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Coriandrum sativum (Linn.) and Petroselinum crispum (Mill.) are the common herbs used for culinary purposes in daily life. The chlorophyll pigment in plants is being identified with various medicinal values, whereas iron is an essential micronutrient for the proper metabolism of the human body. The current research has been aimed at predicting the role of C. sativum and P. crispum in enhancing iron absorption via an in vitro approach. C. sativum and P. crispum have been analyzed for their capability of being a source of chlorophyll and iron concentration. The extracts prepared from solvents like carbinol, petroleum ether, and water were subjected to the identification of phytoconstituents through gas chromatography-mass spectrometry analysis, and the identified compounds were subjected to in silico studies against the iron-binding receptor, transferrin, to depict the binding affinity of the identified compounds. The carbinol extract was then put through in vitro analytical studies in Caco2 cell lines with a concentration of 500 µg/ml. Current research has shown that the leaves of C. sativum and P. crispum are an excellent source of chlorophyll and iron and has also suggested that these herbs efficiently enhance the absorption of iron in human intestinal cells.

The gradual depletion of non-renewable fossil fuels, increase in their price, the toxic exhausts emitted during their combustion, risk associated in their import and its storage made many researchers to focus on deriving suitable alternate fuels. In the present investigation the performance and emission characteristics of the blends and neat methanolized papaya oil were determined on a test engine consisting of single cylinder fuelled by diesel and running at 1500 rpm. The results revealed that the blend B25 of the test biodiesel is found optimum, as it recorded better specific fuel consumption and brake thermal efficiency. Further coating on the piston enhanced the performance of the optimum blend when compared with the standard engine.

Background: Data are limited regarding the use of implantable cardioverter–defibrillators (ICDs) in diverse populations. This study explores cardiovascular (CV) outcomes and mortality from ICD randomized controlled trials (RCTs), by sex, race, and age. Methods: Five electronic databases (PubMed, Emcare, Embase, MEDLINE, and Cumulative Index to Nursing & Allied Health Literature CINAHL) were searched for dates from their inception to July 12, 2021, for RCTs of ICD therapy in adult patients. Data were analyzed for clinical outcomes, including all-cause or CV death, and heart failure hospitalization (HFH). Results: Among 5 RCTs (mean age: 63 years; 78% male; 76% White) with moderate overall risk of bias, clinical outcomes in patients with an ICD (n = 3260) vs a control group (n = 3685) were compared. No between-group sex differences were observed for all-cause death (odds ratio [OR] 0.86, P = 0.51), CV death (OR 0.98, P = 0.96), HFH (OR 0.95, P = 0.87), or HFH and all-cause death (OR 0.83, P = 0.51) in the ICD group, in a comparison of male vs female sex. All-cause death (OR 1.20, P = 0.67) did not differ for White vs Black patients receiving ICD therapy. Outcomes data for other non-White, non-Black race groups were often unreported. Most RCTs originated in North America, had male leadership, and were evenly sponsored by industry vs peer-reviewed funding. Conclusions: Outcomes data are sparse, by sex, race, and age, in current RCTs evaluating ICD therapy. Although ICD patient outcomes did not significantly differ by sex or race, improved data analyses and reporting are needed to determine the relationship between these sociocultural factors and clinical outcomes among distinct ICD patient cohorts. Résumé: Contexte: Les données sur l’utilisation des défibrillateurs cardioverteurs implantables (DCI) dans diverses populations sont limitées. Cette étude porte sur les résultats cardiovasculaires (CV) et les décès liés aux DCI qui ont été signalés dans le cadre d'essais contrôlés randomisés (ECR), en fonction du sexe, de la race et de l’âge. Méthodologie: Des recherches ont été effectuées dans cinq bases de données électroniques (PubMed, EmCare, Embase, Medline et CINAHL [Cumulative Index to Nursing & Allied Health Literature]) en ciblant une période allant de la date de leur création jusqu’au 12 juillet 2021 afin de recenser les ECR menés chez des patients adultes ayant reçu un DCI. Les données ont été analysées en fonction des résultats cliniques, notamment les décès toutes causes confondues ou d’origine CV et les hospitalisations pour insuffisance cardiaque (hIC). Résultats: Cinq ECR (âge moyen des patients : 63 ans; 78 % d’hommes; 76 % de race blanche) présentant globalement un risque de biais modéré ont permis de comparer les résultats cliniques obtenus chez les patients ayant reçu un DCI (n = 3 260) et ceux du groupe témoin (n = 3 685). Aucune différence intergroupe entre les sexes n’a été observée pour les décès toutes causes confondues (rapport de cotes [RC] : 0,86, p = 0,51), les décès d’origine CV (RC : 0,98, p = 0,96) et les hIC (RC : 0,95, p = 0,87), ou les hIC et les décès toutes causes confondues (RC : 0,83, p = 0,51) au sein du groupe de patients ayant reçu un DCI, dans une comparaison entre les sexes. Aucune différence entre les patients de race blanche et de race noire ayant reçu un DCI n’a été notée pour ce qui est des décès toutes causes confondues (RC : 1,20, p = 0,67). Souvent, les données sur les résultats obtenus au sein de groupes de patients de race autre que blanche ou noire n’étaient pas signalées. La plupart des ECR avaient été menés en Amérique du Nord, étaient dirigés par des hommes et commandités à parts égales par l’industrie et des organismes offrant du financement approuvé par les pairs. Conclusions: Les ECR portant sur l’utilisation des DCI fournissent actuellement peu de données sur les résultats en fonction du sexe, de la race et de l’âge. Les résultats obtenus chez les patients ayant reçu un DCI ne différaient pas significativement selon le sexe ou la race. Néanmoins, des analyses de données et des rapports plus détaillés sont nécessaires pour déterminer la relation entre ces facteurs socioculturels et les résultats cliniques au sein de cohortes distinctes de patients ayant reçu un DCI.

