Design of Novel Molecular Micelles for Capillary Electrophoresis

The research presented in this dissertation involves the synthesis, characterization, and application of novel anionic and cationic chiral molecular micelles in capillary electrophoresis (CE) for the separation of diverse chiral compounds. Chapter 1 presents brief overview of the surfactants, micelle polymer, CE and micellar electrokinetic chromatography (MEKC). Chapter 2 describes the simultaneous enantioseparation of eight single chiral center â-blockers using two novel leucine and isoleucine based polymeric surfactants. The simultaneous enantioseparation of multichiral center bearing â-blockers, nadolol and labetalol is described in chapter 3. A synergistic approach, using a combination of polysodium N-undecenoxycarbonyl-L-isoleucinate (poly-L-SUCIL) and sulfated â-CD showed dramatic enantioseparation of four stereoisomers of nadolol. On the other hand for labetalol, enantiomeric separation remains unaffected using the dual chiral selector system. Chapter 4 deals with the enantiomeric separation of the binaphthyl derivatives that was found to be influenced by pH, type and concentration of the background electrolyte as well as concentration of the polymeric surfactant. In chapter 5, characterization of five alkenoxy leucine-based surfactants with variations in chain length (C8-C11), polymerization concentration and degree of polymerization showed significant effects on the chiral resolution and efficiency of hydrophobic â-blockers. The synthesis and characterization of two positively charged amino acid derived chiral ionic liquids (ILs) and their corresponding polymers is presented in chapter 6. Chiral separation of two acidic analyte (difficult to resolve with anionic micelles) can be achieved with both monomers and polymers of ILs. In chapter 7, the synthesis and detailed characterization of three pH independent amino acids derived (L-leucinol, L-isoleucinol and L-valinol) sulfated chiral polymeric surfactants is presented. These chiral sulfated surfactants are thoroughly characterized and the morphological behavior of polymeric sulfated surfactants is revealed using cryogenic high-resolution electron microscopy. The work clearly demonstrates for the first time the superiority of chiral separation in MEKC coupled to mass spectrometry at low pH. Finally, in chapter 8, six amino acid derived chiral surfactants with carboxylate and sulfate head groups were compared for enantioseparation of broad range of structurally diverse racemic compounds at neutral and basic pH conditions

Multicultural Teacher Preparation in Practice: A Hermeneutical Disposition

It is a fact that learning to teach is basically a social and practical activity that is supported and informed by theoretical reflections. Field experience and realities should be the core component of any teacher preparation program. That is why, most of the teacher education programs based on theory into practice model. The main aim of this research is not to reject this model, but to sketch out an alternative way of teacher preparation that is based upon teacher’s own context and socio cultural settings or in other words teacher preparation must be organized Hermeneutically. The hermeneutical approach of Hans-Georg Gadamer, is not only of philosophical importance but contains practical implications also. The concepts of understanding, interpretation and application are the core concepts of teacher preparation. In contrast to adopting an entire theory as the guiding principle to the whole content and practice of teacher preparation courses, this research argue for the focus to be on inculcating a hermeneutic disposition in all teachers preparation programs and courses. Hermeneutics is basic to human interaction, especially in dealing with student-teachers belongs to diverse socio-cultural settings or multicultural environment. The main argument or focus of this research is that it is necessary that the teacher preparation programs must be consider the problem of multiculturalism (inter and intra cultural). Multicultural Teacher Preparation (MTP) or hermeneutical mode of teacher preparation plays an important role in the preparation of teachers. It will be helpful for teachers to develop a deep level understanding of students needs belongs to various backgrounds and perspectives, not through applying a predetermined model of classroom activities, but through helping future teachers to recognize their own prejudices and how these help to determine their understandings of diversity in their future classrooms. Developing a hermeneutic disposition in teachers training facilitates and enrich experience of future teachers. A mixed method design was used to conduct the study

Value Related Practices Used by Teacher Educators at a Public University, Islamabad

Values play a vital role in any teacher-training program. The value practices, used by teacher educators affect students’ understanding and practicing of values. This study aimed to explore the value related practices of teacher educators and to rank the value practices of education programs at a public sector university. Survey method was used for the study and the population comprised prospective teachers of education program at the university.100 prospective teachers were selected through simple random sampling technique. Data were collected through questionnaire and analyzed by using mean. It was found that there were several value related practices used by teacher educators such as realness, prizing, empathic understanding, fully functioning person, humility, lovingness, courage – overcoming one’s own fears, tolerance, decisiveness, living the tension between patience and impatience and the joy of living. With reference to ranking, realness stood above all other values. It is recommended that there may be more focus on different value related practices and that these are introduced in contents of teacher education program

Fundamentals of micellar electrokinetic chromatography (MEKC)

Micellar electrokinetic chromatography (MEKC) is a useful branch of capillary electrophoresis (CE) that utilizes surfactant above critical micelle concentration (CMC) as pseudo-stationary phase. MEKC can be employed to separate both charged and neutral molecules, individually or simultaneously, including chiral compounds. MECK benefits from high peak efficiency due to electroosmotic flow (EOF) in the separation capillary, compounded with large variety of synthetic surfactants, organic modifiers, temperature and variable separation voltage has made MECK the method of choice for separation scientists. In this review, we present the introduction of CE, fundamentals of surfactant chemistry as it relates to MEKC, separation principles in MECK including equations involved in calculating separation parameters (capacity factor, resolution etc.)

