Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals.

The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3' direction several hundred kilobases downstream of genes. The YFFF mutant shows reduced Pol II at promoter-proximal pause sites, a loss of interaction with the Mediator and Integrator complexes, and impaired recruitment of these complexes to chromatin. Consistent with these observations, Pol II loading at enhancers and maturation of snRNAs are altered in the YFFF context genome-wide. We conclude that tyrosine1 residues of the CTD control termination of transcription by Pol II.

Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes.

Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain-associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain-associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain-associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.

Effect of vigorous-intensity physical activity on incident cognitive impairment in high-risk hypertension.

INTRODUCTION: We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. METHODS: Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. RESULTS: Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9 vs 19.7), probable dementia (6.3 vs 9.0), and MCI/probable dementia (18.5 vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. DISCUSSION: This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. HIGHLIGHTS: Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.

Surgical outcome of angular deformity correction of lower limbs in rickets: a cross-sectional study.

PURPOSE: This study aims to compare the functional and radiological outcomes following both guided growth surgery (GGS) and acute corrective osteotomy (ACO) correction of angular deformities in children with rickets. METHODS: A total of 8 and 7 children who had gradual GGS and ACO correction, respectively, for angular deformities due to rickets from 2002 to 2022 were recalled for follow-up. Demographic data, types of rickets, data on pharmacological treatment, biochemical parameters, recurrence of angular deformity and postoperative complications were obtained from the medical records. A radiographic evaluation of the leg was performed to determine the tibiofemoral angle. For functional evaluation, the Active Scale for Kids (ASK) and Lower Extremity Functional Scale (LEFS) instruments were used for children below and above 15 years old, respectively. RESULTS: In terms of the tibiofemoral angle, the GGS group documented greater angle changes compared to the ACO group, but the difference was not significant. In terms of functional outcomes, the overall score percentage of both groups was comparable with the GGS group showing a trend of higher score percentage compared to the ACO group. The GGS group presented no complication while 2 neurovascular injuries and 1 implant failure were recorded in the ACO group. CONCLUSION: Both GGS and ACO procedures resulted in similar radiographic and functional outcomes for the treatment of rickets in children. GGS may be advantageous in terms of reducing complications of surgery. Nevertheless, the choice of surgical intervention should be made based on the patient's circumstances and the surgeon's preference.

Investigation on synthesis of ternary g-C3N4/ZnO-W/M nanocomposites integrated heterojunction II as efficient photocatalyst for environmental applications.

The rapid industrialization of the world is disparagingly manipulating our environment and natural ecosystem. The researchers are taking keen interest to invent novel material as photocatalyst for non-degradable organic pollutants. Solar energy-driven practices employing semiconductors are a novel approach towards wastewater remediation. Here in, we successfully synthesized a vigorous photocatalysts comprising of g-C3N4 and doped ZnO-W/M (M = Co, Ce, Yb, Sm) by co-precipitation followed by metals doping via calcination approach. The structural, morphological, and photocatalytic applications for organic pollutants of synthesized heterostructure nanocomposites were examined by XRD, FTIR, SEM, EDX and UV visible spectrophotometer. Diffraction peaks attributed to both g-C3N4 and ZnO-W were detected in the XRD spectra. The FTIR spectra also inveterate the formation of g-C3N4/ZnO-W/M composites. The SEM images reveal an agglomerated morphology and EDS analysis also confirmed close contact between g-C3N4, ZnO-W and doped metals. The abridged energy band gap of g-C3N4/ZnO-W/M (M = Ce, Yb, Sm, Co) nanocomposites calculated via Tauc plot are 2.68, 2.88, 3.24 and 3.29 eV respectively. Narrowing of bandgap is considered an imperative triumph for the degradation of industrial effluents. The photocatalytic activity was performed against four different dyes and follows the trend Ce > Yb > Sm > Co. The recyclability tests were carried out for different dyes and no substantial catalytic activity loss was observed even after the fourth experimental run, which proves that reported ternary heterojunctions exhibit high mechanical stability and reusability.The species trapping experiment exposed that generated h+ are the principal active specie for dye photodegradation reactions. This work disseminates a novel photocatalyst for the removal of synthetic dyes.

Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.

The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) where it contributes to tumor aggressiveness. To address its transcriptional actions in TNBCs, we combined transcriptomics, ChIP-seqs, machine learning and NG Capture-C. Additionally, we studied its Fos family kin Fra-2 also expressed in TNBCs, albeit much less. Consistently with their pleiotropic effects, Fra-1 and Fra-2 up- and downregulate individually, together or redundantly many genes associated with a wide range of biological processes. Target gene regulation is principally due to binding of Fra-1 and Fra-2 at regulatory elements located distantly from cognate promoters where Fra-1 modulates the recruitment of the transcriptional co-regulator p300/CBP and where differences in AP-1 variant motif recognition can underlie preferential Fra-1- or Fra-2 bindings. Our work also shows no major role for Fra-1 in chromatin architecture control at target gene loci, but suggests collaboration between Fra-1-bound and -unbound enhancers within chromatin hubs sometimes including promoters for other Fra-1-regulated genes. Our work impacts our view of AP-1.

The prevailing trend of consanguinity in the Arab society of Israel: is it still a challenge?

The aim of this study was to determine the trend of consanguineous marriage among the Arab population in Israel. Socio-demographic data for the Arab population were extracted from national health surveys conducted in Israel in 2007 and 2017. The prevalence of consanguineous marriage among the Arab population in Israel increased significantly from 36.3% to 41.6% in the decade from 2007 to 2017. First-cousin and closer marriages constituted about 50% of total consanguineous marriages in the two periods surveyed. Consanguinity was found to be significantly related to religion and place of residence. Thus, the prevalence of consanguineous marriage remains high among the Arab population in Israel, similar to other Arab societies. These findings affect the health of future generations and impose a challenge for health care professionals.

Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multicenter placebo-controlled randomized clinical trial.

Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID-19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo-controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg-1 day-1 ) and Nigella sativa seeds (80 mg kg-1 day-1 ) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30-day mortality in the intention-to-treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46-6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76-8.14, p < 0.0001) and severe cases (8.5 vs. 12 days, HR: 4.32; 95% CI: 2.62-7.13, p < 0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% vs. 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03-0.13, p < 0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01-0.09, p < 0.0001). In severe cases, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02-0.92, p = 0.029). No HNS-related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID-19 patients. This trial was registered on April 15, 2020 with ClinicalTrials.gov Identifier: NCT04347382.

Advancing Brain Tumor Classification through Fine-Tuned Vision Transformers: A Comparative Study of Pre-Trained Models.

This paper presents a comprehensive study on the classification of brain tumor images using five pre-trained vision transformer (ViT) models, namely R50-ViT-l16, ViT-l16, ViT-l32, ViT-b16, and ViT-b32, employing a fine-tuning approach. The objective of this study is to advance the state-of-the-art in brain tumor classification by harnessing the power of these advanced models. The dataset utilized for experimentation consists of a total of 4855 images in the training set and 857 images in the testing set, encompassing four distinct tumor classes. The performance evaluation of each model is conducted through an extensive analysis encompassing precision, recall, F1-score, accuracy, and confusion matrix metrics. Among the models assessed, ViT-b32 demonstrates exceptional performance, achieving a high accuracy of 98.24% in accurately classifying brain tumor images. Notably, the obtained results outperform existing methodologies, showcasing the efficacy of the proposed approach. The contributions of this research extend beyond conventional methods, as it not only employs cutting-edge ViT models but also surpasses the performance of existing approaches for brain tumor image classification. This study not only demonstrates the potential of ViT models in medical image analysis but also provides a benchmark for future research in the field of brain tumor classification.

Reshaping Insanity in Pakistani Law: The Case of Safia Bano.

