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Abstract Background To determine the etiology, management, bacteriological spectrum and outcome of neonatal patients admitted in Civil Hospital Karachi (CHK) and to examine the factors associated with it. Methods This hospital based descriptive study of 1463 patients from both sexes who were admitted to Paediatric department, CHK from 1st January 2008 till 31st December 2010 with an established cause according to modified Wigglesworth classification and fulfilling other inclusion criteria were included in the study. Data regarding their demographic profile and potential risk factors was collected on a well structured proforma. Cases were followed until discharge or expiry. Data was analyzed using descriptive statistics. Results The male to female ratio in our study was 1.12:1. Seven hundred and thirty-four patients were delivered at home (50.2%) and 1010 were less than 7 days old (69%). Out of the total cohort of expired subjects, 89 participants (74.8%) were Conclusions These results suggest that neonates with illiterate mothers with high parity and below average socioeconomic level were more susceptible to mortality in the early neonatal period. Most of the cases of mortality were due to specific infections.

Abstract Background An ongoing evaluation system is essential to determine if the academic system in place has worked to produce a better product, hence the objective of our study was to evaluate the satisfaction level among medical students regarding their academic teaching and assessment method and what measures will they suggest for the future to rectify the current situation. This questionnaire based cross sectional study was conducted in a public sector medical university from February to July 2010. A well structured questionnaire was administered to a random sample of 375 final year medical students. However 292 of the students provided informed consent and filled in the questionnaire which included their demographic profile as well as questions in line with the study objective. Data was entered in a Statistical Package for Social Sciences (SPSS version.16) and analyzed using descriptive statistics. Findings The male to female ratio in our study was 1:2. Most of the students (57.2%) were dissatisfied with the quality of teaching in the university. Fifty-seven percent of the participants believed that the current standard of their institute were not at par with those of international medical universities. BCQ's were the mode of examination questions preferred by the majority of the students. Most of the students (66.1%) wanted the university to conduct career planning seminars to help them plan their career. Conclusions These results suggest that the students of public sector medical universities are unsatisfied from current academic facilities and teaching activities. Students recommend increased emphasis on better lectures and practical training as well as a need to incorporate career planning sessions for the students to help plan them their future career paths.

Abstract Background To determine the agents of poisoning and demographic distribution of children brought to Civil Hospital Karachi (CHK) with a history of accidental poison intake and to examine the factors associated with it. Methods This hospital based descriptive study of first 100 patients from both sexes who presented to Pediatric department, CHK from 1st January 2006 till 31st December 2008 with exposure to a known poisonous agent and fulfilling other inclusion criteria were included in the study. Data regarding their demographic profile and potential risk factors was collected on a well structured proforma, cases were followed until discharge or expiry. Data was analyzed using frequencies, proportions, group means, median and standard deviations. Results The male to female ratio in our study was 1.2:1, with kerosene (50%) being the most common household agent followed by medicines (38%), insecticides (7%) and bathroom cleaners (5%). Factors such as mother's education level, number of siblings and storage place of poison correlated significantly with the cases of accidental poisoning. Most of the children (70%) presented within 3 hours of ingestion. Dyspnea was the most common symptom observed. The mortality rate in our study was 3%. Conclusions Children belonging to age group 2-3 years are the most susceptible both in terms of morbidity and mortality. Preventive strategies need to be adopted at a national level to spread awareness among parents.

This study evaluates the biocontrol efficacy of three bacterial strains (Pseudomonas fluorescens DTPF-3, Bacillus amyloliquefaciens DTBA-11, and Bacillus subtilis DTBS-5) and two fungal strains ( Trichoderma harzianum Pusa-5SD and Aspergillus niger An-27) antagonists, along with their combinations at varying doses (5.0, 7.5, and 10.0 g/kg of seeds), against wheat powdery mildew. The most effective dose (10 g/kg seeds) was further analyzed for its impact on induced resistance and plant growth promotion under greenhouse conditions. The study measured defense enzyme activities, biochemical changes, and post-infection plant growth metrics. All tested microbial antagonists at 10 g/kg significantly reduced PM severity, with B. subtilis strain DTBS-5 outperforming others in reducing PM severity and achieving the highest biocontrol efficacy. It was followed by B. amyloliquefaciens strain DTBA-11 and P. fluorescens strain DTPF-3, with the fungal antagonists showing no significant effect. Wheat crops treated with B. subtilis strain DTBS-5 exhibited substantial increases in defense-related enzyme activities and biochemicals, suggesting an induced resistance mechanism. The study found a 45% increase in peroxidase (POD) activity, a 50% increase in catalase (CAT) activity, a 30% increase in phenolic content, and a 25% increase in soluble protein content in the wheat plants treated with microbial antagonists. The study highlights the effectiveness of microbial antagonists, particularly B. subtilis strain DTBS-5, in managing wheat PM through biocontrol, induced resistance, and enhanced plant growth, offering a sustainable alternative to chemical treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Choudaker, Singh, Kashyap, Patel, Sameriya, Yadav, Manzar, Kamil, Prasad and Saharan.)

Modern agriculture has encountered several challenges in achieving constant yield stability especially due to disease outbreaks and lack of long-term disease-resistant crop cultivars. In the past, disease outbreaks in economically important crops had a major impact on food security and the economy. On the other hand climate-driven emergence of new pathovars or changes in their host specificity further poses a serious threat to sustainable agriculture. At present, chemical-based control strategies are frequently used to control microbial pathogens and pests, but they have detrimental impact on the environment and also resulted in the development of resistant phyto-pathogens. As a replacement, cultivating engineered disease-resistant crops can help to minimize the negative impact of regular pesticides on agriculture and the environment. Although traditional breeding and genetic engineering have been instrumental in crop disease improvement but they have certain limitations such as labour intensity, time consumption, and low efficiency. In this regard, genome editing has emerged as one of the potential tools for improving disease resistance in crops by targeting multiple traits with more accuracy and efficiency. For instance, genome editing techniques, such as CRISPR/Cas9, CRISPR/Cas13, base editing, TALENs, ZFNs, and meganucleases, have proved successful in improving disease resistance in crops through targeted mutagenesis, gene knockouts, knockdowns, modifications, and activation of target genes. CRISPR/Cas9 is unique among these techniques because of its remarkable efficacy, low risk of off-target repercussions, and ease of use. Some primary targets for developing CRISPR-mediated disease-resistant crops are host-susceptibility genes (the S gene method), resistance genes (R genes) and pathogen genetic material that prevents their development, broad-spectrum disease resistance. The use of genome editing methods has the potential to notably ameliorate crop disease resistance and transform agricultural practices in the future. This review highlights the impact of phyto-pathogens on agricultural productivity. Next, we discussed the tools for improving disease resistance while focusing on genome editing. We provided an update on the accomplishments of genome editing, and its potential to improve crop disease resistance against bacterial, fungal and viral pathogens in different crop systems. Finally, we highlighted the future challenges of genome editing in different crop systems for enhancing disease resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Manzoor, Nabi, Rather, Gani, Mir, Wani, Ali, Tyagi and Manzar.)

