Knowledge of personal and sexual development amongst young people in Pakistan

Pakistan has one of the largest cohorts of young people in its history, yet research on adolescents is still relatively new in Pakistan. This study conducted 24 focus group discussions to explore young peoples’ experiences of gaining knowledge on personal and sexual development. One of the most striking findings is the gendered pattern of knowledge acquisition. Young women typically gain information from a limited number of sources within the home; while young men accessed a wide variety of information sources outside the home. These findings highlight the need for gender specific information dissemination programs to young people in Pakistan. Also prominent is the event-based nature of gaining information, whereby specific events (i.e. puberty, marriage) trigger information provision to young people, however often too late to be educative. Young people were critical of the quality of information they received, which often led to confusion and stress in understanding sexual development and relations. These findings highlight a gap in formal, neutral information sources for young people in Pakistan on personal and sexual development. Although the merits of school-based information delivery were highlighted, this strategy may have little impact on young women due to their low levels of school attendance and high drop out during adolescence

B-type natriuretic peptide versus amino terminal pro-B type natriuretic peptide: selecting the optimal heart failure marker in patients with impaired kidney function

Background: The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF). Methods: In this cross sectional study adults with estimated glomerular filtration rate (eGFR)/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of \u3c 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP. Results: A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold increase from chronic kidney disease (CKD) stage 3 to stage 5 in patients with and without SHF respectively. NT-proBNP levels in non-heart failure group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with SHF. Optimal BNP and NT-proBNP cutoffs of SHF diagnosis for the entire CKD group were 300 pg/ml and 4502 pg/ml respectively. Conclusion: BNP and NT-proBNP were elevated in kidney dysfunction even in the absence of SHF; however the magnitude of increase in NT-proBNP was greater than that of BNP. BNP and NT-proBNP can be useful in diagnosing SHF, nonetheless, by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict heart failure better than BNP

An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls for reliable quantification of fluorescence signal. This streamlined methodology reads out the high density of information embedded in 3D culture systems, while maintaining a level of speed and efficiency traditionally achieved with global colorimetric reporters in order to facilitate broader implementation of 3D tumour models in therapeutic screening

Pattern of benzodiazepine use in psychiatric outpatients in Pakistan: a cross-sectional survey.

Background: Benzodiazepines (BDZ) are the largest-selling drug group in the world. The potential of dependence with BDZ has been known for almost three decades now. In countries like Pakistan where laws against unlicensed sale of BDZ are not implemented vigorously the risk of misuse of and dependence on these drugs is even higher. Previous studies have shown that BDZ prevalence among Patients/visitors to general outPatient clinics in Pakistan may be as high as 30%. However, no research has been carried out on the prevalence of BDZ use in psychiatric Patients in Pakistan. Methods: We carried out a cross-sectional survey over 3 months in psychiatry outPatient clinics of two tertiary care hospitals in Karachi and Lahore. Besides basic socio-demographic data the participants were asked if they were taking a BDZ at present and if yes, the frequency, route and dosage of the drug, who had initiated the drug and why it had been prescribed. We used chi-square test and t-test to find out which socio-demographic or clinical factors were associated with an increased risk of BDZ use. We used Logistic Regression to find out which variable(s) best predicted the increased likelihood of BDZ use. Results: Out of a total of 419 participants 187 (45%) of the participants had been currently using at least one BDZ. Seventy-three percent of the users had been using the drug for 4 weeks or longer and 87% were taking it every day. In 90% of cases the BDZ had been initiated by a doctor, who was a psychiatrist in 70% of the cases. Female gender, increasing age, living in Lahore, and having seen a psychiatrist before, were associated with an increased likelihood of using BDZ. Conclusion: The study shows how high BDZ use is in psychiatric outPatients in Pakistan. Most of the users were taking it for a duration and with a frequency which puts them at risk of becoming dependent on BDZ. In most of the cases it had been initiated by a doctor. Both Patients and doctors need to be made aware of the risk of dependence associated with the use of BDZ