This Article analyzes the 2021 judgment of the Supreme Court of Pakistan in the case of Mst. Safia Bano v. Home Department, Government of Punjab. The case has garnered significant local and international attention due to the Court's ruling that a death sentence may not be carried out on a defendant who has a mental illness. Setting the case against the backdrop of Pakistan's Islamic and colonial contexts, this article argues that the Supreme Court has reshaped the insanity defense in Pakistani law by placing the determination of a defendant's mental state mainly in the hands of medical professionals. However, the Court's reliance on medical professionals and the subsequent downplaying of the "moral capacity" element of the insanity defense-a determination of law made by courts-has created an obstacle for courts to punish offenders more stringently in future cases due to the popular belief that mental health professionals are ill-equipped to answer broader questions of justice for victims and society. The article recommends that this issue can be remedied by establishing an objective legal test for insanity that considers Islamic law, Pakistani precedent, and advances in medical science.

Gasdermin D Deficiency Does Not Protect Mice from High-Fat Diet-Induced Glucose Intolerance and Adipose Tissue Inflammation.

The adipose tissue NLRP3 inflammasome has recently emerged as a contributor to obesity-related metabolic inflammation. Recent studies have demonstrated that the activation of the NLRP3 inflammasome cleaves gasdermin D (GSDMD) and induces pyroptosis, a proinflammatory programmed cell death. However, whether GSDMD is involved in the regulation of adipose tissue function and the development of obesity-induced metabolic disease remains unknown. The aim of the present study was to investigate the role of GSDMD in adipose tissue inflammation as well as whole-body metabolism using GSDMD-deficient mice fed a high-fat diet (HFD) for 30 weeks. The effects of GSDMD deficiency on adipose tissue, liver, and isolated macrophages from wild-type (WT) and GSDMD knockout (KO) mice were examined. In addition, 3T3-L1 cells were used to examine the expression of GSDMD during adipogenesis. The results demonstrate that although HFD-induced inflammation was partly ameliorated in isolated macrophages and liver, adipose tissue remained unaffected by GSDMD deficiency. Compared with the WT HFD mice, GSDMD KO HFD mice exhibited a mild increase in HFD-induced glucose intolerance with increased systemic and adipose tissue IL-1ß levels. Interestingly, GSDMD deficiency caused accumulation of fat mass when challenged with HFD, partly by suppressing the expression of peroxisome proliferator-activated receptor gamma (PPARγ). The expression of GSDMD mRNA and protein was dramatically suppressed during adipocyte differentiation and was inversely correlated with PPARγ expression. Together, these findings indicate that GSDMD is not a prerequisite for HFD-induced adipose tissue inflammation and suggest a noncanonical function of GSDMD in regulation of fat mass through PPARγ.

Critical role for TRIM28 and HP1ß/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.

Naive CD4+ T lymphocytes differentiate into different effector types, including helper and regulatory cells (Th and Treg, respectively). Heritable gene expression programs that define these effector types are established during differentiation, but little is known about the epigenetic mechanisms that install and maintain these programs. Here, we use mice defective for different components of heterochromatin-dependent gene silencing to investigate the epigenetic control of CD4+ T cell plasticity. We show that, upon T cell receptor (TCR) engagement, naive and regulatory T cells defective for TRIM28 (an epigenetic adaptor for histone binding modules) or for heterochromatin protein 1 ß and γ isoforms (HP1ß/γ, 2 histone-binding factors involved in gene silencing) fail to effectively signal through the PI3K-AKT-mTOR axis and switch to glycolysis. While differentiation of naive TRIM28-/- T cells into cytokine-producing effector T cells is impaired, resulting in reduced induction of autoimmune colitis, TRIM28-/- regulatory T cells also fail to expand in vivo and to suppress autoimmunity effectively. Using a combination of transcriptome and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses for H3K9me3, H3K9Ac, and RNA polymerase II, we show that reduced effector differentiation correlates with impaired transcriptional silencing at distal regulatory regions of a defined set of Treg-associated genes, including, for example, NRP1 or Snai3. We conclude that TRIM28 and HP1ß/γ control metabolic reprograming through epigenetic silencing of a defined set of Treg-characteristic genes, thus allowing effective T cell expansion and differentiation into helper and regulatory phenotypes.

