Cisplatin-induced increase in heregulin 1 and its attenuation by the monoclonal ErbB3 antibody seribantumab in bladder cancer.

Cisplatin-based combination chemotherapy is the foundation for treatment of advanced bladder cancer (BlCa), but many patients develop chemoresistance mediated by increased Akt and ERK phosphorylation. However, the mechanism by which cisplatin induces this increase has not been elucidated. Among six patient-derived xenograft (PDX) models of BlCa, we observed that the cisplatin-resistant BL0269 express high epidermal growth factor receptor, ErbB2/HER2 and ErbB3/HER3. Cisplatin treatment transiently increased phospho-ErbB3 (Y1328), phospho-ERK (T202/Y204) and phospho-Akt (S473), and analysis of radical cystectomy tissues from patients with BlCa showed correlation between ErbB3 and ERK phosphorylation, likely due to the activation of ERK via the ErbB3 pathway. In vitro analysis revealed a role for the ErbB3 ligand heregulin1-ß1 (HRG1/NRG1), which is higher in chemoresistant lines compared to cisplatin-sensitive cells. Additionally, cisplatin treatment, both in PDX and cell models, increased HRG1 levels. The monoclonal antibody seribantumab, that obstructs ErbB3 ligand-binding, suppressed HRG1-induced ErbB3, Akt and ERK phosphorylation. Seribantumab also prevented tumor growth in both the chemosensitive BL0440 and chemoresistant BL0269 models. Our data demonstrate that cisplatin-associated increases in Akt and ERK phosphorylation is mediated by an elevation in HRG1, suggesting that inhibition of ErbB3 phosphorylation may be a useful therapeutic strategy in BlCa with high phospho-ErbB3 and HRG1 levels.

Androgen receptor transcriptional activity is required for heregulin-1ß-mediated nuclear localization of the HER3/ErbB3 receptor tyrosine kinase.

Prostate cancer is initially regulated by the androgen receptor (AR), a ligand-activated, transcription factor, and is in a hormone-dependent state (hormone-sensitive prostate cancer (HSPC)), but eventually becomes androgen-refractory (castration-resistant prostate cancer (CRPC)) because of mechanisms that bypass the AR, including by activation of ErbB3, a member of the epidermal growth factor receptor family. ErbB3 is synthesized in the cytoplasm and transported to the plasma membrane for ligand binding and dimerization, where it regulates downstream signaling, but nuclear forms are reported. Here, we demonstrate in prostatectomy samples that ErbB3 nuclear localization is observed in malignant, but not benign prostate, and that cytoplasmic (but not nuclear) ErbB3 correlated positively with AR expression but negatively with AR transcriptional activity. In support of the latter, androgen depletion upregulated cytoplasmic, but not nuclear ErbB3, while in vivo studies showed that castration suppressed ErbB3 nuclear localization in HSPC, but not CRPC tumors. In vitro treatment with the ErbB3 ligand heregulin-1ß (HRG) induced ErbB3 nuclear localization, which was androgen-regulated in HSPC but not in CRPC. In turn, HRG upregulated AR transcriptional activity in CRPC but not in HSPC cells. Positive correlation between ErbB3 and AR expression was demonstrated in AR-null PC-3 cells where stable transfection of AR restored HRG-induced ErbB3 nuclear transport, while AR knockdown in LNCaP reduced cytoplasmic ErbB3. Mutations of ErbB3's kinase domain did not affect its localization but was responsible for cell viability in CRPC cells. Taken together, we conclude that AR expression regulated ErbB3 expression, its transcriptional activity suppressed ErbB3 nuclear translocation, and HRG binding to ErbB3 promoted it.

Feasibility and Acceptability of an Online Mindfulness-Based Intervention for Stress Reduction and Psychological Wellbeing of University Students in Pakistan: A Pilot Randomized Controlled Trial.

