Effects of Phoenix dactylifera against Streptozotocin-Aluminium Chloride Induced Alzheimer's Rats and Their In Silico Study.

Phoenix dactylifera is known for medicinal importance due to its antioxidant, antidiabetic, antidepressant, and anti-inflammatory properties. This study is aimed at evaluating the effect of P. dactylifera seeds to cure Alzheimer's disease (AD). AD was induced in the rats with streptozotocin + aluminium chloride followed by treatment of methanolic extract of P. dactylifera seeds. The blood glucose levels were determined at regular intervals, which showed a prominent decrease in the extracts treated group. Behavior tests, including the Elevated Plus Maze (EPM) test and Morris Water Maze (MWM) test, were used to evaluate memory patterns in rats. The results indicated that extract-treated rats significantly improved memory behavior compared to the diseased group. After dissection, the serum electrolytes, antioxidant enzymes, and choline esterase enzymes were measured in different organs. The serum parameters creatinine, urea, and bilirubin increased after extract treatment. Similarly, the level of antioxidant enzymes like peroxidases (POD), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and thiobarbituric acid reactive substance (TBARS) in the extract-treated group showed improved results that were close to the normal control group. The enzyme (lipase, insulin, amylase, and acetylcholine) levels were found enhanced in extract groups as compared to diseased rats. High-performance liquid chromatography (HPLC) was used to determine the level of dopamine and serotonin neurotransmitters, which were increased significantly for P. dactylifera seeds with values of 0.18 µg/mg tissue and 0.56 µg/mg tissue, respectively. Overall, results showed that P. dactylifera seeds proved to be quite efficient in improving the memory and behavior of treated rats. The antioxidants and enzymes were also increased; therefore, it may be a potential candidate for treating AD.

Comparative appraisal of in vitro biological profile and in vivo wound healing attributes of bergenin and Bergenia ciliata (Haw.) Sternb.

ETHNOPHARMACOLOGICAL RELEVANCE: People of all ages experience injuries, whether mild or severe. The most available option to treat wounds as an alternative to allopathic care in both urban and rural populations is traditional medicine, which is mostly target inflammation. Bergenia ciliata (Haw.) Sternb rhizome and leaf powder are used in Ayurveda and local communities for various ailments including healing of wounds and burns. Owing to this property it is traditionally known as "Zakham-e-hayat" (wound healer). AIM OF THE STUDY: In the present study, we compared biological activity and wound healing potential of B. ciliata rhizome (R) extract and bergenin, a glycoside isolated from B. ciliata. MATERIALS AND METHODS: Reverse-phase high performance liquid chromatography (RP-HPLC) was performed to analyze polyphenols and bergenin in B. ciliata R extract. Samples were subjected to in vitro antioxidant assays including free radical scavenging, ferric chloride reducing power and total antioxidant capacity. Micro-broth dilution method, brine shrimp lethality assay and isolated RBC hemolysis assay were conducted to assess in vitro antibacterial and cytotoxic activities. Moreover, in vivo wound healing potential was determined by an excision wound model in mice. RESULTS: RP-HPLC showed significant content of polyphenols and bergenin (6.05 ± 0.12 µg/mg) in B. ciliata R extract. Crude extract possesses higher overall antioxidant and antibacterial capacities than bergenin due to presence of multiple phytoconstituents in extract. Both samples showed low hemolytic activity indicating their safe profile. Furthermore, mice treated with B. ciliata R extract depicted substantial decrease in wound area (99.3%; p < 0.05) as compared to bergenin, which showed 88.8% of wound closure after 12 days of treatment. Additionally, both treatments reduced epithelization duration by 1.6- and 1.4-fold in B. ciliata R extract (12.0 ± 0.6 days) and bergenin (14.2 ± 0.8 days) treated mice, respectively. This was supported by histopathological examination that showed greater epithelization, fibroblast proliferation, collagen synthesis, and revascularization in mice treated with B. ciliata R. CONCLUSION: Concisely, it is evident that B. ciliata R contains phytoconstituents in addition to bergenin, which potentiated wound healing activity of the extract. Hence, B. ciliata R is good source of compounds for treating wounds.