Intelligent Sensors for dc Fault Location Scheme Based on Optimized Intelligent Architecture for HVdc Systems.

We develop a probabilistic model for determining the location of dc-link faults in MT-HVdc networks using discrete wavelet transforms (DWTs), Bayesian optimization, and multilayer artificial neural networks (ANNs) based on local information. Likewise, feedforward neural networks (FFNNs) are trained using the Levenberg-Marquardt backpropagation (LMBP) method, which multi-stage BO optimizes for efficiency. During training, the feature vectors at the sending terminal of the dc link are selected based on the norm values of the observed waveforms at various frequency bands. The multilayer ANN is trained using a comprehensive set of offline data that takes the denoising scheme into account. This choice not only helps to reduce the computational load but also provides better accuracy. An overall percentage error of 0.5144% is observed for the proposed algorithm when tested against fault resistances ranging from 10 to 485 Ω. The simulation results show that the proposed method can accurately estimate the fault site to a precision of 485 Ω and is more robust.

Correlates of Hookah Smoking among Arab Adults in Israel Identified by a Machine Learning Algorithm.

BACKGROUND: Hookah smoking is a common activity around the world and has recently become a trend among youth. Studies have indicated a relationship between hookah smoking and a high prevalence of chronic diseases, cancer, cardiovascular, and infectious diseases. In Israel, there has been a sharp increase in hookah smoking among the Arabs. Most studies have focused mainly on hookah smoking among young people. OBJECTIVES: To examine the association between hookah smoking and socioeconomic characteristics, health status and behaviors, and knowledge in the adult Arab population and to build a prediction model using machine learning methods. METHODS: This quantitative study based is on data from the Health and Environment Survey conducted by the Galilee Society in 2015-2016. The data were collected through face-to-face interviews with 2046 adults aged 18 years and older. RESULTS: Using machine learning, a prediction model was built based on eight features. Of the total study population, 13.0% smoked hookah. In the 18-34 age group, 19.5% smoked. Men, people with lower level of health knowledge, heavy consumers of energy drinks and alcohol, and unemployed people were more likely to smoke hookah. Younger and more educated people were more likely to smoke hookah. CONCLUSIONS: Hookah smoking is a widespread behavior among adult Arabs in Israel. The model generated by our study is intended to help health organizations reach people at risk for smoking hookah and to suggest different approaches to eliminate this phenomenon.

Platelet-Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi.

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.

MIR sequences recruit zinc finger protein ZNF768 to expressed genes.

Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression.

Prevalence of reduced visual acuity among school-aged children and adolescents in 6 districts of Changsha city: a population-based survey.

BACKGROUND: To calculate and evaluate the prevalence of reduced uncorrected distant visual acuity (UCDVA) in primary, middle and high schools in 6 districts of Changsha, Hunan, China. METHODS: A population-based retrospective study was conducted in 239 schools in 6 districts of Changsha. After routine eye examination to rule out diseases that can affect refraction, 250,980 eligible students from primary, middle and high schools were enrolled in the survey. Then the uncorrected distant and near visual acuity of each eye were measured. Categories of schools, districts, grades, eye exercises and sports time were also documented and analyzed. RESULTS: The overall prevalence of reduced UCDVA was 51.8% (95% confidence interval [CI]: 51.6-52.0%) in 6 districts of Changsha. Results of individual districts were as follows: Furong district 59.9%(95% CI: 57.9-61.8%), Tianxin district 62.3%(95% CI: 60.5-64.0%), Wangcheng district 47.8%(95% CI: 46.8-48.8%), Kaifu district 58.5%(95% CI: 58.0-58.9%), Yuhua district 47.0%(95% CI: 46.7-47.4%) and Yuelu district 52.6%(95% CI: 52.3-52.9%). The proportion of normal VA is seen to decrease from primary grade 3. The proportion of mildly reduced UCDVA is higher in primary grade 1 and 2. The proportion of moderately reduced UCDVA remains similar during 12 grades. The proportion of severely reduced UCDVA increases with grades. Multivariate analysis shows that the prevalence of reduced UCDVA is higher in key schools (risk ratio [RR] = 1.47, 95% CI 1.44-1.50) than non-key schools. CONCLUSIONS: According to the existing data analysis results, the prevalence of reduced UCDVA among primary, middle and high school students in Changsha is very high. Some effective measures need to be taken to prevent it.

