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Rapidly advancing biotechnological research and easy access to biological information have created challenges for preventing their intentional misuse. Because of the dedicated efforts of science and policy leaders in Pakistan, the country is on the road to becoming a regional role model in ensuring biosafety and capacity for biosecurity. Although Pakistan has made remarkable efforts promoting a culture of biosafety and biosecurity, several constraints persist related to sustainable development and the expansion of the biosecurity capacity in Pakistan. Studies suggest there is little understanding of dual-use research of concern among the majority of life scientists in Pakistan. Further, Pakistan has yet to fully develop and implement approaches for risk assessment, frameworks for oversight and regulation, or tools and procedures for monitoring and reporting situations in which misuse of biological materials might occur. More data are needed to answer questions about key biosecurity hazards specific to the country or region and the procedures that may be required for periodic risk assessments. Integrating biosecurity into the existing infrastructure with limited resources is key challenge in implementation. More coordination is required among various stakeholders to develop an effective biosecurity framework. This article focuses on Pakistan's strides toward biosecurity preparedness in terms of protecting pathogens, toxins, or biological technologies with dual-use risks to prevent their malevolent use. We propose a multidimensional biosecurity management model at the national level to strengthen the biosecurity enterprise in Pakistan.

Objective: To develop a Bayesian inversion framework on longitudinal chest CT scans which can perform efficient multi-class classification of lung cancer. Methods: While the unavailability of large number of training medical images impedes the performance of lung cancer classifiers, the purpose built deep networks have not performed well in multi-class classification. The presented framework employs particle filtering approach to address the non-linear behaviour of radiomic features towards benign and cancerous (stages I, II, III, IV) nodules and performs efficient multi-class classification (benign, early stage cancer, advanced stage cancer) in terms of posterior probability function. A joint likelihood function incorporating diagnostic radiomic features is formulated which can compute likelihood of cancer and its pathological stage. The proposed research study also investigates and validates diagnostic features to discriminate accurately between early stage (I, II) and advanced stage (III, IV) cancer. Results: The proposed stochastic framework achieved 86% accuracy on the benchmark database which is better than the other prominent cancer detection methods. Conclusion: The presented classification framework can aid radiologists in accurate interpretation of lung CT images at an early stage and can lead to timely medical treatment of cancer patients.

Interindividual differences in cytochrome P450 (CYP) 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for CYP2C19*2 and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for CYP2C19*2 and 8.14% for CYP2C19*3. For CYP2C19*2, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for CYP2C19*3, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19., GRAPHICAL ABSTRACT

Radiomic features based classifiers and neural networks have shown promising results in tumor classification. The classification performance can be further improved greatly by exploring and incorporating the discriminative features towards cancer into mathematical models. In this research work, we have developed two radiomics driven likelihood models in Computed Tomography(CT) images to classify lung, colon, head and neck cancer. Initially, two diagnostic radiomic signatures were derived by extracting 105 3-D features from 200 lung nodules and by selecting the features with higher average scores from several supervised as well as unsupervised feature ranking algorithms. The signatures obtained from both the ranking approaches were integrated into two mathematical likelihood functions for tumor classification. Validation of the likelihood functions was performed on 265 public data sets of lung, colon, head and neck cancer with high classification rate. The achieved results show robustness of the models and suggest that diagnostic mathematical functions using general tumor phenotype can be successfully developed for cancer diagnosis.

A prospective survey of neurotrauma admitted to neurosurgical units in three low and middle income countries (LMIC) indicated a frequent lack of organised prehospital care. On site care was usually provided by a member of the public. The accident victim was rarely accompanied within an equipped ambulance by trained personnel. Intensive care management and intracranial pressure monitoring was rare. There appeared to be limited rehabilitation in all regions.

Background Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. Methods The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. Results The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. Conclusions This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Background Traumatic brain injury (TBI) and stroke have devastating consequences and are major global public health issues. For patients that require a cerebral decompression after suffering a TBI or stroke, a decompressive craniectomy (DC) is the most commonly performed operation. However, retrospective non-randomized studies suggest that a decompressive craniotomy (DCO; also known as hinge or floating craniotomy), where a bone flap is replaced but not rigidly fixed, has comparable outcomes to DC. The primary aim of this project was to understand the current extent of usage of DC and DCO for TBI and stroke worldwide. Method A questionnaire was designed and disseminated globally via emailing lists and social media to practicing neurosurgeons between June and November 2019. Results We received 208 responses from 60 countries [40 low- and middle-income countries (LMICs)]. DC is used more frequently than DCO, however, about one-quarter of respondents are using a DCO in more than 25% of their patients. The three top indications for a DCO were an acute subdural hematoma (ASDH) and a GCS of 9-12, ASDH with contusions and a GCS of 3-8, and ASDH with contusions and a GCS of 9-12. There were 8 DCO techniques used with the majority (60/125) loosely tying sutures to the bone flap. The majority (82%) stated that they were interested in collaborating on a randomized trial of DCO vs. DC. Conclusion Our results show that DCO is a procedure carried out for TBI and stroke, especially in LMICs, and most commonly for an ASDH. The majority of the respondents were interested in collaborating on a is a future randomized trial.

Background: Dengue fever is one of the most common human arbovirus infections worldwide. In Pakistan, dengue initially became endemic in the big cities and then expanded to remote areas of the country. The current study reports the dengue epidemics, anti-DENV antibodies prevalence during the active and post-dengue infection, risk factors, disease symptoms, and spotting dengue infection densities in district Swat of Pakistan. Methods: Clinical signs and demographic data of dengue suspected individuals were collected at the time of screening through non-structural protein-1 antigen detection test during 2013–2015. Moreover, selected dengue confirmed individuals were screened for the presence of anti-dengue immunoglobulin (Ig) M and G during the active infection period and post-dengue infection. Results: A total of 8,770 individuals were infected with dengue in 2013 with 36 (0.41%) case fatalities, 307 in 2014 with no case fatality, and 13 in 2015 with no case fatality. The number of male and female cases were 6,139 and 2,631 in 2013, 183 and 124 in 2014, and only 10 and 3 in 2015, respectively. Among all the localities, Tehsil Babozai, an urban setting, reported the highest number of dengue patients during all the study years, that is, 7,673 (87.49% of the total cases) in 2013, 294 (95.76% of the total cases) in 2014, and 13 (100% cases) in 2015. Among 6 age groups, 21–30 years was found to be highly infected in 2013 (37.13% of all cases) and 2014 (33.55%). Furthermore, 1,231 (21.94% of all cases) had IgM antibodies and 71 (1.26%) had IgG antibodies in 2013, 78 (26% of all cases) had IgM antibodies and 7 (2.33%) had IgG antibodies in 2014, and only 4 (30.76%) patients had IgM and 0 (0%) had IgG antibodies in 2015. Furthermore, urban areas had the highest infection density in district Swat. The majority of the patients in rural areas had a traveling history to the urban areas before their illness. Conclusion: To sum up, male gender, young individuals, and those living in urban areas were at the greater risk of dengue infection.