The rise in mental health concerns of university students is causing a serious hinderance to their wellbeing, impeding their functioning. The socio-economic and political friction in low- and middle-income countries adds to their vulnerability and calls for a cost-effective indigenous intervention. Consequently, this study aimed to inform a large definitive trial by assessing the feasibility and acceptability of a randomized controlled trial (RCT) design evaluating a culturally adapted online Mindfulness Training Course (MTC) used to improve stress and wellbeing among Pakistani university students. A two-arm pilot randomized controlled trial was conducted. University students (n = 156) were randomly assigned to either the MTC group (n = 80) or Wait-list (WL) control group (n = 76) and completed baseline and post-intervention self-report measures for mindfulness, stress and psychological wellbeing. Additionally, semi-structured interviews were conducted with consenting MTC group participants (n = 18) to explore their views about MTC, employing reflexive thematic analysis. Of 80 participants randomized to the MTC group, 32 completed the course, whereas, from the 156 randomized participants, 102 completed assessment surveys. Feasibility and acceptability indicators showed high recruitment, compliance, and adherence to MTC, with practical steps for randomization and online data collection. Further results showed higher levels of mindfulness and psychological wellbeing and lowered stress levels in the MTC group compared to the control group. The attrition and dropout rates were high; however, the feedback from participants who completed the MTC was highly positive and encouraging. In conclusion, if the trial proceeds with increased outreach in a large-scale RCT, the recruitment might be revised to reduce attrition rates. Further recommendations are discussed.

Interpretations and revenge goals in response to peer provocations: Comparing adolescents in the United States and Pakistan.

This study examined cultural specificity in how interpretations about peer provocation are associated with revenge goals and aggression. The sample consisted of young adolescents from the United States (369 seventh-graders; 54.7% male; 77.2% identified as White) and from Pakistan (358 seventh-graders; 39.2% male). Participants rated their interpretations and revenge goals in response to six peer provocation vignettes and completed peer nominations of aggressive behavior. Multi-group SEM models indicated cultural specificity in how interpretations were related to revenge goals. Interpretations that a friendship with the provocateur was unlikely were uniquely related to revenge goals for Pakistani adolescents. For U.S adolescents positive interpretations were negatively related to revenge but self-blame interpretations were positively related to vengeance goals. Revenge goals were related to aggression similarly across groups.

Coronaviruses: An overview with special emphasis on COVID-19 outbreak with musculoskeletal manifestations.

An acute respiratory illness caused by a novel coronavirus, namely, severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19), began spreading across China in late December 2019. The disease gained global attention as it spread worldwide. Since the COVID-19 pandemic began, many studies have focused on the impact of the disease on conditions such as diabetes, cardiovascular disease, pulmonary disorders, and renal malfunction. However, few studies have focused on musculoskeletal disorders related to COVID-19 infection. In this review, we update the current knowledge on the coronavirus with special reference to its effects during and after the pandemic on musculoskeletal aliments, which may inform clinical practice.

Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes.

To our knowledge, our group is the first to demonstrate that NRDP1 is located in the nucleus as well as the cytoplasm of CaP cells. Subcellular fractionation, immunohistochemistry, and immunofluorescence analysis combined with confocal microscopy were used to validate this finding. Subcellular fractionation followed by western blot analysis revealed a strong association between AR and NRDP1 localization when AR expression and/or cellular localization was manipulated via treatment with R1881, AR-specific siRNA, or enzalutamide. Transfection of LNCaP with various NRDP1 and AR constructs followed by immunoprecipitation confirmed binding of NRDP1 to AR is possible and determined that binding requires the hinge region of AR. Co-transfection with NRDP1 constructs and HA-ubiquitin followed by subcellular fractionation confirmed that nuclear NRDP1 retains its ubiquitin ligase activity. We also show that increased nuclear NRDP1 is associated with PSA recurrence in CaP patients (n = 162, odds ratio; 1.238, p = 0.007) and that higher levels of nuclear NRDP1 are found in castration resistant cell lines (CWR22Rv1 and PC3) compared to androgen sensitive cell lines (LNCaP and MDA-PCa-3B). The combined data indicate that NRDP1 plays a role in mediating CaP progression and supports further investigation of both the mechanism by which nuclear transport occurs and the identification of specific nuclear targets.

Risk Perception and Protective Behavior in the Context of COVID-19: a Qualitative Exploration.

