Title: European MRSA Originated in Sub-Saharan Africa, Study Finds
Category: Health News
Created: 8/29/2014 9:35:00 AM
Last Editorial Review: 8/29/2014 12:00:00 AM

Title: Health Tip: Keeping Foods Separate During Grilling
Category: Health News
Created: 8/26/2016 12:00:00 AM
Last Editorial Review: 8/26/2016 12:00:00 AM

Title: How to Keep Your Kids Trim Through Quarantine
Category: Health News
Created: 8/25/2020 12:00:00 AM
Last Editorial Review: 8/26/2020 12:00:00 AM

Title: How Can You Tell if Your Baby Has an Earache?
Category: Diseases and Conditions
Created: 6/16/2021 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: Pious Parasites: Medieval Monks Battled Nasty Gut Germs
Category: Health News
Created: 8/19/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM

High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions.

Somatic mutations arise and accumulate during tissue culture and vegetative propagation, potentially affecting various traits in horticultural crops, but their characteristics are still unclear. Here, somatic mutations in regenerated woodland strawberry derived from tissue culture of shoot tips under different conditions and 12 cultivated strawberry individuals are analyzed by whole genome sequencing. The mutation frequency of single nucleotide variants is significantly increased with increased hormone levels or prolonged culture time in the range of 3.3 x 10^–8–3.0 x 10^–6 mutations per site. CG methylation shows a stable reduction (0.71%–8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved genome is assembled for the strawberry cultivar "Beni hoppe." The 12 "Beni hoppe" individuals randomly selected from different locations show 4731–6005 mutations relative to the reference genome, and the mutation frequency varies among the subgenomes. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale and nucleotide resolution in plants.

Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here, we show that efficient termination of tTAF-activated transcription relies on testis-specific paralogs of canonical polymerase-associated factor 1 complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants show aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes and thus serves to maintain spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and the PAF1C and identify transcription termination as a developmentally regulated process required for germline-specific gene expression.

Massively parallel reporter assays (MPRAs) are powerful tools for quantifying the impacts of sequence variation on gene expression. Reading out molecular phenotypes with sequencing enables interrogating the impact of sequence variation beyond genome scale. Machine learning models integrate and codify information learned from MPRAs and enable generalization by predicting sequences outside the training data set. Models can provide a quantitative understanding of cis-regulatory codes controlling gene expression, enable variant stratification, and guide the design of synthetic regulatory elements for applications from synthetic biology to mRNA and gene therapy. This review focuses on cis-regulatory MPRAs, particularly those that interrogate cotranscriptional and post-transcriptional processes: alternative splicing, cleavage and polyadenylation, translation, and mRNA decay.

End-to-end RNA-sequencing methods that capture 5'-sequence content without cumbersome library manipulations are of great interest, particularly for analysis of long RNAs. While template-switching methods have been developed for RNA sequencing by distributive short-read RTs, such as the MMLV RTs used in SMART-Seq methods, they have not been adapted to leverage the power of ultraprocessive RTs, such as those derived from group II introns. To facilitate this transition, we dissected the individual processes that guide the enzymatic specificity and efficiency of the multistep template-switching reaction carried out by RTs, in this case, by MarathonRT. Remarkably, this is the first study of its kind, for any RT. First, we characterized the nucleotide specificity of nontemplated addition (NTA) reaction that occurs when the RT extends past the RNA 5'-terminus. We then evaluated the binding specificity of specialized template-switching oligonucleotides, optimizing their sequences and chemical properties to guide efficient template-switching reaction. Having dissected and optimized these individual steps, we then unified them into a procedure for performing RNA sequencing with MarathonRT enzymes, using a well-characterized RNA reference set. The resulting reads span a six-log range in transcript concentration and accurately represent the input RNA identities in both length and composition. We also performed RNA-seq from total human RNA and poly(A)-enriched RNA, with short- and long-read sequencing demonstrating that MarathonRT enhances the discovery of unseen RNA molecules by conventional RT. Altogether, we have generated a new pipeline for rapid, accurate sequencing of complex RNA libraries containing mixtures of long RNA transcripts.