Majority of the BRCA1 and BRCA2 mutations are associated with the risk of sporadic and familial breast cancer. Since these genes are significant in DNA repair mechanisms, we focused homology-directed DNA repair (HDDR) and BRCA complex.We selected BRCA1 variant (rs80356932, 4491C/T) and BRCA2 variant (rs80359182, 319T/C) from the interaction region of BRCA complex and studied in 100 breast cancer patients and 100 controls using tetra-ARMS-PCR.Here we show that BRCA1 and BRCA2 variants are significantly associated with high breast cancer risk (BRCA1 rs80356932; Genotype T/T OR 8.66, 95% CI 3.16-23.71, p 0.0001; Allele-T, OR 2.48, 95% CI 1.62-3.81, p 0.0001 and BRCA2 rs80359182; Genotype C/C OR 4.32, 95% CI 1.95-9.53, p = 0.0001; Allele-C, OR 2.19, 95% CI 1.43-3.34, p = 0.0002). Additionally, bioinformatics analysis showed that BRCA2-tryptophan arginine substitutions result in altered interaction of BRCA1/PALB2/BRCA2/protein complex and impaired HDDR pathway. We also observed that breast cancer risk was significantly increased in over-weighted and obese women.Our results indicate that high risk of breast cancer is significantly associated with BRCA1 and BRCA2 variants, and mutations may alter the protein interactions of BRCA complex that results in tumor genesis.

Lung nodule segmentation in CT images and its subsequent volume analysis can help determine the malignancy status of a lung nodule. While several efficient segmentation schemes have been proposed, only a few studies evaluated the segmentation's performance for large nodules. In this research, we contribute a semi-automatic system which is capable of performing robust 3-D segmentations on both small and large nodules with good accuracy. The target CT volume is de-noised with an anisotropic diffusion filter and a region of interest is selected around the target nodule on a reference slice. The proposed model performs nodule segmentation by incorporating a mean intensity based threshold in Geodesic Active Contour model in level sets. We also devise an adaptive technique using image intensity histogram to estimate the desired mean intensity of the nodule. The proposed system is validated on both lung nodules and phantoms collected from publicly available diverse databases. Quantitative and visual comparative analysis of the proposed work with the Chan-Vese algorithm and statistic active contour model of 3D Slicer platform is also presented. The resulting mean spatial overlap between segmented nodules and reference nodules is 0.855, the mean volume bias is 0.10 ± 0.2 ml and the algorithm repeatability is 0.060 ml. The achieved results suggest that the proposed method can be used for volume estimations of small as well as large-sized nodules.

After Alzheimer's disease, Parkinson's disease (PD) has taken second place in becoming one of the most commonly occurring neurological diseases being responsible for a number of disabling motor symptoms ranging from bradykinesia, akinesia, tremors to rigidity, that mostly targets the elderly population and severely disrupts their quality of life. The true underlying pathology of PD yet remains a mystery, however, recent advances in the field have pointed towards the production of α-synuclein aggregates, oxidative stress, and an imbalance between levels of acetylcholine and dopamine neurotransmitters in the brain that have been shown to result in loss of coordinated movement. Current treatments of PD include the gold standard dopamine precursor L-dopa, dopamine agonists pergolide and bromocriptine, catechol-o-methyl transferases inhibitors, entacapone and tolcapone and monoamine oxidase inhibitors such as Selegine and Rasagiline amongst several other drugs. While these drugs are successful in treating motor symptoms of the disease, they do so with a plethora of side effects that are especially debilitating to the elderly. In the recent years, a considerable amount of attention has been shifted towards phytocompounds such as flavonoids and green tea catechins due to promising experimental results. In this review, we have compiled phytocompounds that have shown potent activity against some of the most important targets for antiparkinsonian therapy. These compounds have exhibited activities that transcend the limits of simply attenuating mitochondrial oxidative stress and have opened doors to the discovery of novel lead compounds for newer, efficacious antiparkinsonian therapies with wider therapeutic windows.

Alzheimer's disease (AD), is the most common type of dementia primarily affecting the later years of life. Its prevalence is likely to increase in any aging population and will be a major burden on healthcare system by the mid of the century. Despite scientific and technological breakthroughs in the last 50 years, that have expanded our understanding of the disease on a system, cellular and molecular level, therapies that could stop or slow the progression of the disease are still unavailable. The Food and Drug Administration (FDA), has approved acetylcholinesterase (AChE) inhibitors (donepezil, galantamine, tacrine and rivastigmine) and glutamate receptor antagonist (memantine) for the treatment of AD. In this review we summarize the studies reporting phytocompounds and extracts from medicinal plants that show AChE inhibitory activities and could be of potential benefit in AD. Future research directions are suggested and recommendations made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.

Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272, Funder: Great Ormond Street Hospital for Children; doi: http://dx.doi.org/10.13039/501100003784, Hinge craniotomy (HC) is a technique that allows for a degree of decompression whilst retaining the bone flap in situ, in a ‘floating’ or ‘hinged’ fashion. This provides expansion potential for ensuing cerebral oedema whilst obviating the need for cranioplasty in the future. The exact indications, technique and outcomes of this procedure have yet to be determined, but it is likely that HC provides an alternative technique to decompressive craniectomy (DC) in certain contexts. The primary objective was to collate and describe the current evidence base for HC, including perioperative parameters, functional outcomes and complications. The secondary objective was to identify current nomenclature, operative technique and operative decision-making. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Fifteen studies totalling 283 patients (mean age 45.1 and M:F 199:46) were included. There were 12 different terms for HC. The survival rate of the cohort was 74.6% (n = 211). Nine patients (3.2%) required subsequent formal DC. Six studies compared HC to DC following traumatic brain injury (TBI) and stroke, finding at least equivalent control of intracranial pressure (ICP). These studies also reported reduced rates of complications, including infection, in HC compared to DC. We have described the current evidence base of HC. There is no evidence of substantially worse outcomes compared to DC, although no randomised trials were identified. Eventually, a randomised trial will be useful to determine if HC should be offered as first-line treatment when indicated.