We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.

Background: Cardiac resynchronization therapy (CRT) is beneficial in patients who have heart failure with reduced ejection fraction or arrhythmic events. However, most randomized controlled trials (RCTs) showing survival benefits primarily enrolled older white men. This study aims to evaluate CRT efficacy by sex, race, and age in RCTs. Methods: Five electronic databases (CINAHL, Embase, Emcare, Medline, and PubMed) were searched from inception to July 12, 2021 for RCTs with CRT in adult patients. Data were analyzed for clinical outcomes including all-cause or cardiovascular (CV) death, worsening heart failure (HF), and HF hospitalization (HFH) according to sex, race, and age. Results: Among six RCTs with up to moderate risk of bias, 54% (n = 3,630 of 6,682; mean age 64 years, 22% female, 8% black patients) had CRT device implantation. All-cause death (odds ratio [OR], 0.51; P = 0.053) was reduced in female versus male CRT patients, whereas CV death, HFH, or all-cause death with worsening HF or HFH did not differ significantly. No difference was seen in CRT patients for all-cause death and worsening HF (OR, 1.32; P = 0.46) among white vs black patients or for all-cause death and HFH (OR, 1.19; P = 0.55) among ≥ 65 versus < 65 years. Conclusions: Whereas all-cause death was lower in female CRT patients, other reported outcomes did not significantly differ by sex, race, or age. Only 6 studies partially reported outcomes. Thus, enhanced reporting and analyses are required to overcome such paucity of data to evaluate the impact of these factors on clinical outcomes in distinct patient cohorts with CRT indication. RÉsumÉ: Contexte: La thérapie de resynchronisation cardiaque (TRC) est salutaire chez les patients qui souffrent d’insuffisance cardiaque avec fraction d’éjection réduite ou qui subissent des épisodes arythmiques. Toutefois, la plupart des essais contrôlés randomisés (ECR) montrant des bienfaits en matière de survie ont été principalement menés chez des hommes blancs âgés. Cette étude vise à évaluer l’efficacité de la TRC en fonction du sexe, de la race et de l’âge des participants aux ECR. Méthodologie: Nous avons effectué des recherches dans cinq bases de données électroniques (CINAHL, Embase, Emcare, Medline et PubMed) en ciblant une période allant de la date de leur création jusqu’au 12 juillet 2021 afin de recenser les ECR menés chez des patients adultes ayant subi une TRC. Les données ont fait l’objet d’une analyse axée sur les résultats cliniques, notamment les décès toutes causes confondues ou d’origine cardiovasculaire (CV), l’aggravation de l’insuffisance cardiaque (IC) et les hospitalisations pour cause d’IC (HIC), en fonction du sexe, de la race et de l’âge des patients. Résultats: Dans six ECR présentant un risque de biais tout au plus modéré, 54 % des patients (n = 3 630 sur 6 682; âge moyen : 64 ans, 22 % de femmes, 8 % de patients noirs) étaient porteurs d’un dispositif de RC. Les décès toutes causes confondues (rapport de cotes [RC] : 0,51; p = 0,053) étaient moins nombreux chez les femmes que chez les hommes parmi les patients ayant subi une TRC. En revanche, aucune différence significative entre les deux sexes n’a été relevée en ce qui concerne les décès d’origine CV, les HIC ou les décès toutes causes confondues liés à l’aggravation de l’IC ou aux HIC. Au sein de la population ayant subi une TRC, aucune différence n’a été observée quant aux décès toutes causes confondues et à l’aggravation de l’IC (RC : 1,32; p = 0,46) chez les patients blancs par rapport aux patients noirs. Il y avait aussi absence de différence quant aux décès toutes causes confondues et aux HIC (RC : 1,19; p = 0,55) chez les patients âgés de 65 ans ou plus par rapport aux patients âgés de moins de 65 ans au sein de la même population. Conclusions: Les décès toutes causes confondues étaient moins nombreux chez les femmes qui avaient subi une TRC, mais les autres résultats rapportés ne différaient pas significativement selon le sexe, la race ou l’âge des patients. Seulement six études ont signalé partiellement les résultats. Des rapports et des analyses plus détaillés sont nécessaires pour remédier à la paucité des données et ainsi permettre d’évaluer l’effet des facteurs étudiés sur les résultats cliniques au sein de cohortes distinctes de patients chez qui la TRC est indiquée.

