Explore the vast range of titles available.

Objectives: The current study set out to look into the relationship between maladaptive daydreaming and traumatic life experiences in emerging adult Design of the Study: Correlational Survey design/comparative study Place and Duration of the Study: Karachi from November 2023 to February2024 at Bahria University Karachi Campus. Sample and Method: The sample consisted of 310 Emerging adults ages 18 - 25 (Female =222 and Males = 88) selected through purposive convenient sampling from various universities and other settings. A demographic form, Traumatic Experiences Checklist (TEC), and Maladaptive daydreaming scale (MDS) were administered. The data was collected in-person and was analyzed through IBM SPSS version 22. Results and Conclusion: The results of the analysis revealed that there is a significant positive relationship of Traumatic life experiences with maladaptive daydreaming in emegeing adults. These findings highlight the need for customized therapies and support programs that concentrate on awareness and processing of traumatic memories by providing a platform to confront repressed pain. The main implication of the study is to add to the body of knowledge about the mechanism of maladaptive daydreaming which is a growing construct at an alarming rate in Pakistan.

The bladder undergoes large shape changes as it fills and empties and experiences complex mechanical forces. These forces become abnormal in diseases of the lower urinary tract such as overactive bladder, neurogenic bladder, and urinary retention. As the primary mechanosensors linking the actin cytoskeleton to the extracellular matrix (ECM), integrins are likely to play vital roles in maintaining bladder smooth muscle (BSM) homeostasis. In a tamoxifen-inducible smooth muscle conditional knockout of β1-integrin, there was concomitant loss of α1- and α3-integrins from BSM and upregulation of αV- and β3-integrins. Masson's staining showed a reduction in smooth muscle with an increase in collagenous ECM. Functionally, mice exhibited a changing pattern of urination by voiding spot assay up to 8 wk after tamoxifen. By 8 wk, there was increased frequency with reductions in voided volume, consistent with overactivity. Cystometrograms confirmed that there was a significant reduction in intercontractile interval with reduced maximal bladder pressure. Muscle strip myography revealed a loss of contraction force in response to electrical field stimulation, that was entirely due to the loss of muscarinic contractility. Quantitative western blotting showed a loss of M3 receptor and no change in P2X1. qPCR on ECM and interstitial genes revealed loss of Ntpd2, a marker of an interstitial cell subpopulation; and an upregulation of S100A4, which is often associated with fibroblasts. Collectively, the data show that the loss of appropriate mechanosensation through integrins results in cellular and extracellular remodeling, and concomitant bladder dysfunction that resembles lower urinary tract symptoms seen in older people. Graphical Abstract Graphical Abstract

Breast cancer is the most diagnosed cancer and the second leading cause of cancer-related death in women in the United States. Mortality is strongly associated with the ability of the cancer to metastasize and propagate outside of the breast. Processes that enhance these features of breast cancer include changes in cell-cell and cell-extracellular matrix adhesion, increased invasiveness, and transitions between epithelial and mesenchymal states (EMT/MET). However, the upstream regulators of these processes are not well-characterized, which limits therapeutic intervention. G protein-coupled receptors (GPCRs) deserve increased attention in this realm, as they are the largest class of cell membrane-bound receptors, rapidly transmit critical signals between the extracellular and intracellular environments, and are the most common target of FDA-approved small-molecule drugs. Transcriptomic data of resected breast tumors shows that low mRNA expression of the orphan GPCR GPR52 correlates with reduced overall survival of breast cancer patients, leading to the hypothesis that loss of GPR52 supports breast cancer progression. We used CRISPR-Cas9 to knockout GPR52 in human triple-negative breast cancer (TNBC) cell lines MDA-MB-468 and MDA-MB-231, and in the non-cancerous breast epithelial cell line MCF10A. Loss of GPR52 was associated with increased cell-cell interaction in 2D, altered 3D spheroid morphology, and increased propensity of cancer to invade collectively in Matrigel. Furthermore, GPR52 loss was associated with features of EMT in MDA-MB-468 cells. To determine the in vivo impact of GPR52 loss, we used a zebrafish xenograft model and found that loss of GPR52 was associated with a greater total cancer area thirty hours post-cancer cell injection. RNA-sequencing and proteomic analyses of GPR52-null and -expressing breast cell lines and tumors demonstrated expression signatures consistent with increased cAMP signaling. Furthermore, the melanoma cell adhesion molecule (MCAM) was upregulated in GPR52 KO cells. Consistently, modulation of cAMP levels in the wild-type and GPR52 KO cells partially induced or rescued some of the phenotypes observed with GPR52 loss, respectively, including expression of MCAM. Our results reveal GPR52 loss as a mechanism by which breast cancer progression may occur and support the investigation of GPR52 agonism as a therapeutic option for breast cancer.