Metal nanoparticles (MNPs) have gained significant attention in recent years for their potential use as effective antimicrobial agents for controlling plant pathogens. This review article summarizes the recent advances in the role of MNPs in the control of plant pathogens, focusing on their mechanisms of action, applications, and limitations. MNPs can act as a broad-spectrum antimicrobial agent against various plant pathogens, including bacteria, fungi, and viruses. Different types of MNPs, such as silver, copper, zinc, iron, and gold, have been studied for their antimicrobial properties. The unique physicochemical properties of MNPs, such as their small size, large surface area, and high reactivity, allow them to interact with plant pathogens at the molecular level, leading to disruption of the cell membrane, inhibition of cellular respiration, and generation of reactive oxygen species. The use of MNPs in plant pathogen control has several advantages, including their low toxicity, selectivity, and biodegradability. However, their effectiveness can be influenced by several factors, including the type of MNP, concentration, and mode of application. This review highlights the current state of knowledge on the use of MNPs in plant pathogen control and discusses the future prospects and challenges in the field. Overall, the review provides insight into the potential of MNPs as a promising alternative to conventional chemical agents for controlling plant pathogens., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Curvularia leaf spot affects maize plants worldwide and is commonly caused by Curvularia lunata, C. geniculata, and C. pallescens (Manzar et al. 2022; Manzar et al. 2021; Choudhary et al. 2011). In February 2017, leaf spot symptoms were observed in a Deogaon, (25.74 N, 82.99 E) in Uttar Pradesh, India, with disease incidence of less than 10% of the plants in maize fields. On the leaves and sheaths, variously shaped yellow spots were developed. The spots were 2.5 mm in diameter and frequently grew larger, reaching a diameter of 1 cm. They were encircled by a chlorotic halo with dark borders. The symptomatic tissue showing leaf spots of 10 plants was taken and cut into pieces (4 mm2) then surface sterilized with 1% sodium hypochlorite for 1 min, and rinsed three times with distilled water. The cut leaf tissue was placed on the Petri plate containing potato dextrose agar medium amended with streptomycin sulfate (125 ppm). Then incubated at 25±2°C with a 12-h light and dark period, after 5 days of incubation, five pure cultures were obtained using the hyphal tip technique. The pure culture was incubated at 26±2°C for 10 days. The upper surface of the colony was dark grayish black with fluffy mycelia, and the reverse colony was dark brown. The conidia have three septa, are light brown to dark brown in color, straight to curved, ellipsoidal to fusiform, and have two bigger, darker central cells than terminal cells. On average, conidia are between 27.22 to 31.21 mm long and 10.61 to 12.62 mm wide (n=30). The morphological description is similar to the Curvularia verruculosa morphological traits described by Tandon & Bilgrami (Ellis 1966). Molecular identification was done in addition to supporting morphological identification. The nucleopore GDNA Fungus Kit (Genetix Brand, India) was used to extract the genomic DNA of the E40 isolate. The ITS rDNA region (White et al. 1990) and the glyceraldehyde-3-phosphate dehydrogenase (gpd) gene (Berbee et al. 1999) were amplified through PCR(Manzar et al., 2022).The amplicons were bidirectional sequenced through the Sanger sequencing method. The similarity percentage of E40 isolate matched 100% with MH859788 (CBS444.70 ) of Curvularia verruculosa strain for ITS, and 100% with LT715824 (CBS150.63) of Curvularia verruculosa strain for gpd after Blastn analysis. The gene sequences were deposited to GenBank and accession no. OR262893 for ITS, and LC773704 for gpd were assigned. As a result, C. verruculosa was determined to be the presumed pathogen by both morphology and molecular characteristics. The pathogenicity of E40 isolate was performed twice by spraying (106 conidia/ml in sterile water) onto the leaves of 25 days old maize plant cv. Kanchan (n = 10). Uninoculated healthy maize plants (n=5) were sprayed only with autoclaved water. All pots are kept in a glass house at 25°C±2°C with 90% relative humidity. After 15 days of pathogen inoculation the foliar spots with chlorotic halo, enlarger upto 1cm, and from these spots the identical fungus was reisolated. The reisolated fungus showed similar morphological characteristics to C. verruculosa. Control plants showed no symptoms. C. verruculosa has been previously reported as a causative agent of leaf spot disease in Common beans (Wei et al., 2022), Cotton (Shirsath et al., 2018). To our knowledge, this is the first report of leaf blight caused by C. verruculosa on maize in India.

Elevated serine peptidase inhibitor, Kazal type 1 (SPINK1) levels in ∼10%-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis and identified tyrosine kinase KIT as highly enriched. Furthermore, high to moderate levels of KIT expression were detected in ∼85% of SPINK1-positive PCa specimens. We show KIT signaling orchestrates SPINK1-mediated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/β-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling led to restoration of AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide distinct treatment modalities for advanced-stage SPINK1-positive patients., Competing Interests: N.P. is a consultant to Astrazeneca., (© 2024 The Authors.)

