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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a clinically challenging cancer, mainly due to limited therapeutic options and the presence of a highly prominent tumor microenvironment (TME), facilitating tumor progression. The TME is predominated by heterogeneous populations of cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs), in constant communication with each other and with tumor cells, influencing many tumoral abilities such as therapeutic resistance. However how the crosstalk between CAFs and macrophages evolves following chemotherapeutic treatment remains poorly understood, limiting our capacity to halt therapeutic resistance. METHODS: We combined biological characterization of macrophages indirectly cocultured with human PDAC CAFs, under FOLFIRINOX treatment, with mRNAseq analyses of such macrophages and evaluated the relevance of the specific gene expression signature in a large series of primary PDAC patients to search for correlation with overall survival (OS) after FOLFIRINOX chemotherapy. RESULTS: Firstly, we demonstrated that CAFs polarize naïve and M1 macrophages towards an M2-like phenotype with a specific increase of CD200R and CD209 M2 markers. Then, we demonstrated that CAFs counteract the pro-inflammatory phenotype induced by the FOLFIRINOX on Macrophages. Indeed, we highlighted that, under FOLFIRINOX, CAFs limit the FOLFIRINOX-induced cell death of macrophages and further reinforce their M2 phenotype as well as their immunosuppressive impact through specific chemokines production. Finally, we revealed that under FOLFIRINOX CAFs drive a specific macrophage gene expression signature involving SELENOP and GOS2 that correlates with shortened OS in FOLFIRINOX-treated PDAC patients. CONCLUSION: Our study provides insight into the complex interactions between TME cells under FOLFIRINOX treatment. It suggests potential novel candidates that could be used as therapeutic targets in combination with FOLFIRINOX to prevent and alleviate TME influx on therapeutic resistance as well as biomarkers to predict FOLFIRINOX response in PDAC patients. Video Abstract.
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Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Fibroblastos Associados a Câncer/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Macrófagos/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Microambiente TumoralRESUMO
OBJECTIVE: Intercellular communication within pancreatic ductal adenocarcinoma (PDAC) dramatically contributes to metastatic processes. The underlying mechanisms are poorly understood, resulting in a lack of targeted therapy to counteract stromal-induced cancer cell aggressiveness. Here, we investigated whether ion channels, which remain understudied in cancer biology, contribute to intercellular communication in PDAC. DESIGN: We evaluated the effects of conditioned media from patient-derived cancer-associated fibroblasts (CAFs) on electrical features of pancreatic cancer cells (PCC). The molecular mechanisms were deciphered using a combination of electrophysiology, bioinformatics, molecular and biochemistry techniques in cell lines and human samples. An orthotropic mouse model where CAF and PCC were co-injected was used to evaluate tumour growth and metastasis dissemination. Pharmacological studies were carried out in the Pdx1-Cre, Ink4afl/fl LSL-KrasG12D (KICpdx1) mouse model. RESULTS: We report that the K+ channel SK2 expressed in PCC is stimulated by CAF-secreted cues (8.84 vs 2.49 pA/pF) promoting the phosphorylation of the channel through an integrin-epidermal growth factor receptor (EGFR)-AKT (Protein kinase B) axis. SK2 stimulation sets a positive feedback on the signalling pathway, increasing invasiveness in vitro (threefold) and metastasis formation in vivo. The CAF-dependent formation of the signalling hub associating SK2 and AKT requires the sigma-1 receptor chaperone. The pharmacological targeting of Sig-1R abolished CAF-induced activation of SK2, reduced tumour progression and extended the overall survival in mice (11.7 weeks vs 9.5 weeks). CONCLUSION: We establish a new paradigm in which an ion channel shifts the activation level of a signalling pathway in response to stromal cues, opening a new therapeutic window targeting the formation of ion channel-dependent signalling hubs.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt , Carcinogênese , Transformação Celular Neoplásica , Transdução de Sinais , Neoplasias PancreáticasRESUMO
OBJECTIVES: To assess the prevalence of metabolic syndrome (MS) and association of central obesity measures such as body mass index (BMI), visceral fat adiposity (VFA) and superficial fat adiposity (SFA) with MS, diabetes (DM) and hypertension (HTN). DESIGN: Cross-sectional study design. SETTING: Tertiary care hospital in Pakistan. PARTICIPANTS: 165 participants. There were 124 male participants and 41 female participants of Pakistani population. All participants above 18 years, who had unenhanced CT abdomen examination and relevant blood workup, were included. Patients with a known clinical history of coronary artery disease, HTN and DM as well as pregnant patients were excluded. INTERVENTIONS: VFA and SFA were estimated, at the level of the umbilicus. Data of BMI, MS, DM and HTN were extracted from patient files. Data for MS, DM and HTN were recorded as binary variables. OUTCOME MEASURES: The primary outcome measures were the prevalence of MS and the association of MS, DM and HTN with gender, VFA, SFA and BMI. P value of <0.05 was taken as significant with CI of 95%. RESULTS: The prevalence of MS was 29.7%. There was a significant association of MS, DM and HTN with VFA, SFA and BMI. In gender-based analysis 48.7% of the female participants had MS. In subset analysis, 47% of male subjects in the third tertile of VFA revealed significant association with MS (p value <0.05) while only 32.7% of subjects in the obesity category of BMI had MS. SFA revealed a significant association with DM only (p value <0.5). CONCLUSION: In conclusion, VFA shows a significant association with MS, DM and HTN. Considering these results, further studies with a larger sample size are warranted to generate gender-based cut-offs for VFA for obesity screening purposes.