We showed that loss of the orphan G protein-coupled receptor GPR52 in human breast cell lines leads to increased cell clustering, hybrid/partial EMT, and increased tumor burden in zebrafish. G protein-coupled receptors (GPCRs) are the largest class of membrane-bound receptors that transmit critical signals from extracellular to intracellular spaces. Transcriptomic data of resected breast tumors show that low mRNA expression of orphan GPCR GPR52 correlates with reduced overall survival in patients with breast cancer, leading to the hypothesis that loss of GPR52 supports breast cancer progression. CRISPR-Cas9 was used to knockout GPR52 in the human triple-negative breast cancer (TNBC) cell lines MDA-MB-468 and MDA-MB-231, and in the non-cancerous breast epithelial cell line MCF10A. 2D and 3D studies, electron microscopy, Matrigel culture, and a zebrafish xenograft model were used to assess the morphology and behavior of GPR52 KO cells. RNA-sequencing and proteomic analyses were also conducted on these cell lines, and transcriptomic data from The Cancer Genome Atlas (TCGA) database were used to compare GPR52-null and wild-type (WT) signatures in breast cancer. Loss of GPR52 was found to be associated with increased cell-cell interaction in 2D cultures, altered 3D spheroid morphology, and increased propensity to organize and invade collectively in Matrigel. Furthermore, GPR52 loss was associated with features of EMT in MDA-MB-468 cells, and zebrafish injected with GPR52 KO cells developed a greater total cancer area than those injected with control cells. RNA sequencing and proteomic analyses of GPR52-null breast cancer cells revealed an increased cAMP signaling signature. Consistently, we found that treatment of wild-type (WT) cells with forskolin, which stimulates the production of cAMP, induces phenotypic changes associated with GPR52 loss, and inhibition of cAMP production rescued some GPR52 KO phenotypes. GPR52 is an orphan GPCR and its role in cancer progression has not been previously characterized. We found that GPR52 loss in breast cancer cells can lead to increased cell clustering, collective invasion, and EMT . These are features of increased cancer aggression. Our results reveal that GPR52 loss is a potential mechanism by which breast cancer progression may occur and support the investigation of GPR52 agonism as a therapeutic option for breast cancer.

Abstract Disclosure: S. Arbuiso: None. Y. Chen: None. N.A. Vernice: None. A. Zhang: None. I.J. Rhodes: None. C.C. Alston: None. S. Hanif: None. S. Liu: None. P. Bhardwaj: None. D. Janhofer: None. G.G. Black: None. D.M. Otterburn: None. K.A. Brown: None. Introduction: Autologous fat grafting is commonly used in breast reconstruction as it is associated with good cosmetic outcomes, high patient satisfaction, and minimal risks. Adipose tissue is known to support cancer growth via the secretion of adipokines and the modulation of estrogen levels due to aromatase expressed in adipose stromal cells. A higher body mass index (BMI) and postmenopausal status are associated with higher levels of aromatase. With novel processing techniques being developed to increase fat graft retention, there is a need to better understand how these will affect the biology of lipoaspirates for women who have previously had breast cancer. This study aims to assess how different processing techniques used in fat grafting (1) impact aromatase gene expression, (2) affect breast cancer cell proliferation, and (3) affect the cellular composition of the engrafted lipoaspirate. Methods: Patients who underwent breast reconstruction for breast cancer treatment or for prophylactic measures, and were receiving autologous fat grafting, were enrolled in a prospective randomized controlled trial (NCT04891510). Patients were randomized to one of three processing techniques: standard decantation, active filtration, and low-pressure decantation. Conditioned media (CM) was created from each sample. Aromatase mRNA was measured in the lipoaspirate using qRT-PCR for aromatase (CYP19A1) and related to patient BMI or menopausal status. The effect of CM on the proliferation of MCF7 cells (estrogen receptor positive (ER+) breast cancer cell line) was measured using CyQUANT. Formalin-fixed lipoaspirate samples were embedded in HistoGel and paraffin. Adipocyte diameter was measured in hematoxylin and eosin (H&E) stained sections using ImageJ. Results: Aromatase mRNA levels were correlated with BMI and were higher in postmenopausal women (p≤0.05), with the standard decantation group demonstrating a stronger correlation with BMI. Samples processed via active filtration were associated with weaker correlations between aromatase gene expression and BMI and menopausal status. CM induced MCF7 cell proliferation to a similar extent to cells plated in fetal bovine serum-containing media. There was no difference in proliferation patterns between treatment groups. Upon histological assessment, adipocytes were intact, and adipocyte diameter was significantly correlated with patient BMI. Conclusion: Lipoaspirate may contain factors that promote breast cancer cell proliferation, unaffected by processing technique. Caution should be used to ensure local control of the cancer has been achieved prior to reconstruction. Our data suggest that active filtration selects for a lower percentage of adipose stromal cells, which may be beneficial for patients who previously had ER+ breast cancer. Presentation: 6/1/2024

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Dysregulated cell metabolism is now an accepted hallmark of cancer. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we found that long-term education of breast cancer cells (MCF7, T47D) with EVs from breast adipose tissue of women who are overweight or obese (O-EVs) leads to sustained increased proliferative potential. RNA-Seq of O-EV-educated cells demonstrates increased expression of genes, such as ATP synthase and NADH: ubiquinone oxidoreductase, involved in oxidative phosphorylation. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. Mitochondrial complex I inhibitor, metformin, reverses O-EV-induced cell proliferation. Several miRNAs, miR-155-5p, miR-10a-3p, and miR-30a-3p, which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing the metabolic reprogramming of ER+ breast cancer cells.