Novel approach for preparing nontoxic stealth microspheres for drug delivery

Polyethylene glycol 2000 (PEG) entrapped, bovine serum albumin (BSA) microspheres were prepared and optimized. These microspheres were then analyzed to understand the stealth effect to the microspheres imparted by incorporated polyethylene glycol (PEG). Microsphere preparations (formulations) were studied for particle size, zeta potential, free BSA content, and in-vitro uptake by human micro-vascular endothelial cells (HMECs). The results demonstrate, a formulation containing 37.5 % PEG (w/w) exhibits an acceptable particle size of <5 µm, good suspendibility with zeta potential of -35 mV, and confers some degree of stealth property to the microspheres. These non-toxic, biodegradable and long circulating microspheres have the potential to be used for extended intravenous (IV) drug delivery. Statistical analysis done by ANOVA and results with p<0.05 were considered significant

Global variation of COVID-19 mortality rates in the initial phase

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastation in over 200 countries. Italy, Spain, and the United States (US) were most severely affected by the first wave of the pandemic. The reasons why some countries were more strongly affected than others remain unknown. We identified the most-affected and less-affected countries and states and explored environmental, host, and infrastructure risk factors that may explain differences in the SARS-CoV-2 mortality burden.Methods: We identified the top 10 countries/US states with the highest deaths per population until May 2020. For each of these 10 case countries/states, we identified 6 control countries/states with a similar population size and at least 3 times fewer deaths per population. We extracted data for 30 risk factors from publicly available, trusted sources. We compared case and control countries/states using the non-parametric Wilcoxon rank-sum test, and conducted a secondary cluster analysis to explore the relationship between the number of cases per population and the number of deaths per population using a scalable EM (expectation-maximization) clustering algorithm.Results: Statistically significant differences were found in 16 of 30 investigated risk factors, the most important of which were temperature, neonatal and under-5 mortality rates, the percentage of under-5 deaths due to acute respiratory infections (ARIs) and diarrhea, and tuberculosis incidence (p \u3c 0.05).Conclusion: Countries with a higher burden of baseline pediatric mortality rates, higher pediatric mortality from preventable diseases like diarrhea and ARI, and higher tuberculosis incidence had lower rates of coronavirus disease 2019-associated mortality, supporting the hygiene hypothesis

Outcome of cranial firearm injuries in civilian population based on a novel classification system

Background: Cranial firearm injuries (CFAIs) are expected to be frequent during warfare; however, it is becoming increasingly common among civilian population in our part of the world. These injuries are associated with significant morbidity and mortality in addition to financial loss. The objective of our study is to evaluate the pattern of gunshot injuries to cranium and their outcome.Methods: The study was conducted on 114 patients presenting with CFAIs to Jinnah Postgraduate Medical Centre, Karachi, Pakistan, between June 2015 and January 2019. Patients were evaluated with respect to age, gender, pattern of injury, Glasgow coma scale on arrival, radiological and clinical assessment, surgical intervention, and Glasgow outcome score measured at 6 months follow-up.Results: Among patients with cranial gunshot, injuries most were males (76.3%). More than 50% patients aged between 18 and 35 years. About 46.5% of patients presented with moderate traumatic brain injury commonly involving the temporal lobe (36.8%). Of total 114 patients, 84.2% were managed conservatively but wound debridement was done in all patients. At 6 months, the overall mortality in our patients was 33.3%. Patients with good outcome (GOS 4 and 5) were 30.7% and 35.9% patients had bad outcome (GOS 2 and 3). Complication rate was 14.9% and the most common complication was disseminated intravascular coagulation in 5.2%.Conclusion: Surgical intervention has no significant benefit over conservative management on long-term mortality and should be limited to patients with large intracranial hematomas and intraventricular hematomas causing hydrocephalus

Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan

Background: Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan\u27s first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country.Findings: In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin.Conclusion: Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required

Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting

Background: Maternal vaccines against pertussis are not yet recommended in the developing world. Besides unclear burden estimates, another concern is that transplacental transfer of maternal pertussis antibodies could result in attenuation of the immune response to whole cell pertussis (DTwP) primary vaccination series in infants. This study was taken up to determine whether higher levels of maternal pertussis antibodies attenuate immune response of infants to DTwP vaccination series given at 6-10-14 weeks of age.Methodology: A total of 261 pregnant women and their infants from four low-income settlements in Karachi, Pakistan were enrolled in this study. The study endpoints were infant antibody titers for Pertussis toxin (PTx), Filamentous hemagglutinin antigen (FHA), Pertactin (PRN) and Fimbriae type 2/3 (FIM) - from birth through 18 weeks of age. Cord blood or pre-vaccine pertussis antibody titers indicate the concentration of maternal antibodies transferred to infants. Linear regression models were used to determine the association between higher maternal antibody titers and infant immune response to DTwP vaccine. Geometric Mean Ratio (GMR) was calculated as the ratio of infant antibody titers at specified time points against the maternal antibody titers at the time of delivery.Results: At eighteen weeks of age, the adjusted β regression coefficient for PTx was 0.06 (95% CI: -0.49-0.61), FHA 0.02 (95% CI: -0.26 -0.29), PRN 0.02 (95%CI -0.38- 0.43), and FIM 0.17 (95%CI: -0.21-0.54). Among infants who received at least two doses of DTwP vaccine, higher maternal antibody titers did not have any attenuating effect on infant post-immunization antibody titers against all four pertussis antigens.Conclusion: Maternal pertussis antibodies did not attenuate infant\u27s immune response to pertussis antigens in DTwP primary vaccine given at 6-10-14 weeks of age