CSM-CROPGRO model to simulate safflower phenological development and yield.

Crop simulation models are valuable tools for decision making regarding evaluation and crop improvement under different field conditions. CSM-CROPGRO model integrates genotype, environment and crop management portfolios to simulate growth, development and yield. Modeling the safflower response to varied climate regimes are needed to strengthen its productivity dynamics. The main objective of the study was to evaluate the performance of DSSAT-CSM-CROPGRO-Safflower (Version 4.8.2) under diverse climatic conditions. The model was calibrated using the field observations for phenology, biomass and safflower grain yield (SGY) of the year 2016-17. Estimation of genetic coefficients was performed using GLUE (Genetic Likelihood Uncertainty Estimation) program. Simulated results for days to flowering, maturity, biomass at flowering and maturity and SGY were predicted reasonably with good statistical indices. Model evaluation results elucidate phenological events with low root mean square error (6.32 and 6.52) and high d-index (0.95 and 0.96) for days to flowering and maturity respectively for all genotypes and climate conditions. Fair prediction of safflower biomass at flowering and maturity showed low RMSE (887.3 and 564.3 kg ha-1) and high d-index (0.67 and 0.93) for the studied genotypes across the environments. RMSE for validated safflower grain yield (101.8 kg ha-1) and d-index (0.95) depicted that model outperformed for all genotypes and growing conditions. Longer appropriate growing conditions at NARC-Islamabad took optimal duration to assimilate photosynthetic products lead to higher grain yield. Safflower resilience to different environments showed that it can be used as an alternate crop for different agroecological regions. Furthermore, CROPGRO-Safflower model can be used as tool to further evaluate inclusion of safflower in the existing cropping systems of studied regions.

Laboratory selection of chlorpyrifos resistance in an Invasive Pest, Phenacoccus solenopsis (Homoptera: Pseudococcidae): Cross-resistance, stability and fitness cost.

The cotton mealybug, Phenacoccus solenopsis is an important polyphagous sucking pest of ornamentals, horticultural and fiber crops worldwide. Some P. solenopsis populations have developed insecticide resistance. This study evaluated cross-resistance, stability of insecticide resistance and life history traits affected by chlorpyrifos resistance in P. solenopsis. After nine generations selected with chlorpyrifos, P. solenopsis exhibited a 539.76-fold resistance level compared to an unselected population (UNSEL Pop). Chlorpyrifos selected population (Chlor-SEL Pop) displayed moderate cross-resistance to profenofos, nitenpyram and high cross-resistance to lambda-cyhalothrin. Biological parameters of P. Solenopsis were affected by chlorpyrifos resistance. The Chlor-SEL Pop had a significant reduction in fitness (relative fitness=0.10), along with significant decreases in pupal weight, fecundity, egg hatching %, intrinsic rate of natural population increase, biotic potential, and mean relative growth rate. It is concluded that selection with chlorpyrifos had marked effect on resistance development in P. solenopsis and upon removal of selection pressure chlorpyrifos resistance declined significantly indicating unstable resistance. Development of resistance led to high fitness costs for the chlorpyrifos-selected strain. These findings should be helpful for better and more successful resistance management of P. solenopsis.

Gene expression and anticancer evaluation of Kigelia africana (Lam.) Benth. Extracts using MDA-MB-231 and MCF-7 cell lines.

