The introduction of anti-angiogenic drugs especially tyrosine kinase inhibitors (TKIs) was a breakthrough in the treatment of renal cell carcinoma (RCC). Although TKIs have significantly improved ...outcome in patients with metastatic disease, the majority still develop resistance over time. Because different combinations and sequences of TKIs are tested in clinical trials, resistance patterns and mechanisms underlying this phenomenon should be thoroughly investigated. From a clinical point of view, resistance occurs either as a primary phenomenon (intrinsic) or as a secondary phenomenon related to various escape/evasive mechanisms that the tumor develops in response to vascular endothelial growth factor (VEGF) inhibition. Intrinsic resistance is less common, and related to the primary redundancy of available angiogenic signals from the tumor, causing unresponsiveness to VEGF-targeted therapies. Acquired resistance in tumors is associated with activation of an angiogenic switch which leads to either upregulation of the existing VEGF pathway or recruitment of alternative factors responsible for tumor revascularization. Multiple mechanisms can be involved in different tumor settings that contribute both to evasive and intrinsic resistance, and current endeavor aims to identify these processes and assess their importance in clinical settings and design of pharmacological strategies that lead to enduring anti-angiogenic therapies.
Cancer stem Cells or Cancer Stem-like Cells are thought to be associated with chemoresistance and recurrence in cancer patients following chemotherapy. Developing a method to study these malignant ...populations is the key to successful development of drug or immunotherapeutic assays. Here, we present a method of identification, isolation of Prostate Cancer Stem Cells (PCSCs) from the DU145 prostate cancer cell line using the NANOG-GFP expression system.
Cell-cell adhesions constitute the structural "glue" that retains cells together and contributes to tissue organisation and physiological function. The integrity of these structures is regulated by ...extracellular and intracellular signals and pathways that act on the functional units of cell adhesion such as the cell adhesion molecules/adhesion receptors, the extracellular matrix (ECM) proteins and the cytoplasmic plaque/peripheral membrane proteins. In advanced cancer, these regulatory pathways are dysregulated and lead to cell-cell adhesion disassembly, increased invasion and metastasis. The Metastasis suppressor protein 1 (MTSS1) plays a key role in the maintenance of cell-cell adhesions and its loss correlates with tumour progression in a variety of cancers. However, the mechanisms that regulate its function are not well-known. Using a system biology approach, we unravelled potential interacting partners of MTSS1. We found that the secretory carrier-associated membrane protein 1 (SCAMP1), a molecule involved in post-Golgi recycling pathways and in endosome cell membrane recycling, enhances Mtss1 anti-invasive function in HER2+/ER-/PR- breast cancer, by promoting its protein trafficking leading to elevated levels of RAC1-GTP and increased cell-cell adhesions. This was clinically tested in HER2 breast cancer tissue and shown that loss of MTSS1 and SCAMP1 correlates with reduced disease-specific survival. In summary, we provide evidence of the cooperative roles of MTSS1 and SCAMP1 in preventing HER2+/ER-/PR- breast cancer invasion and we show that the loss of Mtss1 and Scamp1 results in a more aggressive cancer cell phenotype.
This study presents for the first time a case of Hyalomma excavatum hyperparasitism and an analysis of this phenomenon in terms of its potential role in the biology of ticks and epidemiology of ...tick-borne diseases.
Two partially engorged H. excavatum females, one fully engorged female, and 5 males were collected from a naïve rabbit and placed together in a rearing chamber at a temperature of 25°C and 75% humidity.
3-4 days after tick detachment from the host's skin, one partially engorged H. excavatum female was observed attached to the idiosoma of the fully engorged conspecific female.
This study and observations of other authors confirm that partially engorged ixodid ticks can re-infest the host, and even co-feeding fully engorged ticks in order to collect the blood meal that is indispensable for important physiological processes. However, inefficient feeding of a partially engorged female on another conspecific female may reduce its reproductive performance and disturb the development of eggs and larvae. It seems that parasitism of a tick on another conspecific specimen, when at least one of them is infected by a microorganism, may be a yet poorly explored route of transmission of pathogens or symbionts between the ticks. Initiation of feeding by a hungry or partially engorged tick on a fully engorged specimen is an attempt to obtain food in the drastic conditions of the absence of a target host. Tick hyperparasitism with concurrent pathogen transmission can contribute to the genospecific diversity of pathogens in vectors and hosts.
The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: "This study was supported by the European Union's Horizon 2020 research and ...innovation program under the Marie Sklodowska-Curie grant agreement no 641549, Immutrain." The PDF and HTML versions of the paper have been modified accordingly.
This paper presents the findings of research of a short-pulse low pressure carburizing technology developed for a new large-chamber furnace for high-performance and precision thermal treatment of ...parts of mechanical gear. Sections of the article discuss the novel constructions of the device in which parts being carburized flow in a stream, as well as the low-pressure carburizing experiment. The method has been found to yield uniform, even and repeatable carburized layers on typical gear used in automotive industry.
To assess cannabis and alcohol involvement among motor vehicle crash (MVC) fatalities in the United States.
In this repeated cross-sectional analysis, we used data from the Fatality Analysis ...Reporting System from 2000 to 2018. Fatalities were cannabis-involved if an involved driver tested positive for a cannabinoid and alcohol-involved based on the highest blood alcohol concentration (BAC) of an involved driver. Multinomial mixed-effects logistic regression models assessed cannabis as a risk factor for alcohol by BAC level.