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Adiposidade , Índice de Massa Corporal , Hipertensão , Síndrome Metabólica , Obesidade Abdominal , Centros de Atenção Terciária , Humanos , Feminino , Masculino , Paquistão/epidemiologia , Síndrome Metabólica/epidemiologia , Estudos Transversais , Adulto , Prevalência , Pessoa de Meia-Idade , Hipertensão/epidemiologia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Gordura Intra-Abdominal/diagnóstico por imagem , Diabetes Mellitus/epidemiologiaRESUMO
Understanding the metal-semiconductor heterostructure interface is crucial for the development of spintronic devices. One of the prospective candidates and extensively studied semiconductors is molybdenum disulfide (MoS 2 ). Herein, utilizing Kerr microscopy, we investigated the impact of thick MoS 2 on the magnetic properties of the 10 nm Co layer. A comparative study on Co / MoS 2 and Co/Si shows that coercivity increased by 77% and the Kerr signal decreased by 26% compared to Co grown on Si substrate. In addition, the Co domain structure significantly changed when grown on MoS 2 . The plausible reason for the observed magnetic behavior can be that the Co interacts differently at the interface of MoS 2 as compared to Si. Therefore, our studies investigate the interfacial effect on the magnetic properties of Co grown on thick MoS 2 layer. Furthermore, our results will help in developing next-generation spintronic devices.
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Stroke is a global public health concern, contributing to high rates of morbidity and mortality. In Syria, the current conflict and associated challenges have had a profound impact on healthcare infrastructure, including education and awareness programs related to stroke. An essential aspect of preventing stroke is the awareness of individuals. The study aimed to investigate factors associated with knowledge and awareness of stroke among Syrian people. A cross-sectional national representative study was conducted in Syria. The questionnaire was created on Google form and disseminated as a link through online platform social media like Facebook, WhatsApp, and Twitter. The population of the study was divided using proportionate random sampling into the 14 governorates. A random sample was selected from each area. The STROBE reporting guideline for cross-sectional studies was followed. Logistic regression analysis was performed to identify the factors associated with poor knowledge of stroke. A total of 1013 Syrian adults participated in the study. With more than half of them were females (53.5%) and employed (55.6%). Significant associations were found between ability to identify at least one correct risk factor and employability status (p = 0.029), single group (p = 0.036) and smokers (p < 0.001). In addition, significant associations were found between identifying at least one correct stroke symptom and smokers (p < 0.001) and no-obese people (p = 0.048). Furthermore, younger age group (below 30 years) were significantly able to list at least one correct stroke consequence compared to the older age groups (p = 0.025). Moreover, a significantly higher number of smokers compared to non-smokers correctly identified at least one stroke consequence (p = 0.019). The study revealed that there is a relatively weak understanding of the preventable nature of stroke among Syrian population. The overall awareness is still inadequate and varies depending on lifestyle factors and employment status.