In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. In this study, we aimed to assess the cytotoxic activity of Kigelia Africana (KA) extracts on breast cancer (MDA-MB-231 and MCF-7) and noncancerous kidney cells (HEK-293T) to develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS to analyze the constituents of EKA and HKA extracts meanwhile the crystal violet and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used to examine the possible cytotoxic effects of plant extracts on our cancer cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run on cell samples to evaluate the differential expression of cell proliferative markers of cancer (BCL-2 and TP53). These phytochemicals have been reported to have binding affinity for some other growth factors and receptors as well which was evaluated by the in-silico molecular docking against Bcl2, EGFR, HER2, and TP53. Our Morphological observation showed a significant difference in the cell morphology and proliferation potential which was decreased under the effect of plant extracts treatment as compared to the control samples. The ethanol extract exhibited a marked antiproliferative activity towards MDA-MB-231 and MCF-7 cell lines with IC50 = 20 and 32 µg/mL, respectively. Quantitative RT-PCR gene expression investigation revealed that the IC50 concentration of ethanolic extract regulated the levels of mRNA expression of apoptotic genes. With the target and active binding site amino acids discovered in the molecular docking investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is the best-docked ligand. The use of this plant in folk remedies justifies its high in vitro anti-cancer capabilities. This work highlights the role of phytochemicals in the inhibition of cancer proliferation. Based on all these findings, it can be concluded that EKA extract has promising anti-proliferative effect on cancerous cells but more study is required in future to further narrow down the active ingredients of total crude extract with specific targets in cancer cells.

Improving safe post-abortion care practices: A study on interventions implemented by Ipas Pakistan.

An estimated 50 million induced abortions occur in developing countries annually, and an estimated 7 million women are treated for complications associated with unsafe abortions. According to a 2012 estimate, 15 per 1,000 women aged 15-49 years seek treatment for abortion-related health complications in both private and public sectors. A high unmet need for family planning in Pakistan and a low percentage of women adopting a contraceptive method in the post-partum period led to unwanted pregnancy becoming one of the reasons for unsafe abortion. Post-abortion care (PAC) is an integrated service delivery model that includes both maternal health and family planning interventions. The study aims to examine improvement in abortion-related practices through the implementation of the PAC model at all tiers of public health service delivery systems in the two most populous provinces-Punjab, Sindh, Khyber Pakhtunkhwa, and Islamabad Capital Territory (ICT) region-of Pakistan. The improvement model comprises clinical training of healthcare providers, community engagement, and counseling of community women on safe post-abortion practices. It was a descriptive study utilizing data of 27,616 PAC clients recorded and reported by the service providers on the logbooks from 104 selected public health facilities from March 2018 to December 2021 in ICT, Punjab, Sindh, and Khyber Pakhtunkhwa provinces of Pakistan. Women who received PAC services were older than 25 years, 22,652 (82%), with a mean age of 29 years. Most of these women were in their first trimester, 26,110 (95%), and the majority diagnosed with PAC (incomplete, missed, or threatened abortion), 26,838 (97%). The majority of women, 25,324 (92%), received safe methods for post-abortion care that included the use of misoprostol, 15,804 (58%), and manual vacuum aspiration, 8,898 (32%). In total, 17,105 (72%) of women opted for a contraceptive method that included long-acting reversible contraceptives, 2,313 (10%); short-term excluding condoms, 3,436 (27%); and condoms, 8,113 (34%). The key predictors identified for uptake of the post-abortion family planning method indicated that women more than 25 years of age, in the early second trimester, and who were counseled on post-abortion family planning were more likely to adopt the contraceptive method than others. Increased access to post-abortion care and family planning could potentially reduce the incidence of unsafe abortion, unintended pregnancies, and associated maternal mortality. The experience of Pakistan suggests that the integrated post-abortion care service delivery model can be effectively implemented across the public health systems.

Expression profiling of TaARGOS homoeologous drought responsive genes in bread wheat.

