Criminal Defendants in Pennsylvania, While Constitutionally Entitled to the Right to Counsel, May Forfeit That Right if They Undertake Extreme Dilatory Conduct: Commonwealth v. Lucarelli

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GUCY2C maintains intestinal LGR5+ stem cells by opposing ER stress

Long-lived multipotent stem cells (ISCs) at the base of intestinal crypts adjust their phenotypes to accommodate normal maintenance and post-injury regeneration of the epithelium. Their long life, lineage plasticity, and proliferative potential underlie the necessity for tight homeostatic regulation of the ISC compartment. In that context, the guanylate cyclase C (GUCY2C) receptor and its paracrine ligands regulate intestinal epithelial homeostasis, including proliferation, lineage commitment, and DNA damage repair. However, a role for this axis in maintaining ISCs remains unknown. Transgenic mice enabling analysis of ISCs (Lgr5-GFP) in the context of GUCY2C elimination (Gucy2c-/-) were combined with immunodetection techniques and pharmacological treatments to define the role of the GUCY2C signaling axis in supporting ISCs. ISCs were reduced in Gucy2c-/- mice, associated with loss of active Lgr5+ cells but a reciprocal increase in reserve Bmi1+ cells. GUCY2C was expressed in crypt base Lgr5+ cells in which it mediates canonical cyclic (c) GMPdependent signaling. Endoplasmic reticulum (ER) stress, typically absent from ISCs, was elevated throughout the crypt base in Gucy2c-/- mice. The chemical chaperone tauroursodeoxycholic acid resolved this ER stress and restored the balance of ISCs, an effect mimicked by the GUCY2C effector 8Br-cGMP. Reduced ISCs in Gucy2c-/-mice was associated with greater epithelial injury and impaired regeneration following sub-lethal doses of irradiation. These observations suggest that GUCY2C provides homeostatic signals that modulate ER stress and cell vulnerability as part of the machinery contributing to the integrity of ISCs. © Kraft et al

O acordo de leniência como instrumento de defesa da concorrência no Brasil

Orientador: Alexandre Ditzel Faraco. Coorientador: Egon Bockmann MoreiraMonografia (graduação) - Universidade Federal do Paraná, Setor de Ciências Jurídicas, Curso de Graduação em DireitoResumo: O presente estudo pretende abordar com destaque o Acordo de Leniência firmado entre o Conselho Administrativo de Defesa Econômica - CADE - e aqueles que são praticantes de cartéis. O acordo de leniência foi inserido na legislação concorrencial brasileira em 2000, tendo sido reformulado e modernizado desde então. Apesar ser uma ferramenta de grande destaque e notável eficiência no combate aos cartéis, no Brasil e no mundo, este tipo de acordo ainda provoca em nosso âmbito jurídico algumas questões importantes que merecem destaque. A doutrina aponta como uma das críticas principalmente o campo de intersecção do trabalho investigativo do CADE e das investigações dos crimes contra a ordem econômica, discutindo, portanto, qual deve ser o papel do Ministério Público no firmamento destes acordos. Além disso, com o advento da Lei nº 12.529/11 passou a ser possível firmar o Acordo de Leniência com aquele que é o líder da prática anticompetitiva, o que demanda do CADE uma análise mais minuciosa do caso a fim de excluir a possibilidade da procura pelo acordo para prejudicar os concorrentes. Apesar da necessidade de alguns ajustes, o programa de leniência do CADE já apresentou diversos casos de sucesso que serão brevemente abordados ao final do presente trabalh

Reconnecting with Exes and Having Sex with Platonic Roommates During the First Five Months of the COVID - 19 Pandemic

The first few months of the COVID-19 pandemic limited people’s interactions as a result of social distancing and stay-at-home orders across the U.S., and research documented declines in partnered sex during this time (Hensel et al., 2020). It is unclear if people who were single during the first few months of the pandemic found sexual connections with ex-partners or roommates. In the present study, we examined the prevalence of people contacting ex-partners and non-romantic roommates to engage in sex. We analyzed data from a national sample of people who were currently single in the U.S. as part of The Kinsey Institute’s annual Singles in America study (N = 4,264; 57.3% women; 42.5% men). Data was collected in June-August of 2020 when most states issued social distancing guidelines. Results show that 15% of people initiated re-engagement with an ex during these months. Of 736 people (out of 4264) who reached out to their ex, 55% texted or direct messaged, 26.5% phone/video chatted, 8.2% met in person, 5.8% sexted/had phone sex, and 2 people had sex in-person with their ex. Eleven percent of single people had sex with their platonic roommate for the first time, 13% said that they had sex with their roommate prior to lockdown, and 76% said that they did not have sex with their roommate. In the future, we plan to examine potential gender and orientation differences in engaging in sexual activity with ex-partners and roommates. We hypothesize that LGBTQ individuals will show a higher frequency of initiating sexual contact with ex-partners or roommates because gay individuals have reported higher levels of post-breakup connectedness than heterosexuals (Harkless & Fowers, 2005)

Online Dating During the COVID-19 Pandemic: Is it the New Norm?