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Conhecimentos, Atitudes e Prática em Saúde , Acidente Vascular Cerebral , Humanos , Síria/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Acidente Vascular Cerebral/epidemiologia , Inquéritos e Questionários , Fatores de Risco , Adulto Jovem , Adolescente , IdosoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is associated with a vast stromal reaction that arises mainly from cancer-associated fibroblasts (CAFs) and promotes both immune escape and tumor growth. Here, we used a mouse model with deletion of the activin A receptor ALK4 in the context of the KrasG12D mutation, which strongly drives collagen deposition that leads to tissue stiffness. By ligand-receptor analysis of single-cell RNA-sequencing data, we identified that, in stiff conditions, neoplastic ductal cells instructed CAFs through sustained platelet-derived growth factor (PDGF) signaling. Tumor-associated tissue rigidity resulted in the emergence of stiffness-induced CAFs (siCAFs) in vitro and in vivo. Similar results were confirmed in human data. siCAFs were able to strongly inhibit CD8+ T-cell responses in vitro and in vivo, promoting local immunosuppression. More importantly, targeting PDGF signaling led to diminished siCAF and reduced tumor growth. Our data show for the first time that early paracrine signaling leads to profound changes in tissue mechanics, impacting immune responses and tumor progression. Our study highlights that PDGF ligand neutralization can normalize the tissue architecture independent of the genetic background, indicating that finely tuned stromal therapy may open new therapeutic avenues in pancreatic cancer.
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Introduction: Neonatal mortality remains a significant challenge not only to the world,but especially to a developing country like Pakistan. It can be majorly attributed to the sub-par healthcare, insufficient and under-recognised community health workers, and the lack of knowledge of proper newborn care on the part of the parents. This study targets the level of knowledge of the mothers and the services provided by community health care workers as the main factors determining neonatal care. Methods: A cross-sectional study was conducted in the OBS (obstetrics) wards of Hospitals affiliated with Rawalpindi Medical University from January 2022 to June 2022. The sample size was 138. Data was collected by one-on-one interviews, using a standardized USAID Community Health Worker Assessment and Improvement Matrix questionnaire. Data analysis was done using SPSS v28. Chi-square test was applied to check for significance. Results: Out of the total 138 participants, 47.8% (n = 66/138) were between the ages of 21-25. Results showed that women between the ages of 21-25 (P = 0.000058) and women who had their first child between the ages of 23-27 had good knowledge about neonatal care. 45% (n = 62/138) of the participants had poor knowledge of neonatal care, whereas 55% (n = 76/138) had good knowledge (P = 0.000002). As for the role of community health workers, only 20-30% of the participants were being provided with their services; hence their performance was not found to be adequate. Conclusions: The world of medicine is moving rapidly toward a new framework of the health systems in which the real foundation will be based on what actually takes place in the community, therefore, community health workers can play an important role in improving maternal and neonatal care. Family-centered care, appropriate age of first conception and motherhood, and proper guidance to first-time parents can ensure significant improvement in neonatal care in the future.
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Introduction: Organ donation is the act of removing an organ or tissue from a donor and transplanting the said organ/tissue to a recipient. Despite being the only definitive treatment for end-organ failure, there is a lot of hesitation surrounding the practice of organ donation. Even among medical students, who are more aware of the benefits of organ donation than the general public, this reluctance is widespread.Therefore, we conducted this research to determine the basis of this skepticism, so that the root causes can be identified and eradicated. Our research sought to ascertain the overall attitudes of Rawalpindi Medical University, Pakistan's students towards organ donation, the associated factors that influenced this attitude (religious devotion, gender, age, year of study) and the reasons for the hesitance. Methods: A cross-sectional study targeting the students of first to final year MBBS was conducted at Rawalpindi Medical University, Pakistan in the year 2022. The sample size was calculated using OpenEpi software, and came out to be 292. The students enrolled at Rawalpindi Medical University during the year 2021-2022 were made a part of the study. A self-structured questionnaire that was developed after substantial research was used to collect the data using a non-random convenience sample technique. Chi Square test was used to determine significance after data analysis using SPSS-22. Results: A total of 290 students participated in the study, 58 from each year. All of the participants were Muslim. A very strong correlation was found between high devoutness and willingness towards organ donation (p = 7.4252E-13). Only 9/290 (3%) of people in Pakistan have joined The Transplantation Society of Pakistan; the main cause of this low ratio is that very few people were aware that such a group even existed (according to 62% of the responders). The mistrust of doctors and the belief that appropriate efforts would not be done to resuscitate patients who have signed up for organ donation is a significant factor in the anxiety surrounding organ donation. Conclusions: There are several reasons why people are reluctant to donate their organs, including a lack of understanding of religious perspectives on the subject, mistrust of medical professionals and medical administration, and general public ignorance. We can make a significant progress toward closing the gap between the demand for and supply of organ donations if these problems are remedied. The most effective strategy to stop organ trafficking is through organ donation. Through seminars, conversations, and workshops, we need to raise awareness about organ donation.