Background

Exacerbations of noncystic fibrosis bronchiectasis (bronchiectasis) are associated with reduced health-related quality of life and increased mortality, likelihood of hospitalisation and lung function decline. This study investigated patient clinical characteristics associated with exacerbation frequency.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We used OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (K_i) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our nine metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3-mediated, but not OATP1B1-mediated, uptake of CP-I in vitro, with an estimated K_i of 3.93 μM. Baseline CP-I concentrations were simulated to be 0.81 ± 0.26 ng/ml and determined to be 0.72 ± 0.16 ng/ml among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low.

Antifolates are important for chemotherapy in non–small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates, with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Michaelis-Menten constant (K_m) value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found that antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0–7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC₅₀ value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated that increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors.

A STING (stimulator of interferon genes) agonist GSK3996915 under investigation in early discovery for hepatitis B was orally dosed to a mouse model for understanding the parent drug distribution in liver, the target organ. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to quantify the distribution of GSK3996915 in liver collected from mice administered a single oral dose at 90 mg/kg. GSK3996915 was detected with a zonal distribution localized in the portal triad and highly concentrated in the main bile ducts, indicating clearance through biliary excretion. High spatial resolution imaging showed the distribution of the parent drug localized to the cellular populations in the sinusoids, including the Kupffer cells. Additionally, a series of drug-related metabolites were observed to be localized in the central zones of the liver. These results exemplify the potential of utilizing MALDI IMS for measuring not only quantitative drug distribution and target exposure but also drug metabolism and elimination in a single suite of experiments.

Pregnane X receptor (PXR) belongs to the nuclear receptor superfamily that plays a crucial role in hepatic physiologic and pathologic conditions. Phase separation is a process in which biomacromolecules aggregate and condense into a dense phase as liquid condensates and coexist with a dilute phase, contributing to various cellular and biologic functions. Until now, whether PXR could undergo phase separation remains unclear. This study aimed to investigate whether PXR undergoes phase separation. Analysis of the intrinsically disordered regions (IDRs) using algorithm tools indicated a low propensity of PXR to undergo phase separation. Experimental assays such as hyperosmotic stress, agonist treatment, and optoDroplets assay demonstrated the absence of phase separation for PXR. OptoDroplets assay revealed the inability of the fusion protein of Cry2 with PXR to form condensates upon blue light stimulation. Moreover, phase separation of PXR did not occur even though the mRNA and protein expression levels of PXR target, cytochrome P450 3A4, changed after sorbitol treatment. In conclusion, for the first time, these findings suggested that exogenous PXR does not undergo phase separation following activation or under hyperosmotic stress in nucleus of cells.

Aberrant type 2 inflammatory responses are the underlying cause of the pathophysiology of allergic asthma, allergic rhinitis, and other atopic diseases, with an alarming prevalence in relevant parts of the Western world. A bulk of evidence points out the important role of the DP2 receptor in these inflammation processes. A screening of different polyunsaturated fatty acids at a fluorescence resonance energy transfer–based DP2 receptor conformation sensor expressed in human embryonic kidney (HEK) cells revealed an agonistic effect of the prostaglandin (PG)-D₂ precursor arachidonic acid on DP2 receptor activity of about 80% of the effect induced by PGD₂. In a combination of experiments at the conformation sensor and using a bioluminescence resonance energy transfer–based G protein activation sensor expressed together with DP2 receptor wild type in HEK cells, we found that arachidonic acid acts as a direct activator of the DP2 receptor, but not the DP1 receptor, in a concentration range considered physiologically relevant. Pharmacological inhibition of cyclooxygenases and lipoxygenases as well as cytochrome P450 did not lead to a diminished arachidonic acid response on the DP2 receptor, confirming a direct action of arachidonic acid on the receptor.