Background: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach. Methods: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries. Results: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval. Conclusions: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction. publishedVersion

The rising burden of cancer worldwide calls for an alternative treatment solution. Herbal medicine provides a very feasible alternative to western medicine against cancer. This article reviews the selected plant species with active phytochemicals, the animal models used for these studies, and their regulatory aspects. This study is based on a meticulous literature review conducted through the search of relevant keywords in databases, Web of Science, Scopus, PubMed, and Google Scholar. Twenty plants were selected based on defined selection criteria for their potent anticancer compounds. The detailed analysis of the research studies revealed that plants play an indispensable role in fighting different cancers such as breast, stomach, oral, colon, lung, hepatic, cervical, and blood cancer cell lines. The in vitro studies showed cancer cell inhibition through DNA damage and activation of apoptosis-inducing enzymes by the secondary metabolites in the plant extracts. Studies that reported in vivo activities of these plants showed remarkable results in the inhibition of cancer in animal models. Further studies should be performed on exploring more plants, their active compounds, and the mechanism of anticancer actions for use as standard herbal medicine.

Background Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program. Methods This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy (n = 325) or placebo as control (n = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat. Results A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna (n = 116), Stramonium (n = 33), Arsenicum album (n = 25), Sulfur (n = 18), Opium (n = 17), and Nux vomica (n = 10). Conclusion Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated.

Exposure to Pb among automobile technicians in selected towns of Khyber Pakhtunkhwa Province, Pakistan, was studied using a questionnaire, biological sampling (blood, hair, nails), and analysis of Pb biomonitoring data across various subgroups of occupation, age, and years of exposure. The study population included exposed automobile technicians (n = 50) and a control group (n = 50). The automobile technicians were further stratified into 4 groups: mechanics, auto-body technicians, electricians, and painters. Mean Pb levels in biological samples of the automobile technicians were significantly higher than in the control group (P 50 μg dL−1, but only 14% of the control group exceeded this level. Considering that Pb blood levels of 50 μg dL−1 exceed maximum concentrations recommended by leading public health organizations, appropriate measures should be taken to protect the welfare of the exposed automobile technicians and their families.

Variants of DNA repair genes are extensively reported to cause genetic instability and increase the risk of breast cancer. In combination with NBS1, MRE11 and RAD50 constitute an MRN (MRE11–RAD50–NBS1) complex that repairs DNA damage. However, certain genetic alterations in MRE11 and RAD50 produce abnormal protein that affects the repairing process and may result in malignancy. We aimed to investigate the association of MRE11 and RAD50 polymorphisms with breast risk in the female population of Punjab, Pakistan. We collected blood samples of 100 breast cancer patients and 100 tumor-free females selected as controls. Extracted DNA was genotyped by tetra ARMS-PCR followed by gel electrophoresis. Results were analyzed by SPSS and SNPstats to analyze the association of different clinical factors and SNPs (single nucleotide polymorphisms) with the risk of breast cancer. We found that the increased risk of breast cancer is associated with MRE11 variant rs684507 (odds ratio-OR 3.71, 95% confidence interval-CI 1.68–8.18, p value

In different clinical investigations of thrombocytopenia, ketoprofen was found to be the associated cause. Ketoprofen alone or in combination with other therapeutic regimens leads to a decrease in platelet count. Thrombocytopenia due to ketoprofen use can be a threatening condition to the patients who require uncompromised platelet function.In order to establish a mechanism for thrombocytopenia associated with ketoprofen use, the enzyme inhibition effects of ketoprofen on lactic dehydrogenase (LDH) were investigated in this study. LDH is essentially involved in platelet energy production.LDH isolated from human platelets was subjected to different concentrations of ketoprofen (250, 500, 750, 1000 and 1500 µg/mL) and pyruvate as a substrate (45, 60 and 90 µM/mL) to gain insight into the enzyme inhibition effects for forward reaction. Oxidation of nicotinamide adenine dinucleotide (NADH) was measured at 340 nm to evaluate enzyme activity. Enzyme inhibition kinetics were studied via Lineweaver Burk plot.Ketoprofen was found to be a competitive inhibitor of LDH in human platelets. 89% of enzyme activity was inhibited by a 1500 µg/mL concentration of the drug and the enzyme inhibition constant was 882 µg/mL.The possible main cause of thrombocytopenia due to ketoprofen use is LDH inhibition in platelets, which are essential for platelet energy metabolism. So patients who require uncompromised platelet function and are receiving ketoprofen in their prescription should be monitored for platelet count and blood clotting.

The Global Polio Eradication Initiative to eradicate polio completely by the year 2000 has been successful, except for three endemic and some non-endemic countries. Pakistan, one of the three endemic polio reservoirs, is posing a serious threat to the success of the initiative. Currently, the expanded programme on immunisation has been geared to win the race over polio virus in Pakistan. After the remarkable decrease in polio cases from 198 in 2011 to only 58 in 2012, Pakistan seemed to be at the verge of success. However, hurdles continue to retard the campaign. The war against terrorism, misconceptions about polio vaccine, religious misinterpretations, frustration among vaccinators, lack of awareness, social considerations, natural calamities, inaccessibility, and inefficient vaccines and so on are continually rupturing the foundations of the worldwide initiative in the country. Weak health management is found at the hub of majority of the challenges. Stricter policies, well managed and supervised plans and strategic actions, risk analysis and enhanced communication may help giving the final punch to polio virus in the country. Analysis suggested that there is some literature available on the challenges to polio elimination, yet there is not a single publication up to date that considers all the possible hurdles in a single manuscript. This paper sorts out the breaches that hamper the goal of eliminating polio from Pakistan. We have evaluated all the possible barriers and explained them with a perspective that will help develop area specific strategies against polio virus and thus eradicate polio virus from the world.

Viral warts or verruca pedis (plantar warts) are common skin conditions seen in both children and adults. Human papilloma virus (HPV), a DNA virus, is responsible for plantar verrucae. It needs an epidermal abrasion and a transiently impaired immune system to inoculate a keratinocyte. These entities are a therapeutic conundrum for many practitioners. This article discusses HPV infiltration and its subtypes involved in plantar warts; the evaluation of patients with plantar warts; and subsequent treatment options, such as laser, Candida albicans immunotherapy, topical therapy such as phytotherapy, and surgical excision.