Drought tolerant germplasm is needed to increase crop production, since water scarcity is a critical bottleneck in crop productivity worldwide. Auxin Regulated Gene involved in Organ Size (ARGOS) is a large protein family of transcription factors that plays a vital role in organ size, plant growth, development, and abiotic stress responses in plants. Although, the ARGOS gene family has been discovered and functionalized in a variety of crop plants, but a comprehensive and systematic investigation of ARGOS genes in locally used commercial wheat cultivars is still yet to be reported. The relative expression of three highly conserved TaARGOS homoeologous genes (TaARGOS-A, TaARGOS-B, TaARGOS-D) was studied in three drought-tolerant (Pakistan-2013, NARC-2009 and NR-499) and three sensitive (Borlaug-2016, NR-514 and NR-516) wheat genotypes under osmotic stress, induced by PEG-6000 at 0 (exogenous control), 2, 4, 6, and 12 h. The normalization of target genes was done using ß-actin as endogenous control, whereas DREB3, as a marker gene was also transcribed, reinforcing the prevalence of dehydration in all stress treatments. Real-time quantitative PCR revealed that osmotic stress induced expression of the three TaARGOS transcripts in different wheat seedlings at distinct timepoints. Overall, all genes exhibited significantly higher expression in the drought-tolerant genotypes as compared to the sensitive ones. For instance, the expression profile of TaARGOS-A and TaARGOS-D showed more than threefold increase at 2 h and six to sevenfold increase after 4 h of osmotic stress. However, after 6 h of osmotic stress these genes started to downregulate, and the lowest gene expression was noticed after 12 h of osmotic stress. Among all the homoeologous genes, TaARGOS-D, in particular, had a more significant influence on controlling plant growth and drought tolerance as it showed the highest expression. Altogether, TaARGOSs are involved in seedling establishment and overall plant growth. In addition, the tolerant group of genotypes had a much greater relative fold expression than the sensitive genotypes. Ultimately, Pakistan-2013 showed the highest relative expression of the studied genes than other genotypes which shows its proficiency to mitigate osmotic stress. Therefore, it could be cultivated in arid and semi-arid regions under moisture-deficient regimes. These findings advocated the molecular mechanism and regulatory roles of TaARGOS genes in plant growth and osmotic stress tolerance in contrasting groups of wheat genotypes, accompanied by the genetic nature of identified genotypes in terms of their potential for drought tolerance.

Minimal invasive plate osteosynthesis of close fractures of distal tibia.

BACKGROUND: The limited soft tissue, subcutaneous location and poor vascularity render the tibial fractures very challenging. Treatment of distal tibial fractures using minimally invasive plate osteosynthesis (MIPO) technique may minimise damage to soft tissues and the vascular integrity of bony fragments, leaving comminuted fragments out of the mechanical construct, preserving soft tissues with limited operative exposure. This descriptive study was conducted to assess the outcome of patients treated with MIPO technique for distal tibial fractures. METHODS: Seventy three cases of multifragmentary fractures of the distal tibia admitted in Bahawal Victoria Hospitals, Bahawalpur between April 2009 and October 2010 were included in this study. Patient's outcome in terms of period of radiologic union of the fractured segments and period of full weight bearing capacity were accessed. RESULTS: There were 66 males and 7 females of mean age 43 years. The mean follow-up period was 13 weeks. (Ranging from 9-16 weeks). All patients were fully weight bearing at 16 weeks (ranging 9-16 weeks) showing radiological union. There were two superficial infections treated successfully using oral antibiotics and no failures of fixation. There were no cases of rotational malalignment. CONCLUSION: MIPO is an effective method of treatment for distal tibial fractures. The use of indirect reduction techniques and small incisions is technically demanding but decreases surgical trauma to soft tissues.

Is it an institution, digital or social inclusion that matters for inclusive growth? A panel data analysis.

This study empirically examines the impact of institutional quality, social inclusion and digital inclusion on inclusive growth across different economies characterized by different income groups. Particularly, the study examines the impact of institutions on inclusive growth by using the panel data for 83 countries over the period 2010-2017. For empirical specification, we used two-steps system-GMM estimation technique to tackle endogeneity and min-max normalized indexing technique to construct the indices for inclusive growth, social inclusion, digital inclusion and institutional quality. The results of this study show that there is a direct link between institutional quality and inclusive growth for a higher-income group of countries but not in the rest of the income groups. Contribution of social and digital inclusivity is significant in all three income groups, except for social inclusion in middle-income countries. From the policy point of view, these findings suggest that establishing and strengthening the institutional structure in low- and middle-income countries can contribute towards better and higher inclusive growth.

Identification of drought tolerant Chickpea genotypes through multi trait stability index.