Background In 2006, the Government of Pakistan introduced community midwives to provide maternal care services to rural communities. Despite huge investments, evidence from several rural regions of Pakistan suggests that the utilization of maternal care through community midwives is very low and the maternal health indicators have not shown significant improvements. A qualitative study was conducted in Thatta, a rural district of Pakistan to explore the challenges faced by community midwives in the provision of skilled care. Methods We used an exploratory qualitative study design by conducting in-depth interviews using a semi-structured interview guide and a purposive sampling approach. The data was collected using the four domains of the community midwifery model. Interviews were conducted with officials from the health department, three categories of midwives including (i) midwifery students; (ii) trained and working community midwives; and (iii) trained and non-working community midwives. We also carried out interviews with community women. A total of 25 interviews were conducted. A thematic analysis approach was used for analysis. Results Based on the four domains of the community midwifery model that guided our data collection, two overarching themes were identified: (I) Social and cultural challenges faced by CMWs including the young age of midwives, and community women’s varied preferences for their delivery and childbirth processes were major challenges for community midwives (II) Support and acceptance including nonacceptance of community midwives’ services by doctors, other healthcare providers, and community women were identified as significant barriers to community midwives services. Conclusion The study provides key insights to program implementers to work on strategies and interventions to resolve the challenges faced by community midwives and to help achieve the aim of increasing skilled birth attendants in rural regions of Pakistan.

Background To address the issue of high maternal mortality, the Government of Pakistan initiated a community midwifery program in 2006 to provide skilled birth attendance to women living in rural areas. Despite a large investment in the community midwifery program, research evidence from rural districts of Pakistan suggests that the utilization of maternal and newborn services through community midwives is very low. This exploratory study aimed to understand the facilitators and barriers influencing community midwives’ services utilization in district Thatta. Methods A qualitative study was conducted in the rural district Thatta, Pakistan. Key-informant interviews (KIIs) were conducted with district officials of the Health department (Thatta), Maternal and Newborn Child Health Program, and Midwifery Association of Pakistan (MAP). In-depth Interviews (IDIs) were conducted with midwifery students who were currently enrolled in the midwifery program of the district; trained community midwives providing services in district Thatta, and trained community midwives not continuing their profession. IDIs were also conducted with community women to explore their views about the scope of midwifery practice and the factors influencing the utilization of community midwives’ services in district Thatta, Pakistan. Data were analyzed using qualitative thematic analysis. Results A total of 25 interviews (KIIs = 5; IDIs = 20) were conducted. Two overarching themes were identified: (I) community midwives’ skills and competencies; and (II) ownership and supportive supervision. The major hindering factors for community midwives’ service utilization included deficiencies in community midwives’ training particularly in clinical hands-on training, lack of ownership of community midwifery program, and lack of service structure by the CMWs regulatory body. Conclusion The study has identified serious gaps in the CMWs program at the level of training and supervision of midwives in Pakistan. The study has also identified factors related to the training of CMWs that could facilitate the program in the context of Pakistan and similar settings.

Energy poverty is a global challenge and the scarcity has been emerging as a global issue. Therefore, the relationship among energy scarcity, sustainable finance, and carbon emissions is analyzed with the help of global data from 40 developing countries until the beginning of the COVID-19 era. For empirical results’ estimation, the study analyzed a panel data ranging from 2000 to 2019. To measure the energy poverty, some part of population that has no access to energy is considered, and empirical analysis based on augmented mean group (AMG) regression method was carried out. The findings of the study suggest the inverse relation among energy poverty and carbon emissions. Moreover, a negative relationship was also observed between sustainable finance and carbon emissions. These findings highlight that alleviation of energy poverty can intensify environmental pollution. While improvement in access to clean energy will benefit society by alleviating energy poverty and controlling carbon emissions. Moreover, improvement in the share of sustainable finance in total investment may improve the environment quality by reducing carbon emissions. Therefore, it is suggested that regional plans along with sustainable finance are required on a priority basis for the promotion of clean energy to control carbon emissions and alleviate energy poverty at the household level.

Furthermore, a boycott of the polio vaccination campaign in three states in Nigeria following misinformation was resolved when Nigerian religious leaders received assurance about vaccine safety, subsequently confirming its acceptability to the communities.4 Growing concerns around uptake of the COVID-19 vaccine during Ramadan are focused on whether the injection invalidates the fast, any possible side-effects, and whether people have to break the fast. [...]there is an urgent need for a global call for action to reduce vaccine hesitancy. The statement, made in March, 2021, from the president of Two Holy Mosques in Saudi Arabia, should allay any religious concerns.5 Ebola and polio vaccination programmes highlight the key role that religious leaders play in promoting acceptability and education of their communities towards vaccination during Ramadan. Dan Kitwood/Getty Images KK is a director at the University of Leicester Centre for Black Minority Ethnic Health, chair of the Ethnicity Subgroup of the Scientific Advisory Group for Emergencies (SAGE), and a member of Independent SAGE.