Role of T Regulatory Cells in Pathogenesis of HIV-2 Infection

Infection with the HIV-2 virus can result in progression to acquired immunodeficiency syndrome (AIDS) similar to that seen in HIV-1 infections. However, the majority of HIV-2 infected individuals do not show evidence of disease progression and maintain a functional immune system. It was hypothesized that there was a better balance between effector and regulatory responses in HIV-2 infection that contributed to virus control and immune activation. Furthermore, the role of T regulatory cells was investigated in the development of Immune Reconstitution Syndrome in HIV-1 and HIV-2 patients commencing antiretroviral therapy. In the present study I first determined the appropriate immunological signature of Tregs in HIV infections. Tregs were defined on the basis of CD4+CD127lo/-FOXP3+ and were shown to be strongly correlated with CD4+CD25+FOXP3+ or CD4+FOXP3+ cells. However measurement of Tregs using flow cytometry and real time PCR did not correlate. Hence measurement of Tregs from whole blood using flow cytometry was used in subsequent studies. HIV-2 infected subjects had a significantly lower percentage and absolute number of Tregs compared to HIV-1 infected individuals when matched by CD4 count. In both infections, Treg percentage increased as CD4 T cell count declined while the absolute level was positively correlated with CD4 T cell count. In addition the percentage levels of Tregs positively correlated with the immune activation and viral load in HIV-2 infection only. The next study measured the level of HIV specific immune responses and immune activation in asymptomatic HIV-1 and HIV-2 patients. HIV-2 infected subjects showed much higher percentage levels of HIV specific CD4 and CD8 T cell and lower percentage levels of activated T cells. Furthermore, it was shown that Tregs in HIV-2 patients were functional as their depletion resulted in increased HIV specific immune responses from CD4 and CD8 T cells. To assess whether Tregs contributed to the development of Immune Reconstitution Inflammatory Syndrome, HIV-1 and HIV-2 infected patients that were scheduled to commence antiretroviral therapy were recruited and followed up for six months. Longitudinal measurement of Tregs showed no differences in the magnitude or trend of percentage or absolute numbers in patients that developed IRIS compared to those that did not. Collectively these results suggest that the balance between effector and regulatory responses is maintained in HIV-2 infections which may in turn contribute to the improved prognosis of these patients compared to HIV-1 infections. The IRIS study showed that Tregs did not influence the development of IRIS though further functional characterization of these cells is required

Emergency incisional hernia repair: a difficult problem waiting for a solution

Background Emergency repair of incarcerated incisional hernia with associated bowel obstruction in potentially or contaminated field is technically challenging due to edematous, inflamed and friable tissues with occasional need for concurrent bowel resection and carries high rates of post-operative infectious complications. The aim of this study was to retrospectively assess the wound related morbidity of use of permanent prosthetic mesh in emergency repair of incarcerated incisional hernia with associated bowel obstruction. We also describe a new technique of leaving the mesh exposed to heal by secondary intention with granulation tissue. Methods Between 2000 and 2010 a total of 60 patients underwent emergency surgery for incarcerated incisional hernia with associated bowel obstruction with placement of permanent prosthetic mesh. The wound was closed after hernia repair in 55 patients while it was left open to granulate in 5 patients. Results In the group of patients with primary wound closure, 11 patients developed superficial surgical site infection, 5 developed deep wound infection and one patient had cellulitis. These patients were treated with wound debridement and antibiotics. Mesh removal was required in one patient. There were no infections in the group of patients who had their surgical wounds left open. One patient in this group died on the fifth postoperative day from septicemia. Conclusion Use of permanent prosthetic mesh in emergency repair of incarcerated incisional hernia with associated bowel obstruction. in contaminated field is associated with high risk of wound infection

Current state of knowledge of basic life support in health professionals of the largest city in Pakistan: A cross-sectional study

Background: Basic Life Support (BLS) is the recognition of sudden cardiac arrest and activation of the emergency response system, followed by resuscitation, and rapid defibrillation. According to WHO, Pakistan has one of the highest mortality rates from accidental deaths therefore assessment and comparison of BLS knowledge in health professionals is crucial. We thereby aim to assess and compare the knowledge of BLS in doctors, dentists and nurses. Methods: A multi-centric cross-sectional survey was conducted in Karachi at different institutions belonging to the private as well as government sector from January to March 2018. We used a structured questionnaire which was adapted from pretested questionnaires that have been used previously in similar studies. Descriptive statistics were analyzed using SPSS v22.0, where adequate knowledge was taken as a score of at least 50%. P \u3c 0.05 was considered as significant. Logistic regression was used to identify the factors affecting the knowledge regarding BLS in health care professionals. Results: The responders consisted of 140 doctors, nurses and dentists each. Only one individual (dentist) received a full score of 100%. In total, 58.3% of the population had inadequate knowledge. Average scores of doctors, dentists and nurses were 53.5, 43.3 and 38.4% respectively. Doctors, participants with prior training in BLS and those with 6 to 10 years after graduation were found to be a significant predictor of adequate knowledge, on multivariate analysis. Conclusion: Even though knowledge of BLS in doctors is better than that of dentists and nurses, overall knowledge of health care professionals is extremely poor. Present study highlights the need for a structured training of BLS for health care workers