Drought is a major and constantly increasing abiotic stress factor, thus limiting chickpea production. Like other crops, Kabuli Chickpea genotypes are screened for drought stress through Multi-environment trials (METs). Although, METs analysis is generally executed taking into account only one trait, which provides less significant reliability for the recommendation of genotypes as compared to multi trait-based analysis. Multi trait-based analysis could be used to recommend genotypes across diverse environments. Hence, current research was conducted for selection of superior genotypes through multi-trait stability index (MTSI) by using mixed and fixed effect models under six diverse environments. The genotypic stability was computed for all traits individually using the weighted average of absolute scores from the singular value decomposition of the matrix of best linear unbiased predictions for the genotype vs environment interaction (GEI) effects produced by a linear mixed-effect model index. A superiority index, WAASBY was measured to reflect the MPS (Mean performance and stability). The selection differential for the WAASBY index was 11.2%, 18.49% and 23.30% for grain yield (GY), primary branches per plant (PBP) and Stomatal Conductance (STOMA) respectively. Positive selection differential (0.80% ≤ selection differential ≤ 13.00%) were examined for traits averaged desired to be increased and negative (-0.57% ≤ selection differential ≤ -0.23%) for those traits desired to be reduced. The MTSI may be valuable to the plant breeders for the selection of genotypes based on many characters as being strong and simple selection process. Analysis of MTSI for multiple environments revealed that, the genotypes G20, G86, G31, G28, G116, G12, G105, G45, G50, G10, G30, G117, G81, G48, G85, G17, G32, G4, and G37 were the most stable and high yielding out of 120 chickpea genotypes, probably due to high MPS of selected traits under various environments. It is concluded that identified traits can be utilized as genitors in hybridization programs for the development of drought tolerant Kabuli Chickpea breeding material.

Telehealth for Addressing Sexual and Reproductive Health and Rights Needs During the COVID-19 Pandemic and Beyond: A Hybrid Telemedicine-Community Accompaniment Model for Abortion and Contraception Services in Pakistan.

The COVID-19 pandemic led overburdened health care systems to deprioritize essential sexual and reproductive healthcare, including abortion and contraception care, while accelerating shifts in healthcare delivery to digital technologies. However, in many countries, including Pakistan, inequalities in access to digital technologies remain, presenting an opportunity for interventions that both increase access to deprioritized sexual and reproductive health and rights (SRHR) services and overcome the digital divide in delivering digital solutions to those in need of SRHR services. In June 2020, Ipas Pakistan partnered with Sehat Kahani (SK), a local health care NGO and telehealth service, and an existing network of Lady Health Workers (LHWs) to launch a novel hybrid telemedicine-community accompaniment pilot. The model linked women via LHWs with mobile devices to online providers for telemedicine consultations for SRH, including abortion services, contraception, and other gynecological consultations. In June 2020, we trained 98 LHWs and 22 telehealth doctors. Between June 2020 and March 2021, a total of 176 women were referred by LHWs for telehealth consultations. Among women who received abortion services, nearly all (90%) reported complete uterine evacuation. No serious adverse events were reported. Overall satisfaction was high; 81% reported being satisfied, and 86% said it is likely they would recommend the telehealth service to others. Data show that the provision of SRHR services via a telehealth-accompaniment model can be successfully implemented in Pakistan. Outcome data show high satisfaction and good clinical outcomes for women accessing care through this model. However, more data are needed to understand the full potential of this model. Barriers to digital health models, such as poor or inconsistent internet access, remain in places like Pakistan, especially in rural settings. This approach has its limitations but should be considered as an option in settings with similarly established community health networks and inequitable access to digital health.

Overexpression of SlGSNOR impairs in vitro shoot proliferation and developmental architecture in tomato but confers enhanced disease resistance.