Objective To present a brief historical review of treatment options for pelvic organ prolapse with a focus on anterior vaginal wall defects and highlight changing practice patterns in the era of synthetic mesh controversy. Methods A MEDLINE and PubMed search was performed using the keywords pelvic organ prolapse, anterior colporrhaphy, and cystocele followed by a manual search of bibliographies. Results Ancient treatments included Hippocratic succession, local astringent, and use of pomegranates as crude pessaries. More sophisticated surgical techniques evolved in the 19th century with further refinement in the early 20th century. Numerous native tissue apposition techniques were popularized by Kelly, Kennedy, Burch, and Raz. Due to poor durability, surgeons sought alternate approaches including biologic and synthetic grafts. Synthetic transvaginal mesh (TVM) initially included use of Tantalum and Marlex to repair anterior wall defects. Both were eventually abandoned due to complications. TVM was re-designed, re-marketed, and re-introduced. Type 1 polypropylene monofilament TVM use became ubiquitous in female pelvic surgery peaking between 2004 and 2008. Initial promising outcomes were soon eclipsed by a surge of adverse events leading to multiple FDA warnings, reclassification to Class III, high-risk medical device, and ultimately a complete recall in 2019. Conclusion The bidirectional pendulum swing on use of synthetic TVM has been occurring since its introduction 50 years ago. In the current era of mesh controversy, more practitioners are now revisiting previously described native tissue and biologic graft techniques. It appears that history has repeated itself.