Epidermolysis bullosa (EB) results from genetic defects of molecules in the skin concerned with adhesion. Some of the most common problems seen with EB sufferers are blisters, vesicles, and bullas. Maintaining foot cleanliness, exercising, and wearing shoes are all good preventative measures and important in EB foot care.

Skin and soft tissue infections account for 0.5% of outpatient visits to primary care. Skin and soft tissue infections can usually be managed in an outpatient setting. However, there are certain circumstances as discussed in this article that require more urgent care or inpatient management. Primary care providers should be able to diagnose, manage, and provide appropriate follow-up care for these frequently seen skin infections. This article provides family physicians with a comprehensive review of the assessment and management of common bacterial skin infections.

Green chemistry is the design of chemical products and processes that reduce or eliminate the generation of hazardous substances. Since the last few years, natural products especially plant secondary metabolites have been extensively explored for their potency to synthesize silver nanoparticles (AgNPs). The plant-based AgNPs are safer, energy efficient, eco-friendly, and less toxic than chemically synthesized counterparts. The secondary metabolites, ubiquitously found in plants especially the terpenoid-rich essential oils, have a significant role in AgNPs synthesis. Terpenoids belong to the largest family of natural products and are found in all kinds of organisms. Their involvement in the synthesis of plant-based AgNPs has got much attention in the recent years. The current article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present the pertinent role of plant terpenoids in the biosynthesis of AgNPs, as capping and reducing agents for development of uniform size and shape AgNPs. An emphasis on the important role of FTIR in the identification and elucidation of major functional groups in terpenoids for AgNPs synthesis has also been reviewed in this manuscript. It was found that no such article is available that has discussed the role of plant terpenoids in the green synthesis of AgNPs.

PURPOSE The aim of this study was to determine the efficacy and safety of scleral buckling surgery in retinal detachment due to retinal dialysis. DESIGN This study was a prospective, interventional case series. METHODS A total of 48 eyes of 48 consecutive patients were included after obtaining informed written consent. Besides taking a thorough history, all eyes were examined by a retinal surgeon. The macula status, site, and extent of retinal dialysis and rhegmatogenous retinal detachment (RRD) were particularly noted. Proliferative vitreoretinopathy grading was done. Buckling was performed by a single surgeon. At every follow-up, visual acuity, intraocular pressure, retina status, and buckle position were noted. Any complication found was recorded. Follow-up was done for at least 6 months. SPSS version 16 was used for data analysis. RESULTS We included 48 cases of RRD due to retinal dialysis. The mean ± SD age of the patients was 26.85 ± 15.1 years. The macula was detached in 85.4% of the cases, and proliferative vitreoretinopathy grade C was found in 25% of the cases. A surgical reattachment rate of 95.8% was attained after a single primary buckling procedure. Final Snellen best-corrected visual acuity of 6/18 or better was attained in 12.5% of the cases. However, 62.5% of the cases had best-corrected visual acuity in the range of 6/24 to 6/60. Subretinal hemorrhage occurred in 8.3% of cases intraoperatively after subretinal fluid drainage. CONCLUSIONS We conclude that scleral buckling has a definite role in the management of RRD due to retinal dialysis.

The aim of this study was to determine visual outcomes, complications, and long-term effects of drainage of preretinal (premacular) hemorrhage into the vitreous with Neodymium (Nd)-YAG laser in patients due to Valsalva retinopathy. A total of 12 patients with preretinal and premacular hemorrhage presumably caused by Valsalva maneuver was studied. All patients denied any history of ocular disease prior to presentation. Conservative treatment with observation, Nd-YAG hyaloidotomy, and vitrectomy were offered to all patients. A total of 11 patients opted for laser treatment, and one opted for conservative treatment with observation after counseling and informed consent. Nd-YAG-laser hyaloidotomy was performed to drain the hemorrhage into the vitreous cavity. Visual acuity and was recorded prior to treatment and at 1- and 6-month intervals after treatment. Complete retinal examination was undertaken at each visit when possible. Visual acuity improved in 11 patients after the Nd-YAG hyaloidotomy. No postlaser complications were noted at 6 months follow-up. One patient declined treatment and was monitored. Drainage of premacular preretinal hemorrhage due to Valsalva retinopathy into the vitreous with a Nd-YAG laser is a treatment alternative with potential of quick visual rehabilitation. Long-term results are unknown; however, short-term (up to 6 months) follow-up showed good results.

Hydatid disease, a parasitic infection is caused by Echinococcus granulosus. It has serious impact on health and economy especially in countries where it is endemic. It occurs frequently in liver and lung. The disease is chronic and cyst can localize in different organs. A hydatid cyst occurrence in the head and neck is extremely rare. To know the distribution of disease can help in its control and prevention. We report a case of primary cervical hydatid cyst in 20 year old female. A high index of suspicion is required to diagnose hydatid cyst in rare locations like this. Hydatid cyst should be considered in differential diagnosis of benign swellings of head and neck region, so that it can be managed during surgery to prevent acute anaphylaxis. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4915595218376646

To assess the effects of hepatitis B vaccination on the antibody titer in patients with chronic hepatitis C and to compare it with response in normal healthy subjects.Interventional study.Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012.Hepatitis vaccination (Heberbiovac-HB 20) was given intramuscularly to the patients of chronic hepatitis C (HCV group) and normal healthy subjects (control group) at 0, 1 and 6 months intervals. Anti-HBs titer was determined after second and third injection to assess the antibody response.There were 46 patients in the HCV group and 45 patients in the control group. Mean age was 40.9 ± 9.8 years in the HCV group and 33.18 ± 8.35 years in the control group. Weight was 67.04 ± 13.5 kg in the HCV group and 71.78 ± 14.63 kg in the control group. Height was 162.45 ± 9.06 cm in the HCV group and 167.03 ± 7.83 cm in the control group. Anti-HBs antibody levels after the second injection were 253.89 ± 76.76 mlU/mL in the HCV group and 245.81 ± 72.65 mlU/mL in the control group (p=0.172). After third injection, the antibody levels were slightly higher in both groups.In patients with chronic hepatitis C and normal healthy subjects, Heberbiovac HB in standard dosage gave sero-protective levels in both groups and antibody titers were not significantly different in control and HCV group.

