Search

Summary: Mitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin‐like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP106–126in vitro as well as in prion strain‐infected hamster brain in vivo. Suppression of DLP1 expression by DPL1 RNAi inhibited prion‐induced mitochondrial fragmentation and dysfunction (measured by ADP/ATP ratio, mitochondrial membrane potential, and mitochondrial integrity). We also demonstrated that DLP1 RNAi is neuroprotective against prion peptide in N2a cells as shown by improved cell viability and decreased apoptosis markers, caspase 3 induced by PrP106–126. On the contrary, overexpression of DLP1 exacerbated mitochondrial dysfunction and cell death. Moreover, inhibition of DLP1 expression ameliorated PrP106–126‐induced neurite loss and synaptic abnormalities (i.e., loss of dendritic spine and PSD‐95, a postsynaptic scaffolding protein as a marker of synaptic plasticity) in primary neurons, suggesting that altered DLP1 expression and mitochondrial fragmentation are upstream events that mediate PrP106–126‐induced neuron loss and degeneration. Our findings suggest that DLP1‐dependent mitochondrial fragmentation and redistribution plays a pivotal role in PrPSc‐associated mitochondria dysfunction and neuron apoptosis. Inhibition of DLP1 may be a novel and effective strategy in the prevention and treatment of prion diseases. [ABSTRACT FROM AUTHOR]

Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrPSc) in the brain. PrPSc accumulation in the endoplasmic reticulum (ER) result in a dysregulated calcium (Ca2+) homeostasis and subsequent initiation of unfolded protein response (UPR) leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stressinduced apoptosis are still unclear. Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases that rule the signaling of many extracellular stimuli from plasma membrane to the nucleus. However the identification of numerous points of cross talk between the UPR and MAPK signaling pathways may contribute to our understanding of the consequences of ER stress in prion diseases. Indeed the MAPK signaling network is known to regulate cell cycle progression and cell survival or death responses following a variety of stresses including misfolded protein response stress. In this article, we review the UPR signaling in prion diseases and discuss the triad of MAPK signaling pathways. We also describe the role played by MAPK signaling cascades in Alzheimer's (AD) and Parkinson's disease (PD). We will also overview the mechanisms of cell death and the role of MAPK signaling in prion disease progression and highlight potential avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the anatomic location of cysts, operative characteristics of intrathoracic extrapulmonary hydatid cyst and to determine the outcome of aggressive surgical interventions. Study Design: Case series. Place and Duration of Study: Thoracic Surgery Unit Lady Reading Hospital Peshawar from 1st July 2008 to 30th June 2011. Methodology: All patients admitted to Thoracic unit from July 2008 to June 2011 with intra thoracic hydatid cysts were evaluated prospectively as to age, sex, symptoms, diagnostic procedures, anatomic location of cysts, surgical procedures, complications, and outcomes. Chest radiography, computed tomography, and thoracic and abdominal ultrasonography had been performed preoperatively in all of them. Bronchoscopy and spirometry was also performed in all patients for assessment and operability. Echocardiography had been used in 2 patients to determine the contiguity of the cyst to the pericardium. Cystectomy and wide resection were the chief operative procedures. Most of the patients were having cysts in the pulmonary parenchyma only 10 patients had intrathoracic cysts in extrapulmonary locations. This group of patients was included in the study. We excluded patients who had a parenchymal cyst that had perforated to the pleura, myocardial hydatid and patients who had experienced transdiaphragmatic transmission. Results: Total of 149 patients were operated for hydatid cystectomy, out of these 139 patients had pulmonary hydatid and 10 patients had intrathoracic extrapulmonary hydatid cysts. These 10 patients constitute our study group; out of these 7 were men and 3 women whose mean age was 39.14 ± 16.8 years (range, 16-69 years). Eight (80%) of these were symptomatic, most commonly with chest pain, two patients were asymptomatic. There were 2 (20%) mediastinal hydatid, 2 (20%) diaphragmatic, 2 (20%) pericardial, 2 (20%) oblique fissure, and 1 (10%) each in chest wall and pleural hydatid in our study. Albendazole (10 mg/kg) was prescribed to all patients for as long as 3 months postoperatively. No complication, recurrence, or death occurred during the follow up period of 13 ± 15.4 months (range, 2-36 months). Conclusion: The extrapulmonary location of Hydatid cysts within the thorax is very rare. This rarity may cause difficulties in diagnosis. To avoid recurrence, it is necessary to resect the affected tissues completely and an anthelmintic medical regimen post operatively. [ABSTRACT FROM AUTHOR]