Background: This study evaluates the ability to predict the response of locally advanced breast cancers to neoadjuvant therapy (NAT) using patient-specific magnetic resonance imaging (MRI) data and a biophysical mathematical model. The 3D mathematical model consists of three parts: tumor cell proliferation, tumor spread (diffusion), and treatment. In particular, the tumor cells proliferate according to logistic growth, and the diffusion term is coupled to the mechanical properties of the surrounding fibroglandular and adipose tissues to inform individual tumor growth patterns (specific to each patient’s anatomy). The model’s treatment term accounts for tumor cell reduction according to approximate local drug delivery for each patient. Methods: Patients (N = 21) with intermediate to high grade invasive breast cancers with varying receptor status, who were eligible for NAT as a component of their clinical care, were recruited. Each patient was treated with standard-of-care consisting of one or two NAT regimens in sequence followed by surgical resection of any residual tumor. MRI data are acquired at four time points: 1) prior to initiation of NAT, 2) after 1 cycle of NAT, 3) after 2-4 cycles of NAT, and 4) 1 cycle after scan 3. The MRI data is processed and evaluated using our semi-automated pipeline. Specifically, diffusion-weighted MRI data is utilized to characterize the cellularity throughout the tumor tissue, and dynamic contrast-enhanced (DCE-) MRI data is used to segment the breast tissue and analyze the local drug delivery using pharmacokinetic analysis and population-derived plasma curves of drug concentrations. The model’s predictive ability is assessed using three different strategies. First, the model is calibrated using each patient’s first two scans to enable predictions of the total tumor cellularity, volume, and longest axis that are directly compared to the values measured from their third scan. Second, the model’s predictions for tumor response are compared to the corresponding response evaluation criteria in solid tumors (RECIST) results. Third, the model is re-calibrated using scans 3 and 4 and simulated to the time of surgery to compare the model’s predictions to each patient’s response status determined by surgical pathology. Results: Calibrating the model with MRI data for one cycle of therapy yields predictions strongly correlated with tumor response measured from each patient’s third scan, concordance correlation coefficients of 0.91, 0.90, and 0.86 for total cellularity, volume, and longest axis, respectively (p < 0.01, N = 18). The model’s predictions are significantly (p < 0.01) correlated with tumor response as designated by RECIST for the cohort. Specifically, the model predicts greater percent reduction in the longest axis for the RECIST designated responder group (i.e., complete response and partial response) compared to non-responders. At the time of surgery, the model predicts changes in total tumor cellularity from baseline that are significantly (p < 0.01) correlated with pathological response status—an area under the receiver operator characteristic curve of 0.92 and a sensitivity and specificity of 1.0 and 0.74, respectively. Discussion: These preliminary results suggest that this clinical-mathematical approach can be predictive of tumor response very early in the course of NAT on a patient-specific basis. Moreover, the study was performed in the community-care setting across a heterogenous group of patients, indicating the approach may be practical for wide-spread application. NCI U01 CA174706, NCI U01 CA154602, CPRIT RR160005, ACS-RSG-18-006-01-CCE, R01CA240589, NCI-U24CA226110, CPRIT RR160093 Citation Format: Angela M Jarrett, David A. Hormuth, II, Anum K Syed, Chengyue Wu, John Virostko, Anna G Sorace, Julie C DiCarlo, Jeanne Kowalski, Debra Patt, Boone Goodgame, Sarah Avery, Thomas E Yankeelov. Predicting breast cancer response to neoadjuvant therapies using a mathematical model individualized with patient-specific magnetic resonance imaging data: Preliminary Results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-18.

Introduction. X-ray mammography is the standard-of-care screening protocol for breast cancer due to its low cost, widespread availability, and greater specificity. While magnetic resonance imaging (MRI) has lower specificity, it has superior tissue contrast, and dynamic contrast-enhanced (DCE) MRI has been shown to increase MRI specificity due to its ability to estimate tissue vascular properties. Because of the increased expense and scan time for MRI, there is an ongoing effort to develop abbreviated breast MRI scans for screening high-risk patients at a lower cost without compromising quantitative information. Here we investigate the effects of the limited dynamic time course afforded by an abbreviated breast MRI exam on the quantitative tissue information computed from retrospectively abbreviated DCE-MRI data. Methods. Data acquisition. We evaluate the error in perfusion model parameters computed using DCE-MRI time courses sourced from three datasets acquired with very different temporal resolutions (dt). These datasets are the ACRIN 6883 multi-site breast trial (dt = 15 s), The University of Texas at Austin (UTA) neoadjuvant therapy study (dt = 7.3 s), and The University of Chicago (UC) ultra-fast breast DCE-MRI study (dt = 3.4 s). Ten representative patients are chosen from each of these datasets for a total of 30 DCE-MRI patient datasets. All 30 full-time courses (FTCs) are retrospectively truncated into a series of abbreviated-time courses (ATCs). An ATC containing the first n post-contrast injection time points of a DCE-MRI time course is referred to as “ATC n.” For the ACRIN dataset, n is the inclusive set of integers from 7 to 18; and, similarly, for the UC data, n is the inclusive set of integers from 12 to 23. For the UTA dataset, n is the inclusive set ranging from 13 through 53, incrementing by eight. Data Analysis. The groups of FTCs and ATCs are analyzed by one of three models, determined by the specifics of the acquisition details of each dataset. The standard Kety-Tofts (SKT) model is fit to the UTA time courses, the reference-region (RR) model is fit to the ACRIN time courses, and the Patlak model is fit to the UC time courses. The volume transfer constant (Ktrans) characterizes tissue enhancement in all three models; whereas, the extravascular/extracellular volume fraction (ve) is specific to the SKT and RR models, and the plasma volume fraction (vp) is specific to the Patlak model. Due to the absence of an arterial input function (AIF) for the ACRIN dataset, the RR model was most appropriate with the pectoral muscle serving as the reference region. The UTA dataset has a population AIF and is thus able to be modeled by the SKT. Lastly, the UC dataset does not capture the tissue washout necessary for ve estimation, so the Patlak model was chosen for analyzing tissue enhancement. Results and Conclusion. The longest ATCs of 4.5, 6.4, and 1.3 min. yielded average errors of 9.1%, 7%, and 3.6% in Ktrans for the ACRIN, UTA, and UC datasets, respectively; and the shortest ATCs of 2, 1.6, and 0.6 min. yielded higher average errors of 24.2%, 22.8%, and 65% in Ktrans, respectively. This is expected from simulations as even the most aggressive ATCs did not substantially exclude the tissue enhancement, characterized by Ktrans. Errors in ve were higher overall since shorter ATCs exclude much of the washout phase. As Ktrans has been shown to discriminate between malignant and benign lesions in full length DCE-MRI scans, it is promising that tolerable errors are observed in the abbreviated MRI setting. There is potential for implementing quantitative abbreviated DCE-MRI scans in the clinic for enhanced diagnostic specificity while freeing up scan time for additional imaging sequences without interfering with standard-of-care image acquisition. Citation Format: Kalina P Slavkova, Julie C DiCarlo, Anum K Syed, Chengyue Wu, John Virostko, Anna G Sorace, Thomas E Yankeelov. Characterizing errors in perfusion model parameters derived from retrospectively abbreviated quantitative DCE-MRI data [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-26.