As a result of the devastating health effects of the COVID-19 outbreak, the lockdown has been considered a safety measure in many countries. In Pakistan, the first case of COVID-19 was reported in February 2020. The purpose of this qualitative study was to investigate people's risk perception and protective behavior during the lockdown. Twenty-two (22) participants from eight big cities across Pakistan were interviewed. A six-step reflective thematic analysis was used for data analysis. The study focused on risk perception and protective behaviors. Our main analytical goal was to understand how risk perception shapes human behavior in the context of lockdown, pandemic-related information flow, and corresponding meaning-making. The study revealed that people influenced by information and advice campaigns form a perception of risk that has shaped their protective behavior. They used familiar means of coping with distress, including the search for strength through religious belief practices and following the precautions recommended by health professionals through the media.

CCN3 Proteins as a diagnostic marker in osteosarcoma patients: A case control study.

BACKGROUND: Osteosarcoma is the most prevalent type of primary bone sarcoma and is the major cause of deaths associated with cancer in children and adolescents. Despite novel and innovative therapies, early diagnosis of the osteosarcoma is still critically needed. Our study aimed to analyse the CCN3 proteins as a diagnostic marker and correlate their expression level with the severity of primary osteosarcoma patients. METHODS: In this prospective case-control study, after ethical clearance and informed consent, a total of 35 cases with primary osteosarcoma and ten otherwise healthy controls were enroled according to our strict inclusion-exclusion criteria. Tissue samples were collected during biopsy procedures in suspected cases and in controls during bone grafting procedures. The CCN3 expression level was measured by the western blotting assay. The clinic-radiological examinations were done in cases and graded according to the AJCC classification. Comparisons of CCN3 expression were measured between cases and controls, followed by correlation of their expression level with severity/grade of osteosarcoma in cases. RESULTS: All the demographic parameters showed insignificant differences. The CCN3 protein expressions were significantly upregulated in tissue samples of osteosarcoma patients (cases) compared to controls. The mean difference (p<0.0001) in CCN3 protein expression between cases' and controls' bony tissues was significant but showed insignificant correlation with the different grades of osteosarcoma. CONCLUSIONS: The upregulated CCN3 protein expression in osteosarcoma tissue along with significant differential manifestation in accordance with different grades of osteosarcoma make CCN3 suitable for a potential diagnostic biomarker. However, the author recommends further extensive multi-centric collaborative studies to increase our study reliability and generalizability.

Molecular Speciation of Size Fractionated Particulate Water-Soluble Organic Carbon by Two-Dimensional Nuclear Magnetic Resonance (NMR) Spectroscopy.

Particulate matter is associated with increased morbidity and mortality; its effects depend on particle size and chemical content. It is important to understand the composition and resultant toxicological profile of particulate organic compounds, the largest and most complex fraction of particulate matter. The objective of the study was to delineate the nuclear magnetic resonance (NMR) spectral fingerprint of the biologically relevant water-soluble organic carbon (WSOC) fraction of size fractionated urban aerosol. A combination of one and two-dimensional NMR spectroscopy methods was used. The size distribution of particle mass, water-soluble extract, non-exchangeable organic hydrogen functional types and specific biomarkers such as levoglucosan, methane sulfonate, ammonium and saccharides indicated the contribution of fresh and aged wood burning emissions, anthropogenic and biogenic secondary aerosol for fine particles and primary traffic exhausts and pollen for large particles. Humic-like macromolecules in the fine particle size range included branched carbon structures containing aromatic, olefinic, keto and nitrile groups and terminal carboxylic and hydroxyl groups such as terpenoid-like polycarboxylic acids and polyols. Our study show that 2D-NMR spectroscopy can be applied to study the chemical composition of size fractionated aerosols.

The p14ARF tumor suppressor restrains androgen receptor activity and prevents apoptosis in prostate cancer cells.