While trends in fatalities involving alcohol have remained stable, the percentage of fatalities involving cannabis and cannabis and alcohol increased from 9.0% in 2000 to 21.5% in 2018, and 4.8% in 2000 to 10.3% in 2018, respectively. In adjusted analyses, fatalities involving cannabis had 1.56 (95% confidence interval CI = 1.48, 1.65), 1.62 (95% CI = 1.52, 1.72), and 1.46 (95% CI = 1.42, 1.50) times the odds of involving BACs of 0.01% to 0.049%, 0.05% to 0.079%, and 0.08% or higher, respectively.
The percentage of fatalities involving cannabis and coinvolving cannabis and alcohol doubled from 2000 to 2018, and cannabis was associated with alcohol coinvolvement. Further research is warranted to understand cannabis- and alcohol-involved MVC fatalities. (
. 2021;111(11):1976-1985. https://doi.org/10.2105/AJPH.2021.306466).
Background:
Infant feeding data are often collected retrospectively through maternal report. Validation studies show that maternal report of initiation and duration of any breastfeeding is accurate ...but that report of duration of exclusive breastfeeding may be less accurate.
Objective:
This study aimed to compare infant feeding data collected longitudinally throughout the first 6 months of life with maternal report of duration of exclusive breastfeeding collected 2 years postpartum.
Methods:
Infant feeding data were collected prospectively throughout the first 6 months of life from medical records and maternal report, including maternal 24-hour recall. At 2 years postpartum, we asked mothers of these same infants how long they exclusively breastfed their infants. Their responses were compared to the prospectively collected data. Simple and multiple linear regressions tested for any significant predictors of the difference between the prospectively collected data and maternal report at 2 years.
Results:
Of the 292 mothers included in the final analysis, only 88 (30.1%) mothers reported a duration of exclusive breastfeeding at 2 years postpartum that matched the prospectively collected data. Sixty-four women reported exclusively breastfeeding for the recommended 6 months (21.9%), but according to the prospectively collected data, only 2 women (0.7%) breastfed exclusively through 6 months. The median difference between the prospectively collected data and maternal report at 2 years was 1 month (IQR, 0-4).
Conclusion:
In this sample of mothers, report of exclusive breastfeeding practices 2 years after birth was often inaccurate and mothers tended to overestimate duration.
Introduction: Mortality associated with hepatitis C virus (HCV) infection is increasing, yet only a small percentage of HCV-infected individuals are aware of their infections, complete treatment, and ...achieve a cure, defined as a sustained virologic response. In March 2015, the Section of General Internal Medicine at Boston Medical Center (BMC), New England’s largest safety-net hospital, implemented the Adult Primary Care HCV Treatment and Triage Program to increase access to treatment. We are unaware of prior studies that have explored a pharmacist-centered primary care-based HCV treatment model in the era of newer direct-acting antiviral (DAA) medications. Objectives: To gain a deeper understanding of the roles of each program staff member, as well as an understanding of how primary care providers (PCPs) who refer patients to the program perceive and interact with the program. Such an understanding will help promote implementation and dissemination of the program. Methods: We conducted in-depth semi-structured interviews with six staff members and with five PCPs in the Section of General Internal Medicine at BMC who refer patients to the program. We asked staff members about their roles and their perception of the program’s impact on patient linkage to HCV treatment. We probed PCPs about their experiences with HCV screening, referral, and follow-up processes, and differences in accessing HCV treatment for their patients prior to and following the implementation of the program. We audiotaped and transcribed interviews, and identified major themes through qualitative analysis. Results: We identified five major themes that characterize how the HCV treatment program delivers care: 1) efficiency (“So here I feel like…they get evaluated…they get treated. Boom, it’s done”); 2) clear and open communication (“…one of the strengths of our program is that we have…a lot of direct contact with patients…”); 3) personalized medicine (“…I've set up the pill box for them patients…we tailor it to whatever they need”); 4) high patient engagement (“So if I get a referral for a patient…I call the patient three times. If I haven’t heard from the patient…I send them a letter and I tell the PCP”); 5) patient empowerment through education (“I think patient education is the best thing…if the patient is involved then… they’ll do what they need to do”). Additionally, the public health social worker and the pharmacist play key roles in the program. The social worker supports patients throughout treatment and addresses psychosocial barriers to treatment engagement (“I had a patient…who stopped taking his medication because his apartment was infested with bed bugs…Social worker got the patient furniture for free and got an exterminator…”). The pharmacist provides medication management during face-to-face patient visits (“…I go over everything imaginable...proper adherence…adverse effects, interactions…”). Conclusions: The HCV treatment program at BMC is a promising model to deliver HCV treatment to urban, underserved patient populations. Our findings suggest that public health social workers and pharmacists may be one approach to increasing access to HCV treatment in primary care settings in the era of DAA medications. Further study of the program’s efficacy in improving HCV outcomes is warranted.
This study examined the relationship between parental emotion regulation and discipline behavior. Adaptive and maladaptive emotion regulation strategies were evaluated as both correlates and ...predictors of lax and overreactive disciplinary styles and as the possible mechanism by which negative affect impacts parenting behavior. Participants, 170 mothers of children ages 2-7, were asked to complete a series of self-report questionnaires. Results indicated significant relationships between the emotion regulation strategies of positive reappraisal, planning, blaming others, catastrophizing, rumination, and self-blame with overreactive discipline. Lax discipline was found to be related to planning, self-blame, catastrophizing, blaming others, and suppression. Additionally, refocusing on planning and blaming-others independently emerged as predictors of lax discipline, whereas as self-blame was found to significantly predict overreactive discipline. Blaming-others was also identified as a mediator in the relationship between negative affect and lax discipline. These results add to the limited understanding of the role of emotion regulation in parent disciplinary behavior and may have important implications for the treatment of disruptive behavior disorders.
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