Characterization and in vitro antiparasitic activities of plant extracts containing natural and modified proanthocyanidins

This thesis focused on the proanthocyanidins (PAs), a class of plant specialized metabolites that have a wide range of industrial applications. They play a vital role in the production of various food and feed products. Despite the abundance of natural PAs globally, many of them are still unexploited and could be used for various other industrial purposes. Further studies are needed to find ways to exploit these resources and make them useful for industrial purposes; this could include the extraction of PAs from plants and chemically modifying their structure to form other attractive products. The goal of this study was to investigate the possibility of modifying the natural PAs by studying their susceptibility to oxidation in alkaline conditions. This study investigated oxidized and non-oxidized PA-rich plant extracts from various plant kingdoms. It provides us to formulate a better understanding of PA oligomers and polymers in different PArich plants. The UHPLC-DAD-MS/MS method was used to provide these quantitative and qualitative data. The study revealed that the various structural features of PAs can be used to predict their susceptibility to oxidation. Overall, the results of the study revealed that the main reaction paths for procyanidins (PCs) and prodelphinidins (PDs) containing plant extracts were different under alkaline conditions. For instance, the former had an intramolecular route, while the latter had both intra and intermolecular reactions. Besides, the selected plant extracts were analyzed using orbitrap high-resolution mass spectrometry, which revealed the complex structural information and diverse reactions within the PA classes. Plant extracts were found to contain natural PAs from both A- and B-type structural families, as well as galloylated PAs. The A- and B-type PCs were relatively stable following oxidation, but some plant extracts produced new ether linkages. Conversely, PAs containing plant extracts that consisted only of PDs or PC/PD mixtures were found to be more reactive under alkaline conditions. Extracts rich in galloylated PCs were generally stable after oxidation, but those containing galloylated PDs or PC/PD mixtures were found to be more reactive. However, in certain cases, the addition of two or more galloyl groups to galloylated PCs increased their reactivity compared to those with only a single galloyl group. In addition, this study investigated the in vitro antiparasitic effects of various extracted Pas samples (original and oxidized) against Ascaris suum nematodes. The selected plant extracts were subjected to a detailed analysis of the antiparasitic properties by a highly reproducible in vitro larval migration inhibition assay. The modifications made to the PA-rich plant extracts significantly increased their antiparasitic activity. Some of the samples that showed no apparent antiparasitic activity prior to oxidation showed significant activity after the treatment and exhibited high levels of other polyphenols. Through the in vitro screening, we were able to gain a deeper understanding of how treating a plant with alkaline oxidation can improve its biological activity, which has the potential for novel anthelmintic drugs

Microextraction of Xenobiotics and Biomolecules from Different Matrices on Nano Structures

Sample preparation is the backbone of any analytical procedure; it involves extraction and pre-concentration of the desired analytes; often at trace levels. The present article describes the applications of nanomaterials (carbon based inorganic and polymeric materials) in miniaturized extraction such as solid phase micro-extraction, stir-bar sorptive extraction, liquid phase micro-extraction, and dispersive liquid phase micro-extraction in the analyses of aqueous samples. The nanoparticles used for micro-extractions are discussed on the basis of their chemical natures. The synthetic route and the preparation of nanomaterials are described along with the optimization strategies for micro-extraction. A comparison between the conventional materials and nanomaterials for micro-extraction is proposed. The key roles of the nanomaterials for the micro-extraction of different analytes such as drugs, pesticides, polycyclic aromatic hydrocarbons, proteins and peptides from aqueous samples are reported. The use of nanomaterials, combined with miniaturized micro-extraction techniques, proved to be highly promising for sample preparation of various matrices with analytes at trace levels

Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole

Based upon the known potential interaction between omeprazole (OMP) and clopidogrel (CLOP), the current study was designed to evaluate the effect of CLOP on disposition of OMP and its two major metabolites, 5-hy- droxyomeprazole (5-OH-OMP) and omeprazole sulfone (OMP-S) in healthy clinical subjects. A randomized, open label, 2-period, crossover study was designed. Twelve volunteers were selected, of whom eight were extensive metabolizers (EM) of CYP2C19 and 4 were poor metabolizers (PM). They received single dose of OMP either alone or in combination with CLOP (single dose) and samples were collected periodically to calculate various pharmacokinetic parameters. Changes in most of the pharmacokinetic parameters of OMP, 5-OH-OMP and OMP- S were insignificant (P ˃ 0.05) both in EM and PM except for the maximum concentration (Cmax) of 5-OH-OMP and OMP-S in EM. The OMP Cmax and AUC0-∞ was increased both in EM and PM after concomitant administration of OMP with CLOP. The 5-OH-OMP Cmax was decreased in both EM and PM, demonstrating that CLOP inhibits hydroxylation of OMP. The OMP-S Cmax and AUC0-∞ were increased both in EM and PM showing that CLOP may induce sulfoxidation of OMP. It was concluded that CLOP may inhibit hydroxylation of OMP to a greater extent in EM than in PM, leading to higher OMP Cmax and AUC0-∞. Furthermore, the sulfoxidation of OMP may also be induced by CLOP. So, it is suggested that both these drugs should be carefull prescribed together to avoid any harm to the patients. (Application number13/EC/Pharm. Ref number 12/Pharm)