Prostate cancer (PCa) is characterized by a unique dependence on optimal androgen receptor (AR) activity where physiological androgen concentrations induce proliferation but castrate and supraphysiological levels suppress growth. This feature has been exploited in bipolar androgen therapy (BAT) for castrate resistant malignancies. Here, we investigated the role of the tumor suppressor protein p14ARF in maintaining optimal AR activity and the function of the AR itself in regulating p14ARF levels. We used a tumor tissue array of differing stages and grades to define the relationships between these components and identified a strong positive correlation between p14ARF and AR expression. Mechanistic studies utilizing CWR22 xenograft and cell culture models revealed that a decrease in AR reduced p14ARF expression and deregulated E2F factors, which are linked to p14ARF and AR regulation. Chromatin immunoprecipitation studies identified AR binding sites upstream of p14ARF. p14ARF depletion enhanced AR-dependent PSA and TMPRSS2 transcription, hence p14ARF constrains AR activity. However, p14ARF depletion ultimately results in apoptosis. In PCa cells, AR co-ops p14ARF as part of a feedback mechanism to ensure optimal AR activity for maximal prostate cancer cell survival and proliferation.

Can impaired diaphyseal fracture healing be predicted early?: A cohort study of biomarkers.

BACKGROUND: Currently, the clinico-radiological method was used to analyze the healing progression of fractures globally, but even they are also unable to presume the impaired healing early. Hence till date, no reliable methods are available to predict the impaired healing early, so that it could be interventionally managed as required within the time. METHODS: In this prospective observational study, a total of 121 adults fractured patients and 108 healthy controls were analyzed. Peripheral blood samples were taken from controls (at once) and fractured cases (at different follow-ups) to quantify the Osteocalcin and Osteopontin mRNA and protein expression using qRT-PCR and western blotting assay respectively. In parallel to that the clinico-radiological follow-up examinations also done at various specific follow-up intervals up to 24th post-fracture weeks. RESULTS: As per the clinico-radiological status at the 24th week, fracture patients were divided into normal healing (n = 102) and impaired healing (n = 19) groups. Mean RUST score between normal healing and the impaired healing group showed a significant statistical difference at each follow-up. In both groups, expressions of Osteocalcin (mRNA & protein) were gradually up-regulated from the baseline to end of follow-ups, whereas Osteopontin mRNA as well as protein gradually up-regulated from the baseline to a peak value at 10th day, then declined. In general, the Osteocalcin and Osteopontin mean fold expressions were higher in normal healing as compared to the impaired healing groups.A significant correlation was found between the mRNA expressions of Osteocalcin and Osteopontin with the RUST score at most of the follow-ups. However, the protein expressions were not shown any significant correlation. CONCLUSIONS: The Osteocalcin and Osteopontin expression will provide an early prediction of the healing outcomes of tibial fractures. This may open a new horizon for innovations to deal with complications associated with impaired fracture healing, especially in tibial bone fractures.

Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice.

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy.

Determining the caregivers' burden in caregivers of patients with mental illness.

OBJECTIVE: To examine the factors associated with caregivers' burden in individuals providing care to family members suffering from serious mental illness. METHODS: This Cross Sectional Study was carried out at Armed Forces Institute of Mental Health, Rawalpindi, from May 2015 to December 2015. A purposive sample of 120 family caregivers (60 males and 60 females, age range= 18-65) who were taking care of patients with serious mental illness (i.e. Major Depressive Disorder, Bipolar Disorder & Schizophrenia) for at least one year were recruited from the hospital and assessed through Zarit Burden Interview (ZBI) and Brief COPE inventory. The decline in functional status, and diminished physical capacity compromising the independent living of the care recipient was assessed through Katz Index of Independence in Activities of daily living (ADL) and Lawton Instrumental activities of daily living (IADL). RESULTS: The results suggest that the longer the duration of illness (F=25.71, p < 0.01), with increased impairments of care-recipients, (decline in functional status, F=21.33, p < 0.001; diminished physical capacity F =32.41, p < 0.001) the more the burden experienced by the caregivers. Moreover, caregivers who were married (t=-2.98, p < .01), less educated (t =5.48, p < .01), lived in rural area (t = -7.99, p < .01), had lower monthly income (t = -4.95, p < .01) provide longer hours of caregiving (F=19.12, p < 0.001) and used avoidant coping behavior (F= 56.37, p < 0.001) reported significantly higher caregiver burden than caregivers who were unmarried, more educated, lived in urban area and had better income. CONCLUSION: The results of study demonstrate that caring for family members with serious mental illness impacts the caregivers' wellbeing. It, therefore, highlights the need for support and counseling services for the caregivers to reduce the burden of caring.