ABSTRACTIntroduction:Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality. A new clinical intervention (E-MOTIVE) holds the potential to improve early PPH detection and management. We aimed to develop and pilot implementation strategies to support uptake of this intervention in Kenya, Nigeria, South Africa, and Tanzania.Methods:Implementation strategy development: We triangulated findings from qualitative interviews, surveys and a qualitative evidence synthesis to identify current PPH care practices and influences on future intervention implementation. We mapped influences using implementation science frameworks to identify candidate implementation strategies before presenting these at stakeholder consultation and design workshops to discuss feasibility, acceptability, and local adaptations. Piloting: The intervention and implementation strategies were piloted in 12 health facilities (3 per country) over 3 months. Interviews (n=58), case report forms (n=1,269), and direct observations (18 vaginal births, 7 PPHs) were used to assess feasibility, acceptability, and fidelity.Results:Implementation strategy development: Key influences included shortages of drugs, supplies, and staff, limited in-service training, and perceived benefits of the intervention (e.g., more accurate PPH detection and reduced PPH mortality). Proposed implementation strategies included a PPH trolley, on-site simulation-based training, champions, and audit and feedback. Country-specific adaptations included merging the E-MOTIVE intervention with national maternal health trainings, adapting local PPH protocols, and PPH trollies depending on staff needs. Piloting: Intervention and implementation strategy fidelity differed within and across countries. Calibrated drapes resulted in earlier and more accurate PPH detection but were not consistently used at the start. Implementation strategies were feasible to deliver; however, some instances of limited use were observed (e.g., PPH trolley and skills practice after training).Conclusion:Systematic intervention development, piloting, and process evaluation helped identify initial challenges related to intervention fidelity, which were addressed ahead of a larger-scale effectiveness evaluation. This has helped maximize the internal validity of the trial.

BACKGROUND AND PURPOSE:

Gadolinium-based contrast agents are widely used for meningioma imaging; however, concerns exist regarding their side effects, cost, and environmental impact. At the standard gadolinium dose, most meningiomas show avid contrast enhancement, suggesting that administering a smaller dose may be feasible. The purpose of this study was to evaluate the impact of a lower gadolinium dose on the differentiation between meningiomas and adjacent intracranial tissues.

BACKGROUND AND PURPOSE:

Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances.

Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.

Pitched as a mix of ‘Blade Runner’ and ‘Jurassic Park,’ Neom is the world’s biggest construction project. Twenty-one thousand people have died so far to make it happen.

Online interactions are based on trust, since there are few definitive ways to certify the identity of the person with whom one is communicating. Naturally, this situation can lead to deception and manipulation, as it has—to tormenting effect—for Tegan and Sara, the popular indie rock duo whose lives have been turned upside down by a mysterious bad faith actor who, for more than a decade, has impersonated Tegan with fans, friends, and business partners.

Fanatical: The Catfishing of Tegan and Sara is an investigation into the myriad means by which the internet can be wielded to nefarious ends. More than that, though, it’s an anatomy of a crime and the complicated wreckage wrought by it, not just for the famous artists but also for the innocent admirers who were tricked into believing that fiction was reality.

Premiering on Hulu on Oct. 18, following its premiere at the Toronto International Film Festival, Erin Lee Carr’s documentary is a chilling snapshot of the unholy marriage of corrosive fandom and online duplicity. At its center are Tegan and Sara, the identical twin songstresses who began making a name for themselves in the early 2000s both for their talent and for being openly gay. This earned them a loyal fanbase of queer women and men who saw themselves reflected in Tegan and Sara, and that bond was strengthened by the siblings’ active interest in interacting with fans in person—Tegan would chat with show attendees in line and at the merch table—and on LiveJournal and other budding message-board platforms that afforded a previously unavailable degree of contact.

Read more at The Daily Beast.

There must be hundreds of typewriters in the hall, their collective clacks a tidal wave of soulless automation, rising up to greet agent Kiran Estevez as she enters, pistol and flashlight in hands. Exploring rooms to the side, Alan Wake 2: The Lake House’s star finds whiteboards and documents revealing the typewriter’s purpose: to mimic Wake’s writing. Pages are graded along criteria such as ‘style’, ‘tone’, and ‘content’, then “fed into the algorithm” as references until “near-identical stories” to Wake’s can be produced.