Traditional kitchen utensils of South India are unique. In those days, people used them to cook food, grind rice, millet and grains, and so on. They lived a healthy life by making food items with these utensils. After the invention of electronic machines, people stopped using these utensils. They thought that modern equipment like grinder, mixie and cooker would save their time and energy. But in recent days, people have begun to realize the benefit of using these utensils. Even the people of other countries are showing interest in using traditional kitchen equipment. So there comes the need for them to know their names. Hence the equivalent words for most Indian utensils are brought into the English language. Lakshmi Holmstrom, a well-known woman translator introduced many Tamil authors to the readers of the English language. Through her translations, many words from the Tamil language have been brought into English. The present paper aims to analyze Lakshmi Holmstrom’s translations of such utensils in the novel “Sangathi” by Bama.

Traditional kitchen utensils of South India are unique. In those days, people used them to cook food, grind rice, millet and grains, and so on. They lived a healthy life by making food items with these utensils. After the invention of electronic machines, people stopped using these utensils. They thought that modern equipment like grinder, mixie and cooker would save their time and energy. But in recent days, people have begun to realize the benefit of using these utensils. Even the people of other countries are showing interest in using traditional kitchen equipment. So there comes the need for them to know their names. Hence the equivalent words for most Indian utensils are brought into the English language. Lakshmi Holmstrom, a well-known woman translator introduced many Tamil authors to the readers of the English language. Through her translations, many words from the Tamil language have been brought into English. The present paper aims to analyze Lakshmi Holmstrom’s translations of such utensils in the novel “Sangathi” by Bama.

Context: Tobacco usage is associated with the derailment of antioxidant status. Salivary studies for diagnostic potential as a biofluid. Saliva may provide acumen into disease pathogenesis. Aims: To determine the influence of tobacco on salivary superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) enzyme levels in individuals with and without tobacco habits. Settings and Design: One mL of unstimulated whole saliva was collected, centrifuged immediately at 2000 RPM, and stored at 4°C for analysis. The supernatant was aspirated and assayed. Methods and Material: Eighty males subjects aged 25–40 years were selected and included 20 controls, 20 smokers, 20 chewers, and 20 with both habits. The saliva samples were collected and SOD, GPX, CAT levels were analyzed using UV spectrophotometric assay. Statistical Analysis Used: Mann-Whitney U test was used for comparison taking the probability value of P ≤ 0.05 as statistically significant using SPSS 20.0 version. Results: SOD, CAT, GPX enzyme levels in the saliva were significantly lower in those with tobacco habit than in the controls (P < 0.05). A significant correlation existed between SOD, CAT, GPX levels, and the type of the habit. The antioxidant status is affected by the impact of tobacco. Conclusions: This study emphasizes the importance of saliva as an easy noninvasive tool in diagnosing patients who are more prone to precancerous lesions and conditions, and its importance in patient education and motivation programs for tobacco habit cessation.