The pervasive presence of nitric oxide (NO) in cells and its role in modifying cystein residues through protein S-nitrosylation is a remarkable redox based signalling mechanism regulating a variety of cellular processes. S-NITROSOGLUTATHIONE REDUCTASE (GSNOR) governs NO bioavailability by the breakdown of S-nitrosoglutathione (GSNO), fine-tunes NO signalling and controls total cellular S-nitrosylated proteins. Most of the published data on GSNOR functional analysis is based on the model plant Arabidopsis with no previous report for its effect on in vitro regeneration of tissue cultured plants. Moreover, the effect of GSNOR overexpression (O.E) on tomato growth, development and disease resistance remains enigmatic. Here we show that SlGSNOR O.E in tomato alters multiple developmental programs from in vitro culture establishment to plant growth and fruit set. Moreover, constitutive SlGSNOR O.E in tomato showed enhanced resistance against early blight (EB) disease caused by Alternaria solani and reduction in hypersensitive response (HR)-mediated cell death after Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) infiltrations. High GSNOR transcript levels led to the inhibition of in vitro shoot proliferation in transformed explants as revealed by the fluorescence microscopy after YFP labelling. Transgenic tomato lines overexpressing SlGSNOR showed defective phenotypes exhibiting stunted plant growth and bushy-type plants due to loss of apical dominance, along with reduced seed germination and delayed flowering. Furthermore, SlGSNOR O.E plants exhibited altered leaf arrangement, fruit shape and modified locules number in tomato fruit. These findings give a novel insight into a multifaceted regulatory role of SlGSNOR in tomato plant development, reproduction and response to pathogens.

Assessing the climate change impacts and adaptation strategies for rice production in Punjab, Pakistan.

Climate change is a serious threat to agriculture and food security. The development of adaptation measures is one of the key strategies to offset the climate change impacts on rice crop. A study was planned to develop adaptation strategies for future rice crop through simulation model. This study was consisted of six transplanting dates and three seedling densities which were tested to develop adaptations at three locations, i.e., Faisalabad, Hafizabad, and Gujranwala during the years 2015 and 2016. Climate change scenarios were developed for selected locations through statistical downscaling by selecting five general circulation models under representative concentration pathways (RCPs 8.5) for mid-century (2039-2069). The APSIM-ORYZA model was calibrated well with experimental data which showed an error of 2.35% between observed and simulated grain yield. The impact of climate change was studied by calculating the difference of baseline (1980-2010) and future yield. Model simulated results indicated that the rise in temperature will reduce the rice yield by 7.3%. To overcome this decrease in rice yield, suitable adaptation strategies were tested for mid-century. The developed adaptations, i.e., increased in plant population, nitrogen amount, and early transplanting, improved the rice yield by 8.7% under RCPs 8.5 for mid-century scenarios. Overall, this study provide better understanding of the adaptation processes for sustainable rice yield under anticipated future climate change.

Phenotyping for drought resistance in bread wheat using physiological and biochemical traits.

Drought is one of the most prominent limiting factors that negatively affect crop productivity by manipulating its physiological pathway. One hundred twenty diverse bread wheat genotypes were used in a pot experiment to explore the relationship among their fifteen physio-biochemical traits (PBT) by using multivariate analysis, heatmapping and stress tolerance index (STI) for grain yield as a marker trait to identify high yielding genotype with maximum stress tolerance capability. Increased proline and sugar accumulation were observed from control to moisture deficient environments by 159% and 122%, respectively. Moreover, leaf membrane stability index (LMSI), leaf relative water content (LRWC), relative dry weight (RDW), chlorophyll content, leaf surface area (LSA), Leaf succulence (LS), canopy temperature depression (CTD), relative excised leaf water loss (RELWL) and leaf osmotic potential (LOP) showed significantly decreasing trend in drought stress treatment as compared to well-watered plants by -21%, -21%, -34%, -22%, -38%, -37%, -46%, -18% and -35% respectively. Additionally, principal component analysis and genotype by trait biplot analysis showed that initial 7 principal components (PC1 to PC7) represented 77.27% and 79.02% of total cumulative variation under control and drought stress respectively. Genotypic-Phenotypic correlation revealed that most of the attributes were higher in case of genotypic correlation component (rg) as compared to the phenotypic correlation component (rp) indicating more genetic association between traits. The darker and lighter colour scale produced by heatmap exhibited contrasting nature of genotypes, as positive side with higher values represented drought resistance while values on the negative side with lower values showed susceptible performance of genotypes. Our results concluded that the studied PBT associated with STI for grain yield are the main factors which may contribute in improved productivity of wheat crop and if these traits show appropriate performance under stress condition the crop will show the more productive returns under changing climate.