Advanced Filler Network Characterization in Rubber

The present work is aimed at introducing new characterization techniques in filled rubber compounds. Rubber fillers such as carbon black are often used to enhance the physical properties of rubber compounds. With a sufficient amount of carbon black, a percolated filler network is formed, spanning the volume of the rubber compound. This phenomenon not only significantly improves the mechanical material behaviour, but also introduces a more complex mechanical response. Further enhancement is possible with the addition of reinforcing resins such as Novolaks, phenol–formaldehyde resins with a formaldehyde-to-phenol molar ratio of less than one. Based on the systematic studies performed, the two reinforcing materials are observed to exhibit synergistic behaviour resulting from their physical and chemical interaction. The reinforcing resin modifies the activity of the filler surface creating a more compact filler network. This leads to a lower filler network percolation threshold as well as increasing the reinforcing behaviour. This conclusion was derived from various thermo-mechanical measurements such as temperature stress scanning relaxation (TSSR) and dynamic mechanical analysis (DMA). The findings were also validated with advanced microscopical techniques such as atomic force microscopy (AFM) and transmission electron microscopy (TEM). A direct consequence of the filler network is a strain dependent behaviour such as the dynamic and quasi-static strain dependent softening effects known as Payne and Mullins effects, respectively. Within the conventional dynamic mechanical analysis (DMA) of rubber compounds, the mechanical response signal is often assumed to be rheologically linear (sinusoidal function) since in Fourier space, the first harmonic is more pronounced than the subsequent higher harmonics. However, valuable information contained in the higher harmonics can be utilised in order to further characterise the compound properties. One such approach is the large amplitude oscillatory shear (LAOS) technique which analyses the harmonics as a function of large strain deformation. While several studies have contributed to the understanding of this strain dependent nonlinearity, less emphasis was placed on the nonlinearity of the frequency domain. Utilising a resonance-based high frequency DMA, nonlinearities in the frequency domain were established by the observation of the superharmonic resonance, for the first time in rubber technology. Two distinct nonlinearities were observed, polymer induced nonlinearity and filler induced nonlinearity. The new method based on the superharmonic resonance has been successfully applied to characterise the filler network through the evaluation of the microdispersion of carbon black and its interaction with reinforcing resins.Die vorliegende Arbeit hat das Ziel, innovative Methoden zur Charakterisierung von gefüllten Kautschukmischungen einzuführen. Füllstoffe, wie Ruß, werden in Kautschuk eingesetzt, um seine physikalischen Eigenschaften zu verstärken. Mit einer ausreichenden Menge an Ruß wird ein perkolierendes Netzwerk erzeugt, das das Volumen der Kautschukmischung durchdringt. Diese Erscheinung verstärkt nicht nur das mechanische Materialverhalten, sondern führt zu einer komplexeren mechanischen Reaktion. Eine weitere Verstärkung ist durch den Einsatz netzwerkbildender Harze möglich, z.B. von Novolaken, Phenolharzen mit einem Formaldehyd-Phenol-Verhältnis kleiner eins. Auf der Basis von systematischen Studien wird ein synergistisches Verhalten der beiden verstärkenden Materialien infolge ihrer physikalischen und chemischen Wechselwirkung beobachtet. Das Verstärkungsharz verändert die Aktivität der Füllstoffoberfläche und erzeugt damit ein kompakteres Füllstoffnetzwerk. Dies führt zu einer reduzierten Perkolationsschwelle sowie zu einer zusätzlich höheren Verstärkung. Diese Schlussfolgerung wurde aus Messungen mit verschiedenen thermomechanischen Verfahren abgeleitet, wie der anisothermen Spannungsrelaxation (TSSR) und der dynamisch-mechanischen Analyse (DMA). Die Ergebnisse wurden auch mit anspruchsvollen mikroskopischen Techniken validiert, wie der Rasterkraftmikroskopie (AFM) und Transmissionselektronenmikroskopie (TEM). Eine direkte Folge des Füllstoffnetzwerks ist die Entstehung eines dehnungsabhängigen Verhaltens, das als dynamischer oder quasi-statischer Erweichungseffekt beobachtet und jeweils als Payne- oder Mullins-Effekt bezeichnet wird. Bei der dynamisch-mechanischen Analyse (DMA) von Kautschukmischungen wird häufig eine Linearität der Antwort in Bezug auf das angelegte Verformungssignal angenommen, da die Stärke der ersten Harmonischen viel höher ist als die der nachfolgenden Harmonischen. Es gibt jedoch wertvolle Informationen in den höheren Harmonischen, die verwendet werden könnten, um die Materialeigenschaften weiter zu charakterisieren. Ein solcher Ansatz ist die LAOS-Technik (engl. Large Amplitude Oscillatory Shear), mit der die Harmonischen als Funktion der Dehnung analysiert werden. Während einige Studien bereits zum Verständnis dieses dehnungsabhängigen Phänomens beigetragen haben, wurde weniger Wert auf die Nichtlinearität im Frequenzbereich gelegt. Unter Verwendung einer resonanzbasierten Hochfrequenz-DMA wurden erstmals in der Kautschuktechnologie Nichtlinearitäten im Frequenzraum durch Beobachtung von superharmonischen Resonanzen festgestellt. Zwei unterschiedliche Typen von Nichtlinearitäten wurden beobachtet, die polymerinduzierte und die füllstoffinduzierte Nichtlinearität. Die neue Methode auf der Basis der superharmonischen Resonanz wurde zur Charakterisierung des Füllstoffnetzwerkes durch Bewertung der Mikrodispersion von Ruß und dessen Wechselwirkung mit verstärkenden Harzen erfolgreich eingesetzt

Awareness regarding breast feeding and complementary feeding in mothers of children with severe acute malnutrition at stabilization centre Multan

Breast feeding is the most natural way of feeding the infants and help to reduce child mortality and morbidity and millions of deaths could be prevented each year if mothers were aware of benefits of exclusive breast feeding for 4 -6 months and early initiation of breast feeding. In current study, awareness regarding breast feeding and complementary feeding in mothers of severely malnourished children was evaluated. The results showed that 99% mothers considered breast milk safe and effective but practically only 23% babies were breast fed while 77% were bottle fed. According to 58% mothers, there should be a early initiation of breast feeding, while 57% were un aware of the facts that clostrum should be given while 43% (43/100) of then considered it unhealthy and non effective. The current awareness reveals that most of the mothers prefer to give commercially available foods for their infants instead of breast feeding. This situation is alarming regarding child health and there is need to educate the mothers especially about the beneficial and health curing effects of breast feeding