Problems and Issues in Implementing Innovative Curriculum in the Developing countries: the Pakistani experience

ABSTRACT: BACKGROUND: The Government of Pakistan identified 4 medical Colleges for introduction of COME, one from each province. Curriculum was prepared by the faculty of these colleges and launched in 2001 and despite concerted efforts could not be implemented. The purpose of this research was to identify the reasons for delay in implementation of the COME curriculum and to assess the understanding of the stakeholders about COME. METHODS: Mixed methods study design was used for data collection. In-depth interviews, mail-in survey questionnaire, and focus group discussions were held with the representatives of federal and provincial governments, Principals of medical colleges, faculty and students of the designated colleges. Rigor was ensured through independent coding and triangulation of data. RESULTS: The reasons for delay in implementation differed amongst the policy makers and faculty and included thematic issues at the institutional, programmatic and curricular level. Majority (92% of the faculty) felt that COME curriculum couldn't be implemented without adequate infrastructure. The administrators were willing to provide financial assistance, political support and better coordination and felt that COME could improve the overall health system of the country whereas the faculty did not agree to it. CONCLUSION: The paper discusses the reasons of delay based on findings and identifies the strategies for curriculum change in established institutions. The key issues identified in our study included frequent transfer of faculty of the designated colleges and perceived lack of * Continuation at the policy making level * Communication between the stakeholders * Effective leadership.     

Localization of Burkholderia cepacia Complex Bacteria in Cystic Fibrosis Lungs and Interactions with Pseudomonas aeruginosa in Hypoxic Mucus

The localization of Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) lungs, alone or during coinfection with Pseudomonas aeruginosa, is poorly understood. We performed immunohistochemistry for Bcc and P. aeruginosa bacteria on 21 coinfected or singly infected CF lungs obtained at transplantation or autopsy. Parallel in vitro experiments examined the growth of two Bcc species, Burkholderia cenocepacia and Burkholderia multivorans, in environments similar to those occupied by P. aeruginosa in the CF lung. Bcc bacteria were predominantly identified in the CF lung as single cells or small clusters within phagocytes and mucus but not as “biofilm-like structures.” In contrast, P. aeruginosa was identified in biofilm-like masses, but densities appeared to be reduced during coinfection with Bcc bacteria. Based on chemical analyses of CF and non-CF respiratory secretions, a test medium was defined to study Bcc growth and interactions with P. aeruginosa in an environment mimicking the CF lung. When test medium was supplemented with alternative electron acceptors under anaerobic conditions, B. cenocepacia and B. multivorans used fermentation rather than anaerobic respiration to gain energy, consistent with the identification of fermentation products by high-performance liquid chromatography (HPLC). Both Bcc species also expressed mucinases that produced carbon sources from mucins for growth. In the presence of P. aeruginosa in vitro, both Bcc species grew anaerobically but not aerobically. We propose that Bcc bacteria (i) invade a P. aeruginosa-infected CF lung when the airway lumen is anaerobic, (ii) inhibit P. aeruginosa biofilm-like growth, and (iii) expand the host bacterial niche from mucus to also include macrophages.     

Tezepelumab Pharmacokinetics,Safety, and Tolerability After Administration via Vial-and-syringe,Accessorized Prefilled Syringe,or Autoinjector: A Randomized Trial in Healthy Volunteers

PurposeTezepelumab is an anti–thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V–S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V–S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI).MethodsThis single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18–65 years. Participants, stratified according to weight (50 to <70 kg, 70 to <80 kg, or 80–90 kg), were randomized evenly to 9 groups representing injections to the abdomen, thigh, or upper arm via V–S, APFS, or AI. Tezepelumab PK parameters over 113 days were evaluated after a single 210-mg SC dose. The primary end points were comparison of C_max and AUC_0–∞ between device groups. Further PK parameters, immunogenicity, safety (including injection site reactions [ISRs] and injection site pain [visual analog scale]) were also assessed.FindingsA total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of C_max, AUC_0–∞, and AUC_0–last were close to 1, with 90% CIs all within the range of 0.8–1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V–S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V–S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V–S, APFS, and AI groups. Median visual analog scale pain score (0–100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups.ImplicationsTezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V–S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V–S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.     