Notes from the field: political norm change for abortion in Pakistan.

This commentary describes positive political norm change on abortion despite a restrictive abortion law. As we describe it, the approach in Pakistan has involved careful efforts to maintain government ownership, leadership, and accountability for safe abortion care and service delivery by Pakistani health authorities early and throughout, with technical support from civil society as requested. This commentary suggests that careful collaboration and mutual support by NGOs working on expanding access to abortion can have a lasting and efficient impact on improving political norms and government ownership over abortion care. In most restrictive settings, political norms may be extremely challenging to address due to the institutionalised nature of abortion stigma and resistance, and NGOs can spend many years of resources trying unsuccessfully to challenge and eliminate these barriers. The experience in Pakistan has been a nontraditional approach to political norm change, as it starts by centring the issue of unsafe abortion squarely within the authority and responsibility of the Pakistani government to avert maternal deaths, within the current legal parameters. Emphasis on the public health needs for safe abortion care and current government obligations in Pakistan, as we describe, has led to increased dialogue and discussion about the need for further reforms by government stakeholders who were previously less willing to meaningfully address this health topic. We believe this approach demonstrates significant promise for future progressive change, and we hope this information will be a valuable resource for others working in the field.

Encephalitis and myelitis associated with dengue viral infection clinical and neuroimaging features.

OBJECTIVES: The objective of this study was to identify clinical and neuroimaging features and outcome of patients with encephalitis and myelitis associated with dengue viral infection. PATIENTS AND METHODS: We retrospectively reviewed 225 cases of dengue viral infection. The diagnosis of dengue was confirmed by serology (presence of IgM antibodies). RESULTS: Six patients (3%) had evidence of neurological infection (encephalitis: 5 patients; encephalomyelitis: 1 patient). Age range was 18-35 years (Mean 27 years). Five patients (83%) were women. All patients (100%) had drowsiness, five patients (83%) had fever, four patients (67%) presented with seizures and one patient presented with paraparesis (16%). All patients had elevated CSF cell count (range 25-102; mean 61) with predominant lymphocytes. Five patients (83%) had abnormal CT or MRI scan. Cerebral edema was present in three patients. Other findings included low density signals in right temporal and occipital lobe (1 patient), bi temporal hyperintensities and meningeal enhancement (1 patient), Frontal and subcortical hyperintense lesion (1 patient) and hyperintense lesion on T2 in Pons and cervical and thoracic spinal cord (1 patient). EEG was done in four patients and showed generalized slowing (2 patients), bi temporal spikes (1 patient) and burst suppression pattern (1 patient). Two patients (32%) died and one patient was discharged in bedridden state. CONCLUSION: The involvement of brain and spinal cord is uncommon in dengue viral infection. Most patient present with seizures. Neuroimaging features are diverse. Prognosis is poor in patients presenting with encephalitis or myelitis.

Expression of PTEN and its correlation with proliferation marker Ki-67 in head and neck cancer.

INTRODUCTION: PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of human cancers. AIMS: In the present study we have tried to determine the association of the expression patterns of this gene with carcinogenesis. METHODS: First, a systematic review was carried out to ascertain the importance of the PTEN gene and its role in carcinogenesis. In the second phase, a case-control study was designed using different expression analysis techniques. Expression of PTEN mRNA was analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Significantly downregulated expression of PTEN was observed in patients with head and neck cancer (HNC) compared to adjacent normal-tissue controls. These results were confirmed with quantitative polymerase chain reaction (qPCR). Significant downregulation of the gene was observed in HNC patients compared to adjacent normal-tissue controls. PTEN expression was correlated with different histopathological parameters of the study cohort by Spearman's correlation coefficient and a significant negative correlation was observed with pT stage (r = -0.271*; p<0.02) and grade (r = -0.228*; p<0.02) of HNC tissues. Furthermore, the expression variations of PTEN were correlated with the expression pattern of the proliferation marker Ki-67. Significantly (p<0.008) upregulated expression of Ki-67 was observed in HNC patients compared with adjacent normal-tissue controls This upregulation of Ki-67 was confirmed at the protein level by immunohistochemistry in HNC patients. When Spearman's correlation was carried out a significant negative correlation was observed between PTEN and Ki-67 (r = -0.230*; p<0.03). CONCLUSIONS: Our data suggest that downregulation of PTEN and overexpression of Ki-67 may contribute to the initiation and progression of HNC.