Soil salinization is a global issue that negatively impacts crop yield and has become a prime concern for researchers worldwide. Many important crop plants are susceptible to salinity-induced stresses, including ionic and osmotic stress. Approximately, 20% of the world's cultivated and 33% of irrigated land is affected by salt. While various agricultural practices have been successful in alleviating salinity stress, they can be costly and not environment-friendly. Therefore, there is a need for cost-effective and eco-friendly practices to improve soil health. One promising approach involves utilizing microbes found in the vicinity of plant roots to mitigate the effects of salinity stress and enhance plant growth as well as crop yield. By exploiting the salinity tolerance of plants and their associated rhizospheric microorganisms, which have plant growth-promoting properties, it is possible to reduce the adverse effects of salt stress on crop plants. The soil salinization is a common problem in the world, due to which we are unable to use the saline land. To make proper use of this land for different crops, microorganisms can play an important role. Looking at the increasing population of the world, this will be an appreciated effort to make the best use of the wasted land for food security. The updated information on this issue is needed. In this context, this article provides a concise review of the latest research on the use of salt-tolerant rhizospheric microorganisms to mitigate salinity stress in crop plants., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Increasing soil salinity depreciates the quantity of the crop produce. Looking at the tremendous potential of plant-associated microorganisms in salinity stress mitigation, it would be very useful in exploring and deciphering salt-tolerant microorganisms from halophytic plants and their utilization in cultivated plants. With this aim, in the present study, four halophytic plants were taken from Rann of Kutch, and bacterial endophytes were isolated from different plant organs. These endophytes were characterized by plant growth and health promotion features. The molecular identification was done based on 16 s rRNA sequence similarity. It was found that the endophytic bacteria isolated from 4 different halophytes found sharing phylogenetic relatedness. Four potential endophytes Alkalihalobacillus gibsonii 2H2, Achromobacter insuavis 2H18, Terribacillus halophilus 2H20, and Bacillus siamensis 4H1 were tested in tomato for salinity stress alleviation. Changes in the levels of antioxidants were analyzed. Total chlorophyll, total phenolics, malondialdehyde, and proline content indicated reduced damage in the plant system due to salinity by the application of endophytes. All the treatments exhibited low levels of electrolyte leakage. The accumulation of enzymatic reactive oxygen species scavengers was assessed from the levels of peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, ascorbate peroxidase, and guiacol peroxidase. The NBT and DAB staining confirmed the findings. The reduction in the accumulation of Na + ions in tomato leaves was visualized using Sodium Green probes under CSLM and found to be lowest in Terribacillus halophilus 2H20 and Bacillus siamensis 4H1 inoculated plants. The endophyte Terribacillus halophilus 2H20 was the most promising isolate. The colonization in tomato roots was confirmed using a cell tracker system. Results showed that the endophytes were found to have salinity stress mitigation traits. The efficiency could be further improved with the combination of other endophytes tested earlier., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sahu, Shafi, Singh, Ojha, Jayalakshmi, Tilgam, Manzar, Sharma and Srivastava.)

Microbial inoculants may be called magical bullets because they are small in size but have a huge impact on plant life and humans. The screening of these beneficial microbes will give us an evergreen technology to manage harmful diseases of cross-kingdom crops. The production of these crops is reducing as a result of multiple biotic factors and among them the bacterial wilt disease triggered by Ralstonia solanacearum is the most important in solanaceous crops. The examination of the diversity of bioinoculants has shown that more microbial species have biocontrol activity against soil-borne pathogens. Reduced crop output, lower yields, and greater cost of cultivation are among the major issues caused by diseases in agriculture around the world. It is universally true that soil-borne disease epidemics pose a greater threat to crops. These necessitate the use of eco-friendly microbial bioinoculants. This review article provides an overview of plant growth-promoting microorganisms bioinoculants, their various characteristics, biochemical and molecular screening insights, and modes of action and interaction. The discussion is concluded with a brief overview of potential future possibilities for the sustainable development of agriculture. This review will be useful for students and researchers to obtain existing knowledge of microbial inoculants, their activities, and their mechanisms, which will facilitate the development of environmentally friendly management strategies for cross-kingdom plant diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kashyap, Manzar, Meshram and Sharma.)

In the present study, Trichoderma harzianum culture filtrate (CF) was used as a reducing and capping agent to synthesize silver nanoparticles (Ag NPs) in a quick, simple, cost-effective, and eco-friendly manner. The effects of different ratios (silver nitrate (AgNO 3 ): CF), pH, and incubation time on the synthesis of Ag NPs were also examined. Ultraviolet-visible (UV-Vis) spectra of the synthesized Ag NPs showed a distinct surface plasmon resonance (SPR) peak at 420 nm. Spherical and monodisperse NPs were observed using scanning electron microscopy (SEM). Elemental silver (Ag) was identified in the Ag area peak indicated by energy dispersive x-ray (EDX) spectroscopy. The crystallinity of Ag NPs was confirmed by x-ray diffraction (XRD), and Fourier transform infrared (FTIR) was used to examine the functional groups present in the CF. Dynamic light scattering (DLS) revealed an average size (43.68 nm), which was reported to be stable for 4 months. Atomic force microscopy (AFM) was used to confirm surface morphology. We also investigated the in vitro antifungal efficacy of biosynthesized Ag NPs against Alternaria solani , which demonstrated a significant inhibitory effect on mycelial growth and spore germination. Additionally, microscopic investigation revealed that Ag NP-treated mycelia exhibited defects and collapsed. Apart from this investigation, Ag NPs were also tested in an epiphytic environment against A. solani . Ag NPs were found to be capable of managing early blight disease based on field trial findings. The maximum percentage of early blight disease inhibition by NPs was observed at 40 parts per million (ppm) (60.27%), followed by 20 ppm (58.68%), whereas in the case of the fungicide mancozeb (1,000 ppm), the inhibition was recorded at 61.54%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Narware, Singh, Manzar and Kashyap.)

Plants are very often confronted by different heavy metal (HM) stressors that adversely impair their growth and productivity. Among HMs, chromium (Cr) is one of the most prevalent toxic trace metals found in agricultural soils because of anthropogenic activities, lack of efficient treatment, and unregulated disposal. It has a huge detrimental impact on the physiological, biochemical, and molecular traits of crops, in addition to being carcinogenic to humans. In soil, Cr exists in different forms, including Cr (III) "trivalent" and Cr (VI) "hexavalent", but the most pervasive and severely hazardous form to the biota is Cr (VI). Despite extensive research on the effects of Cr stress, the exact molecular mechanisms of Cr sensing, uptake, translocation, phytotoxicity, transcript processing, translation, post-translational protein modifications, as well as plant defensive responses are still largely unknown. Even though plants lack a Cr transporter system, it is efficiently accumulated and transported by other essential ion transporters, hence posing a serious challenge to the development of Cr-tolerant cultivars. In this review, we discuss Cr toxicity in plants, signaling perception, and transduction. Further, we highlight various mitigation processes for Cr toxicity in plants, such as microbial, chemical, and nano-based priming. We also discuss the biotechnological advancements in mitigating Cr toxicity in plants using plant and microbiome engineering approaches. Additionally, we also highlight the role of molecular breeding in mitigating Cr toxicity in sustainable agriculture. Finally, some conclusions are drawn along with potential directions for future research in order to better comprehend Cr signaling pathways and its mitigation in sustainable agriculture.

