HETERODIMERIZATION BETWEEN CHEMOKINE RECEPTORS CXCR4 AND CCR7 AND ITS ROLE IN CANCER

In physiology, the functional and physical interactions between cell surface receptors for signal molecules such as hormones, neurotransmitters, and cytokines, provides an important mechanism of diversity and regulation of signal transduction. Therefore, investigating the functional interactions between these receptors is of great importance for understanding their role in physiology and pathophysiology with potential application in drug discovery. In this context, numerous evidences support the implication of two chemokine receptors, CXCR4 and CCR7, in many cancer types. In this study, we hypothesized that the functional, and perhaps the physical interaction, occurring between CXCR4 and CCR7 may constitute one of the key molecular mechanisms of their implication in cancer. Therefore, we investigated such CXCR4-CCR7 interaction in vitro using different cell lines endogenously (HepG2, MDA-MB231, and HT-29) or transiently (human embryonic kidney (HEK 293)) co-expressing the two receptors. For this, RT-PCR was used for the analysis of the relative expression of CXCR4 and CCR7. Moreover, bioluminescence resonance energy transfer (BRET) technology in live cells combined with SDS-PAGE followed by western blot were applied to study the possible impact of CXCR4-CCR7 interaction on their signaling pathways inside the cells. Our results showed differential expression of the CXCR4 and CCR7 in the different cell lines. More importantly, we revealed an interesting pharmacological and signaling fingerprint supporting the existence of a functional CXCR4-CCR7 interaction. This was mainly characterized by the cross-inhibition of both receptor/G protein coupling as well as receptor/β-arrestin pathway between CXCR4 and CCR7 with an inhibitory impact on the intracellular kinase activation and cell viability. Whether such observations were due to the physical CXCR4-CCR7 interaction (heterodimerization) or simply to an intracellular crosstalk, this needs further investigation. Our study sheds more light on the relationship between CXCR4 and CCR7 and their implication in cell signaling with potential implication in cancer. This may open new perspectives to develop alternative therapeutics by considering the existence of the functional interaction between CXCR4-CCR7 in vitro

Disentangling the Qatari identity discourse: social engineering and the dialectics of identity formation

This study starts with the premise that a complex identity discourse is forming in Qatar, which must be traced and deconstructed to enable an understanding of the processes and the social and cultural formations that constituted this discourse. Over the past three decades, a number of social engineering endeavours have been implemented in the Qatari nationalism project to consolidate a national identity and establish a hegemonic national culture. These endeavours have contributed to shaping the ‘question of identity’ and the dialectics and social contentions within the Qatari identity discourse. The aim of this research is to explore and understand the emergence of the ‘question of identity’ and what turned the Qatari identity discourse into a contemporary debate. The study is conducted through a Foucauldian genealogical inquiry, that involves the ‘problematization’ of the present Qatari reality, in order to approach the Qatari identity discourse and its dialectics and formation process outside and independently from the normative investigative parameters and theoretical lenses that currently define it. This is done using interviews with policy instigators and social influencers (of different age ranges and social and professional backgrounds), a set of two surveys conducted with the general public (pre and post blockade), as well as informal observations to understand the current socio-cultural capital, undercurrents and changes from the perspective of the local society. The multiple dimensions of the Qatari identity discourse are investigated in order to comprehend the society’s perceptions, understandings and dialectics – about the identity - during an era of rapid nation-state building and modernization. The thesis contends that the endeavours of the Qatari nationalism project along with processes of globalization and modernity, as well as the blockade imposed on Qatar have played a role in both challenging and re-articulating the Qatari identity discourse, in addition to enabling the cultivation of a hegemonic national Qatari culture

Effects of Smartphone Usage on Social Wellbeing of School Going Children (5-16 years) in Lahore, Pakistan