Gastric volvulus in children: our experience

Gastric volvulus is an extremely rare disorder in the pediatric age group. It is a complex entity as to the etiology and management. The study was conducted to evaluate etiology, mode of presentation, management, and outcome in our patients with gastric volvulus. It was a retrospective study of 10 patients with gastric volvulus managed during May 2006 and October 2010. The medical record of these patients including history, clinical examination, investigations, operative notes, and the outcome was reviewed. Of the ten patients, seven were males and three females. The mean age of presentation was 2.87?years. Half (50?%) of the patients showed typical Borchardt triad whereas in other patients the presentation was variable. In eight patients, the diagnosis was precisely made with the help of radiological investigations. At operation, three patients had primary gastric volvulus, and seven had secondary gastric volvulus. The predisposing factors leading to secondary gastric volvulus were eventration of diaphragm, hiatus hernia, congenital diaphragmatic hernia, malrotation, and traumatic diaphragmatic rupture. Seven patients had organoaxial volvulus and three showed mesenterioaxial. Gastropexy was performed in three patients (primary gastric volvulus). In seven patients (secondary gastric volvulus), the predisposing anatomical defects were corrected without adding gastropexy in the regime. One patient with traumatic rupture of the diaphragm died. There was no recurrence in any patient over a mean follow up of 3.7?years (SD?±?1.27). Secondary gastric volvulus is prevalent with diaphragmatic defects sharing major contribution in the etiology. Classical Borchardt triad is seen in 50?% cases of pediatric gastric volvulus. Correction of predisposing factors alone is sufficient to manage secondary gastric volvulus in children.     

Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure

The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients likely involves poor mucus clearance. A recent model of mucus clearance predicts that mucus flow depends on the relative mucin concentration of the mucus layer compared with that of the periciliary layer; however, mucin concentrations have been difficult to measure in CF secretions. Here, we have shown that the concentration of mucin in CF sputum is low when measured by immunologically based techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage at antibody recognition sites. Using physical size exclusion chromatography/differential refractometry (SEC/dRI) techniques, we determined that mucin concentrations in CF secretions were higher than those in normal secretions. Measurements of partial osmotic pressures revealed that the partial osmotic pressure of CF sputum and the retained mucus in excised CF lungs were substantially greater than the partial osmotic pressure of normal secretions. Our data reveal that mucin concentration cannot be accurately measured immunologically in proteolytically active CF secretions; mucins are hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict mucus layer–dependent osmotic compression of the periciliary liquid layer in CF lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which contributes to key infectious and inflammatory components of CF lung disease.     

Joubert syndrome labeled as hypotonic cerebral palsy

Joubert syndrome (JS) is a rare autosomal recessive disorder with cerebellar vermis hypoplasia and complex brainstem malformation. The diagnosis of cases can be difficult as the presentation can be similar to cases of cerebral palsy. We present a case of JS in an 18-month-old girl who presented to pediatric rehabilitation with a diagnosis of hypotonic cerebral palsy and abnormal eye movements. The brain MRI confirmed the typical brain malformations.Cerebral palsy (CP) is a group of disorders of posture and movement development due to a non-progressive insult to the developing brain.1 The timing of the insult could be in the prenatal, perinatal, or postnatal period.2 Most of the clinical classifications of CP depend primarily on the tone and distribution of the motor abnormality; notwithstanding, interest in the functional classification has become popular among clinicians and therapists.3 Cerebral palsy can be classified according to the tone into spastic, dyskinetic, hypotonic, or mixed type. Spastic CP is the most common type of CP; in which, the muscle tone is increased whereas hypotonic CP is usually rare and present in children with varying degrees of reduced tone and delayed motor milestones.4 The brain MRI was found to have a strong correlation with clinical findings in most cases of CP and has helped in identifying the various etiologies.5 Our objective in presenting this particular case is to highlight the importance of thorough investigations in those labeled as hypotonic CP.     

Systemic review of the epidemiology of autism in Arab Gulf countries

Objective:

To assess the current state of knowledge on the epidemiology of autism in Arab Gulf countries, and identify gaps for future research.

Methods:

PubMed and ScienceDirect databases were used to identify relevant articles published until the 3rd of April 2013 (date of search). The search was conducted using the electronic library of King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Studies were eligible for inclusion if they concerned the epidemiology of autism, conducted in any Arab Gulf country, and published in English.

Results:

Twelve articles met the inclusion criteria. Studies showed a prevalence ranging from 1.4 to 29 per 10,000 persons. Identified risk factors were metabolic, autoimmune, and environmental in nature. The following determinants were found as possible contributing factors for autism: suboptimal breast-feeding, advanced maternal and paternal age, cesarean section, and prenatal complications.