“If Jules could simply cut the painter open and pull the painting out of him, he would,” reads one of the real Alan’s typewritten pages. That’s Jules Marmont, the obsessive head of the titular FBC centre. The Marmonts - Jules and his wife Diana - are running experiments to forcibly and synthetically create works of art, aiming to mimic creative passion convincingly enough for the paranatural entity inside Cauldron Lake to respond, as it has in the past.

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JUDY WOODRUFF: The hashtag #MeToo has millions of women sharing stories of abuse, shining a spotlight on a troubling reality in our society.

It was first used in 2007, but when actor Alyssa Milano tweeted it Sunday night to talk about sexual harassment and assault in the wake of the Harvey Weinstein story, it went viral. The hashtag was tweeted nearly a million times in just 48 hours. Facebook reported 45 percent of its users have friends who posted #MeToo, as women wrote about their experiences about the workplace and culture, and what should change.

We explore some of those issues with Fatima Goss Graves. She’s president of the National Women’s Law Center. Lisa Senecal wrote about her own experience for the online news site Daily Beast. She’s with the Vermont Commission on Women. And Melissa Silverstein is the founder of the blog and Web site Women and Hollywood.

Thank you all for joining us.

Lisa Senecal, I’m going to start with you.

You have had a personal experience with sexual harassment. That’s in part what has drawn you to this #MeToo campaign movement.

Just tell us briefly about what happened.

LISA SENECAL, Member, Vermont Commission on Women: Sure.

Like most women, I have had a number of experiences with sexual harassment, beginning with my first job, when I was 15 years old. And it’s really been a threat off and on throughout my entire professional career.

The most egregious offense was an actual assault that occurred with a male executive. Unfortunately, because of an NDA — and we can go into the evils of nondisclosures another time — but because of that, there isn’t a lot that I’m able to say about the specific event.

But the issue of sexual harassment and finally having this come to the fore, so many women are already familiar with it from being on the receiving end. And I think, especially with the #MeToo campaign, it’s been really wonderful and an eye-opening experience for men to realize just how pervasive an issue this is.

JUDY WOODRUFF: So, in your experience, it was a business setting.

Melissa Silverstein, you have been writing about women in Hollywood for 10 years. Of course, that’s where the Harvey Weinstein story came from.

If it’s been going on in Hollywood forever, why hasn’t it been talked about more before now?

MELISSA SILVERSTEIN, Founder, Women and Hollywood: Well, I think there was a culture of silence created around this man and also within this industry.

People were afraid. People are afraid for their jobs. It’s a very relational industry, where if someone is going to blacklist you, you are not going to get your next job.

So I think the way that a person was able to conduct himself for 30 years like this was to build a culture of fear, to make people sign nondisclosure agreements, and to get them to shut up.

JUDY WOODRUFF: Fatima Goss Graves, here with me in Washington with the National Women’s Law Center, we have been talking about Hollywood.

We have talking about the business workplace. Is there any field of work where this isn’t going on?

FATIMA GOSS GRAVES, President, National Women’s Law Center: Right.

The issue of harassment and assault, it’s a Hollywood problem, but really it’s an everywhere problem. It infects industries across the board, whether you’re high-wage jobs, low-wage jobs, male-dominated fields, but also female-dominated fields.

Restaurants are some of the areas where you have some of the highest rates of EEOC charges. And that’s not a male-dominated field.

JUDY WOODRUFF: EEOC, the Equal Employment Opportunity Commission.

Lisa Senecal, some people are saying that they’re uncomfortable with this #MeToo campaign movement because they’re saying, once again, women are being asked to go public with what happened to them, but there is no promise that there is going to be anything done about it. How do you see this?

LISA SENECAL: I don’t necessarily believe that women are being asked to come forward.

I think this is an opportunity to come forward, if that’s something that women want to do, but there’s no obligation to do it. And there’s been a lot of support for letting women know that if this isn’t something you’re comfortable with at this time, no one is obligated to tell their story, and no one is allowed to force you to tell your story before you’re ready.

But the stories are important. Without them, the degree to which this happens across all industries, across genders as well — we know that this happens to men. This happens to the transgender.

It’s not specific to women, although it affects us most frequently. Until we have a critical mass of women who are able to get the men in their lives, the men that they work with to understand how pervasive a problem it is, and then can get men to begin to act on this, because this isn’t a women’s issue.

