Global proteomics profiling improves drug sensitivity prediction: results from a multi-omics, pan-cancer modeling approach

Motivation: Proteomics profiling is increasingly being used for molecular stratification of cancer patients and cell-line panels. However, systematic assessment of the predictive power of large-scale proteomic technologies across various drug classes and cancer types is currently lacking. To that end, we carried out the first pan-cancer, multi-omics comparative analysis of the relative performance of two proteomic technologies, targeted reverse phase protein array (RPPA) and global mass spectrometry (MS), in terms of their accuracy for predicting the sensitivity of cancer cells to both cytotoxic chemotherapeutics and molecularly targeted anticancer compounds.Results: Our results in two cell-line panels demonstrate how MS profiling improves drug response predictions beyond that of the RPPA or the other omics profiles when used alone. However, frequent missing MS data values complicate its use in predictive modeling and required additional filtering, such as focusing on completely measured or known oncoproteins, to obtain maximal predictive performance. Rather strikingly, the two proteomics profiles provided complementary predictive signal both for the cytotoxic and targeted compounds. Further, information about the cellular-abundance of primary target proteins was found critical for predicting the response of targeted compounds, although the non-target features also contributed significantly to the predictive power. The clinical relevance of the selected protein markers was confirmed in cancer patient data. These results provide novel insights into the relative performance and optimal use of the widely applied proteomic technologies, MS and RPPA, which should prove useful in translational applications, such as defining the best combination of omics technologies and marker panels for understanding and predicting drug sensitivities in cancer patients

Hospital-based ultra-sonographic prevalence and spectrum of thyroid incidentalomas in Pakistani population

Introduction: Thyroid incidentalomas (TIs) are clinically asymptomatic nodules found accidentally during imaging studies ordered for some other reasons. Being easily accessible, non-invasive, and inexpensive, thyroid ultrasound (US) is a key investigation in the management of thyroid nodules.Methods: This ultrasound-based cross-sectional study was performed in the radiology department of a major tertiary care hospital. Every second patient visiting the emergency department was a potential candidate for a thyroid ultrasound. Patients having ages greater than 20 years were included in the study.Results: A total of 250 patients were included in the study. Out of these, 175 were female and 75 were male. The majority (54.80%) were in the age group 21-30 years. Nodules were found in 65 (26%) patients and in the majority of cases (67.7%) they were multiple in number. Associated lymphadenopathy was seen in only one patient. Thyroid nodules were more common in females as compared to males (75.38% versus 24.62%). According to Thyroid Imaging and Reporting Data System (TI-RADS) classification, the majority of the nodules were falling in TI-RADS 1 (74%) followed by TI-RADS 3 (9.60%) and 4A (8.80%).Conclusion: The thyroid nodules are more commonly seen in females as compared to males. A significant association is seen between the frequency of thyroid nodules and increasing age. The majority of thyroid nodules fall in TI-RADS 1 category followed by TI-RADS 3 and 4A

Breeding performance of sustainable fish Ctenopharyngodon idella through single intramuscular injection of Ovaprim-C at Bahawalpur, Pakistan

Effect of intramuscular injection of Ovaprim–C on the number of eggs/kg,  fertilization rate and hatching percentage were studied at a private Fish Hatchery at Bahawalpur, Pakistan, during April to June 2008, on Ctenopharyngodon idella (Grass carp). Studied fish specimens were spawned successfully following a single dose of injection of Ovaprim-C (LH-RH analogue) with 0.6 ml kg-1 for female and 0.2 ml kg-1 for male brooders. Ova and milt were stripped simultaneously and mixture was stirred for 15 to 30 s during which fertilization occurred. Hatching occurred within 18 to 30 h after fertilization. The experiment was conducted in circular spawning tank with 2 m diameter. It was observed that body weight has positive influence on absolute fecundity (r = 0.967), while relative fecundity remained constant with increasing body weight. If it is impossible to determine the absolute and relative fecundity then these parameters can be determined from the body weight.Key words: Induced spawning, Ovaprim-C, fecundity, Ctenopharyngodon idella