Dacomitinib, but not lapatinib, suppressed progression in castration-resistant prostate cancer models by preventing HER2 increase.

BACKGROUND: Despite overexpression of the ErbB (EGFR/HER2/ErbB3/ErbB4) family in castration-resistant prostate cancer (CRPC), some inhibitors of this family, including the dual EGFR/HER2 inhibitor lapatinib, failed in Phase II clinical trials. Hence, we investigated mechanisms of lapatinib resistance to determine whether alternate ErbB inhibitors can succeed. METHODS: The CWR22 human tumour xenograft and its CRPC subline 22Rv1 and sera from lapatinib-treated CRPC patients from a previously reported Phase II trial were used to study lapatinib resistance. Mechanistic studies were conducted in LNCaP, C4-2 and 22Rv1 cell lines. RESULTS: Lapatinib increased intratumoral HER2 protein, which encouraged resistance to this treatment in mouse models. Sera from CRPC patients following lapatinib treatment demonstrated increased HER2 levels. Investigation of the mechanism of lapatinib-induced HER2 increase revealed that lapatinib promotes HER2 protein stability, leading to membrane localisation, EGFR/HER2 heterodimerisation and signalling, elevating cell viability. Knockdown of HER2 and ErbB3, but not EGFR, sensitised CRPC cells to lapatinib. At equimolar concentrations, the recently FDA-approved pan-ErbB inhibitor dacomitinib decreased HER2 protein stability, prevented ErbB membrane localisation (despite continued membrane integrity) and EGFR/HER2 heterodimerisation, thereby decreasing downstream signalling and increasing apoptosis. CONCLUSIONS: Targeting the EGFR axis using the irreversible pan-ErbB inhibitor dacomitinib is a viable therapeutic option for CRPC.

Behavioural and emotional problems among school children in Pakistan: A telephonic survey for prevalence and risk factors.

AIM: Escalating rates of childhood mental health disorders constitute a serious issue for countries like Pakistan. However, due to a scarce number of studies on childhood behavioural problems, understanding the magnitude and gap of the problem is a challenge. Thus, the present study is intended to bridge this gap. This study provides estimates for prevalence, associated demographic risk factors and the impact of behavioural and emotional problems among school children. METHODS: A sample of children (n = 800) from public schools of Islamabad were selected using two-stage cluster random sampling. Data were collected from parents through telephonic interviews using the Strengths and Difficulties Questionnaire. RESULTS: Prevalence of overall behaviour problems accounted for 15.9%. For conduct problems, estimates were around 26.6%, for emotional problems 22.5%, for peer problems 13%, for hyperactivity 10.6% and for social problems 3% in the initial analysis. Mother's education also appeared to be a significant predictor for mental health problems of youth, where low maternal education was associated with high prevalence and higher impact of emotional and behavioural problems in the present sample. CONCLUSIONS: Prevalence estimates of the current study call for attention towards improving mental health services and access to children who are at risk or are having mental health problems. In the context of scarcity of the data from countries like Pakistan, the findings should be considered a call for mental health service providers, researchers and policymakers to scale up mental health services for youth in Pakistan.

XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner. The decrease in cell viability was due to an induction of apoptosis and cell cycle arrest. These results were recapitulated in in vivo studies where selinexor decreased tumor growth. Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. Cells expressing wildtype RB, a potent tumor suppressor that promotes growth arrest and apoptosis, were most susceptible to selinexor. Cell fractionation and immunofluorescence studies showed that selinexor treatment increased nuclear RB levels and mechanistic studies revealed that RB ablation curtailed the response to the drug. Conversely, limiting CDK4/6 dependent RB phosphorylation by palbociclib was additive with selinexor in reducing bladder tumor cell viability, confirming that RB activity has a role in the response to XPO1 inhibition. These results provide a rationale for XPO1 inhibition as a novel strategy for the treatment of bladder malignancies.