Elevated ex vivo monocyte chemotactic protein-1 (CCL2) in pulmonary as compared with extra-pulmonary tuberculosis

BACKGROUND: Tuberculosis causes 3 million deaths annually. The most common site of tuberculosis is pulmonary however; extra-pulmonary forms of the disease also remain prevalent. Restriction of Mycobacterium tuberculosis depends on effective recruitment and subsequent activation of T lymphocytes, mononuclear and polymorphonuclear cells to the site of infection. Tumor necrosis factor (TNF)-α is essential for granuloma formation and is a potent activator of monocyte chemotactic protein (MCP-1, CCL2). CCL2 is essential for recruitment of monocytes and T cells and has been shown to play a role in protection against tuberculosis. Interleukin -8 (CXCL8) is a potent activator of neutrophils. Increased levels of CCL2, CXCL8 and TNFα are reported in tuberculosis but their significance in different forms of tuberculosis is as yet unclear. We have used an ex vivo assay to investigate differences in immune parameters in patients with either pulmonary or extra-pulmonary tuberculosis. METHODS: Serum levels of CCL2, CXCL8 and TNFα were measured in patients with pulmonary tuberculosis (N = 12), extra-pulmonary tuberculosis (N = 8) and BCG-vaccinated healthy volunteers (N = 12). Whole blood cells were stimulated with non-pathogenic Mycobacterium bovis bacille-Calmette Guerin (BCG) vaccine strain or bacterial lipopolysaccharide (LPS) and cyto/chemokines were monitored in supernatants. RESULTS: Circulating serum levels of CXCL8 and TNFα were raised in all tuberculosis patients, while CCL2 levels were not. There was no difference in spontaneous cytokine secretion from whole blood cells between patients and controls. M. bovis BCG-induced ex vivo CCL2 secretion was significantly greater in pulmonary as compared with both extra-pulmonary tuberculosis patients and endemic controls. In response to LPS stimulation, patients with pulmonary tuberculosis showed increased CCL2 and TNFα responses as compared with the extra-pulmonary group. BCG-, and LPS-induced CXCL8 secretion was comparable between patients and controls. CONCLUSION: CCL2 is activated by TNFα and is essential for recruitment of monocytes and T cells to the site of mycobacterial infection. Increased CCL2 activation in pulmonary tuberculosis may result in a stronger cellular response as compared with extra-pulmonary tuberculosis patients, and this may contribute to the localization of infection to the pulmonary site

The contribution of NGOs to the cultural diversity: the case of Balochistan

An NGO- though not a permissible term- is a nongovernmental organization or an association made for the welfare of society as a charitable trust, non-profit corporation, foundation or other common person who is a part of governmental sector. NGOs have played a considerably important role in the development of countries and 60% developing countries obtain their aid through NGOs. In Balochistan the NGOs have been actively engaged in regional, local, national and international matters with government and business since their beginning. Therefore, over time the NGOs are often said to have shifted the cultural diversity of the province in some ways or the others either directly or indirectly through their operations, struggles and improved understanding of societies. In this study we have discussed the impact of NGOs and their limits in the province which is a critical part and an opportunistic state of Pakistan, Balochistan

The Effect of Tele-ICU Innovation on Progressive Care Unit Patient Population

Introduction: Although, Tele-ICU is integrated into 11% of US critical care delivery, Tele-innovation\u27s advanced monitoring, clinical decision-support functions and cognitive affordances have not been examined in PCU. We compared significant well established outcomes and quality measures between PCU standard of care and PCU Tele-intervention, namely, hospital length of stay (LOS), mortality, APACHE IV severity adjusted mortality and MSDRG severity adjusted mortality. Methods: Data about n = 13, 421 patients from 6 hospitals (Observational Case Control design) from Jan 2012 – Mar 2015 were analyzed. PCU standard of care control n=7047, PCU Tele-intervention n=6374. PCU inclusion time was defined as PCU Index = first contiguous PCU census encounter \u3e 24 hours (time thresholds derived from greater than median LOS). Intervention group inclusion defined as \u3e 24 hours Tele-intervention during PCU Index time. Results:The two groups were fairly balanced. Comparing outcomes in PCU Tele-intervention vs. PCU standard of care, respectfully, the intervention group is older (70+/-16 vs. 65+/-18, p Conclusions: In our population, Tele-ICU approach resulted in significantly decreased mortality and much shorter PCU Index LOS. These findings provide evidence of the effectiveness of Tele-innovation and validate the impact on quality and cost in the progressive care setting, providing a rationale for extension of access to Tele-PCU care services across broader hospital populations. Further investigation is needed to examine influence of Tele-PCU care service on severity adjusted predictions across varying practice settings