Salinity is one of the major challenges for cultivation of crops in a sustainable way because it severely affects plant growth and yield. Keeping this challenge in view, in the current study, a salt-tolerant Halomonas MV-19 was isolated from an extreme niche of mud volcano of Andaman Nicobar Island, India and identified on the basis of standard morphological, biochemical, and physiological tests and identified as Halomonas sulfidaeris strain MV-19 by 16S rRNA gene sequencing. The bacterium can grow on nutrient agar and nutrient broth supplemented with 3.5 M (≥ 20%) sodium chloride (NaCl). Sugar utilization assay revealed that H. sulfidaeris MV-19 utilizes only three sugars (dextrose, fructose, and mannose) from among twenty four tested sugars. The best growth of H. sulfidaeris MV-19 was observed in nutrient broth supplemented with 8% NaCl. When the broth was supplemented with dextrose, fructose, and mannose, the H. sulfidaeris MV-19 grew maximally in nutrient broth supplemented with 8% NaCl and 5% fructose. This strain produced exopolysaccharides (EPS) in nutrient broth supplemented with 8% NaCl and sugars (dextrose, fructose, and mannose). The EPS production was increased by 350% (three and half time) after addition of 5% fructose in nutrient broth compare with the EPS production in nutrient broth without supplemented with sugars. H. sulfidaeris MV-19 strain can produce EPS, which can help aggregate soil particle and reduced osmotic potential in soil, thus, be useful in alleviation of salinity stress in different crops cultivated in saline soils. The findings of the current investigation are expected to contribute towards effective abiotic stress management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Transcription factors (TFs) represent the most commonly deregulated DNA-binding class of proteins associated with multiple human cancers. They can act as transcriptional activators or repressors that rewire the cistrome, resulting in cellular reprogramming during cancer progression. Deregulation of TFs is associated with the onset and maintenance of various cancer types including prostate cancer. An emerging subset of TFs has been implicated in the regulation of multiple cancer hallmarks during tumorigenesis. Here, we discuss the role of key TFs which modulate transcriptional cicuitries involved in the development and progression of prostate cancer. We further highlight the role of TFs associated with key cancer hallmarks, including, chromatin remodeling, genome instability, DNA repair, invasion, and metastasis. We also discuss the pluripotent function of TFs in conferring lineage plasticity, that aids in disease progression to neuroendocrine prostate cancer. At the end, we summarize the current understanding and approaches employed for the therapeutic targeting of TFs and their cofactors in the clinical setups to prevent disease progression., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Bipolaris sorokiniana , a key pathogenic fungus in the wheat leaf blight complex, was the subject of research that resulted in the development of fifty-five polymorphic microsatellite markers. These markers were then used to examine genetic diversity and population structure in Indian geographical regions. The simple sequence repeat (SSR) like trinucleotides, dinucleotides, and tetranucleotides accounted for 43.37% (1256), 23.86% (691), and 16.54% (479) of the 2896 microsatellite repeats, respectively. There were 109 alleles produced by these loci overall, averaging 2.36 alleles per microsatellite marker. The average polymorphism information content value was 0.3451, with values ranging from 0.1319 to 0.5932. The loci's Shannon diversity varied from 0.2712 to 1.2415. These 36 isolates were divided into two main groups using population structure analysis and unweighted neighbour joining. The groupings were not based on where the isolates came from geographically. Only 7% of the overall variation was found to be between populations, according to an analysis of molecular variance. The high amount of gene flow estimate (N M = 3.261 per generation) among populations demonstrated low genetic differentiation in the entire populations (F ST = 0.071). The findings indicate that genetic diversity is often minimal. In order to examine the genetic diversity and population structure of the B. sorokiniana populations, the recently produced microsatellite markers will be helpful. This study's findings may serve as a foundation for developing improved management plans for the leaf blight complex and spot blotch of wheat diseases in India., Competing Interests: The authors declare no conflicts of interest.

Human E TS R elated G ene, ERG, a master transcription factor, turns oncogenic upon its out-of-context activation in diverse developmental lineages. However, the mechanism underlying its lineage-specific activation of Notch (N), Wnt, or EZH2-three well-characterized oncogenic targets of ERG-remains elusive. We reasoned that deep homology in genetic tool kits might help uncover such elusive cancer mechanisms in Drosophila . By heterologous gain of human ERG in Drosophila , here we reveal Chip, which codes for a transcriptional coactivator, LIM-domain-binding (LDB) protein, as its novel target. ERG represses Drosophila Chip via its direct binding and, indirectly, via E(z)-mediated silencing of its promoter. Downregulation of Chip disrupts LIM-HD complex formed between Chip and Tailup (Tup)-a LIM-HD transcription factor-in the developing notum. A consequent activation of N-driven Wg signaling leads to notum-to-wing transdetermination. These fallouts of ERG gain are arrested upon a simultaneous gain of Chip, sequestration of Wg ligand, and, alternatively, loss of N signaling or E(z) activity. Finally, we show that the human LDB1 , a homolog of Drosophila Chip , is repressed in ERG-positive prostate cancer cells. Besides identifying an elusive target of human ERG, our study unravels an underpinning of its lineage-specific carcinogenesis.