For many who were single during the COVID-19 pandemic, this public health crisis may have led to issues with dating or finding a romantic partner. To understand the impact of the pandemic on dating life, in the present study, we examined single people’s dating app usage collected as part of The Kinsey Institute’s annual Singles in America project. Using a nationally representative sample of people who were currently single in the U.S. (N = 4,877 with an average age of 45.92), we found that the vast majority of single people (96%) were using dating apps (e.g., Tinder, Bumble, Match) during the COVID-19 pandemic. Sixty-two percent of the sample identified as women and 37.4% identified as men; 88.5% identified as heterosexual and 11.5% identified as a sexual minority (gay, lesbian, or bisexual). One-quarter (24.9%) of single people were using dating apps more frequently than compared to before the pandemic; nearly one-half (42.5%) were less active during the pandemic (the remaining reported no change in dating app usage). Multiple linear regression results show that men and sexual minorities were using dating apps at a higher frequency during the pandemic, compared to women and heterosexual people, respectfully (B = .16, p = .006 and B = .19, p = .01). Age was not associated with dating app usage during the pandemic. Information about video date usage and enjoyment will be discussed as well as common video date activities (e.g., long conversations, sex, games) during the pandemic. Taken together, these results suggest that dating app usage decreased during the pandemic (except for men and sexual minorities), which is likely due to health concerns. At the same time, video dating may have become a new norm during this time period

Noninvasive amniotic fluid sampling to establish PK of azithromycin in pregnancy

Background PK studies to guide dosing of azithromycin (AZ) for pregnancy specific conditions, such as preterm premature rupture of membranes (PPROM), and data on accumulation of AZ in fetal compartment are lacking. We aim to evaluate feasibility of non-invasive collection of amniotic fluid (AF), validate an assay for AZ in AF, and describe concentration of AZ in the amniotic cavity over one week following a single maternal dose. Methods Patients with PPROM treated with 1g AZ PO once and wore underwear lining pads to collect AF as it leaked. AF strained from each pad, up to 10cc collected, centrifuged and frozen. Calibration curve established using range of 1 to 200 ng/mL, with Azithromycin-D3 as internal standard. Spiked standards and samples were extracted with plasma to ACN ratio as 1:2, and centrifuged. The clean supernatant was subjected to LCMS runs using Thermo-Orbitrap coupled with Dionex 3000 UHPLC system under +ve ion mode and sample 5µL injection volume. The chromatographic separations were done using HSS XSelect C18 reverse phase column using 50:50 water and ACN with 0.1% FA as mobile phase, flow rate of 0.250 mL/min. The linearity equation (y= 10945x, r2\u3e0.99) established using average of 8 injections over 4 days; 2 injections per day. AZ from AF samples was quantitated in duplicate and expressed as concentration/time profile. Results Five patients were enrolled. Mean gestational age on admission with PPROM was 27.5 ±2.3wk with a median latency of 7 days [IQR 4-13]. A median of 2 samples/day [IQR 1-3] were collected per participant. Azithromycin was quantified in duplicate; intra-assay coefficient of variation was 17%. Azithromycin concentration was \u3c60ng/ml after day 3. Azithromycin concentration was positively correlated with IL-8 (r=0.38, p=0.03), IL1a (r=0.39, p=0.03), and IL-1b (r=0.36, p=0.04) in amniotic fluid. Conclusion This simple technique for noninvasive collection of AF allows for precise quantification of AZ in AF with LCMS. AZ persists in the fetal compartment for at least seven days after a single maternal dose, although not necessarily at an adequate inhibitory concentration.https://jdc.jefferson.edu/obgynposters/1014/thumbnail.jp

ranacapa: An R package and Shiny web app to explore environmental DNA data with exploratory statistics and interactive visualizations.

Environmental DNA (eDNA) metabarcoding is becoming a core tool in ecology and conservation biology, and is being used in a growing number of education, biodiversity monitoring, and public outreach programs in which professional research scientists engage community partners in primary research. Results from eDNA analyses can engage and educate natural resource managers, students, community scientists, and naturalists, but without significant training in bioinformatics, it can be difficult for this diverse audience to interact with eDNA results. Here we present the R package ranacapa, at the core of which is a Shiny web app that helps perform exploratory biodiversity analyses and visualizations of eDNA results. The app requires a taxonomy-by-sample matrix and a simple metadata file with descriptive information about each sample. The app enables users to explore the data with interactive figures and presents results from simple community ecology analyses. We demonstrate the value of ranacapa to two groups of community partners engaging with eDNA metabarcoding results