The contribution of NGOs to the cultural diversity: the case of Balochistan

An NGO- though not a permissible term- is a nongovernmental organization or an association made for the welfare of society as a charitable trust, non-profit corporation, foundation or other common person who is a part of governmental sector. NGOs have played a considerably important role in the development of countries and 60% developing countries obtain their aid through NGOs. In Balochistan the NGOs have been actively engaged in regional, local, national and international matters with government and business since their beginning. Therefore, over time the NGOs are often said to have shifted the cultural diversity of the province in some ways or the others either directly or indirectly through their operations, struggles and improved understanding of societies. In this study we have discussed the impact of NGOs and their limits in the province which is a critical part and an opportunistic state of Pakistan, Balochistan

The implication of the value added tax in Pakistan: administration, experiences and fears

Since its first imposition in France, the value added taxation has become so popular that except USA there is no other country left that does not have VAT in use. Pakistan has fulfilled its international obligation to replace its sales tax with VAT by the year 2010. This paper examines the available literature and reflects as to how successfully the country has implemented the new taxation, what has it experienced in its efforts in the replacement of sales tax and the fear relating to VAT that still remain unaddressed. It was found that the country has, as a whole, very successfully implemented the new taxation in terms of economic gains and costs to the government. Nonetheless, it is feared that the social aspects relating thereto are altogether ignored and thus this replacement is not socially optimal

The implication of the value added tax in Pakistan: administration, experiences and fears

Since its first imposition in France, the value added taxation has become so popular that except USA there is no other country left that does not have VAT in use. Pakistan has fulfilled its international obligation to replace its sales tax with VAT by the year 2010. This paper examines the available literature and reflects as to how successfully the country has implemented the new taxation, what has it experienced in its efforts in the replacement of sales tax and the fear relating to VAT that still remain unaddressed. It was found that the country has, as a whole, very successfully implemented the new taxation in terms of economic gains and costs to the government. Nonetheless, it is feared that the social aspects relating thereto are altogether ignored and thus this replacement is not socially optimal

Analisis nilai-nilai budaya dalam kisah surah Al-Kahfi

Nilai budaya merupakan corak kehidupan manusia yang merangkumi aspek dalaman dan luaran yang terdiri daripada tingkah laku, pegangan agama, adat, pakaian dan sebagainya serta berkembang mengikut peredaran zaman dan kemajuan teknologi moden. Sehingga kini, nilai budaya masih belum difahami dengan jelas kerana perbezaan nilai budaya bagi setiap masyarakat yang terdiri daripada pelbagai bangsa dan kadang kala berlaku persamaan dan pertembungan budaya. Pemahaman yang baik terhadap sistem nilai budaya dan orientasi nilai budaya akan menjadi panduan kepada manusia dalam menjalani kehidupan seharian seterusnya menyumbang kepada ketamadunan masyarakat. Maka, objektif utama kajian ini bertujuan untuk mengenal pasti dan menganalisis nilai budaya daripada empat kisah dalam surah al-Kahfi. Metodologi penyelidikan yang digunakan adalah analisis deskriptif melalui kaedah analisis kandungan. Data yang dikenal pasti, dikumpul dan dianalisis daripada kisah Ashabul Kahfi, kisah Pemilik Dua Kebun, Kisah Musa Bersama Khidir AS dan kisah Zulkarnain berlandaskan Teori Orientasi Nilai Budaya (C. Kluckhohn, 1951). Dapatan analisis menemukan 6 kutipan nilai budaya yang berkait permasalahan utama dalam kehidupan iaitu yang pertama, hakikat kehidupan manusia yang mempunyai 4 nilai budaya; A) Nilai keimanan kepada Tuhan, B) Nilai ketaqwaan, C) Nilai Keteguhan dan D) Nilai kesabaran. Manakala kedua, hakikat hubungan manusia sesamanya yang terdapat 2 nilai budaya; A) Nilai Kepimpinan dan B) Nilai Kerjasama. Secara keseluruhannya, kisah yang dikaji memaparkan nilai budaya yang dapat dijadikan panduan dan pedoman dalam menjalani kehidupan