Bipolaris species are known to be important plant pathogens that commonly cause leaf spot, root rot, and seedling blight in a wide range of hosts worldwide. In 2017, complex symptomatic cases of maydis leaf blight (caused by Bipolaris maydis ) and maize leaf spot (caused by Curvularia lunata ) have become increasingly significant in the main maize-growing regions of India. A total of 186 samples of maydis leaf blight and 129 maize leaf spot samples were collected, in 2017, from 20 sampling sites in the main maize-growing regions of India to explore the diversity and identity of this pathogenic causal agent. A total of 77 Bipolaris maydis isolates and 74 Curvularia lunata isolates were screened based on morphological and molecular characterization and phylogenetic analysis based on ribosomal markers-nuclear ribosomal DNA (rDNA) internal transcribed spacer (ITS) region, 28S nuclear ribosomal large subunit rRNA gene (LSU), D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA), and protein-coding gene-glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Due to a dearth of molecular data from ex-type cultures, the use of few gene regions for species resolution, and overlapping morphological features, species recognition in Bipolaris has proven difficult. The present study used the multi-gene phylogenetic approach for proper identification and diversity of geographically distributed B . maydis and C . lunata isolates in Indian settings and provides useful insight into and explanation of its quantitative findings.

Microbial volatiles benefit the agricultural ecological system by promoting plant growth and systemic resistance against diseases without harming the environment. To explore the plant growth-promoting efficiency of VOCs produced by Pseudomonas fluorescens PDS1 and Bacillus subtilis KA9 in terms of chili plant growth and its biocontrol efficiency against Ralstonia solanacearum , experiments were conducted both in vitro and in vivo. A closure assembly was designed using a half-inverted plastic bottle to demonstrate plant-microbial interactions via volatile compounds. The most common volatile organic compounds were identified and reported; they promoted plant development and induced systemic resistance (ISR) against wilt pathogen R. solanacearum . The PDS1 and KA9 VOCs significantly increased defensive enzyme activity and overexpressed the antioxidant genes PAL, POD, SOD, WRKYa, PAL1, DEF-1, CAT-2, WRKY40, HSFC1, LOX2, and NPR1 related to plant defense. The overall gene expression was greater in root tissue as compared to leaf tissue in chili plant. Our findings shed light on the relationship among rhizobacteria, pathogen, and host plants, resulting in plant growth promotion, disease suppression, systemic resistance-inducing potential, and antioxidant response with related gene expression in the leaf and root tissue of chili.

Plant growth-promoting rhizobacteria (PGPR) is a microbial population found in the rhizosphere of plants that can stimulate plant development and restrict the growth of plant diseases directly or indirectly. In this study, 90 rhizospheric soil samples from five agro climatic zones of chilli ( Capsicum annuum L.) were collected and rhizobacteria were isolated, screened and characterized at morphological, biochemical and molecular levels. In total, 38% of rhizobacteria exhibited the antagonistic capacity to suppress Ralstonia solanacearum growth and showed PGPR activities such as indole acetic acid production by 67.64% from total screened rhizobacteria isolates, phosphorus solubilization by 79.41%, ammonia by 67.75%, HCN by 58.82% and siderophore by 55.88%. We performed a principal component analysis depicting correlation and significance among plant growth-promoting activities, growth parameters of chilli and rhizobacterial strains. Plant inoculation studies indicated a significant increase in growth parameters and PDS1 strain showed maximum 71.11% biocontrol efficiency against wilt disease. The best five rhizobacterial isolates demonstrating both plant growth-promotion traits and biocontrol potential were characterized and identified as PDS1- Pseudomonas fluorescens (MN368159), BDS1- Bacillus subtilis (MN395039), UK4- Bacillus cereus (MT491099), UK2- Bacillus amyloliquefaciens (MT491100) and KA9- Bacillus subtilis (MT491101). These rhizobacteria have the potential natural elicitors to be used as biopesticides and biofertilizers to improve crop health while warding off soil-borne pathogens. The chilli cv. Pusa Jwala treated with Bacillus subtilis KA9 and Pseudomonas fluorescens PDS1 showed enhancement in the defensive enzymes PO, PPO, SOD and PAL activities in chilli leaf and root tissues, which collectively contributed to induced resistance in chilli plants against Ralstonia solanacearum . The induction of these defense enzymes was found higher in leave tissues (PO-4.87-fold, PP0-9.30-fold, SOD-9.49-fold and PAL-1.04-fold, respectively) in comparison to roots tissue at 48 h after pathogen inoculation. The findings support the view that plant growth-promoting rhizobacteria boost defense-related enzymes and limit pathogen growth in chilli plants, respectively, hence managing the chilli bacterial wilt.

Soy isoflavones (SI) have strong estrogenic effect in tissues by binding to estrogen receptors and might be beneficial for women with polycystic ovarian syndrome (PCOS) by reduction in testosterone, cholesterol, insulin, weight gain, inflammatory markers, and oxidative stress. The study was planned to examine the effect of various levels of SI on nutrient intake, digestibility, lipid profile, insulin, and reproductive hormones of estradiol valerate (4 mg/rat/IM) PCOS induced rat models. Thirty-six Wistar 45 days old rats weighing 95 ± 5 g were divided into 4 groups, each having 9 rats: C (control: without SF), SF10 (SF 0.10 g/kg BW), SF15 (SF 0.15 g/kg BW), and SF20 (SF 0.20 g/kg BW). SF was given through the oral gavage. Food and water were offered ad libitum, and intake was recorded daily. During last week of trial, collected feces by total collection method and blood samples were used to calculate nutrient digestibility and biochemical analysis, respectively. Estrogen, progesterone, and prolactin were ( p  < .05) high in rats fed SF diet that was 4% and 30% increase from C, respectively. Insulin, testosterone, FSH, and LH were lowest in rats fed diet SF20. Significant ( p  < .05) reduction in cholesterol was observed in rats fed SF15 and SF20 as compared to C. Serum HDL was improved ( p  < .05) in all SIF 0.10 , SIF 0.15, and SIF 0.20 in comparison with PC. Serum LDL was significantly reduced to 68.89 ± 4.36 (mg/dl) in SIF 0.20 and to 108.20 ± 4.14 (mg/dl) in SIF 0.15, whereas insignificant reduction was observed in SIF 0.10 as compared to PC. Highly significant reduction was noted in triglycerides level in SIF 0.20; however, significant reduction was observed in both SIF 0.10 and SIF 0.15 as compared to PC after 3 months of treatment with soy isoflavones., Competing Interests: The authors have no conflict of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Interactions between pro- and anti-apoptotic Bcl-2 proteins decide the fate of the cell. The BH3 domain of pro-apoptotic Bcl-2 proteins interacts with the exposed hydrophobic groove of their anti-apoptotic counterparts. Through their design and development, BH3 mimetics that target the hydrophobic groove of specific anti-apoptotic Bcl-2 proteins have the potential to become anticancer drugs. We have developed a novel computational method for designing sequences with BH3 domain features that can bind specifically to anti-apoptotic Mcl-1 or Bcl-X L . In this method, we retained the four highly conserved hydrophobic and aspartic residues of wild-type BH3 sequences and randomly substituted all other positions to generate a large number of BH3-like sequences. We modeled 20000 complex structures with Mcl-1 or Bcl-X L using the BH3-like sequences derived from five wild-type pro-apoptotic BH3 peptides. Peptide-protein interaction energies calculated from these models for each set of BH3-like sequences resulted in negatively skewed extreme value distributions. The selected BH3-like sequences from the extreme negative tail regions have highly favorable interaction energies with Mcl-1 or Bcl-X L . They are enriched in acidic and basic residues when they bind to Mcl-1 and Bcl-X L , respectively. With the charged residues often away from the binding interface, the overall electric field generated by the charged residues results in strong long-range electrostatic interaction energies between the peptide and the protein giving rise to high specificity. Cell viability studies of representative BH3-like peptides further validated the predicted specificity. This study has revealed the importance of non-hot spot residues in BH3-mimetic peptides in providing specificity to a particular anti-apoptotic protein.

