like subgroups, which displayed the highest and the lowest levels, respectively. Inspired by these clinical data, we tested the activation of ERBB4 by Neuregulins as a potential anticancer strategy for HER2+ breast cancers. To this end, we employed two HER2+ breast cancer cellular models (BT474 and SKBR3), which express intermediate/high and low ERBB4 levels, respectively. Cell proliferation and motility were evaluated on these cellular models following treatments with Neuregulin 1 (NRG1), which activates both ERBB3 and ERBB4, or Neuregulin 4 (NRG4), which specifically activates ERBB4. Both NRG1 and NRG4 were used alone or in combination with anti-ERBB2 neutralizing antibodies, namely trastuzumab and pertuzumab. In vitro treatment with NRG1 on BT474 cells restrained cell growth and reduced the anti-proliferative efficacy of trastuzumab. In contrast, treatment with NRG1 on SKBR3 cells increased cell proliferation and migration, and partially or completely impaired the anti-proliferative/anti-migratory action of trastuzumab and/or pertuzumab. Importantly, in both the cell lines, treatment with NRG4 robustly potentiated the anti-proliferative action of trastuzumab and pertuzumab. Collectively, our data in HER2+ breast cancer cells highlight that NRG1 may exert both pro- and anti-proliferative effects, and may reduce the efficacy of anti-HER2 agents, whereas NRG4 may boost the anti-proliferative effects of anti-ERBB2 agents. We propose a provocative paradigm shift in the field of growth factors in cancer progression, suggesting the administration of ERBB4 ligands, such as Neuregulin 4, as a strategy to improve the efficacy of anti-ERBB2 agents

Sonnolenza e incidentalità stradale notturna:uno studio sulle percezioni di rischio in giovani guidatori/ Sleepiness and nocturnal driving safety: a study on risk perception in young drivers

The present study is aimed to evaluate: 1) the factors that affect the risk perception of young people in nocturnal driving; 2) how the way of presenting information about the sleepiness-accident relationship influences attributions, goals and decisions about driver sleepiness. 572 young drivers answered to a questionnaires, composed according to the paradigms of study framing, on three decisional problems about sleepiness and nocturnal vehicle accidents. 285 answered to questionnaires with problems presented in a positive frame of and 287 in a negative frame. All subjects were requested to answer to questions on drive risk perception and nocturnal sleepiness, on nocturnal driving experience and on the adopted strategies to counterattack sleepiness. Results show that experiences of sleep attacks during driving and nocturnal driving frequency are factors that affect both the risk perception and the commitment in adopting preventive strategies. Furthermore, the manipulation on two out of the three problems (attributions and risk decisions frames) clearly affected the choices of responders. Present results can give useful suggestions about how to present information in educational programs aimed to the prevention of vehicle accidents among young peopl

AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants?

<p>Abstract</p> <p>Background</p> <p>Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease.</p> <p>Methods</p> <p>Cutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern.</p> <p>Results</p> <p>The B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B).</p> <p>Conclusions</p> <p>Our preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.</p