Treat-to-target approach in daily clinical practice in Pakistani patients with early Rheumatoid Arthritis.

OBJECTIVE: To determine the frequency of patients with early Rheumatoid Arthritis (RA) achieving disease remission and/or low disease activity after 6 months of treatment with conventional Disease Modifying Anti-Rheumatic Drugs (DMARDs) by using treat-to-target approach in routine clinical practice. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Division of Rheumatology, Fatima Memorial Hospital (FMH), College of Medicine and Dentistry, Lahore, from March 2011 to February 2012. METHODOLOGY: Patients with early RA defined as disease duration ² 1 year were enrolled by purposive sampling, diagnosed as per American College of Rheumatology (ACR) 1987 criteria. Treat-to-target approach was defined as per European League Against Rheumatism (EULAR) 2010 guidelines for treatment of RA with conventional DMARDs. Outcome measures of remission and low disease activity were defined as per DAS 28 score criteria. Patient response to treatment was also determined by EULAR response criteria. RESULTS: Out of 67 patients, 50 patients completed the 6 months study period, rest were lost to follow-up. All patients were started on Methotrexate and mean weekly dose at 6 months was 18.9 ± 3.8 mg. Remission was achieved in 17 (34%) and target of low disease activity was achieved in 29 (58%) of patients. EULAR good response was seen in 28 (56%), moderate response in 21 (42%) and no response to treatment in 1 (2%). CONCLUSION: By applying treat-to-target approach in early RA, achievement of clinical remission or low disease activity with conventional DMARDs is a realistic goal in routine practice.

Major artery occlusion: a rare complication of sickle cell disease.

Sickle cell disease is hereditary hemoglobinopathy which causes haemolytic anemia, vaso-occlusive crisis, ischemic injuries and many other morbidities like cerebral infarction. In this report, we describe a case of a young patient with sickle cell disease presenting with right-sided weakness and slurring of speech with examination confirming right-sided hemiparesis with motor aphasia. On further investigation, she was found to have frontotemporal infarction. On magnetic resonance imaging with angiography, she was found to have absent circulation in left internal carotid artery probably secondary to sickle cell disease. Major vessel occlusion is rare complication of sickle cell disease that one must bear in mind.

The control of gene conversion properties and corresponding-site interference: the effects of conversion control factor 5 on conversion at locus w9 in Ascobolus immersus.

The controls of various aspects and parameters of gene conversion at locus w-9 in the fungus Ascobolus immersus were investigated, along with positive and negative corresponding-site interference in meiotic chromatid pairing. When conversion control factor 5 alleles A and B were heterozygous, conversion frequencies at the closely linked target locus w9 were reduced to 3%, compared with 10.7% when A or B was homozygous, through effects on hybrid-DNA (h-DNA) formation parameters gamma1 and gamma2. In different ways, not related to whether ccf-5 alleles were homozygous or heterozygous, ccf-5 also affected parameters relating to the relative frequencies of asymmetric and symmetric h-DNA, the frequency with which the chromatid bearing the wild-type allele was the invading chromatid in asymmetric h-DNA, and h-DNA correction parameters for the frequency and direction of correction of mispairs. Corresponding-site interference is interference between the two pairs of non-sister chromatids of a bivalent in h-DNA formation at exactly corresponding sites. This interference was positive in the high conversion frequency crosses homozygous for ccf-5 alleles but was strongly negative in the low conversion frequency crosses heterozygous for ccf-5 alleles, through differential effects on parameters gamma1 and gamma2. Models of chromatid pairing are discussed.