Peptide therapeutics, unlike small-molecule drugs, display crucial advantages of target specificity and the ability to block large interacting interfaces, such as those of transcription factors. The transcription co-factor of the Hippo pathway, YAP/Yorkie (Yki), has been implicated in many cancers, and is dependent on its interaction with the DNA-binding TEAD/Sd proteins via a large Ω-loop. In addition, the mammalian vestigial-like (VGLL) proteins, specifically their TONDU domain, competitively inhibit YAP-TEAD interaction, resulting in arrest of tumor growth. Here, we show that overexpression of the TONDU peptide or its oral uptake leads to suppression of Yki-driven intestinal stem cell tumors in the adult Drosophila midgut. In addition, comparative proteomic analyses of peptide-treated and untreated tumors, together with chromatin immunoprecipitation analysis, reveal that integrin pathway members are part of the Yki-oncogenic network. Collectively, our findings establish Drosophila as a reliable in vivo platform to screen for cancer oral therapeutic peptides and reveal a tumor suppressive role for integrins in Yki-driven tumors.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Despite the current advances in the treatment for prostate cancer, the patients often develop resistance to the conventional therapeutic interventions. Therapy-induced drug resistance and tumor progression have been associated with cellular plasticity acquired due to reprogramming at the molecular and phenotypic levels. The plasticity of the tumor cells is mainly governed by two factors: cell-intrinsic and cell-extrinsic. The cell-intrinsic factors involve alteration in the genetic or epigenetic regulators, while cell-extrinsic factors include microenvironmental cues and drug-induced selective pressure. Epithelial-mesenchymal transition (EMT) and stemness are two important hallmarks that dictate cellular plasticity in multiple cancer types including prostate. Emerging evidence has also pinpointed the role of tumor cell plasticity in driving anti-androgen induced neuroendocrine prostate cancer (NEPC), a lethal and therapy-resistant subtype. In this review, we discuss the role of cellular plasticity manifested due to genetic, epigenetic alterations and cues from the tumor microenvironment, and their role in driving therapy resistant prostate cancer., (Copyright © 2020 Tiwari, Manzar and Ateeq.)

Emergence of an aggressive androgen receptor (AR)-independent neuroendocrine prostate cancer (NEPC) after androgen-deprivation therapy (ADT) is well-known. Nevertheless, the majority of advanced-stage prostate cancer patients, including those with SPINK1-positive subtype, are treated with AR-antagonists. Here, we show AR and its corepressor, REST, function as transcriptional-repressors of SPINK1, and AR-antagonists alleviate this repression leading to SPINK1 upregulation. Increased SOX2 expression during NE-transdifferentiation transactivates SPINK1, a critical-player for maintenance of NE-phenotype. SPINK1 elicits epithelial-mesenchymal-transition, stemness and cellular-plasticity. Conversely, pharmacological Casein Kinase-1 inhibition stabilizes REST, which in cooperation with AR causes SPINK1 transcriptional-repression and impedes SPINK1-mediated oncogenesis. Elevated levels of SPINK1 and NEPC markers are observed in the tumors of AR-antagonists treated mice, and in a subset of NEPC patients, implicating a plausible role of SPINK1 in treatment-related NEPC. Collectively, our findings provide an explanation for the paradoxical clinical-outcomes after ADT, possibly due to SPINK1 upregulation, and offers a strategy for adjuvant therapies.

Growth factor receptor-binding protein 10 (GRB10) is a well-known adaptor protein and a recently identified substrate of the mammalian target of rapamycin (mTOR). Depletion of GRB10 increases insulin sensitivity and overexpression suppresses PI3K/Akt signaling. Because the major reason for the limited efficacy of PI3K/Akt-targeted therapies in prostate cancer (PCa) is loss of mTOR-regulated feedback suppression, it is therefore important to assess the functional importance and regulation of GRB10 under these conditions. On the basis of these background observations, we explored the status and functional impact of GRB10 in PCa and found maximum expression in phosphatase and tensin homolog (PTEN)-deficient PCa. In human PCa samples, GRB10 inversely correlated with PTEN and positively correlated with pAKT levels. Knockdown of GRB10 in nontumorigenic PTEN null mouse embryonic fibroblasts and tumorigenic PCa cell lines reduced Akt phosphorylation and selectively activated a panel of receptor tyrosine kinases. Similarly, overexpression of GRB10 in PTEN wild-type PCa cell lines accelerated tumorigenesis and induced Akt phosphorylation. In PTEN wild-type PCa, GRB10 overexpression promoted mediated PTEN interaction and degradation. PI3K (but not mTOR) inhibitors reduced GRB10 expression, suggesting primarily PI3K-driven regulation of GRB10. In summary, our results suggest that GRB10 acts as a major downstream effector of PI3K and has tumor-promoting effects in prostate cancer.-Khan, M. I., Al Johani, A., Hamid, A., Ateeq, B., Manzar, N., Adhami, V. M., Lall, R. K., Rath, S., Sechi, M., Siddiqui, I. A., Choudhry, H., Zamzami, M. A., Havighurst, T. C., Huang, W., Ntambi, J. M., Mukhtar, H. Proproliferatve function of adaptor protein GRB10 in prostate carcinoma.