Conclusion:

Only a few studies explored the epidemiology of autism in Arab Gulf countries and none have investigated the burden of the disease on the child, family, or society. More research is needed to better identify the burden and risk factors of autism in Gulf countries.Autism or autistic disorder is a neurodevelopmental disorder that impairs a person’s ability to communicate, interact socially with others, and respond to certain stimuli in their surroundings. The condition is usually diagnosed by the age of 3 and is more prevalent in males than females.1 Other closely related terminologies are autism spectrum disorders (ASD), and pervasive developmental disorders (PDD). Autism spectrum disorder is characterized by delayed language development, repetitive and stereotyped patterns of behavior, imagination, and hindered social interaction,2 while PDD refers to a group of conditions that include autistic disorder, Rett’s disorder, Asperger’s disorder, as well as a group of other related conditions.3 The first studies on autism were circulated in the 1960s, and many less severe types of autism were not identified until the 1980s. Since then, epidemiologists have conducted numerous surveys on autism that yielded higher prevalence rates year after year.4,5 This might be attributed to: increased awareness by both healthcare professionals and families of autistic children, and changes in diagnostic criteria. However, it is likely that the prevalence remains underestimated as many cases of autism are probably undiagnosed or unrecognized in the community, particularly the mild ones. This might be partly due to lack of awareness of both public and health care providers. Lack of screening programs and difficult access to care due to various reasons might have also contributed.6 Although there is little research into the global burden of autism, some studies in the USA and UK estimated the annual cost of autism on the economy and community to be more than several billion US dollars.7,8 The prevalence of autism is variable; Europe reported a median of 18.75 per 10,000, and the USA reported a median of 21.6 per 10,000. However, China reported a lower median of 11.6 per 10,000. Similarly, the male to female case ratio ranged from 1.33:1 to 16:1.1 Socioeconomical factors affect the prevalence rate prominently. For instance, studies in India have shown that most diagnosed cases belong to middle-class families. Upper class families do not frequent public health centers to treat autistic children, and families from low socioeconomic strata do not access such facilities unless the child is acutely ill.9-11 Obviously, the global prevalence for PDD was higher than that of autistic disorder due to the more inclusive definition of PDD.A multitude of heritable and non-heritable exposures were studied in relation to ASD.12 Based on extensive review of ASD epidemiology; Newschaffer et al12 suggested a model that categorized potential risk factors into: 1) genetic predisposition of the mother, 2) environmental factors acting the mother, 3) genetic predisposition of the child, and 4) environmental factors affecting the child. Early diagnosis and subsequent intervention for ASD and PDD are paramount, as research has shown the potential of greater benefit with early intervention.13-15The Gulf Cooperation Council (GCC) countries comprise 6 Arab countries, which are located in the Arab peninsula; namely: Bahrain, Kuwait, Qatar, Saudi Arabia, Sultanate of Oman, and United Arab Emirates (UAE). These countries have a shared geographical location, ethnic backgrounds, and life styles. Moreover, genetic exposures such as consanguinity and multiparity is common in this area. Epidemiological research into autism in the GCC is relatively new, and the burden of autism in this part of the world is still unclear. Our objective was to review the current state of knowledge of epidemiology on autism in the GCC, and make recommendations for future research.     

Negative regulation of glucose metabolism in human myotubes by supraphysiological doses of 17β-estradiol or testosterone

Objective

Exposure of skeletal muscle to high levels of testosterone or estrogen induces insulin resistance, but evidence regarding the direct role of either sex hormone on metabolism is limited. Therefore, the aim of this study was to investigate the direct effect of acute sex hormone exposure on glucose metabolism in skeletal muscle.

Materials/Methods

Differentiated human skeletal myotubes were exposed to either 17β-estradiol or testosterone and metabolic characteristics were assessed. Glucose incorporation into glycogen, glucose oxidation, palmitate oxidation, and phosphorylation of key signaling proteins were determined.

Results

Treatment of myotubes with either 17β-estradiol or testosterone decreased glucose incorporation into glycogen. Exposure of myotubes to 17β-estradiol reduced glucose oxidation under basal and insulin-stimulated conditions. However, testosterone treatment enhanced basal palmitate oxidation and prevented insulin action on glucose and palmitate oxidation. Acute stimulation of myotubes with testosterone reduced phosphorylation of S6K1 and p38 MAPK. Exposure of myotubes to either 17β-estradiol or testosterone augmented phosphorylation GSK3β^Ser9 and PKCδ^Thr505, two negative regulators of glycogen synthesis. Treatment of myotubes with a PKC specific inhibitor (GFX) restored the effect of either sex hormone on glycogen synthesis. PKCδ silencing restored glucose incorporation into glycogen to baseline in response to 17β-estradiol, but not testosterone treatment.

Conclusion

An acute exposure to supraphysiological doses of either 17β-estradiol or testosterone regulates glucose metabolism, possibly via PKC signaling pathways. Furthermore, testosterone treatment elicits additional alterations in serine/threonine kinase signaling, including the ribosomal protein S6K1 and p38 MAPK.