To assess the quality and patient satisfaction in Endoscopy Unit of Shifa International Hospital.Cross-sectional survey.Division of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan, from July 2011 to January 2012.Quality and patient satisfaction after the endoscopic procedure was assessed using a modified GHAA-9 questionnaire. Data was analyzed using SPSS version 16.A total of 1028 patients were included with a mean age of 45 ± 14.21 years. Out of all the procedures, 670 (65.17%) were gastroscopies, 181 (17.60%) were flexible sigmoidoscopies and 177 (17.21%) were colonoscopies. The maximum unsatisfactory responses were on the waiting time before the procedure (13.13 %), followed by unsatisfactory explanation of the procedure and answers to questions (7.58%). Overall, unsatisfied impression was 4.86%. The problem rate was 6.22%.The quality of procedures and level of satisfaction of patients undergoing a gastroscopy or colonoscopy was generally good. The factors that influence the satisfaction of these patients are related to communication between doctor and patient, doctor's manner and waiting time for the procedure. Feedback information in an endoscopy unit may be useful in improving standards, including the performance of endoscopists.

To determine the frequency of development of hepatocellular carcinoma in patients with chronic liver disease secondary to hepatitis C who had achieved sustained virological response with Interferon and Ribavirin therapy.Retrospective descriptive study.Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012.Hepatitis C related chronic liver disease patients who were treated with interferon and ribavirin, after they achieved sustained virological response, they were followed for a mean of 42 ± 17 months. During this time, development of hepatocellular carcinoma was ascertained. All underwent surveillance with alpha-feto-protein and ultrasonography every 6 months.Out of the 58 patients who had achieved sustained virological response, 3 developed hepatocellular carcinoma after a mean follow-up of 38 ± 14 months. It was multifocal in 2 cases and was single lesion in the 3rd. Two patients ultimately died, one with upper GI bleeding and the other with hepatic encephalopathy, while 3rd patient with single lesion is still surviving.Three out of 58 patients of hepatitis C related chronic liver disease developed hepatocellular carcinoma during follow-up in patients who had achieved sustained virological response. These patients need closer follow-up, for development of complications, even if they have achieved sustained viral response.

Background: Hepatitis B virus (HBV) infection is a major cause of severe liver diseases including fibrosis, hepatocellular carcinoma (HCC) and cirrhosis related end stage liver diseases (ESLD) in mankind. It is a common belief that infectious diseases have historically been responsible for the massiveness of warrelated deaths, so the aim of this study was to estimate the prevalence of HBV infection and to demonstrate the various socio-economic, demographic and possible risk factors related to HBV infection among the conflict-affected peoples due to war against terrorism in North Waziristan. Methods: Blood samples were collected from total 790 suspected individuals from the conflict-affected population of North Waziristan and were analyzed initially tested for the presence of HBsAg, HBeAg antigens, Anti-HBc and Anti-HBs antibodies using ELISA methods. All the positive samples were tested by real time PCR to confirm the presence of HBV DNA in ELISA positive specimens. Results: Total of 126 (15.94%) samples were found positive for HBV DNA by real-time PCR. Among these positive subjects, 95 (75.5%) were males while 31 (24.5%) were females in a ratio of approximately 3:1. High HBV prevalence (41.26%) was observed among the subjects of subdivision Miran Shah relating to the high frequency of military activities against terrorism as compared to Mir Ali subdivision (35.7%) and Razmak subdivision (19.8%). Among the age groups, high prevalence (38.88%) was observed in age group 21–30 as compared to children and in older age groups. The modes of HBV transmission in this area was associated with re-uses of contaminated needles/syringes in medical care, barbers shops, sexual exposure and tattooing are the principal causal risks factors. Furthermore HBV infection was significantly higher in people with low socioeconomic status, in illiterate persons and in drivers. Conclusion: Our results indicate high prevalence rate of HBV infection in young subjects obviously confirms the entire absence of any program to fight HBV. Mass Immunization programs, awareness campaigns and education efforts should be practiced immediately to reduce HBV transmission among young peoples of this conflict zone.

To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital.Observational study.Shifa International Hospital, Islamabad, from January 2011 to January 2012.A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test.Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p0.001).Hyponatremia was a common feature in patients with cirrhosis and its severity increased with the severity of liver disease. The existence of serum sodium concentration135 mmol/L was associated with greater frequency of hepatic encephalopathy compared with patients with serum sodium concentration135 mmol/L.

To determine the presenting characteristics of rhegmatogenous retinal detachment (RRD) in a consecutive series of Pakistani patients.Case series.Layton Rahmatullah Benevolent Trust (LRBT), Lahore, from June 2010 to October 2011.A total of 107 eyes underwent RRD surgery. Detailed diagrams were drawn pre-operatively for all. Other recorded details included, bio-data, age, gender, visual acuity, autorefractometery, predisposing risk factors, lens state and duration of symptoms. The data was analyzed with respect to age and gender distribution, frequency of various risk factors for RRD, duration of RRD and its various presenting characteristics.Mean age of the patients were 33.1 ± 1.5 years, 85% were males. Bilateral RRD was discovered in 2.8% patients. No identifiable risk factor for RRD was present in 28%, while in rest of the 72% eyes, the commonest risk factors were intraocular surgery, trauma and peripheral myopic degeneration in decreasing order of frequency. There were 70.1% phakic, 23.4% pseudophakic and 6.5% aphakic eyes. Majority (93.5%) presented with macula off detachment. There was an overall average time lapse of 97.24 ± 16.95 days between presenting and first occurrence of symptoms. In 31.8% of eyes no break could be found pre-operatively, while 38.3% had 1 and 29.9% eyes had ³ 2 breaks. Majority of the primary breaks were horse-shoe tears (42.1%). Total RRD was found in 35.5% eyes. Infero-temporal and supero-temporal were the most frequently involved quadrants (93.5% and 86.9% respectively).Intraocular surgery, trauma and lattice degeneration in myopia are established common risk factors for RRD. These patients deserve meticulous fundus examination with indentation indirect ophthalmoscopy by trained professionals.