Isolated splenic abscess in a previously healthy patient is a rare clinical condition and remains a diagnostic dilemma. Clinical presentation is often non-specific and leads to a delay in diagnosis. Imaging studies help to elucidate the condition. Despite advances in medical diagnostics and therapeutics, splenic abscesses can cause significant morbidity and can be fatal. Although splenectomy was considered the treatment of choice in the past, recent trends have seen a shift towards more conservative management. We present the clinical case of a patient who presented to our emergency room with a chief complaint of left shoulder and left upper quadrant abdominal pain. Abdominal imaging showed an intrasplenic collection suspicious for a hemorrhage or an abscess. Percutaneous drainage was successfully performed, followed by conservative management with intravenous antibiotics. The culture of the fluid drained from the spleen was positive for Salmonella Saintpaul. The patient improved and was discharged. A high degree of clinical suspicion is necessary for early identification of a splenic abscess. Splenectomy can be avoided with the use of interventional radiological drainage.

Theranostic nanostructures serve a dual purpose of therapy and diagnosis. A major fraction of these are based on polymer coated magnetic nanostructures of iron oxides (magnetite and maghemite), owing to the efficient drug loading capacity of polymer shells and enhanced magnetic contrast effects of the iron oxide core. In the current work we are proposing poly(2-ethyl-2-oxazoline) coated linear thermoresponsive nanostructures of maghemite (γ-Fe 2 O 3 ) for potential application in targeted cancer therapy. The polymer coating was obtained via a modified sol-gel technique based on entropically driven phase separation of poly(2-ethyl-2-oxazoline) above its cloud point (CP) temperature of 63 °C in water. The developed nanostructures were further loaded with paclitaxel, a polar anticancer compound at room temperature (25 °C). The entropically driven release of paclitaxel at various concentrations and physiological temperatures was modeled and their application to the PC3 prostrate cancer cell line was investigated by treating in vitro. The steering efficiency of the magnetic nanostructures during their navigation through large blood vessels was also analyzed with the help of a synthetic model of the human axillary artery. The proposed application of these newly developed nanostructures can easily be extended towards localized delivery of additional polar anticancer drugs like cisplatin and doxorubicin.

Background: We present two patients with osteoid osteomas of the lumbar spine to highlight the delay in diagnosis and the utility of precise radiological localization enabling tumor resection without jeopardizing spinal stability., Case Description: Two young patients with refractory back pain presented after having undergone a year of conservative treatment for presumed mechanical back pain. The presence of "red-flag" symptoms (e.g. rest and night pain, and transient pain relief with aspirin) led to the performance of an isotope bone scan, and subsequent computed tomography (CT), which were both consistent with the diagnosis of an osteoid osteoma. After accurate CT-based preoperative planning for tumor excision, a customized conservative surgical technique was utilized that included marginal en-bloc surgical resection of the tumors. As the intervertebral facet joints were also carefully preserved along with stability, no accompanying instrumented fusion was warranted. Both patients returned to full function with complete resolution of their long-standing back pain of more than 2 years., Conclusions: The diagnosis of osteoid osteoma of the spine requires a high index of clinical suspicion. Diagnostic evaluations should include thin-slice CT scan to assist in planning the most restricted/conservative en-bloc surgical resection while preserving vertebral stability with facet preservation, and thus avoiding instrumented fusions. Without the availability of percutaneous radiofrequency ablation, such restricted/conservative approaches to osteoid osteomas are viable options in countries with developing economies.

To determine the agents of recurrence, the demographic features, and the management and outcomes of pterygium cases treated at Aga Khan University Hospital (AKUH), Karachi. This hospital-based descriptive study included 147 patients with pterygium (147 eyes) from both sexes, who presented at the Ophthalmology Department at AKUH between January 1, 2002 and December 31, 2010. Data regarding their demographic profile and other factors were collected in a well-structured proforma. Data were analyzed using frequencies, proportions, group means, standard deviations, and Pearson's chi squared test. The male to female ratio in our study was 2:1, with factors such as younger age (<50 years) at presentation (P = 0.04, Pearson's chi squared test) and the presence of secondary pterygium (P = 0.050) correlated significantly with the recurrence of pterygium. There was a definite trend of decreased recurrence seen with lower grade of pterygium (P = 0.06). The recurrence rate in our study was 8.8 %. These results suggest that a younger age coupled with a higher grade of pterygium as well as a history of multiple recurrences leads to increased susceptibility of recurrence after surgical excision. Early diagnosis and appropriate management will lead to a better prognosis.

To determine the knowledge, attitude, and ethical concerns of medical students and graduates with regard to Embryonic Stem Cell (ESC) research. This questionnaire based descriptive study was conducted at the Civil Hospital Karachi (CHK), Pakistan from February to July 2008. A well structured questionnaire was administered to medical students and graduate doctors, which included their demographic profile as well as questions in line with the study objective. Informed consent was taken and full confidentiality was assured to the participants. Data were entered in a Statistical Package for Social Sciences (SPSS version.12) and analyzed. A total of 204 male and 216 female medical students and doctors were administered questionnaires out of which 105 males (51.4%) and 108 females (50%) were aware of the embryonic stem cell research and its ethical implications. Forty percent males and 47% of females were of the opinion that life begins at conception. Forty-six percent males and 39% females were in favor of stem cell research while only 31% males and 28% females supported the ESC research. Less than 1/3 of students supported using frozen embryos for research purposes while more than 2/3 indicated that they were unlikely to support abortion for stem cell research purposes. The majority of the students were in favor of stem cell research with some reservations regarding ESC research. A sizeable number of students withheld their views, reflecting their poor understanding of medical ethics. The result of the study indicates a need for incorporating bioethics into the medical curriculum.