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Goldston syndrome is a rare entity describing the association of polycystic kidneys and Dandy Walker malformation with or without hepatic fibrosis. A 28 years old pregnant woman came to radiology department for the first antenatal scan. Ultrasound showed a single fetus corresponding to 27 week of gestation. The fetal brain revealed deficient vermis with a posterior fossa cyst communicating with the 4th ventricle suggestive of Dandy-Walker malformation (DWM). The kidneys were enlarged, and echogenic containing small cysts with associated amniotic fluid index of 5 cm suggestive of oligohydramnios. A diagnosis of Goldston syndrome was suggested. These findings were confirmed on post natal head and renal ultrasound.
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Anormalidades Múltiplas , Síndrome de Dandy-Walker , Cisto Pancreático , Ultrassonografia Pré-Natal , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Síndrome de Dandy-Walker/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Cisto Pancreático/diagnóstico por imagem , Gravidez , Resultado da GravidezRESUMO
Deciphering the interactions between tumor and stromal cells is a growing field of research to improve pancreatic cancer-associated therapies and patients' care. Indeed, while accounting for 50 to 90% of the tumor mass, many pieces of evidence reported that beyond their structural role, the non-tumoral cells composing the intra-tumoral microenvironment influence tumor cells' proliferation, metabolism, cell death and resistance to therapies, among others. Simultaneously, tumor cells can influence non-tumoral neighboring or distant cells in order to shape a tumor-supportive and immunosuppressive environment as well as influencing the formation of metastatic niches. Among intercellular modes of communication, extracellular vesicles can simultaneously transfer the largest variety of signals and were recently reported as key effectors of cell-cell communication in pancreatic cancer, from its development to its evolution as well as its ability to resist available treatments. This review focuses on extracellular vesicles-mediated communication between different cellular components of pancreatic tumors, from the modulation of cellular activities and abilities to their biological and physiological relevance. Taking into consideration the intra-tumoral microenvironment and its extracellular-mediated crosstalk as main drivers of pancreatic cancer development should open up new therapeutic windows.
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Introduction Acute right lower quadrant abdominal pain is one of the most common surgical presentations to the emergency department with acute appendicitis being the topmost differential diagnosis. Although computed tomography (CT) is the gold standard in diagnosing appendicitis, in our setup ultrasound is often the initial imaging modality available in urgent care settings especially for children and pregnant females. On ultrasound, an inflamed appendix has a diameter of 6 mm or more and is non-compressible. Increased periappendiceal fat echogenicity is an important ancillary sign of acute appendicitis that supports the sonographic diagnosis of acute appendicitis. To determine the association of periappendiceal fat echo sign (PFES) on ultrasound in surgically proven cases of acute appendicitis. Methods This cross-sectional study was held at the Department of Radiology at the Aga Khan University Hospital in Karachi, Pakistan. Periappendiceal fat echogenicity was assessed and prospectively graded in 59 patients. These patients had sonographic features of acute appendicitis which was later confirmed by surgery. Data were collected on a proforma and later analyzed. Frequency of increased periappendiceal fat echogenicity in acute appendicitis was calculated. Association of PFES with gender and ascites was evaluated with Fischer's exact test and with patient's age and appendiceal diameter was assessed using analysis of variance (ANOVA). Results Increased periappendiceal fat echogenicity was seen in 89.8% of patients with acute appendicitis. 10.2% of patients had acute appendicitis with normal surrounding fat. Mean appendiceal diameter in patients with grade 3 PFES was significantly more than those with grade 2 or grade 1 PFES. PFES had no association with age and gender of the patient or with ascites. Conclusion Increased periappendiceal fat echogenicity is an important ancillary sign of acute appendicitis that helps support its sonographic diagnosis.
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Scattering of spin-up and spin-down electrons while passing through a ferromagnetic domain wall (DW) leads to an additional resistance for transport current, usually observed prominently in constricted magnetic structures. In this report we use the resistance of the DW as a probe to find an indirect signatures of the theoretically predicted spin-singlet supercurrent to spin-triplet supercurrent conversion effect of ferromagnetic DWs. Here we examine the DW induced resistance in Ni stripe in a bilayer Ni/Nb geometry in the normal state and in the superconducting state of Nb. By making a 3µm wide gap in the top Nb layer we routed the transport current through the Ni layer in the normal state and in the superconducting state of Nb. In the normal state of Nb, in-field transport measurements showed a clear domain wall magneto-resistance (DWMR) peak of amplitude â¼5.9 mΩ near the coercive field, where the DW density is expected to be maximum. Interestingly, however, below the superconducting transition temperature of Nb, the DWMR peak of the Ni layer showed a sharp drop in the field range where the number of DWs become maximum. This observation may be a possible signature of magnetic DW induced spin-triplet correlations in the Ni layer due to the direct injection of spin-singlet Cooper pairs from Nb into the magnetic DWs.
