Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor

Introduction Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls. Methods Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets. Results Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma. Conclusions IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma

Developing World Is Not the Only Custodian of Child Labor

The study attempts to look into the menace of the child labor around the contemporary world while also tracing its history. The study endeavors to find traces of child labor in the developing as well as developed world. The worst forms of child labor including armed conflict, trafficking, slavery, sexual exploitation, and hazardous work which absorb three-forth (3/4th) of the total child labor force. Menace of child labor continued either under inappropriate laws or unwilling implementers. The facts reveal that children’s having ages 7-14 years is 145,000 in Italy. Approximately 1.5 million child labor force is estimated in Italy. Although, unpleasant but child labor was considered desirable, at times.  Child labor is an established fact in Europe. Reasonable extent of child labor in Europe is not documented; however, 50% of rural child labor worked under 3 hours a day with only 18% worked more than 8 hours. Child labor is fundamentally dangerous as it adversely affects the child’s productive age. Keywords: Child labor; Developing countries; Developed world

The influence of lipoproteins and peroxides on platelet activation and inhibition

Low density lipoproteins (LDL) have been implicated as possible pro-thrombotic factors by enhancing platelet responsiveness. The aim of this study was to assess how the degree of oxidative modification of LDL altered their effects on platelet function. The effects of native and modified LDL on platelet responsiveness and platelet sensitivity to nitric oxide (NO) in vitro were assessed by conventional aggregometry and flow cytometry combined with immunolabelling. Native LDL (nLDL) inhibited activation in platelet rich plasma (PRP) and aggregation of washed platelets (WP). Oxidised LDL (oxLDL) also inhibited platelet activation in PRP, but was found to inhibit aggregation in both PRP and WP, suggesting that inhibition was induced by a different mechanism to that of nLDL. In contrast, minimally modified LDL (mmLDL) potentiated ADP-induced fibrinogen binding and aggregation, possibly by enhanced release of platelet granules, and induced primary aggregation of WP independently of other agonists. The major physicochemical difference between native and minimally modified LDL was a relatively small increase in the level of lipid hydroperoxides (LPO), these low levels of LPO may account for the contrasting effects of nLDL and mmLDL with respect to platelet function. The data suggest that mmLDL may be potentially important pro-thrombotic factors. The influence of peroxides on platelet aggregation and the sensitivity of platelets to NO were investigated using hydrogen peroxide, cumene hydroperoxide and 15 (S)-hydroperoxyeicosatetraenoic acid as models for LPO. Hydrogen peroxide, and cumene hydroperoxide both potentiated agonist-1 induced aggregation, but only when added post-agonist. These peroxides also attenuated the inhibition of platelet aggregation by NO when added postagonist. 15 (S)-hydroperoxyeicosatetraenoic acid alone did not affect aggregation, but potentiated aggregation when used as a complex with nLDL. 15 (S)-hydroperoxyeicosatetraenoic acid antagonised the inhibitory actions of NO, but this only occurred when the peroxide was incubated with platelets before the addition of NO and thrombin. In contrast, if hydrogen peroxide and NO were added to platelets before thrombin, aggregation was inhibited to a greater extent than by NO alone. The presence of hydrogen peroxide prolonged and enhanced the effects of NO when applied directly to WP. This was due in part to increased stimulation of guanylate cyclase activity, and could be reproduced with an NO-donor. Simultaneous addition of NO with cumene hydroperoxide or 15 (8)- hydroperoxyeicosatetraenoic acid did not produce the same effect. This suggested that hydrogen peroxide may have a physiological role in the enhancement of inhibition of platelets by NO

Demand Side of Pakistan's Population Welfare Programme

Because of a continuously moderate decline in mortality specially during the first two decades of the twentieth century and more remarkably after the Second World War, the population of developing countries, including Pakistan, grew faster over time. High rates of population growth and the characteristics associated with it constituted a serious challenge to desired economic development in these countries [United Nations (1973)]. It was for these reasons that a number of developing countries in the process of development considered and adopted as part of their development efforts a population policy aimed at reducing the rate of population growth through fertility decline. In the early 1960s, few countries including Pakistan considered family planning programmes as an integral part of their development policies. By the end of 1960, family planning programmes had been initiated in many developing countries and such programmes became an integral part of the national plans [Freedman and Berelson (1976)]. By the mid-1970s, it was observed that many developing countries had succeeded in enhancing their programme activities and in achieving contraceptive use which was responsible for reducing fertility levels in those countries. However in many developing countries, including Pakistan, the family planning programmes could not achieve a breakthrough in contraceptive use and fertility decline although the programmes had been ambitiously pursued there for more than a decade [Frinkle and Crane (1975) and Berelson (1975)]