Objective: To establish the usefulness of grading system based on the size and extent of corneal involvement in predicting recurrence in patients undergoing primary pterygium excision with intraoperative use of adjunctive topical Mitomycin-C (MMC)., Study Design: A case series., Place and Duration of Study: Section of Ophthalmology, the Aga Khan University Hospital, Karachi, from 2005 till 2010., Methodology: One hundred and twenty male patients (120 eyes) underwent surgical removal of pterygium using bare sclera method with MMC in concentration of 0.2 mg/ml (0.02%) with exposure time of 3 minutes. Classification of subjects was done according to the grading of pterygium. Patients were followed at 3 months interval for a minimum period of 1 year to record any recurrence., Results: The pterygium recurrence rate was 6.7% at a follow-up of 1 year. There was no significant association of pterygium recurrence with younger age (p = 0.14). A higher level of corneal involvement by the pterygium at presentation correlated significantly with the recurrence (p = 0.01)., Conclusion: These results suggest that a higher grade of pterygium at presentation in patients leads to increased rate of recurrence after surgical excision. Hence, early excision of pterygium is recommended to decrease its recurrence rate.

Background: To determine the demographics, management, bacteriological spectrum, and outcome of brain abscesses of patients brought to Aga Khan University Hospital (AKUH), Karachi, with a history of neurologic symptoms and to examine the factors associated with it., Methods: This hospital-based descriptive study included 53 patients from both sexes who presented to the neurosurgery section at AKUH from January 1, 2000, until December 31, 2008, with neurologic symptomatology and fulfilling other inclusion criteria. Data regarding their demographic profile and other factors were collected in a well-structured proforma. Data were analyzed using frequencies, proportions, group means, and standard deviations., Results: The male-to-female ratio in our study was 3.4:1, with Staphylococcus milleri (20.7%) being the most common etiologic agent followed by anaerobic bacteria (15.1%). The triad of headache, fever, and vomiting was present in 62.7% of patients at the time of presentation. The most important factors influencing mortality was the neurologic condition of the patient at the time of admission. Chronic suppurative otitis media was the most common predisposing factor for temporal lobe infections, and the frontal lobe was the most common site of involvement in majority of the patients (67.8%). The mortality rate in our study was 11.3%., Conclusion: Findings suggest that patients in the second and fourth decades of life are the most susceptible, both in terms of morbidity and mortality. Early diagnosis and appropriate management, along with rapid access to tertiary care centers, will lead to a better prognosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to evaluate the knowledge and attitudes of ultrasound users toward safety aspects during routine obstetric examinations., Methods: A self-administered questionnaire was given to all registered participants of the 10th Annual International Radiological Conference in Karachi, Pakistan., Results: A total of 306 participants completed the questionnaire (response rate, 70%), including 170 consultant radiologists (55%), 90 radiology residents (30%), 31 sonographers (10%), and 15 others (5%). The mean sonography experience of the end users ± SD was 5.1 ± 5 years. Around half of the participants (45.5%) reported that there should be limitations on the use of ultrasound during low-risk pregnancy. Overall, safety knowledge was inadequate among the participants. However, those who were concerned about limitations on the use of ultrasound during pregnancy were 2.5 times more likely to be familiar with the mechanical index (P < .001) and 1.8 times more likely to be familiar with the thermal index (P < .001)., Conclusions: Increased training for professionals on safety issues of ultrasound procedures during pregnancy is needed. Furthermore, the concept of the absolute safety of ultrasound procedures without knowledge of safety parameters such as the mechanical and thermal indices needs to be changed, and more clarity is required when defining parameters under which the procedures can be safely performed.

Objective: To evaluate the KAP of GPs in Karachi who treat most of the cases of STDs in their private clinics., Methods: It was a cross sectional survey conducted by interviewing 103 GPs from different towns of Karachi through an interviewer administered questionnaire based on WHO protocol for control of STDs., Results: Regarding organisms transmitted through sexual intercourse, 94.2% knew about Neisseria gonorrhoeae while only 38.8% knew about T.Pallidum. Only 26.2% had heard about WHO syndromic management of STDs. Regarding treatment of a HIV positive patient 40.8% said they referred them to an AIDS control programme. Ninety four percent knew the value of sexual history but 55.3% were aware of the recommended treatment regimen., Conclusion: Knowledge and Attitudes of GPs was reasonably good but improvement is required with respect to management of STDs & HIV. Targeted continuing medical education programmes and special training sessions are recommended.

Background/objectives: In developing countries, spirometry has not been considered a part of routine medical check-up. The purpose of the study was to establish the usefulness of spirometry as a primary screening tool in detecting air flow obstruction (AFO) during routine medical check-up (RMC)., Methods: This was a hospital based, retrospective, non-randomized case series study of 3696 participants, who presented to hospital for routine medical check-up. All subjects were assisted at the Pulmonary Medicine Department, from January 2003 till December 2008 who, having met other inclusion criteria, underwent spirometry. Data were analyzed using proportion, group means, standard deviations and Pearson Chi Square test., Results: The overall yield from spirometry in detecting AFO was 211 patients (5.7%); 174 males (6.1%) and 37 females (4.4%) (P=0.158, Pearson Chi Square test). Greater age at presentation and BMI correlated significantly with AFO in the target group (P=<0.001; P=<0.005) respectively. Dyspnoea was the most frequent symptomatology observed in those diagnosed with AFO., Conclusion: These results suggest that spirometry during RMC for all persons can detect a significant number of patients with AFO particularly among the middle and older age groups with a low BMI.

Objective: To determine the frequency of type-II Diabetes mellitus (DM) in the endogenous population of Gaddap town and also to evaluate the status of Diabetic retinopathy (DR) in this group., Study Design: Descriptive study., Place and Duration of Study: Isra Postgraduate Institute of Ophthalmology, Al-Ibrahim Eye Hospital, Karachi, from January 2006 till December 2008., Methodology: This community based study of subjects of either gender was carried out in the Gaddap town. Three primary eye care centres were established in the existing primary health care (PHC) facilities, to screen the target Population aged 30 years and above, and who met other inclusion criteria for DM and DR respectively. Patients requiring intervention were managed accordingly. Data was entered and analyzed using Microsoft Visual Basic 6 and Microsoft Access., Results: Out of the cohort of 19211 subjects, 1677 patients were found Diabetic, giving the prevalence of DM in Gaddap town at 8.73%, with 1258 (6.55%) known and 419 (2.18%) newly diagnosed cases. DR was seen in 460 (27.43%) of the Diabetic cases with 126 (7.51%) patients requiring urgent intervention for vision threatening complications., Conclusion: The result validates the importance of early screening of DR in people suffering from DM for possible management and prevention of sight threatening complications in the early stage of the disease and advocates the inclusion of primary eye care as a part of PHC system.