Phenotypic screening is a neoclassical approach for drug discovery. We conducted phenotypic screening for insulin secretion enhancing agents using INS-1E insulinoma cells as a model system for pancreatic beta-cells. A principal regulator of insulin secretion in beta-cells is the metabolically regulated potassium channel Kir6.2/SUR1 complex. To characterize hit compounds, we developed an assay to quantify endogenous potassium channel activity in INS-1E cells. We quantified ligand-regulated potassium channel activity in INS-1E cells using fluorescence imaging and thallium flux. Potassium channel activity was metabolically regulated and coupled to insulin secretion. The pharmacology of channel opening agents (diazoxide) and closing agents (sulfonylureas) was used to validate the applicability of the assay. A precise high-throughput assay was enabled, and phenotypic screening hits were triaged to enable a higher likelihood of discovering chemical matter with novel and useful mechanisms of action.

Inflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor-stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three-dimensional, in vitro, vascularized, microfluidic IBC platform to quantify the spatial and temporal dynamics of tumor-vasculature and tumor-ECM interactions specific to IBC. Platforms consisting of collagen type 1 ECM with an endothelialized blood vessel were cultured with IBC cells, MDA-IBC3 (HER2+) or SUM149 (triple negative), and for comparison to non-IBC cells, MDA-MB-231 (triple negative). Acellular collagen platforms with endothelialized blood vessels served as controls. SUM149 and MDA-MB-231 platforms exhibited a significantly (p < .05) higher vessel permeability and decreased endothelial coverage of the vessel lumen compared to the control. Both IBC platforms, MDA-IBC3 and SUM149, expressed higher levels of vascular endothelial growth factor (p < .05) and increased collagen ECM porosity compared to non-IBCMDA-MB-231 (p < .05) and control (p < .01) platforms. Additionally, unique to the MDA-IBC3 platform, we observed progressive sprouting of the endothelium over time resulting in viable vessels with lumen. The newly sprouted vessels encircled clusters of MDA-IBC3 cells replicating a key feature of in vivo IBC. The IBC in vitro vascularized platforms introduced in this study model well-described in vivo and clinical IBC phenotypes and provide an adaptable, high throughput tool for systematically and quantitatively investigating tumor-stromal mechanisms and dynamics of tumor progression.

Background Therapy targeted to the human epidermal growth factor receptor type 2 (HER2) is used in combination with cytotoxic therapy in treatment of HER2+ breast cancer. Trastuzumab, a monoclonal antibody that targets HER2, has been shown pre-clinically to induce vascular changes that can increase delivery of chemotherapy. To quantify the role of immune modulation in treatment-induced vascular changes, this study identifies temporal changes in myeloid cell infiltration with corresponding vascular alterations in a preclinical model of HER2+ breast cancer following trastuzumab treatment. Methods HER2+ tumor-bearing mice (N = 46) were treated with trastuzumab or saline. After extraction, half of each tumor was analyzed by immunophenotyping using flow cytometry. The other half was quantified by immunohistochemistry to characterize macrophage infiltration (F4/80), vascularity (CD31 and α-SMA), proliferation (Ki67) and cellularity (H&E). Additional mice (N = 10) were used to quantify differences in tumor cytokines between control and treated groups. Results Immunophenotyping showed an increase in macrophage infiltration 24 h after trastuzumab treatment (P ≤ 0.05). With continued trastuzumab treatment, the M1 macrophage population increased (P = 0.02). Increases in vessel maturation index (i.e., the ratio of α-SMA to CD31) positively correlated with increases in tumor infiltrating M1 macrophages (R = 0.33, P = 0.04). Decreases in VEGF-A and increases in inflammatory cytokines (TNF-α, IL-1β, CCL21, CCL7, and CXCL10) were observed with continued trastuzumab treatment (P ≤ 0.05). Conclusions Preliminary results from this study in a murine model of HER2+ breast cancer show correlations between immune modulation and vascular changes, and reveals the potential for anti-HER2 therapy to reprogram immunosuppressive components of the tumor microenvironment. The quantification of immune modulation in HER2+ breast cancer, as well as the mechanistic insight of vascular alterations after anti-HER2 treatment, represent novel contributions and warrant further assessment for potential clinical translation.