The ghostly Mariner in Coleridge's The Rime of the Ancient Mariner parallels in many respects the Jungian Shadow: mysterious, dark, horrible, and intimidating. He appears to be an eternal "Shadow" walking along the eternal "Man." Though not of this world, yet he relates a familiar story that is every bit humanly understandable. Circumscribed by everything that is uninviting, despicable, and horrifying, his woeful story makes intimate connections with our experiential realities that have been pushed to forceful oblivion by all of us. This resistance to the horribly bad in us cannot be sustained for long and at a crucial stage in our psychic imbalances we are unexpectedly waylaid by our "shadowy other" similar in all possibilities to that of the "Ancient Mariner." [ABSTRACT FROM AUTHOR]

The main objectives of this study are to investigate various determiners of students' performance in English at BS (Bachelor of Science) level. Factors related to family, personally, neighborhood, schooling, teachers and other socio-cultural variables expected to be interfering in some measure with students' performance in English were collected from 200 BS students of Islamia College, Peshawar using a pre-designed questionnaire. The data was analyzed through SPSS version 16 carrying out univariate and multivariate analyses to explore factors independency associated with performance in English. Three pre-university factors (gender, father education and schooling) and three on-campus factors (attachment with the subject, embarrassment and teacher medium of communication) independently affect students' performance in our case. Besides, there is significant variation in the performance of female students vis-a-vis male with respect to area (rural-urban) indicating almost a reversal of situations female students' better performance in the urban area and poor in the rural). The study recommends that teachers' training about theories of learning and language, liaison of the teachers of the public and private schools, pleasant and appealing Tonal strategies in English and motherese strategies (motherliness) on the part of the teacher for managing embarrassment can help improve the situation. [ABSTRACT FROM AUTHOR]

Infectious bursal disease (IBD), caused by IBD virus (IBDV), is an acute, highly contagious immunosuppressive avian disease. Although agedependent changes in susceptibility of chickens to IBDV have been established, the relationship between agedependent structural changes in bursa of Fabricius and susceptibility of chickens to IBDV is still unclear. In the present study, we examined the bursa anatomical structure and pathological changes in specific-pathogenfree (SPF) white leghorn chickens 0 to 8 weeks post hatch (w.p.h.) and IBDV BC6/85-infected SPF chickens 2 to 6 w.p.h. respectively, by histology, histopathology, immunohistochemistry, and transmission electron microscopy. Almost all IBDV-exposed chickens (2 to 6 w.p.h.) were infected, with the severest bursal inflammation and complication in chickens at 3 w.p.h. Furthermore, the bursae of healthy chickens at 3 to 6 w.p.h. had decreased laminin immunoreactivities, lots of splits, and irregular shapes in basement membrane (BM) of cortico-medullary epithelium (CME), irregularly arranged CME, and large numbers of immunoglobulin M-bearing (IgM+) B lymphocytes in the medulla. The decreased barrier function of corticomedullary border and large amount of IgM+ B lymphocytes provide a chance for IBDV to easily contact and infect target cells at 3 to 6 w.p.h. By contrast, regular BM, neatly arranged CME, and few IgM+ B lymphocytes in healthy chickens younger than 2 w.p.h., as well as reduced IgM+ B lymphocytes and high immunoglobulin A (IgA) content in healthy chickens older than 8 w.p.h., were observed, suggesting that the integrity of corticomedullary border barrier, a small amount of target cells and high IgA content of the bursa could be the reasons for these chickens being less susceptible to IBDV. Although studies have shown how IBDV affects bursa, we focus first on the age-dependent changes of CME, BM of CME and IgA content, and our findings are the first to elucidate the structural development of bursa in relation to IBDV susceptibility from a morphological perspective. [ABSTRACT FROM AUTHOR]