Initiating or switching to insulin degludec/insulin aspart in adults with type 2 diabetes in Malaysia / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings.@*Methodology@#ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS).@*Results@#Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: –1.3% [95% CI: –1.61 to –0.90]) and fasting plasma glucose levels (ED: –1.8 mmol/L [95% CI: –2.49 to –1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients.@*Conclusion@#Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

Exploiting Recent Trends in the Treatment of Androgenic Alopecia through Topical Nanocarriers of Minoxidil.

Androgenic alopecia, a polygenetic disorder, is characterized by well-defined hair loss that progresses gradually. The disease affects both males and females and exerts a drastic impact on a person's psychological well-being. Minoxidil (MIN) is the commonly prescribed FDA-approved agent for the treatment of disease. It is conventionally administered as a topical solution but is allied with several adverse reactions, such as erythema and dermatitis, resulting in decreased patient compliance. To overcome these side effects, researchers developed various nanocarriers of MIN. Encapsulation of MIN in various nanocarriers enhances the entry of the drug into hair follicles and results in the formation of reservoirs for controlled delivery of the drug. It also increases the therapeutic outcomes in comparison to conventional formulations. The present review discusses the composition and physicochemical properties of different nanocarrier systems of MIN. Although successful encapsulation of MIN has been observed in these nanocarriers, there is still scarce data regarding their loading in a final dosage form. This allows researchers to conduct more in vivo studies and focus on their clinical applications. HIGHLIGHTS: • Androgenic alopecia is a polygenetic disorder with gradual loss of hair that progresses with age. • Minoxidil An FDA-approved drug for the treatment of androgenic alopecia. • Is allied with several adverse reactions, having decreased therapeutic efficacy. • Several nanocarriers including polymeric lipid-based and inorganic nanoparticles have been developed to improve their therapeutic efficacy. • Utilization of these nanocarriers results in increased retention of MIN within the hair follicles and utilizes low concentrations of solvents. • Modifications of different physicochemical properties of these carriers I.e. Particle size Zeta potential and entrapment efficiency are important to attain the above objectives.

A Case Series on Uterine Arteriovenous Malformations: A Life-Threatening Emergency in Young Women.

Uterine arteriovenous malformation (AVM) is a rare condition, with few cases reported in the literature. Despite being rare, it is a potentially life-threatening condition in women of child-bearing age. It should be considered in the differential diagnosis of prolonged or irregular vaginal bleeding, which, otherwise, can lead to critical complications ending up in severe morbidity and mortality. This case series describes four cases of young Asian women aged between 33 and 38 years who presented with irregular vaginal bleeding. Trans-abdominal ultrasound of the pelvis showed increased vascularity with multi-directional blood flow in the uterus. Magnetic resonance imaging (MRI) confirmed an arteriovenous malformation in all cases. All cases remained stable through the diagnostic journey. Embolization of the arteriovenous malformation was performed successfully in three cases and one case was managed conservatively on hormones. Later, two of them conceived within a year and had live births at term. The aim of reporting these cases is to share the common presentation of this condition and our experience in making the diagnosis and treatment of such patients. Although a few cases are reported world over, none was reported earlier from Pakistani Asian women.

Elevated exposure to polycyclic aromatic hydrocarbons (PAHs) may trigger cancers in Pakistan: an environmental, occupational, and genetic perspective.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds which are emitted through incomplete combustion of organic materials, fossil fuels, consumption of processed meat, smoked food, and from various industrial activities. High molecular mass and mobility make PAHs widespread and lethal for human health. A cellular system in human detoxifies these toxicants through specialized enzymatic machinery called xenobiotic-metabolizing (CYP450) and phase-II (GSTs) enzymes (XMEs). These metabolizing enzymes include cytochromes P450 family (CYP1, CYP2), glutathione s-transferases, and ALDHs. Gene polymorphisms in XMEs encoding genes can compromise their metabolizing capacity to detoxify ingested carcinogens (PAHs etc.) that may lead to prolong and elevated exposure to ingested toxicants and may consequently lead to cancer. Moreover, PAHs can induce cancer through reprograming XMEs' gene functions by altering their epigenetic markers. This review article discusses possible interplay between individual's gene polymorphism in XMEs' genes, their altered epigenetic markers, and exposure to PAHs in cancer susceptibility in Pakistan.