Role of alpha-crystallin, early-secreted antigenic target 6-kDa protein and culture filtrate protein 10 as novel diagnostic markers in osteoarticular tuberculosis.

Osteoarticular tuberculosis constitutes about 3% of all tuberculosis cases. Early and accurate diagnosis of tuberculosis is a challenging problem especially in the case of osteoarticular tuberculosis owing to the lower number of bacilli. However, an accurate and timely diagnosis of the disease results in an improved efficacy of the given treatment. Besides the limitations of conventional methods, nowadays molecular diagnostic techniques have emerged as a major breakthrough for the early diagnosis of tuberculosis with high sensitivity and specificity. Alpha-crystallin is a dominantly expressed protein responsible for the long viability of the pathogen during the latent phase under certain stress conditions such as hypoxia and nitric oxide stress. Two other proteins-early secreted antigenic target-6 and culture filtrate protein-10-show high expression in the active infective phase of Mycobacterium tuberculosis. In this article, we focus on the different proteins expressed dominantly in latent/active tuberculosis, and which may be further used as prognostic biomarkers for diagnosing tuberculosis, both in latent and active phases.

Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer.

Prostate cancer (PCa) progression is regulated by the androgen receptor (AR); however, patients undergoing androgen-deprivation therapy (ADT) for disseminated PCa eventually develop castration-resistant PCa (CRPC). Results of previous studies indicated that AR, a transcription factor, occupies distinct genomic loci in CRPC compared with hormone-naïve PCa; however, the cause of this distinction was unknown. The E3 ubiquitin ligase Nrdp1 is a model AR target modulated by androgens in hormone-naïve PCa but not in CRPC. Using Nrdp1, we investigated how AR switches transcription programs during CRPC progression. The proximal Nrdp1 promoter contains an androgen response element (ARE); we demonstrated AR binding to this ARE in androgen-sensitive PCa. Analysis of hormone-naive human prostatectomy specimens revealed correlation between Nrdp1 and AR expression, supporting AR regulation of NRDP1 levels in androgen-sensitive tissue. However, despite sustained AR levels, AR binding to the Nrdp1 promoter and Nrdp1 expression were suppressed in CRPC. Elucidation of the suppression mechanism demonstrated correlation of NRDP1 levels with nuclear localization of the scaffolding protein filamin A (FLNA) which, as we previously showed, is itself repressed following ADT in many CRPC tumors. Restoration of nuclear FLNA in CRPC stimulated AR binding to Nrdp1 ARE, increased its transcription, and augmented NRDP1 protein expression and responsiveness to ADT, indicating that nuclear FLNA controls AR-mediated androgen-sensitive Nrdp1 transcription. Expression of other AR-regulated genes lost in CRPC was also re-established by nuclear FLNA. Thus, our results indicate that nuclear FLNA promotes androgen-dependent AR-regulated transcription in PCa, while loss of nuclear FLNA in CRPC alters the AR-regulated transcription program.

Achieving fertility control through woman's autonomy and access to maternal healthcare: Are we on track? In-depth analysis of PDHS-2012-13.

BACKGROUND AND OBJECTIVE: Fertility control preferences and maternal healthcare have recently become a major concern for developing nations with evidence suggesting that low fertility control rates and poor maternal healthcare are among major obstructions in ensuring health and social status for women. Our objective was toanalyze the factors that influence women's autonomy, access to maternal healthcare, and fertility control preferences in Pakistan. METHODS: Data consisted of 11,761 ever-married women of ages 15-49 years from PDHS, 2012-13. Variables included socio-demographics, women's autonomy, fertility control preferences and access to maternal healthcare. RESULTS: Findings from multivariate analysis showed that women's younger age, having less than three number of children and independent or joint decision-making (indicators of high autonomy) remained the most significant predictors for access to better quality maternal healthcare and better fertility control preferences when other variables were controlled. CONCLUSION: Women's access to good quality maternal health care and fertility control preferences are directly and indirectly influenced by their demographic characteristics and decision-making patterns in domestic affairs.