This is a violence issue, and an issue of power and who has the power. So until the people who still primarily do hold the power, which is primarily men and primarily white men, until they’re going to begin to act, then the problems are going to persist.

JUDY WOODRUFF: Melissa Silverstein, how do you see that? What is it going to take for this to be a change?

MELISSA SILVERSTEIN: The fact that we’re having a global conversation about sexual harassment — I have been doing media for the last week all over the world.

People are really enthralled by this and want to see change. This is a global issue. And, also, Hollywood is a global industry. Seventy cents of every dollar of Hollywood studio movies are made outside the United States.

So what people are looking for is Hollywood to step up. And, today, we had a leader in Hollywood, Kathleen Kennedy, to say we need to have a commission, cross-industry commission, of people who are going to look into this and put a stop to it once and for all.

JUDY WOODRUFF: And pick up on that, Fatima Goss Graves. Just across the board, what is it going to take?

FATIMA GOSS GRAVES: Right.

We know that there are things that would make a difference here. If employers had processes that their employees actually use, you wouldn’t have harassment in the shadows. Right now, most people don’t report harassment to anyone. And it’s because they think their employers won’t do anything, or, worse, that they would experience retaliation.

JUDY WOODRUFF: And that’s — because that’s been what happened.

FATIMA GOSS GRAVES: And that is. They’re right to believe that they will experience retaliation, because they do. They’re shamed. They’re blamed.

But employees could make a difference. Right? They can be — take it seriously and communicate that to their workplace. They can also have the right policies that are in place. And, finally, they could, when someone comes forward, be really clear that they take it seriously and that they will not tolerate retaliation.

Those are things that aren’t happening among employers frequently enough.

JUDY WOODRUFF: Lisa Senecal, as somebody who had it happen to you in a business environment, what changes need to be made in the workplace? What has to happen?

LISA SENECAL: Well, I agree completely with what was just said.

Too often, the workplace education that goes on is incredibly insufficient. It’s more of companies wanting to be able to check the box and say that they did their sexual harassment training. And it isn’t truly something within the culture of companies that they believe that this is a problem and that it is a right of all people working at that company not to be harassed.

So, until it starts to be taken more seriously, and when a woman or anyone comes forward with an accusation, it does have to be taken so much more seriously. And the knee-jerk response, as was in my case, cannot be to shame the woman, can’t be to blame her for somehow bringing this on herself, and putting women back in a position of being victimized a second time because they’re not taken seriously when they come forward.

JUDY WOODRUFF: Melissa Silverstein, yes, go ahead.

MELISSA SILVERSTEIN: I just wanted to add, one of the things that’s so fundamental about this is how this — how it’s so normalized for all of us to go through this kind of harassment, especially in Hollywood, and how people kind of laugh off, oh, you know, that’s locker room talk, or, you know, this is the movie business, get used to it.

And what we need to do is really pierce that veil of the normalization of this kind of conduct, because it starts with, you know, the comments, and then it can escalate very quickly.

So we really need to just change people’s attitudes and get rid of the toxic masculinity. Hollywood has no much institutionalized sexism that sometimes I feel like we need to just start over, if possible.

JUDY WOODRUFF: Joining us also is Leigh Gilmore, a professor at Wellesley College who’s written a book about why — titled “Why We Doubt What Women Say About Their Lives.”

Leigh Gilmore, why don’t women — why haven’t women been believed and taken seriously on this, and could we now be at a moment when they are?

LEIGH GILMORE, Wellesley College: It’s good to be with you, Judy.

I think we have a persistent and a pervasive culture of doubting what women say, especially when they’re bringing forward accounts of harm into the public sphere. So we have these pre-made default cultural narratives of women’s unreliability. We have he said/she said, which is a false equivalence narrative.

We have that notion that nobody knows what really happened. We have that notion that you can’t really trust what women say. None of these are based in fact, but they are part of a kind of cloud that enables us to doubt any woman before she speaks up.

And it’s quite intimidating. And so, if we’re at a point of change, we really are at a moment where I think we have a new level of visibility, and we have the opportunity to amplify the voices of women who are speaking out.