Legacy and emerging flame retardants (FRs) in the urban atmosphere of Pakistan: Diurnal variations, gas-particle partitioning and human health exposure.

Atmospheric concentration of legacy (LFRs) and emerging flame retardants (EFRs) including 8 polybrominated diphenyl ethers (PBDEs), 6 novel brominated flame retardants (NBFRs), 2 dechlorane plus isomers (DP), and 8 chlorinated organophosphate flame retardants (OPFRs) were consecutively measured in eight major cities across Pakistan. A total of 96 samples (48 PM2.5 & 48 PUFs) were analyzed and the concentrations of ∑8PBDEs (gaseous+particulate) ranged between 40.8 and 288 pg/m3 with an average value of 172 pg/m3. ∑6NBFRs ranged between 12.0 and 35.0 pg/m3 with an average value of 22.5 pg/m3 while ∑8OPFRs ranged between 12,900-40,800 pg/m3 with an average of 24,700 pg/m3. Among the studied sites, Faisalabad city exhibited the higher concentrations of FRs among all cities which might be a consequence of textile mills and garment manufacturing industries. While analyzing the diurnal patterns, OPFRs depicted higher concentrations during night-time. The estimated risks of all groups of FRs from inhalation of ambient air were negligible for all the cities, according to USEPA guidelines. Nonetheless, our study is the first to report gaseous and particulate concentrations of FRs in air on a diurnal basis across major cities in Pakistan, offering insights into the atmospheric fate of these substances in urban areas in a sub-tropical region.

OPRM1 A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches.

The epidemic of opioid addiction is shaping up as the most serious clinical issues of current times. Opioids have the greatest propensity to develop addiction after first exposure. Molecular, genetic variations, epigenetic alterations, and environmental factors are also implicated in the development of opioid addiction. Genetic and epigenetic variations in candidate genes have been identified for their associations with opioid addiction. OPRM1 nonsynonymous single nucleotide polymorphism rs1799971 (A118G) is the most prominent candidate due to its significant association with onset and treatment of opioid addiction. Marked inter-individual variability in response to available maintenance pharmacotherapies is the common feature observed in individuals with opioid addiction. Several therapies are only effective among subgroups of opioid individuals which indicate that ethnic, environmental factors and genetic polymorphism including rs1799971 may be responsible for the response to treatment. Pharmacogenetics has the potential to enhance our understanding around the underlying genetic, epigenetic and molecular mechanisms responsible for the heterogeneous response of maintenance pharmacotherapies in opioid addiction. A more detailed understanding of molecular, epigenetic and genetic variants especially the implication of OPRM1 A118G polymorphism in an individual may serve as the way forward to address the opioid epidemic. Personalized medicine, which involves developing targeted pharmacotherapies in accordance with individual genetic and epigenetic makeup, are required to develop safe and effective treatments for opioid addiction.

Remediation of textile bleaching effluent by bacterial augmented horizontal flow and vertical flow constructed wetlands: A comparison at pilot scale.

Fabric bleaching is one of the most widely used processes of the textile industry that also produces a significant amount of highly polluted wastewater. Previously, expensive and chemically extensive conventional remediation systems were used to treat bleaching effluent. Despite this, the potential of constructed wetlands (CWs) as a treatment system remains un-investigated. Furthermore, most research on the use of CWs for textile effluents are conducted at laboratory scale and therefore further research at field-scale is timely. This study compares the efficacy of bacterial augmented vertical flow constructed wetlands (VFCWs) and horizontal flow constructed wetlands (HFCWs) for the remediation of textile bleaching wastewater at pilot scale. To this end, CWs macrocosms of 1000 L water capacity were planted with Phragmites australis and inoculated with bacterial strains possessing pollutant degradation and plant growth-promoting traits. The results showed that both variants of CWs were effective in attenuating pollutants from the wastewater; however, the performance of HFCWs exceeded that of the VFCWs for almost every pollutant measure undertaken. For HFCWs, a significant reduction in COD (89%), BOD (91%), TOC (96%), and toxicity was achieved in a period of 72 h during the first month of operation. Bacterial inoculation in CWs further improved the system's performance and these bacteria also exhibited persistence in the rhizoplane (43%), root interior (56%) and shoot interior (29%) of P. australis. This study, therefore, suggests that the bacterial augmented HFCWs is a suitable approach for industrial scale textile bleach wastewater treatment.