The Pension Bomb and Possible Solutions

Public sector employment remains an attraction for two important reasons: job security and a guaranteed pension (Dixit, 2002). Unlike other countries, Pakistan has not reformed its public sector pension system and has maintained a pay-as-u–go defined benefits type pension system which has resulted in build up of unfunded liability for the government. Pakistan practices a legacy pension system where pensioners are paid directly from the revenues as part of the current expenditures. This practice is inherently unsustainable as pension expenditure growing at around 25 percent, cannot be provided from an economy growing at a significantly lower rate. The pension burden is therefore bound to grow, doubling every four-years. In the fiscal year 2018-19, federal superannuation and pension expenditures were almost 78 percent of the value for PSDP expenditures and it increased in FY 2019-20 to 87 percent (463,419 million Rupees and 533,220 million Rupees respectively). The share of pensions as a percentage of current expenditures is also increasing overtime (for FY 2019-20 it stood around 7.6 percent).

Blended learning: Call of the day for medical education in the global South

Blended learning (BL) is an e-learning approach that combines the strengths of both online and face-to-face learning, creating meaningful interactions between students, teachers, and resources. This paper explores students’ expectations and satisfaction with, and participation in, a basic science course offered through BL approaches in an undergraduate medical education programme in Pakistan. Developmental anatomy (embryology) was redesigned as a BL course and offered to a hundred first-year students. Both online activities and technology-assisted face-to-face interactive discussions were used in each topic. Students’ expectations were gathered at the start of the course and perceptions regarding their satisfaction with the course was collected at the end of the course via questionnaires. A temporal analysis of the website use was conducted to determine any changes in use across the course. The data shows that students were satisfied with their experience in the course. Their expectations regarding technology and pedagogy were met. Online individual learning activities were rated higher than collaborative discussions. Face-to-face discussions received a high rating compared to online learning activities. Students’ access to the website varied throughout the course and declined over time. However, some activity was noted before the exams. Students made extensive use of WhatsApp. In basic science subjects, BL has the potential to offer learners some control over content, learning sequence, and pace and time of learning. Unless made part of an assessment scheme, online discussions and other activities are not likely to be seen as useful learning strategies by students. Teachers’ skills in designing and facilitating BL courses are critical to the success thereof

A Comprehensive Survey on Word Representation Models: From Classical to State-Of-The-Art Word Representation Language Models

Word representation has always been an important research area in the history of natural language processing (NLP). Understanding such complex text data is imperative, given that it is rich in information and can be used widely across various applications. In this survey, we explore different word representation models and its power of expression, from the classical to modern-day state-of-the-art word representation language models (LMS). We describe a variety of text representation methods, and model designs have blossomed in the context of NLP, including SOTA LMs. These models can transform large volumes of text into effective vector representations capturing the same semantic information. Further, such representations can be utilized by various machine learning (ML) algorithms for a variety of NLP related tasks. In the end, this survey briefly discusses the commonly used ML and DL based classifiers, evaluation metrics and the applications of these word embeddings in different NLP tasks

Frequency and clinical spectrum of rare inherited coagulopathies--a tricenter study

OBJECTIVE: To determine the frequency of rare inherited coagulopathies at three centers of haematology in Karachi and to study the clinical spectrum and laboratory data of these coagulopathies. METHODS: This was a descriptive study conducted from September 2003 to December 2004 on subjects from Aga Khan University Hospital, Husaini Blood Bank and Fatimid Blood Transfusion Centre. All the subjects with bleeding tendency without any acquired causes of bleeding were selected for further investigation, and were asked relevant questions as present in the questionnaire. Screening tests including platelet count, PT, APTT and bleeding time were performed on all patients and subsequently, specific tests including factor assay, clot solubility test, platelet aggregation and vWFAg were performed. RESULTS: In total, 1100 patients were evaluated for bleeding tendency at the three centers and 65 patients were diagnosed to have inherited coagulopathy other than haemophilia A and B. Out of these 65 patients, 33 (50.7%) were males and 32 (49.2%) were females. Rare inherited coagulopathies that were found in our population included deficiency of factor VII {n = 21 (32.3%)}, factor X {n = 17 (26.1%)}, factor XIII {n =14 (21.5%)}, factor V {n = 9 (13.8%)}, fibrinogen {n = 2 (3%)}, prothrombin {n = 1 (1.5%)} and factor XII {n = 1 (1.5%)}. CONCLUSION: Inherited coagulopathies other than haemophilia A and B were noted in the study population