Third ventricular tumors: A comprehensive literature review

Third ventricle tumors are uncommon and account for 0.6 - 0.9% of all the brain tumors. Tumors of the third ventricle are classified into primary tumors, such as colloid cysts, choroid plexus papillomas, and ependymomas, or secondary tumors, such as craniopharyngiomas, optic nerve gliomas, pineal tumors, and meningiomas. Third ventricular tumors are uncommon, and their treatment involves significant morbidity and mortality. The colloid cyst has a better surgical outcome and many approaches are available to achieve a complete cure. Choroid plexus papilloma is also a common tumor documented with its treatment majorly based on surgical resection. In addition to multiple treatment options for craniopharyngiomas, surgery is the most preferred treatment option. Ependymomas also have few treatment options, with surgical resection adopted as the first line of treatment

In-vitro Susceptibility of FMD Virus Serotype A Endemic in KPK, Pakistan

Foot and Mouth Disease virus (FMDV) serotype A is considered to be antigenic ally diverse among various geographical locations leading to diverse patterns of resistance and sensitivity. This phenomenon is posing high risks to global trade. This is the first study to quantify the effects of different physical factors (temperature, pH, UV and gamma irradiation) affecting the infectivity of FMDV serotype A.The infectivity of virus was calculated in term of tissue culture infectivity dose-50 (TCID-50) and plaque forming units (PFU). Virus in suspension (6×106 particles/ml) was treated using Cobalt-60 source in BHK-21 cell line grown in 96 well plates. The virus showed complete inactivation on 3, 5, 9 and 11 pH and 10kGy dose of gamma irradiations.The results revealed that increase in temperature (both moist and dry heat) and UV light as well as increase in time of exposure with same dose of UV irradiations significantly decreased the infectivity of virus (p<0.05). These physical factors are a better alternate for virus inactivation than chemicals, which are toxic for the health and accumulate in the animal products. It is recommended that viral strains should be analyzed for their susceptibility to these physical methods. They could also be combined with thermal inactivation to further improve virus inactivity to obtain virus free products.

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a murine model of depression, anxiety and cognition

Background and Objective: Gabapentin is a commonly prescribed antiepileptic agent for seizures, which is also used for pain and addiction management. Due to growing evidence of its abuse liability, there has been an incentive to synthesise potentially useful gabapentin derivatives devoid of adverse effects. A gabapentin adduct with a fluoxetine moiety, GBP1F, was assessed for any sedative, cognitive, anxiolytic, or antidepressant-like actions in murine behavioral models. Materials and Methods: Selected groups of mice were used for each behavioral paradigm, and the effect of GBP1F (5, 10, and 15 mg/kg) was assessed using spontaneous locomotor activity, the tail suspension test, elevated plus maze test, and the Y maze test models. Immediately following behavioral experiments, postmortem striatal and hippocampal tissues were evaluated for the effect of GBP1F on concentrations of dopamine, DOPAC, HVA, serotonin, 5-HIAA, vitamin C, and noradrenaline using high performance liquid chromatography with electrochemical detection. Results: GBP1F induced a mild suppression of locomotor activity, ameliorated anxiety and depression-like behavior, did not alter cognitive behavior, and raised serotonin and 5-HIAA concentrations in the hippocampus and striatum. GBP1F also positively enhanced dopamine and vitamin C tissue levels in the striatum. Thus, GBP1F represents a compound with anxiolytic- and antidepressant-like effects though further studies are warranted at the molecular level to focus on the precise mechanism(s) of action