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We report the complex implications of inter-diffusion between polycrystalline FePt/FeCo layers as an impact of the FeCo underlayer on the structural and magnetic properties of the system. The crystalline growth of FePt strongly reduces in an entirely diffused system compared to the one with lesser diffusion, while the crystalline structure of FeCo is apparently less affected. Charge redistribution occurs between Fe, Co and Pt ensuring increased Co-Pt and Fe-Pt interactions with higher diffusion. Thereafter, we combine hysteresis and magnetic force microscopy measurements to show that the interfacial deformations result in the distinct out-plane magnetic behaviour of the system. FeCo@FePt nano-composite like structure, originating due to interfacial diffusion, shows interactions between two magnetic phases with in-plane low anisotropy exhibiting wasp-shaped out-plane hysteresis loop. Whereas the layered structure of FePt/FeCo films shows random anisotropy with a significant out-plane contribution even in the polycrystalline films. Micromagnetic modelling demonstrates coercivity deterioration and reduction of switching field due to the formation of a slightly diffused interface. Contrarily, the experimental observations for complete diffusion between the two layers are explained by simulating the inhomogeneous distribution of anisotropies along the film plane. These studies provide deep perceptions of the magnetic properties of FePt/FeCo system governed by diffusion kinetics which are valuable to achieve desired magnetic characteristics using this system.
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This study aims to review the effects of various types of carbonated soft drinks on the behavior of different orthodontic materials as well as on the enamel surface and tooth movement. Articles and books from 1990 to 2020 explaining the effects of carbonated soft drinks on general health and orthodontic materials and tooth movement were electronically searched. The major effects of carbonated soft drinks are explained and discussed in this review. Patients with orthodontic problems must be warned about the side effects of carbonated soft drinks on general and dental health and orthodontic appliances in particular.
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Background and objective: Stroke is the second leading cause of death in Jordan and over the world. Knowledge and awareness towards stroke play a crucial role in the management and prevention of its complications. This study aims to assess the knowledge and awareness about stroke among the Jordanian population and determine factors associated with stroke awareness. Methods: This cross-sectional study through a web-based anonymous questionnaire that needed 10 minutes to be completed. It examined sociodemographic characteristics and recognition of the risk factors, warning signs, stroke consequences, and early response to stroke symptoms. Logistic regression analysis identified the factors associated with poor knowledge of stroke. Results: A total of 573 Jordanian adults participated in this study. The participant's ability to identify at least one early symptom of stroke and the proper response to the symptoms were significantly correlated with the educational level (OR of 3.4 and 2.5, respectively). At least one consequence of stroke was significantly associated with different demographic factors such as gender, socioeconomic income, females versus males and those with medium income versus low income had significantly higher odds (OR of 6.6 and 4.1, respectively). Conclusion: This study revealed a good knowledge and awareness level about stroke among Jordanians correlated mainly with their educational level. Therefore, new strategies should be considered to decrease the prevalence of stroke in Jordan, including the need for engagement in enhanced awareness campaigns.
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Conhecimentos, Atitudes e Prática em Saúde , Acidente Vascular Cerebral , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Inquéritos e QuestionáriosRESUMO
Cervical cancer (CC) is one of the most common types of cancer that affect females worldwide with hundreds of thousands of women dying annually due to this disease, mainly in developing countries. Infection with human papillomavirus (HPV) is the main risk factor for this cancer. There are no public awareness and national immunization programs in most Arab countries. This study aimed to investigate the knowledge and awareness about the HPV vaccine among females in four Arab countries and their acceptance to receive the vaccine. A cross-sectional study was conducted in several Arab countries: Jordan, Qatar, the United Arab Emirates (UAE), and Iraq. Respondents that fulfilled the desired criteria and were willing to participate in the study were asked to fill out the survey. Knowledge and awareness were assessed using 13 questions. Ethical approvals were given from the four countries. A total of 3658 individuals participated in the study; however, 2804 responses were included in the analysis and more than one third of participants (n = 1007) were aged between 18 and 25 years old. This study revealed poor awareness and knowledge of the participants about HPV and its vaccine among all four countries' participants with relatively better knowledge among participants from the UAE. Participants who are younger (18-25 years old), have a postgraduate education, have an education or career related to the medical field, or had a Pap smear in the last three years tend to have higher knowledge about the HPV vaccine compared to others. Poor knowledge and awareness findings in this study were expected, considering the lack of public education campaigns regarding the HPV virus coupled with the absence of the HPV vaccination from the national immunization schedule in three participating countries (Jordan, Qatar, and Iraq). It is recommended that there is a need to provide national educational campaigns about the HPV vaccine to the public in all Arab populations.