To study the outcome of conventional scleral buckling procedures performed for primary rhegmatogenous retinal detachment.This prospective study was conducted at Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, Pakistan from 02-08-2008 to 29-04-2009. The outcome of fifty-six consecutive cases, operated in nine months duration, for primary rhegmatogenous retinal detachment using scleral buckling procedures, were analyzed prospectively. The main outcome measure was anatomically reattached retina at two weeks postoperative follow-up.Overall success rate was 85.71% (48 of 56 cases) at 2-weeks post-operative follow-up. The most common intra-operative complication was sub-retinal haemorrhage (23.21% cases), and the most common complication at first post-operative day was increased intra-ocular pressure (IOP), (21.43% cases). The raised pressure was transient in most cases, and only 2 (3.57%) had elevated IOP at 2-weeks post-op follow-up. Choroidal detachment was the second commonest post-operative complication (10.7%) The un-aided visual acuity was PL or HM in 32 (57.14%) cases and better than 6/60 in 3 (5.36%) cases pre-operatively. This improved to PL/HM in 12 (21.43%) and better than 6/60 in 16 (28.57%) cases post-operatively. Not very significant improvement in vision despite flat retina was found to be due to late presentation of patients, high grade PVR (Grade-C) in 24 (42.86%) cases and pre-operative 'off' macula in 52 (92.86%) cases, at a short-term follow up.Scleral buckling procedures are still effective in the treatment of primary rhegmatogenous retinal detachment even in high-grade PVR cases. A fairly good success rate can be achieved by adopting the appropriate procedures.

To determine the visual and anatomic outcome of intravitreal Bevacizumab injection in the treatment of neovascular age-related macular degeneration (AMD).Quasi-experimental study.Layton Rahmatulla Benevolent Trust Eye Hospital (LRBT), Lahore, from January to July 2010.Patients who received, one or more intravitreal Bevacizumab injections (1.25 mg per 0.05 ml) for exudative AMD were included in the study. Outcome measures included standardized visual acuity, optical coherence tomography (OCT), macular thickness, intraocular pressure, and blood pressure at 24 or more weeks follow-up. Descriptive statistics were obtained.Fifty eyes with exudative AMD were observed for six months. The mean VA improved from 0.21 ± 0.11 before injections to 0.43 ± 0.11 after injections at six months. Overall, mean OCT macular thickness decreased by 99 micron at last follow-up. At last follow-up, all eyes received an average of 3.28 ± 0.85 injections. There was no incidence of severe vision loss or adverse effects like endophthalmitis or retinal detachment.Intravitreal Bevacizumab has the potential for improvement of vision in exudative AMD for at least 6 months.

Cataract surgery is constantly evolving. Purpose of this study was two folds: to estimate visual outcome and evaluate safety and efficacy of sutureless manual extra-capsular cataract extraction.This was a prospective, interventional case series, using sutureless manual extra capsular cataract surgery technique from June 2004 to January 2007 at Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex Peshawar. Patients included in the study were those having operable cataracts. All those having corneal co-morbidities extensive enough to block visualisation of posterior segment details, chronic adenexal diseases, long standing glaucoma, advanced diabetic eye disease and retinal detachment evident on B-Scan ultrasonography were excluded from the study. After thorough examination and investigation all the patients were operated upon by a single experienced surgeon using the same technique. Their visual outcome was analysed. The patients were followed for a period of six weeks.A total of 1500 cataract surgeries were carried out, of which 1211 (80.74%) patients completed six weeks of follow up. Seven hundred and fifty seven (62.51%) had an uncorrected good visual acuity (6/6-6/18) on 1st post-op day, 1131 patients (93.40%) had an uncorrected visual acuity of 6/6-6/18 on 6th week follow up. Mean surgically induced astigmatism at 6 weeks was 0.3 dioptres.Sutureless manual extra capsular cataract surgery is a safe and effective technique. It offers faster wound healing and quick rehabilitation of cataract patients at any level of community eye care setting.

To identify and determine the frequency of the intra-operative and early postoperative complications of Conventional Scleral Buckling (CSB) as the primary surgical intervention in patients with Rhegmatogenous Retinal Detachment (RRD).A quasi-interventional study.Khyber Institute of Ophthalmic Medical Sciences (KIOMS), Postgraduate Medical Institute (PGMI), Hayatabad Medial Complex (HMC), Peshawar, from April 2005 to June 2006.Fifty consecutive patients who underwent CSB and fulfilled the inclusion criteria, were included in the study. Operative details and any intra-operative complications were noted. The patients underwent another detailed clinical examination and pain assessment on the first postoperative day. All the patients were followed-up minimum for 3 months. Postoperative complications were identified and recorded. The data was analyzed on SPSS 12.0 for measures of central tendency and dispersion.There were 36 male and 14 female subjects. Mean age was 37.18 + or - 20.045 years. Encirclement (56%) was the most frequently used CSB technique. Sixteen (32%) patients had at least one intra-operative complication. Intra-operative complications were iatrogenic scleral break (2%), accidental Sub Retinal Fluid (SRF) drainage (8%), choroidal haemorrhage (2%), subretinal haemorrhage (14%), retinal incarceration (2%), vitreous haemorrhage (6%), raised (4%) or very low (2%), intra-operative IOP and hyphema (2%). Postoperative complications included systemic complications (24%), choroidal detachment (8%), vitreous haemorrahge (16%), raised IOP (22%), angle closure (2%), conjunctivitis (4%), orbital cellulitis (2%), suspected endophthalmitis (2%), ocular movement disorders (2%) and explant exposure (6%). Mean refractive change in spherical equivalent was -1.478 + or - 0.698 D. Final re-attachment rate was (82%) and final BCVA of6/60 was achieved in 62% of the subjects in the treated eyes.CSB is a safe and effective option for treating uncomplicated RRD, but it is associated with certain complications. Sub-retinal bleed was the most common intra-operative complication. Raised IOP was most the common early postoperative complication followed by choroidal detachment.

Portal vein problems remain a formidable challenge in liver transplantation. In select situations, a portal vein conduit can provide a solution. No long-term results have been reported. This study was designed to assess the impact of portal vein conduits on graft survival after liver transplantation and the safety of portal vein conduits and to establish the long-term results (up to 20 years) of portal vein conduits. Data from 2370 adult liver transplants were prospectively collected into a computerized research database and analyzed. All portal vein conduits were constructed from the donor iliac vein obtained at the liver retrieval. Portal vein conduits were required in 35 (1.5%) first transplants. The long-term (up to 20 years of follow-up) graft survival after liver transplantation using portal vein conduits was excellent and comparable to that of the control group. The graft survival was 65% with the conduit versus 66% without the conduit at 5 years of follow-up, 58% versus 51% at 10 years, and 48% versus 35% at 15 years. There was a higher rate (8.6% versus 1.4%) of portal vein thrombosis after the portal vein conduit, and the majority occurred in the first 3 months after transplantation. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without portal vein conduits. There was no statistically significant difference in graft survival or patient survival for the transplants with portal vein conduits and with portal vein thrombendvenectomy. In conclusion, portal vein conduits can be used safely for liver transplantation with no negative impact on long-term graft survival or patient survival. Despite the higher rate of portal vein thrombosis in the immediate postoperative period, excellent long-term results can be obtained.