A Neonate with Upper GI Bleeding.

Bleeding in the newborn is often a serious problem because of cardiovascular effects associated with a loss of blood and/or the damaging effects of bleeding on neonatal tissues, especially the brain. Gastric polyps are described as abnormal lesions that originate in the gastric epithelium or submucosa and protrude into the stomach lumen. Clinical presentation of gastric polyps in children varies widely, from incidental endoscopic finding to massive gastrointestinal bleeding. However, acute gastrointestinal bleeding in association with hyperplastic gastric polyps has been reported very rarely. We report a case of unusual upper gastrointestinal bleeding in newborn baby on 2nd day of life, secondary to gastric polyp, which was diagnosed and resected through endoscopy.

Correction to: Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis.

The original version of this article is missing the Acknowledgments section.

Integrated perspectives on the use of bacterial endophytes in horizontal flow constructed wetlands for the treatment of liquid textile effluent: Phytoremediation advances in the field.

Constructed wetlands (CWs) have emerged as cost-effective and sustainable treatment systems for the remediation of industrial wastewaters; nevertheless, their potential has mostly been evaluated in laboratory-scale studies. Likewise, endophytic bacteria can enhance plant growth and reduce phytotoxicity under polluted conditions, but their application with pilot-scale CWs has rarely been evaluated. The present study aims to evaluate on-site performance of endophyte-assisted pilot-scale horizontal flow constructed wetlands (HFCWs) for the remediation of effluent from a textile industry. The HFCWs were established by planting Leptochloa fusca in the presence of three endophytic bacterial strains with dye degrading, and plant growth promoting capabilities. We found that the system was able to remove a significant proportion of both organic and inorganic pollutants. Maximum reduction of pollutants was observed in endophyte-augmented HFCWs, where the COD and BOD reduced from 493 to 70 mg l-1 and 190 to 42 mg l-1, respectively, within 48 h. Additionally, survival of endophytic bacteria in different components of the HFCWs was also recorded. Treated wastewater was found to be non-toxic and the inoculated bacteria showed persistence in the wastewater as well as rhizo- and endosphere of L. fusca. Accordingly, a positive impact on plant growth was observed in the presence of bacterial augmentation. The system performance was comparable to the vertical flow constructed wetlands (VFCWs) as high nutrients reduction was seen in the presence of this partnership. This pilot-scale study is a step forward toward the field-scale application of phytoremediation coupled with bacterial endophytes as a cost-effective means of on-site wastewater remediation. To the best of our knowledge, this is among the first pilot-scale studies on use of HFCWs for improvement in quality of textile industry effluent as most previous studies are limited either in the context of engineering or lack effective interplay of plant and bacteria.

Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis.

Single nucleotide polymorphism in OPRM1 gene is associated with hedonic and reinforcing consequences of opioids. Risk and protective alleles may vary in different populations. One hundred healthy controls and 100 opioids (predominantly heroin) addicts from Pakistani origin were genotyped for A118G (N40D) polymorphism in OPRM1. Structural and functional impact of the polymorphism on encoded protein was predicted by in silico analysis. Results show significant association between homozygous GG genotype and opioid addiction in Pakistani population (p value = 0.016). In silico analysis by SIFT (TI = 0.61), PolyPhen (PISC = 0.227), PANTHER (subPSEC = -1.7171), and SNP effect predicted this SNP benign for encoded protein. Superimposing wild-type and mutated proteins by MODELLER shows no change (RMSD = 0.1) in extracellular ligand binding domain of µ-opioid receptor. However, Haploreg and RegulomeDB predicted OPRM1 gene repression by chromatin condensation and increased binding affinity of RXRA transcription factor that may reduce protein translation and hence the number of available receptors to bind with drugs, which may trigger underlying mechanisms for opioids addiction. Thus, this study outlines causal relationship between opioids addiction and genetic predisposition in Pakistani population.

Treatment of the textile industry effluent in a pilot-scale vertical flow constructed wetland system augmented with bacterial endophytes.