Background: 10-15 % of trauma patient has chest injuries. There is a paradigm shift in the last two decades towards rib fixation from conservative management. Rib fixation results in immediate pain reduction in patients. Although rib fixation shows promising results, conservative management is still preferred., Methods: The study was carried out in CMH Lahore from Jan 2017 to March 2018. It was a Controlled Prospective study. Convenient sampling was used. 43 patients are included in the study. Patients with four or more fracture ribs were included. Patients followed at one, two and three months with spirometry/X-ray /clinical response. Rib fixation was done in 21 patients while 22 were managed conservatively. Patients were given choice of both the management options and treated as per their choice resulting in two groups., Results: Mean age of patients is 51.35 years. Majority of them were males (86.05%), had haemothorax as confirmed with CT scan (69.80%) and unilateral fracture (79.10%). 7.40% have flail segment. Operative group shows statistically significant improvement in the recovery to work and less post-operative pain when compared to control group. There were no statistical differences among variables such as pre-operative severity and pain index, length of hospital stay, number of days for ventilator support and post op FEV1. There is statistically significant reduction in pneumonia (p <0.05), Acquired respiratory distress syndrome (ARDS) (p <0.05), ventilatory support greater than 1 day (p < 0.05) but there is no statistically significant reduction in., Conclusions: Rib fixation should be performed early after trauma as it decreases pain, lessens complications and facilitate early recovery to work.

Background: The frequently encountered thoracic trauma in surgical emergencies is a major cause of mortality and morbidity. Eighty percent of thoracic trauma can be managed by simple insertion of tube thoracostomy. Though guidelines for insertion are comprehensively explained in literature, an ideal algorithm for discontinuation is not available. A standard and safe defined protocol would eliminate hesitancy in confident removal among general surgeons. The objective of this study was to determine role of clamping trial prior to removal in terms of frequency of recurrent pneumothorax., Methods: This study was conducted in department of Surgery Combined military hospital/Military Hospital Rawalpindi from April 2013 to March 2014. Total 180 patients with blunt or penetrating thoracic trauma were included in the study. Chest tube (28-36 Fr) was inserted in Trauma centre under strict asepsis. Tubes were then connected to under water seal for minimum six hours. Patients were randomly divided in two equal groups (90 in each). In Group A, Clamping trial was given before attempting removal while in Group B, tube was removed immediately without clamping trial. Patients of both groups were observed two hourly for development of recurrent pneumothorax. Data was analysed using SPSS-18., Results: The comparison of frequency of recurrent pneumothorax in Group A (9 patients, 10%) and in Group B (4 patients, 4.5%) was not found to be statistically significant. (p-value 2.073)., Conclusions: Clamping trial is unnecessary prior to removal of tube thoracostomy in blunt and penetrating non-cardiac thoracic trauma in terms of recurrent pneumothorax.

Background: Eventration of diaphragm is a congenital condition in which there is absence of muscle fibers in the diaphragm while maintaining all the anatomical attachments normally. Surgical treatment is warranted in symptomatic patients so as to reduce the abnormal ascent of diaphragm. The present study was conducted to analyse the perioperative outcome of thoracotomy in adult patients with diaphragmatic eventration., Methods: This descriptive case series was carried out in Cardiothoracic Surgery-Unit, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan. Medical records of patients operated upon for eventration from June 2002 to June 2013 were reviewed. Patients of either gender, above 16 years who were operated for symptomatic eventrtaion were included in study. All the demographic data, presenting complaints, baseline and post-postoperative dyspnea grade, forced expiratory volume at 1 second (FEV1) and forced vital capacity (FVC) were recorded on predesigned pro forma and analysed using SPSS-16., Results: A total of 38 adult patients underwent surgery for diaphragmatic eventration over the past 11 years in our unit out of which 29 (76%) were males and rest of 9 (24%) were females. Mean age of patients was 41.6±13.84 years. In 31 (81.5%) patients left side was involved. Majority of patients had a dyspnea grade-3 on presentation. Preoperative dyspnoea score (MRC), FEV1 and FVC values were 2.6±0.73, 63.5±13.3 and 67.2±14.6 respectively. Pre-operative and 6-months follow-up values of dyspnoea grade, FEV1 and FVC values showed statistically significant improvement., Conclusion: Our study showed that adult patients with symptomatic unilateral eventration of diaphragm significantly benefit from diaphragmmatic plication.