To determine the main causes of visual impairment in children with low vision. To assess the need of spectacles and low vision devices (LVDs) in children and to evaluate visual outcome after using their LVDs for far and near distance.Observational study.Khyber Institute of Ophthalmic Medical Sciences, Peshawar, Pakistan, from June 2006 to December 2007.The clinical record of 270 children with low vision age 4-16 years attending the Low Vision Clinic were included. All those children, aged 4-16 years, who had corrected visual acuity (VA) less than 6/18 in the better eye after medical or surgical treatment, were included in the study. WHO low vision criteria were used to classify into visually impaired, severe visually impaired and blind. Results were described as percentage frequencies.One hundred and eighty nine (70%) were males and 81 (30%) were females. The male to female ratio was 2.3:1. The main causes of visual impairment included nystagmus (15%), Stargardt's disease (14%), maculopathies (13%), myopic macular degeneration (11%) and oculocutaneous albinism (7%). The percentages of visually impaired, severe visually impaired and blind were 33.8%, 27.2% and 39.0% respectively. Spectacles were prescribed to 146 patients and telescopes were prescribed to 75 patients. Spectacles and telescope both were prescribed to 179 patients while Ocutech telescope was prescribed to 4 patients.Retinal diseases nystagmus and macular conditions were mainly responsible for low vision in children. Visually impaired children especially with hereditary/congenital ocular anomalies benefit from refraction and low vision services which facilitate vision enhancement and inclusive education.

The majority of patients with acute decompensated heart failure are admitted with symptoms of congestion. The classic symptoms of “congestive” heart failure reflect fluid overload, that is, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema; these symptoms can be so dramatic that it is not surprising that patients seek hospitalization. Activation of the renin angiotensin system coupled with sympathetic hyperactivity results in marked sodium retention and high filling pressures that ultimately bring about these congestive symptoms. The treatment goal of patients hospitalized with volume overload and high filling pressures is to improve symptoms by normalizing the filling pressure and volume status without worsening renal function. The current use of diuretics, vasodilators, and ultrafiltration, as well as potential future use of investigational agents such as oral vasopressin antagonists and adenosine A1-receptor antagonists, is surrounded by the important issues of when to stop intravenous therapy in hospitalized patients and the exact mechanism by which the filling pressures are normalized. New data from evidence-based clinical trials and optimal strategies for monitoring fluid overload will help define this issue and ultimately reduce mortality in these patients. Journal of Hospital Medicine 2008;3(Suppl 6):S25–S32. © 2008 Society of Hospital Medicine.

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long-term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long-term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long-term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow-up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long-term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long-term results can be obtained.

To assess the role of low vision devices in visual rehabilitation of patients with Stargardt's disease.Descriptive study.The Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, Pakistan, from June 2003 to June 2005.Patients diagnosed as having Stargardt's disease and confirmed by two senior ophthalmologists clinically and after fluorescein fundus angiography and Electro-Retinogram (ERG) when needed, were included in the study. Patients with fundus pathologies other than Stargardt's disease were excluded. Each subject underwent an ophthalmic examination. Visual acuity was tested with a logarithm of the minimum angle of resolution chart; Feinbloom chart and Snellen type. Low vision assessment was performed on all individuals. SPSS version 10 was used for analysis of the data regarding the severity of visual impairment, visual acuity and devices used for aiding vision. Chi-square test was used for comparison of proportions.Of this cohort of 64 patients, 72% were aged between 7 to 15 years and 28% were 16 to 32 years. Using WHO low vision criteria, the percentage of visually impaired, severe visually impaired and blind (at the time of presentation) were 56.3%; 31.3% and 9.4% respectively. Among those patients, 3.1% had distance visual acuity of 6/18 or better in the better eye and 53% had normal near visual acuity of 1M (0.8 print size). Telescopes were prescribed to 53% patients for enhancement of distance visual acuity to meet their needs.Stargardt's patients respond well to magnification. Simple bifocal glasses may be used in the early stages. Visual rehabilitation can help Stargardt's patients to learn independence in their activities of daily living.

A consensus RXRXX(S/T) substrate motif for Akt kinase is conserved in the C-terminal tail of all three inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) isoforms. We have shown that IP3R can be phosphorylated by Akt kinase in vitro and in vivo. Endogenous IP3Rs in Chinese hamster ovary T-cells were phosphorylated in response to Akt activation by insulin. LnCAP cells, a prostate cancer cell line with constitutively active Akt kinase, also showed a constitutive phosphorylation of endogenous type I IP3Rs. In all cases, the IP3R phosphorylation was diminished by the addition of LY294002, an inhibitor of phosphatidylinositol 3-kinase. Mutation of IP3R serine 2681 in the Akt substrate motif to alanine (S2681A) or glutamate (S2681E) prevented IP3R phosphorylation in COS cells transfected with constitutively active Akt kinase. Analysis of the Ca2+ flux properties of these IP3R mutants expressed in COS cell microsomes or in DT40 triple knock-out (TKO) cells did not reveal any modification of channel function. However, staurosporine-induced caspase-3 activation in DT40 TKO cells stably expressing the S2681A mutant was markedly enhanced when compared with wild-type or S2681E IP3Rs. We conclude that IP3 receptors are in vivo substrates for Akt kinase and that phosphorylation of the IP3R may provide one mechanism to restrain the apoptotic effects of calcium.

Ca2+ exerts both a stimulatory and inhibitory effect on type-I IP3R channel activity. However, the structural determinants of Ca2+ sensing in IP3Rs are not fully understood. Previous studies by others have identified eight domains of the type-I IP3R that bind 45Ca2+ when expressed as GST-fusion proteins. We have mutated six highly conserved acidic residues within the second of these domains (aa378-450) in the full-length IP3R and measured the Ca2+ regulation of IP3-mediated Ca2+ release in COS-7 cells. 45Ca2+ flux assays measured with a maximal [IP3] (1 microM) indicate that one of the mutants retained a Ca2+ sensitivity that was not significantly different from control (E411Q), three of the mutants show an enhanced Ca2+ inhibition (D426N, E428Q and E439Q) and two of the mutants were relatively insensitive to Ca2+ inhibition (D442N and D444N). IP3 dose-response relationships indicated that the sensitivity to Ca2+ inhibition and affinity for IP3 were correlated for three of the constructs. Other mutants with enhanced IP3 sensitivity (e.g. R441Q and a type-II/I IP3R chimera) were also less sensitive to Ca2+ inhibition. We conclude that the acidic residues within the aa378-450 segment are unlikely to represent a single functional Ca2+ binding domain and do not contribute to Ca2+ activation of the receptor. The different effects of the mutations may be related to their location within two clusters of acidic residues identified in the crystal structure of the ligand-binding domain [I. Bosanac, J.R. Alattia, T.K. Mal, et al., Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand, Nature 420 (2002) 696-700]. The data support the view that all IP3R isoforms may display a range of Ca2+ sensitivities that are determined by multiple sites within the protein and markedly influenced by the affinity of the receptor for IP3.