A comprehensive framework for thermoeconomic analysis of desalination systems.

Thermoeconomic analysis, a combined application of thermodynamic and economic analyses, has emerged as an important tool to optimize the performance of desalination systems. Contrary to conventional economic analysis, it offers flexibility to investigate and improve the performance of each component in the system, individually. The current paper presents a comprehensive framework for conducting thermoeconomic analysis of desalination systems. In this regard, different energy calculation methods are discussed first. Then a detailed review of theoretical developments of thermoeconomic analyses is conducted to summarize the correlations/magnitude of important economic parameters. This is followed by a discussion on cost balance equations for important desalination components. Finally, a systematic thermoeconomic analysis model is developed for the mechanical vapor compression desalination system operating under different arrangements as an example. The monetary value of each stream calculated using appropriate fiscal parameters in the system is presented in the form of a cost flow diagram. The study can be used to conduct the thermoeconomic analysis of other commercial desalination systems.

Femiject, a once-a-month combined injectable contraceptive: experience from Pakistan.

OBJECTIVES: The aims of the study were to compare the 12 month continuation rate, level of satisfaction and bleeding patterns of a once-a-month combined injectable contraceptive (CIC; Femiject), a 3 monthly progestogen-only injectable contraceptive (depot medroxyprogesterone acetate [DMPA]) and combined oral contraceptives (COCs). METHODS: A prospective observational study was conducted at Aziz Medical Centre, Karachi, Pakistan. The study comprised 171 married women aged 19-35 years and requesting contraception. Participants were offered injectable contraceptives or COCs and evaluated twice: once at the beginning of the study and again after 12 months, or earlier if they discontinued use. RESULTS: Sixty (35.1%) women chose COCs, 53 (31.0%) chose DMPA and 58 (33.9%) chose the CIC. The continuation rate was higher among CIC users (p = .034). CIC users were more satisfied with their method compared with those who chose COCs or DMPA (63.8% vs 25.0% and 28.3%, respectively). Most CIC users said they were likely or very likely to use the method again (63.8%); only 25.9% said they would not recommend it to a friend. CIC users had, however, more spotting compared with COC users (60.3% vs 3.3%; p ˂ .001). CONCLUSION: As the continuation rate, level of satisfaction and bleeding profile of CIC users was promising, increased uptake should be encouraged. Our study shows that CIC is a good option for women requesting contraception.

Breast metastasis from medullary carcinoma of thyroid: A case report with literature view.

Primary Breast cancer is the most common malignancy in females but secondary involvement of breast is very rare. The Most common sites of primaries for breast metastasis are breast carcinoma of contra lateral side, Lymphoma and leukaemia. Medullary Thyroid Carcinoma (MTC) itself is rare and commonly metastasises to liver, lung and bones. Secondary breast involvement by MTC is very rare with only few case reports in literature. Clinically and radiographically breast secondaries mimic benign lesions and may cause diagnostic challenges. To avoid unnecessary surgery and for appropriate treatment decision,accurate diagnosis is important. We present here our experience of a similar case of secondary breast carcinoma from MTC seen at MINAR cancer hospital Multan. The patient presented clinically and radiologically with benign breast lumps. Fine needle aspiration (FNAC) showed atypical cells and Ultra sound guided Trucut biopsy confirmed it to be a secondary from MTC. Patient is under treatment of an oncologist, has been treated with chemotherapy and is on follow up till date.