ObjectivesTo survey on the availability and use of primary care services in slum populations.DesignRetrospective, cross-sectional, household, individual and healthcare provider surveys.SettingSeven slum sites in four countries (Nigeria, Kenya, Pakistan and Bangladesh).ParticipantsResidents of slums and informal settlements.Primary and secondary outcome measuresPrimary care consultation rates by type of provider and facility.ResultsWe completed 7692 household, 7451 individual adult and 2633 individual child surveys across seven sites. The majority of consultations were to doctors/nurses (in clinics or hospitals) and pharmacies rather than single-handed providers or traditional healers. Consultation rates with a doctor or nurse varied from 0.2 to 1.5 visits per person-year, which was higher than visit rates to any other type of provider in all sites except Bangladesh, where pharmacies predominated. Approximately half the doctor/nurse visits were in hospital outpatient departments and most of the remainder were to clinics. Over 90% of visits across all sites were for acute symptoms rather than chronic disease. Median travel times were between 15 and 45 min and the median cost per visit was between 2% and 10% of a household’s monthly total expenditure. Medicines comprised most of the cost. More respondents reported proximity (54%–78%) and service quality (31%–95%) being a reason for choosing a provider than fees (23%–43%). Demand was relatively inelastic with respect to both price of consultation and travel time.ConclusionsPeople in slums tend to live sufficiently close to formal doctor/nurse facilities for their health-seeking behaviour to be influenced by preference for provider type over distance and cost. However, costs, especially for medicines are high in relation to income and use rates remain significantly below those of high-income countries.

Type 2 diabetes (T2D) is associated with defective insulin secretion and reduced β cell mass. Available treatments provide a temporary reprieve, but secondary failure rates are high, making insulin supplementation necessary. Reversibility of β cell failure is a key translational question. Here, we reverse engineered and interrogated pancreatic islet–specific regulatory networks to discover T2D-specific subpopulations characterized by metabolic inflexibility and endocrine progenitor/stem cell features. Single-cell gain- and loss-of-function and glucose-induced Ca(2+) flux analyses of top candidate master regulatory (MR) proteins in islet cells validated transcription factor BACH2 and associated epigenetic effectors as key drivers of T2D cell states. BACH2 knockout in T2D islets reversed cellular features of the disease, restoring a nondiabetic phenotype. BACH2-immunoreactive islet cells increased approximately 4-fold in diabetic patients, confirming the algorithmic prediction of clinically relevant subpopulations. Treatment with a BACH inhibitor lowered glycemia and increased plasma insulin levels in diabetic mice, and restored insulin secretion in diabetic mice and human islets. The findings suggest that T2D-specific populations of failing β cells can be reversed and indicate pathways for pharmacological intervention, including via BACH2 inhibition.

Due to the continued spread of COVID-19 and the emergence of novel mutated viral variants, families all over the world are experiencing wide-ranging stressors that threaten not only their financial well-being but also their physical and mental health. The present study assessed the association between excessive electronic media exposure of pandemic-related news and mental health of the residents of Ha'il Province, Saudi Arabia. The present study also assessed the prevalence of perceived stress, fear of COVID-19, anxiety, depression, and loneliness due to COVID-19-related restrictions in the same population.A total of 490 residents of Ha'il Province participated in a cross-sectional online survey during a two-month period (March to April 2021). A validated 38-item self-report survey was used to collect the data.Significant associations were reported between excessive electronic media exposure and the prevalence of perceived stress (χ2=140.56; p.001), generalized anxiety (χ2=74.55; p.001), depression (χ2=71.58; p.001), COVID-19-related fear (χ2=24.54; p.001), and loneliness (χ2=11.46; p.001). It was also found that participants without depressive symptoms were 0.28 times less likely to have been exposed to excessive electronic media exposure (AOR: 0.28; C.I. 0.16-0.48; p.001). Similarly, participants with no stress/mild stress were 0.32 times less likely to have been exposed to excessive electronic media exposure (AOR: 0.32; C.I. 0.19-0.52; p.001).The findings of the present study suggest an urgent need for educational resilience programs (online and in-person) for susceptible individuals (females, unemployed, urban residents, etc.). Such programs would help them to develop skills to cope with the psychological impact of the COVID-19 pandemic.