To describe the patterns of ocular trauma, cause of injury and its effects on eye.A retrospective case series.Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, from January 1999 to June 2004.Medical records of 1105 patients admitted with ocular trauma were reviewed. The details of patients regarding age, gender, literacy, cause of injury and its effects on eye were entered into specially-designed performa. Sample selection consisted of all patients with history of ocular trauma and who were admitted to hospital. Population details consisted patients who were referred to the hospital from all parts of N.W.F.P. Thus, the frequency of trauma in the hospital admissions was analysed.Ophthalmic trauma comprised 6.78% of the hospital admission. One thousand one hundred and five patients presented with eye injuries. Out of them, 21 patients suffered from trauma to both eyes. Almost 80% patients were male and 69% patients were below 30 years of age. Delayed presentation was more common and 63.61% patients presented after one week. Open globe injuries were more common [520 eyes (46.18%)] than closed globe injuries [484 eyes (42.98%)]. 23.26% of open globe injuries were associated with intraocular and intra-orbital foreign bodies. Superficial non-perforating, eyelid and adnexal and burns were seen in 122 eyes (10.83%). Among the complications, lens damage and hyphema was seen in more than 50% of the patients, 16.60% eyes were infected at the time of admission and 4.88% of eyes needed enucleation or evisceration. The common causes of injury were violence in 37.37%, occupational in 24.43% and domestic accidents in 19.18%.Ophthalmic trauma is a major public health problem. Majority of the involved are male and under 30 years of age. Delayed presentation is more common. Open globe injuries are more frequent. Violence and occupational injuries are the major causes.

To determine the demographic pattern of patients presenting with proptosis and its etiology.A cross-sectional descriptive study.Khyber Institute of Ophthalmic Medical Sciences (KIOMS), Hayatabad Medical Complex, Peshawar from July 2001- December 2002.Sixty cases of proptosis presenting at KIOMS were included. Thirtysix patients were male while 24 were female. They were divided into two age groups; 0-15 years (paediatric group) and above 15 years (adult group). An elaborate work up plan was formulated for all patients, which included detailed history, clinical examination (ocular, orbital and systemic), radiological and histopathological investigations.Neoplasms (33%) were the most common causes of proptosis in all the patients followed by orbital inflammations (23%), orbital infections (20%), structural abnormalities (12%), vascular abnormalities (7%) and trauma (5%).Neoplasms were the most common cause of proptosis in both paediatric and adult group. Proptosis was the cardinal feature and visual deterioration was present in more than half of the patients. Timely referral, early diagnosis and appropriate management can result in reduction of visual morbidity.

To study the clinical profile of amblyopia in children age 3 to 14 years.A cohort study.The study was conducted over a period of two years from June 2001 to June 2003 at Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, Pakistan.This study included 316 children. Visual acuity was tested with Snellen type and Lea symbols chart according to the level of cooperation of the children. Cycloplegic refraction and orthoptic assessment was performed on all children.One hundred and eighty-two children were between 3 to 8 years age and 134 were between 8 to 14 years. Mean age was 8 years. One hundred and twenty children had strabismic amblyopia, 136 children had anisometropic amblyopia, while 60 children had combined mechanism amblyopia (strabismus and anisometropia both).The results indicate the importance of screening school-going children for refractive error and amblyopia and the importance of a future prospective study on the magnitude, cause and treatment of amblyopia at more treatable age.

Pulmonary tuberculosis (PTB) may be easily confused with other chest diseases during its initial presentation. This study was carried out to identify presenting clinical and laboratory features that differentiate PTB from other diseases and to correlate clinical features and laboratory findings.This study was carried out at the Department of Pulmonology, Ayub Teaching Hospital Abbottabad, from September 1999 to December 2000. A total of 46 patients were included in the study after being clinically diagnosed as pulmonary tuberculosis. These patients were subjected to detailed history taking recording age, sex, weight, socioeconomic status and smoking habits. They were clinically evaluated and laboratory tests including Hemoglobin, ESR, TLC, DLC and sputum for AFB were done. They were put on standard antituberculous therapy and followed from 2 to 5 months to monitor treatment effect. Statistical analysis was performed by SPSS 8 computer program.A bimodal presentation (below age 30 years and above age 50 years), fever, productive cough, weight loss, night sweats and raised ESR were the most common findings in PTB patients. Sputum AFB smears were positive in 50% of diagnosed cases. No correlation was found between clinical and laboratory parameters in establishing a confident diagnosis of the disease.The study highlights the importance of further research to pinpoint stronger and more reliable criteria for diagnosis.

A 28-kDa protein (p28) has been purified from Triton X-100 extracts of human erythrocyte plasma membrane by calmodulin affinity chromatography. Based on internal peptide sequencing and its protein amino acid composition, this protein has been shown to be highly related, if not identical to, Ral-A, a Ras-related GTP-binding protein. This protein assignment is consistent with the findings that p28 binds [32P]GTP specifically and has low GTPase activity. In this study we describe the identification and characterization of a calmodulin-binding domain in Ral-A. The Ca2+-dependent interaction of p28 with calmodulin was first detected by a calmodulin affinity column. Gel overlay experiments of both p28 and recombinant Ral-A with biotinylated calmodulin provided strong evidence that Ral-A is a calmodulin-binding protein. A peptide of 18 residues (P18) with the sequence SKEKNGKKKRKSLAKRIR has been identified as a putative calmodulin-binding domain in Ral-A, because it comprises a basic/hydrophobic composition with the propensity to form an amphiphilic helix. P18 was synthesized, and its interaction with calmodulin by gel overlay was shown to be Ca2+-dependent. Circular dichroism analysis demonstrated that this interaction results in less alpha-helical content upon calmodulin complex formation. These results indicate that Ral-A is a calmodulin-binding protein, raising the possibility that it may be associated with Ca2+-dependent intracellular signaling pathways.