So, insofar as we have that opportunity, there is a form of solidarity, and more women speaking can lead to change.

JUDY WOODRUFF: Fatima Goss Graves, as somebody who works on these issues from a legal standpoint, are we, could we be at a watershed point, or is it just a whole lot more complicated?

FATIMA GOSS GRAVES: Well, the culture change typically has to go together with both the enforcement of the laws and the policy change.

And so we’re at a tipping point, surely, on culture change. But I will tell you, you know, the National Women’s Law Center runs a hot line. And over the last two weeks, we have had double the intake on harassment.

And we have a new network called the Legal Network for Gender Equity, so we’re — attorneys are joining with us and will be ready to take these cases. But those people who are making these calls and contacting us, I think that that shows that you have people who are ready to come forward on social media, and there is power there, but it seems like there are people who are ready to come forward in other ways, too.

JUDY WOODRUFF: I want to quickly go around and ask each one of you about the role of men in all of this.

Lisa Senecal?

LISA SENECAL: Oh, I think it’s critical for men as allies to be coming forward and supporting women who do come forward.

Men also need to be willing to call out other men, whether that’s one-on-one, whether it’s in a group setting within a company, or socially. If a man hears, sees someone doing something inappropriate, they need to have the courage to stand up, even in front of other men, and say, it’s not OK, it’s inappropriate behavior, and it’s not going to be tolerated.

And until it’s also men joining in, women can’t do this by themselves. There is an organization, A Call to Men, that I’m a big fan of. And one of their mantras is, if women could have stopped abuse and assault, they would have done it already.

And that’s completely true. It’s not something that women are going to be able to do alone. It shouldn’t be looked at as only a women’s issue. And until people look at this on a larger scale and understand that this affects the bottom line of companies, it affects productivity, it affects, you know, absenteeism, just across the board, this is not a women’s issue.

It is a human issue.

JUDY WOODRUFF: Right.

Melissa Silverstein, what about that?

And we should point out that men are themselves the victims of sexual harassment and abuse at times.

MELISSA SILVERSTEIN: I feel that this is on men.

The men are most of the perpetrators. They’re also the collaborators. And, at The Weinstein Company, their board was all men, and they were all complicit in creating an environment that allowed this to thrive.

In Hollywood, there’s not a single woman, even the people at the tippy-top of the industry, who don’t report to men. This is also about getting more women into leadership positions and getting the men — and holding the men accountable.

The men in this industry need to step up. They need to say, we want to be — we want to create this industry in a way that women can thrive and don’t have to experience this anymore.

JUDY WOODRUFF: Leigh Gilmore?

LEIGH GILMORE: We’re talking about awareness and accountability.

So, as wonderful as it is to have increased visibility, and it enables us to connect the dots and to see the long histories of sexual abuse, harassment and discrimination, we need new levels of accountability.

I will echo the notion that Harvey Weinstein’s board certainly knew about these accusations. There’s a DA who failed to charge him. We have ample examples of failures.

And what we really need to do is to correct those. The role of men is certainly important here. Minimally, they can show up and be witnesses.

JUDY WOODRUFF: And, finally, Fatima Goss Graves, the role of men and how we prevent this.

FATIMA GOSS GRAVES: We have had a little bit of conversation about men as survivors, but the conversation we haven’t really had is about what happens when men are abusers or enablers or allow this to happen in the workplaces, in schools, or in women’s everyday lives?

And so now we have an opportunity culturally for that conversation. That culture is going to have to hit where policy-makers are. It’s going to have to hit where employers are in order to make a real difference.

JUDY WOODRUFF: Well, it’s clear that everyone is hoping this is a watershed moment, that things will change as a result of what’s happened here. But we will see.

And we appreciate all of you joining us in this conversation, Fatima Goss Graves here with me in Washington, Lisa Senecal, Melissa Silverstein, and Leigh Gilmore.

We thank you all.

FATIMA GOSS GRAVES: Thank you.

MELISSA SILVERSTEIN: Thank you.

The post As survivors say #MeToo, what will it take to stop widespread sexual harassment? appeared first on PBS NewsHour.

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