Domestic Violence

Background. Domestic violence, intimate partner violence (IPV), or domestic abuse, is defined as a pattern of behaviors used by one partner to maintain power and control over another partner in an intimate relationship. These behaviors include physical acts and nonphysical acts, including using (a) intimidation, (b) coercion, (c) threats, (d) isolation, and (e) finances to maintain power. Domestic abuse occurs regardless of (a) race, (b) gender, (c) age, (d) sexual orientation, and (e) socioeconomic status. The immediate effects of domestic violence manifest in the form of physical injuries, including (a) cuts, (b) bruises, (c) bitemarks, (d) concussions, and (e) sexually transmitted diseases (STDs). Long term and repetitive abuse leads to chronic emotional and psychological problems, including (a) depression, (b) post-traumatic stress disorder (PTSD), and (c) alcohol and substance abuse. Methods. A comprehensive search was conducted using Google and Google Scholar, utilizing the search terms (a) domestic abuse statistics, (b) domestic violence, and (c) intimate partner violence, for the years 2011 through 2018 and in English. Results. Within the United States, greater than 12 million people are victims of intimate partner violence annually. Greater than 1 in 4 women and 1 in 9 men have been victims of rape, physical violence or stalking in their lifetime resulting in a negative impact such as (a) injury, (b) fear, (c) concern for safety, or (d) needing services. An estimated 19.3% of women and 1.7% of men have been raped during their lifetimes. An estimated 43.9% of women and 23.4% of men experienced other forms of sexual violence during their lifetimes, including (a) being made to penetrate, (b) sexual coercion, (c) unwanted sexual contact, and (d) noncontact unwanted sexual experiences. An estimated 15.2% of women and 5.7% of men have been a victim of stalking during their lifetimes. Prevalence rates for emotional abuse average 80%; 40% of women and 32% of men reported expressive aggression, and 41% of women and 43% of men reported coercive control. Hispanic women (50.7%), black women (63.0%), white women (66.4%), Asian women (29.5%), and multiracial woman (91.5% ) have experienced some form of sexual violence in their lifetime. Additionally, 45.3% of American Indian or Alaska Native men and approximately 40% of Black and multiracial non-Hispanic men in the U.S. reported experiencing rape, physical violence, and/or stalking by an intimate partner during their lifetime. Furthermore, 44% of lesbians and 61% of bisexual women experience rape, physical violence, or stalking by an intimate partner compared to 35% of heterosexual women. 26% of gay men and 37% of bisexual men experience rape, physical violence, or stalking by an intimate partner compared to 35% of heterosexual men. Conclusion/ Recommendations. Recommendations are focused on (a) prevention of domestic violence, (b) raising awareness, specifically for men and the LGBTQ community who are victims of domestic violence, (c) decreasing victim shame, and (d) disseminating information and statistics to the public that are informative, but not misleading. Prevention begins at an early age by promoting healthy, respectful relationships in families

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries

BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10(9) cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2

The N-Terminal Domain of ERK1 Accounts for the Functional Differences with ERK2

The Extracellular Regulated Kinase 1 and 2 transduce a variety of extracellular stimuli regulating processes as diverse as proliferation, differentiation and synaptic plasticity. Once activated in the cytoplasm, ERK1 and ERK2 translocate into the nucleus and interact with nuclear substrates to induce specific programs of gene expression. ERK1/2 share 85% of aminoacid identity and all known functional domains and thence they have been considered functionally equivalent until recent studies found that the ablation of either ERK1 or ERK2 causes dramatically different phenotypes. To search a molecular justification of this dichotomy we investigated whether the different functions of ERK1 and 2 might depend on the properties of their cytoplasmic-nuclear trafficking. Since in the nucleus ERK1/2 is predominantly inactivated, the maintenance of a constant level of nuclear activity requires continuous shuttling of activated protein from the cytoplasm. For this reason, different nuclear-cytoplasmic trafficking of ERK1 and 2 would cause a differential signalling capability. We have characterised the trafficking of fluorescently tagged ERK1 and ERK2 by means of time-lapse imaging in living cells. Surprisingly, we found that ERK1 shuttles between the nucleus and cytoplasm at a much slower rate than ERK2. This difference is caused by a domain of ERK1 located at its N-terminus since the progressive deletion of these residues converted the shuttling features of ERK1 into those of ERK2. Conversely, the fusion of this ERK1 sequence at the N-terminus of ERK2 slowed down its shuttling to a similar value found for ERK1. Finally, computational, biochemical and cellular studies indicated that the reduced nuclear shuttling of ERK1 causes a strong reduction of its nuclear phosphorylation compared to ERK2, leading to a reduced capability of ERK1 to carry proliferative signals to the nucleus. This mechanism significantly contributes to the differential ability of ERK1 and 2 to generate an overall signalling output

Hydraulic force spectroscopy: An interferometry-based approach to micropipette aspiration for mechanobiology studies at the nanoscale

We present a new approach to Micropipette Aspiration (MPA), a pioneering method in mechanobiology, that introduces an all-optical readout to retrieve both applied stress and material response. Our technique, i.e. Hydraulic Force Spectroscopy, expands on the current MPA experimental possibilities, allowing for frequency-dependent complex moduli measurements of soft suspended bodies over a large bandwidth, with nanometric resolution. This is achieved by oscillating the pressure on the sample by tens of Pascals with a multifrequency signal, by means of a fast pump. Our goal is to use this technique to define new label-free biomarkers for different applications, e.g. embryo viability control

Dynamic mechanical analysis of suspended soft bodies via hydraulic force spectroscopy

The rheological characterization of soft suspended bodies, such as cells, organoids, or synthetic microstructures, is particularly challenging, even with state-of-the-art methods (e.g. atomic force microscopy, AFM). Providing well-defined boundary conditions for modeling typically requires fixating the sample on a substrate, which is a delicate and time-consuming procedure. Moreover, it needs to be tuned for each chemistry and geometry. Here, we validate a novel technique, called hydraulic force spectroscopy (HFS), against AFM dynamic indentation taken as the gold standard. Combining experimental data with finite element modeling, we show that HFS gives results comparable to AFM microrheology over multiple decades, while obviating any sample preparation requirements

Interferometry-based micropipette aspiration allows to study of the nanoscale dynamic mechanical behavior of biomaterials

A novel, interferometry-based approach to micropipette aspiration overcomes the spatial resolution limit of current methods, simplifies data retrieval, and enables the study of the dynamic mechanical behavior of biomembranes at the nanoscale