The aim of this study was to analyze the effects of smartphone usage on social wellbeing of school going children (5-16 years). Descriptive cross sectional household survey was carried out in all ten towns of Lahore, Pakistan in five months duration from January 2017 to May 2017. The sampling technique was multistage cluster sampling. The school going smartphone users included in the study were 2889. The study tool was structured questionnaire. The gathered data was analyzed through IBM SPSS Statistics Version 21 in terms of Descriptive statistics and Bivariate logistic regression. Long term smartphone usage was found significantly associated with social networking among school going children. The p-value of hours spent by school going smartphone users with family per day was <0.01, smartphone use during breakfast, lunch & dinner was 0.011, smartphone use when family sitting closer to them was <0.001 and smartphone use to interact with friends and cousins was 0.0001. The study concluded that long term smartphone usage can result in decreased face-to-face communication and decreased interaction between family members living in one home and increased interaction with friends and people outside the home

EMOTIONAL DYSREGULATION, COPING STRATEGIES AND POST-TRAUMATIC STRESS SYMPTOMS AMONG ADOLESCENTS LIVING AT LINE OF CONTROL (LOC)

Background: The current research investigates the relationship between Emotional Dysregulation, Coping Strategies and Post-Traumatic Stress Symptoms in adolescents living at Line of Control (LOC). Subjects and Methods: Cross-sectional research design was used. The sample of 400 adolescent participants was drawn from different private and government schools by using convenient random sampling. The tools employed for collecting data included Difficulties in Emotion Regulation Scale (Gratz & Roemer 2004), Coping Strategies Scale for Adolescents (Sharif & Saleem 2014), and Post-traumatic Stress Symptoms Checklist (Foa et al. 1993). Results: Results of the study revealed that Emotional Dysregulation and Emotion Focused Coping had a positive and highly significant relationship with Post-traumatic stress symptoms. It was also revealed that Emotional Dysregulation and Emotion Focused Coping positively predicted Post-Traumatic Stress Symptoms. Implications of the study and a few limitations have been discussed. Conclusion: The findings of this study will help in regulating adolescents’ psychological well-being by helping future researchers in not only understanding the coping strategies these children are employing at the moment but also developing and enhancing in them the healthy coping styles which they are currently not using. Furthermore, the unique nature of non-combatant civilian trauma remains to be understood from several other perspectives, to which this research was only a foundation stone

PROTECTIVE ROLE OF BREASTFEEDING IN CHILDREN WITH CELIAC DISEASE.

Background; The prevalence of thyroid disease is likely increased among chidren with celiac disease (CD). In addition, exposure to gluten-free treatment may be associated with a risk of thyroid disease, but this association remains controversial. Objective; To Determine the frequency of Prolonged breastfeeding in children with celiac disease at a tertiary care hospital.  Material and Methods; Children with celiac disease (as given in operational definition) were enrolled and their mothers was inquired regarding history of breastfeeding in their child. All the data was entered and analyzed using SPSS-18. Results; Of these 160 study cases, 67 (41.9 %) were male patients while 93 (58.1 %) were female patients. Mean age of our study cases was 51.19 ± 11.25 months (with minimum age of our study cases was 12 months while maximum age was 60 months). Of these 160 study cases, 92 (57.5 %) belonged to rural areas and 68 (42.5 %) belonged to urban areas. Monthly family income up to Rs. 35000 was noted in 68 (42.5%) while more than Rs. 35000 was noted in 92 (57.5%) of our study cases. Mean disease duration of celiac disease was 5.23 ± 4.21 months and 117 (73.1%) had disease duration up to 6 months. Mean duration of breastfeeding was 18.23 ± 5.43 months and prolonged breastfeeding was noted in 124 (77.5%). Conclusion; Prolonged breastfeeding frequency was poor in children with celiac disease in our study. Prolonged breastfeeding was significantly associated with age, disease duration, ethnicity and maternal literacy. A mass campaign to create awareness regarding benefits of breastfeeding should be launched at national electronic and print media. Clinicians treating children having celiac disease should educate the mothers for breastfeeding benefits so as to decrease disease morbidity which will save them future hardships and improve quality of life of such patients. Keywords; Celiac Disease, Breastfeeding, Prolonged. DOI: 10.7176/JMPB/54-19 Publication date: April 30th 2019