A pilot-scale vertical flow constructed wetland (VFCWs) system was designed, implemented and operated for one year for the treatment of dye-rich real textile effluent. Brachiaria mutica was vegetated to develop VFCWs in which five different textile effluent degrading endophytic bacteria were inoculated. These bacteria were screened based on their dye degrading and plant growth promoting capabilities. The system's performance was evaluated by monitoring physicochemical parameters, nutrients removal, heavy metals reduction, detoxification potential, and persistence of endophytic bacteria in the plant rhizo- and endosphere. Although VFCWs were able to remove a majority of the pollutants from the wastewater, bacterial augmentation further enhanced the remediation efficiency. The system promoted an increase in dissolved oxygen up to 188% and, concomitantly, a substantial decrease in the chemical oxygen demand (81%), biochemical oxygen demand (72%), total dissolved solids (32%), color (74%), nitrogen (84%), phosphorous (79%), and heavy metals [Cr(97%), Fe(89%), Ni(88%), Cd(72%)] was recorded. Wastewater treated with VFCWs augmented with bacteria was found to be non-toxic and inoculated bacteria showed persistence in the root and shoot interior of B. mutica. Conclusively, VFCWs proved to be an effective methodology for treatment of textile effluent whereas its smaller size with high efficiency is an advantage for field-scale applications.

Tracing biomarker of PAH-exposure and susceptibility factor (GSTM-polymorphism) among cancer patients in Pakistan.

We studied cancer patients for possible PAH exposure, using urinary concentration of 1-hydroxypyrene (1-OHP) as a biomarker of internal dose of polycyclic aromatic hydrocarbons (PAHs). The subjects included in this study belonged to various socio-demographic backgrounds, and were diagnosed with cancer (i.e. lung, head and neck or digestive tract cancer). In general, we observed high concentration of urinary 1-OHP among digestive tract cancer patients, compared with the controls (CN) (mean 1.06, median 1.03 and mean 0.62, median 0.63 µmol/mol-Cr in digestive tract cancer patients and controls respectively). The concentrations of urinary 1-OHP were higher than the background level of PAHs; therefore, these groups could have been exposed to PAHs. Highest urinary 1-OHP concentration was observed in digestive tract cancer patients (median 1.25 µmol/mol-Cr) with GSTM-1 genotype. The results of PCA were consistent with qualitative and quantitative data analysis. The contribution of urinary 1-OHP eigenvector revealed a relatively high PAH-exposure among cancer patients compared with CN, while diet and age were influential parameters among cancer patients, which could have a strong link in cancer etiology in the selected exposure groups.

The relative abundance and seasonal distribution correspond with the sources of polycyclic aromatic hydrocarbons (PAHs) in the surface sediments of Chenab River, Pakistan.

Chenab River is one of the most important rivers of Punjab Province (Pakistan) that receives huge input of industrial effluents and municipal sewage from major cities in the Central Punjab, Pakistan. The current study was designed to evaluate the concentration levels and associated ecological risks of USEPA priority polycyclic aromatic hydrocarbons (PAHs) in the surface sediments of Chenab River. Sampling was performed from eight (n = 24) sampling stations of Chenab River and its tributaries. We observed a relatively high abundance of ∑16PAHs during the summer season (i.e. 554 ng g(-1)) versus that in the winter season (i.e. 361 ng g(-1)), with an overall abundance of two-, five- and six-ring PAH congeners. Results also revealed that the nitrate and phosphate contents in the sediments were closely associated with low molecular weight (LMW) and high molecular weight (HMW) PAHs, respectively. Source apportionment results showed that the combustion of fossil fuels appears to be the key source of PAHs in the study area. The risk quotient (RQ) values indicated that seven PAH congeners (i.e. phenanthrene, anthracene, fluoranthene, pyrene, benzo(a)pyrene, chrysene and benzo(a)anthracene) could pose serious threats to the aquatic life of the riverine ecosystem in Pakistan.

In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes.

Single nucleotide polymorphisms (SNPs) in PLCE1 and MICB genes increase risk for the development of dengue shock syndrome (DSS). We used Bioinformatics tools to predict alterations at the transcriptional and posttranslational levels driven by PLCE1 and MICB SNPs associated with DSS. Functional and phenotypic analysis conducted to determine deleterious SNPs and impact of amino acid substitution on the structure and function of proteins identified rs2274223 (H1619R) as deleterious to protein coding as it induces structural change in the C2 domain of PLCε, with the mutant residue more positively charged than the wild-type residue (RMSD score, 1.75 Å). Moreover, rs2274223 condenses the chromatin-repressing PLCε expression in DSS. Briefly, this study presents the impact of a single nucleotide transition at SNPs associated with DSS on differential protein binding patterns with PLCE1 and MICB genes and on protein structure modification and their possible role in the pathogenesis of DSS.