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Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/psicologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Pessoa de Meia-Idade , Oriente Médio , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Vacinação/psicologia , Adulto JovemRESUMO
The reasons for sex inequity in medicine are complex and partly interface ethnic background, specialty choice, and practice location. Multiple factors influence career choices including cultural values, balancing family responsibilities with professional growth, and career mentoring and support. Over the last 40 years, the Sophie Davis/CUNY School of Medicine (CSOM) has pursued a mission to increase diversity in medicine at the same time in which it has fostered the importance of primary care and service in underserved areas of New York State. Data from 1524 CSOM graduates show an increase in the number of women and underrepresented groups, with about a quarter of them working in Health Professional Shortage Areas (HPSAs). When compared with their male counterparts, our female graduates report lower income for similar work hours, with this disparity increasing slightly between female and male doctors working in HPSAs. In addition, our female graduates have chosen primary care specialties at a ratio of nearly 2:1 when compared with their male peers. Despite these inequities, our female graduates report satisfaction with their career choices, primarily due to a strong commitment to serving back patients in those communities where some of them come from. More research is needed to identify specific factors that perpetuate pay inequity at the state level to minimize the implications of disparity for women doctors, particularly those working in low-income communities.
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Introduction The RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) nephrometry score (RENAL-NS) has been described as a structured and quantiï¬able method to describe a renal tumor's relevant anatomic features as they relate to the complexity of the lesion. We aim to evaluate a tumor's RENAL-NS and to assess the reproducibility of the score among different observers. Methods This retrospective study included 49 patients diagnosed with renal cell carcinoma (RCC) who had complete computed tomography (CT) data, RENAL-NS, and histopathology results. All patients underwent renal surgery/intervention at our center between January 2008 and December 2018. The radius of the lesion, exophytic/endophytic properties, nearness to the collecting system, anterior or posterior description, and location relative to the polar lines was used to calculate the score. Tumor complexity was graded as low, intermediate, or high. Two body imaging radiologists evaluated the data independently. Results Interobserver agreement for each of the RENAL-NS parameters, respectively, and overall complexity was calculated. The total agreement was 82%, 51%, 84%, 69%, 73%, and 90%, corresponding to Kappa values of 0.72, 0.33, 0.44, 0.49, 0.58, and 0.83, respectively. The radius, nearness to the collecting system, and total complexity showed the best agreement. Exophytic properties of the lesion showed the least agreement. For cases that were discordant in terms of the final score, no major implications in surgical planning were observed. Conclusion The results of this study show that the RENAL-NS is a useful tool to assess the anatomical features of renal tumors and it is easily reproducible, even for less experienced radiologists in a developing nation.
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Background Breast cancer is a progressive disease, with conditions secondary to primary breast cancer being among the more common causes of malignancy-related deaths in women. Early diagnosis can halt disease progression and significantly improve patient's survival. Microcalcifications detected on mammograms may be an indicator of breast cancer. This study assessed the diagnostic accuracy of microcalcifications seen on mammograms for the detection of malignant breast disease when compared with histopathology. Materials and methods This study enrolled 144 women referred to the Radiology Department of Aga Khan University Hospital in Karachi, Pakistan, for mammograms and who were found to have suspicious microcalcifications, for which they underwent subsequent biopsy with histopathology over one year. The accuracy of microcalcifications, along with their sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV), were assessed relative to histopathology results. Results Compared with histopathology results, microcalcifications had a sensitivity of 88%, and specificity of 62.8%, a PPV of 55.7%, and an NPV of 90.8%. The overall accuracy of microcalcifications was 71.5%. Conclusions The presence of microcalcifications on mammograms may predict breast malignancy. Studies with larger numbers of patients are required to determine whether microcalcifications have higher specificity and PPV relative to breast histopathology.