EWOM and brand awareness impact on consumer purchase intention: mediating role of brand image

The basic purpose of this research is to analyze the impact of electronic word of mouth (eWOM) and brand awareness on customer purchase intention with the mediating role of brand image. The research is conducted to analyze the full or partial role of mediator on the said relationship. This research is basically conducted on customers of mobile users of Rawalpindi and Islamabad. To check this relationship a total of 300 questionnaires were floated in four universities of twin cities, of which 262 questionnaires with a response rate of 87.33% were received back on which mediation analysis has been performed. The results show full mediating impact of brand image on Electronic Word of Mouth (eWOM) and customer purchase intention relationship, while partial mediating role of brand image on relationship of brand awareness and customer purchase intention has been observed. This research will help marketers in implementing better marketing techniques for boosting customers purchase intention

Vascular Surprises in Calot’s Triangle during Laproscopic Choleystectomy

Background: To identify the vascular anomalies,variations of Calot’s triangle during laparoscopic cholecystectomy  Methods:  In this prospective observational study one thousand patients with a diagnosis of cholithiasis were included. Exclusion criteria were patients younger than 12 years and older than 80 year.  Calot’s triangle dissection was done meticulously.Cystic artery and hepatic artery anomalies and variations were observed and analyzed on SPSS 21.   Results: The age varied from 12 to 80 years. On the basis of distributional variation the cystic artery was single in 90% cases, branched in 7% cases and absent in 3% cases. On positional variations the cystic artery was superomedial to the cystic duct in 85% cases, anterior in 7% cases, and posterior in 3% cases and low lying in 5% of the cases. On the basis of length variation results showed that 80% cases had a normal cystic artery .A short cystic artery was found in 5% cases and a long cystic artery was present in 5%. Other arterial variations are of hepatic artery i.eMoynihan’s Hump (3%) and right hepatic artery present in Calots triangle in 5% Conclusions:  For the safety of laparoscopic cholecystectomy one should be well aware of the anatomical variations of the cystic and hepatic arter

Short-term Organic Carbon Release and Chlorine Disinfectant Decay for Cross-linked Polyethylene (PEX) Plumbing Pipes

The use of cross-linked polyethylene (PEX) plumbing pipes has grown in popularity for residential applications. However, PEX pipes can leach organic materials into water that can enable biofilm growth, cause off-tastes and -odors, and may react with disinfectants to form disinfection by-products (DBP). Varied manufacturing processes that are applied to create PEX pipes add to the complexity of understanding organic materials released. In this study, organic carbon release from three PEX pipe brands was monitored for up to five days using a series of stagnation periods. Seven stagnation periods of 1, 2, 4, 8, 24, 72, and 120 hours were conducted at 50 degrees Celsius with varying initial chlorine concentrations for a type A (PEX-a), type B (PEX-b), and type C (PEX-c) brand. Pipes were exposed to chlorinated tap water synthesized in the lab. Water exposed to these pipes was analyzed to determine total organic carbon (TOC), assimilable organic carbon (AOC), total chlorine, and free chlorine concentrations. Results show that all pipe brands had different chlorine decay rates and TOC concentrations. Chlorine residual decayed the slowest and fastest for PEX-A pipes and PEX-C pipes, respectively. Chlorine completely decayed in most pipes by 24 hours when the initial chlorine concentration was 2.0 mg/L. PEX-B leached the most amount of contaminants, with a TOC concentration that far exceeded 2.0 mg/L within 24 hours. AOC concentrations tended to increase over time for all pipes. Future work should include additional brands, aged PEX pipes, different flow conditions, temperatures, and longer stagnation periods