COMPARISON OF HIGH-RESOLUTION SONOGRAPHY AND COLOUR DOPPLER FLOW IMAGING IN PATIENTS PRESENTING WITH ACUTE SCROTUM

Introduction: One of the most common urological emergency conditions is acute scrotum. Scrotal pain is commonly seen in early adults in the emergency departments with an association of different pathologies. The aim of this study was to determine the comparison of high-resolution sonography and colour Doppler flow imaging in patients presenting with acute scrotum. Material & Methods: A descriptive study was conducted at the Department of Radiology, Lady Reading Hospital, Peshawar, Pakistan. This study enrolled a purposive sample of emergency department patients presenting with acute scrotal pain. The pattern of blood flow, peak systolic velocity, resistive index, pulsatility index, mean and standard deviation were calculated for the continuous variables. Descriptive analyses were performed to investigate the distribution of data. Results: A total of 72 patients were enrolled in our study. The mean age of patients was recorded 36.33±11.66 years. The most common scrotal pathologies that associated with scrotal pain was hydrocele 31(38.8%), followed by varicocele 22(27.5%), testicular torsion 9(11.3%), cyst 8(10.0%), epididymo-orchitis 7(8.8%), pyocele 6(7.5%), orchitis 4(5.0%), increase scrotal wall thickness 3(3.8%), undescended testis 3(3.8%), inguinoscrotal hernia 1(1.3%), testicular atrophy 1(1.3%), rete testis 1(1.3%), hemangioma 1(1.3%), hematoma 1(1.3%), scrotal mass 1(1.3%), testicular microlithiasis 1(1.3%), and normal scrotal sonography 4(5.0%) of cases respectively. Conclusion: High-resolution ultrasonography along with colour and power Doppler should be used as 1st line imaging modality in patients presenting with acute scrotal pain

Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

<p>Abstract</p> <p>Background</p> <p><it>Callistemon citrinus </it>Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of <it>Callistemon citrinus </it>were reported to have relaxant (antispasmodic) activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it.</p> <p>Methods</p> <p>The crude methanol extract was obtained by maceration with distilled water (500 ml) three times and fractionated successively with <it>n-</it>hexane, chloroform, ethyl acetate and <it>n-</it>butanol (300 ml of each solvent). Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM) -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift.</p> <p>Results</p> <p>Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD₅₀value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4) mg/ml. Similarly, EC₅₀value for brine shrimp cytotoxicity is 65.5 ± 7.28 (60.8- 69.4, n = 4) mg/ml. All the fractions relaxed the spontaneous and KCl-induced contractions. EC₅₀values (mg/ml) for effects of ethyl acetate fraction on spontaneous and KCl induced contractions are 2.62 ± 0.78 (2.15-3.0, n = 4) and 3.72 ± 0.86 (3.38-4.28, n = 4) respectively. Respective EC₅₀values (mg/ml) for <it>n-</it>butanol fraction are 3.59 ± 0.2(3.07-3.9, n = 4) for spontaneous, and 5.57 ± 0.2 (5.07-6.11, n = 4) for KCl- induced contractions. EC₅₀value for control calcium chloride curve (without extract) is -2.73 ± 0.19 (-2.6 - -2.81, n = 4) while EC₅₀for curves treated with 5.0 mg/ml of chloroform is -2.22 ± 0.02 (-2.16 - -2.3, n = 4). EC₅₀value for ethyl acetate treated (1.0 mg/ml) tissues is -1.95 ± 0.10 (-1.88 - -2.0, n = 4) <it>vs</it>. control EC₅₀= -2.71 ± 0.08 (-2.66 - -2.76, n = 4). All the fractions, except <it>n-</it>hexane, showed a right shift like that of verapamil (EC₅₀= -1.72 ± 0.15 (-1.62 - -1.8, n = 4) vs. Control EC₅₀= -2.41 ± 0.06 (-2.38 - - 2.44, n = 4), a standard drug that blocks voltage operated calcium channels.</p> <p>Conclusion</p> <p>Relaxant constituents were more concentrated in ethylacetate fraction followed by chloroform, <it>n -</it>butanol and aqueous fractions that warrant for its isolation. The crude methanol extract is safe at concentration 250 mg/ml or below and results of brine shrimp cytotoxicity assay imply the plant specie may be a source of cytotoxic agents.</p

The Spread of HIV in Pakistan: Bridging of the Epidemic between Populations

In the last two decades, ‘concentrated epidemics’ of human immunodeficiency virus (HIV) have established in several high risk groups in Pakistan, including Injecting Drug Users (IDUs) and among men who have sex with men (MSM). To explore the transmission patterns of HIV infection in these major high-risk groups of Pakistan, 76 HIV samples were analyzed from MSM, their female spouses and children, along with 26 samples from a previously studied cohort of IDUs. Phylogenetic analysis of HIV gag gene sequences obtained from these samples indicated a substantial degree of intermixing between the IDU and MSM populations, suggesting a bridging of HIV infection from IDUs, via MSM, to the MSM spouses and children. HIV epidemic in Pakistan is now spreading to the female spouses and offspring of bisexual MSM. HIV control and awareness programs must be refocused to include IDUs, MSM, as well as bisexual MSM, and their spouses and children