A summary of the Malaysian Clinical Guidance on the management of postmenopausal and male osteoporosis, 2015

AIM: This Clinical Guidance is aimed to help practitioners assess, diagnose and manage their patients with osteoporosis (OP), using the best available evidence. METHODS: A literature search using PubMed (MEDLINE) and The Cochrane Library identified all relevant articles on OP and its assessment, diagnosis and treatment, from 2011, to update from the 2012 edition. The studies were assessed and the level of evidence assigned. For each statement, studies with the highest level of evidence were used to frame the recommendation. RESULTS: This article summarizes the diagnostic and treatment pathways for postmenopausal and male OP, while addressing the risk-benefit ratio for OP treatment. Recognising the limitation of only depending on bone mineral density in assessing fracture risk, a move to assess 10 year fracture risk using tools such as FRAX, is recommended as a guide to decision-making on when to start treatment. A re-evaluation was done of the position of calcium supplementation and on the importance of vitamin D. There has been concern about the potential adverse effects of the long-term usage of bisphosphonates, which have been discussed fully. Algorithms for the management of postmenopausal and male OP have been updated. CONCLUSIONS: Adequate intake of calcium (1000 mg from both diet and supplements) and vitamin D (800 IU) daily remain important adjuncts in the treatment of OP. However, in confirmed OP, pharmacological therapy with anti-resorptives is the mainstay of treatment in both men and postmenopausal women. Patients need to be regularly assessed while on medication and treatment adjusted as appropriate.

Effective communication of critical radiology results: The implementation of panic alert mechanism.

OBJECTIVE: To establish an effective channel of timely communication of life-threatening emergencies to primary physicians by radiology team. METHODS: The observational study was conducted at Aga Khan Hospital for Women and Children, Kharadar, Karachi. Data was collected from the log book from July 2012 to June 2013.Amultidisciplinary "Panic Alert" protocol was formulated and implemented in the Radiology unit. All radiological examinations were screened as soon as possible and panic alerts [provisional findings] were communicated to their primary care taker/relevant nursing staff, attendants within 30 minutes from the time of completion of examination. Complete log was maintained. Data was analysed on SPSS 13. RESULTS: A total of 22,474 patients were seen, and 77(0.34%) had panic provisional findings. The mean time for communicating the panic reporting was 19.5±8 minutes. Implementation of the designed protocol, effective communication and proper follow-up resulted in 100% coverage of panic results. CONCLUSIONS: Life-threatening emergencies identified by radiological imaging can be managed effectively if alerts are generated in time.

A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence.

Single nucleotide polymorphisms (SNPs) both in coding and non-coding regions govern gene functions prompting differential vulnerability to diseases, heterogeneous response to pharmaceutical regimes and environmental anomalies. These genetic variations, SNPs, may alter an individual׳s susceptibility for alcohol dependence by remodeling DNA-protein interaction patterns in prodynorphin (PDYN) and the κ-opioid receptor (OPRK1) genes. In order to elaborate the underlying molecular mechanism behind these susceptibility differences we used bioinformatics tools to retrieve differential DNA-protein interactions at PDYN and OPRK1 SNPs significantly associated with alcohol dependence. Our results show allele-specific DNA-protein interactions depicting allele-specific mechanisms implicated in differential regulation of gene expression. Several transcription factors, for instance, VDR, RXR-alpha, NFYA, CTF family, USF-1, USF2, ER, AR and predominantly SP family show an allele-specific binding affinity with PDYN gene; likewise, GATA, TBP, AP-1, USF-2, C/EBPbeta, Cart-1 and ER interact with OPRK1 SNPs on intron 2 in an allele-specific manner. In a nutshell, transition of a single nucleotide may modify differential DNA-protein interactions at OPRK1 and PDYN׳s SNPs, significantly associated with pathology that may lead to altered individual vulnerability for alcohol dependence.