EVALUATION OF C - REACTIVE PROTEIN AS A PROGNOSTICATOR OF THE COURSE OF COVID 19 DISEASE

Diagnosis of COVID 19 is based on clinical manifestations, history of exposure, positive CT scan findings and laboratory tests. Inflammation plays a key role in pathogenesis of COVID 19. CRP is an acute phase protein in the serum and is also a surrogate marker for the pro inflammatory cytokine IL 6. Significant rise in CRP indicates clinically relevant inflammation. Aim and Objectives: To analyse the CRP levels in COVID 19 infected patients and to validate CRP as an indicator of the severity of SARS CoV 2 infection. Materials and Methods: This retrospective study was carried out at Chettinad Hospital and Research Institute, a tertiary care hospital situated on the outskirts of Chennai, India, for a period of 4 months. A total of 10263 patients were tested for COVID-19 by RT PCR. Viral RNA Extraction was automated and SARS CoV2 RTPCR performed with ROTOR GENE Q(QIAGEN) using SD Biosensor Real Time PCR kit. The CRP levels were measured using QDx Instacheck Fluorescence immunoassay system, Indianapolis, IN. Results: Among 10263 patients, 2694 (26.2%) patients tested SARS CoV-2 positive. CRP levels were measured for 1472 SARS CoV 2 patients (including both OP and IP). Among them 745 (50.6%) patients were found to be CRP reactive. Of the CRP reactive patients, 7 patients (0.9%) were <18 years, 190 patients (25.5%) were between 18 - 45 years and 548 patients (73.5%) were >45 years. Of the 592 patients with elevated CRP levels, 167 patients were from ICU and 425 patients were from non-ICU. Highly elevated CRP levels of >100mg/L were found in 65% (n=109) of the COVID positive ICU patients and 23% (n=101) of the non-ICU patients. Increased CRP levels were noted in SARS CoV- 2 infected individuals. Elevated CRP was common among elder patients aged >45 years and in males. Conclusion This study concludes that the significant rise of CRP levels was noted in hospitalized SARS CoV 2 positive patients aged > 45 years. Thus, estimating the early rise of serum CRP levels in SARS CoV-2 patients is a well affordable and less invasive parameter to guide the clinicians that is readily available in all the health care centers.

Infection with a Hypervirulent Strain of Helicobacter Pylori Primes Gastric Cells Toward Intestinal Transdifferentiation

Background: Intestinal metaplasia, gastric-to-intestinal transdifferentiation, occurs as a result of the misexpression of certain regulatory factors, leading to genetic reprogramming. Here, we have evaluated the H. pylori-induced expression patterns of these candidate genes.Methods: The expression levels of 1)tissue-specific transcription factors (RUNX3, KLF5, SOX2, SALL4, CDX1 and CDX2), 2)stemness factors (TNFRSF19, LGR5, VIL1) and 3)tissue-specific mucins (MUC5AC, MUC2) were evaluated by quantitative real-time PCR in gastric primary cells (GPCs), in parallel with two gastric cancer (MKN45 and AGS) cell lines, up to 96h following H. pylori infection. Results: Following H. pylori infection of GPCs, RUNX3 declined at 24h post infection (PI) (-6.2±0.3) and remained downregulated for up to 96h. Subsequently, overexpression of self-renewal and pluripotency transcription factors, KLF5 (3.6±0.2), SOX2 (7.6±0.5) and SALL4 (4.3±0.2) occurred. The expression of TNFRSF19 and LGR5, demonstrated opposing trends, with an early rise of the former (4.5±0.3) at 8h, and a simultaneous fall of the latter (-1.8±0.5). This trend was reversed at 96h, with the decline in TNFRSF19 (-5.5±0.2), and escalation of LGR5 (2.6±0.2) and VIL1 (1.8±0.3). Ultimately, CDX1 and CDX2 were upregulated by 1.9 and 4.7-fold, respectively. The above scenario was, variably observed in MKN45 and AGS cells.Conclusion: Our data suggests an interdependent gene regulatory network, induced by H. pylori infection. This interaction begins with the downregulation of RUNX3, upregulation of self-renewal and pluripotency transcription factors, KLF5, SOX2 and SALL4, leading to the downregulation of TNFRSF19, upregulation of LGR5 and aberrant expression of intestine-specific transcription factors, potentially facilitating the process of gastric-to-intestinal transdifferentiation.

Vietnam's Military and Political Challenges in Cambodia and the Early Rise of Cambodia's Strongman, Hun Sen, 1977–79

Much has been written about Cambodia's strongman, Prime Minister Hun Sen, who has been in power since 1985. Yet, the history of Hun Sen's early rise to a position of power in the Vietnam-initiated Cambodian revolution after June 1977 remains murky. Relying on Vietnamese and Cambodian archival documents, memoirs and interviews with former veterans of Unit 125 as well as Hun Sen's speeches and personal recollection of his historic journey to Vietnam on 20 June 1977, we make a two-fold argument. First, Hanoi's decision to establish an anti-Pol Pot Cambodian revolution in southern Vietnam to take over Cambodia—after toppling Democratic Kampuchea—was part of Hanoi's strategic plan to handle a double challenge: (1) to avoid being branded as an invader and (2) to establish a capable and friendly regime in Cambodia after the war. This provided an opportunity for a young Khmer Rouge defector, Hun Sen, to change his fortune by quickly earning the Vietnamese military leadership's trust and confidence based on his competence to organize and command the first army unit of the new Cambodian revolution, i.e. Unit 125. Second, as lucky as he was to flee across the heavily militarized border into Vietnam unharmed, Hun Sen's early rise to power is attributed to his survivalist instinct combined with shrewd strategic thinking.

Reye's Syndrome

Reye's syndrome is a rare and potentially fatal pediatric illness defined as acute noninflammatory encephalopathy with fatty liver failure. It rarely occurs in elderly patients and is equally distributed between the sexes [1]. It has been usually associated with acute viral infections and the use of salicylate [1- 3]. There is no specific test to diagnose the disease. However, the most common lab finding is an early rise in serum ammonia levels occurring within 1 to 2 days of mental status changes [4-8]. Treatment of the Reye’s syndrome is mainly supportive and requires close monitoring best accomplished in an intensive care unit setting [9,10].

Initial growth rates of malware epidemics fail to predict their reach

Empirical studies show that epidemiological models based on an epidemic’s initial spread rate often fail to predict the true scale of that epidemic. Most epidemics with a rapid early rise die out before affecting a significant fraction of the population, whereas the early pace of some pandemics is rather modest. Recent models suggest that this could be due to the heterogeneity of the target population’s susceptibility. We study a computer malware ecosystem exhibiting spread mechanisms resembling those of biological systems while offering details unavailable for human epidemics. Rather than comparing models, we directly estimate reach from a new and vastly more complete data from a parallel domain, that offers superior details and insight as concerns biological outbreaks. We find a highly heterogeneous distribution of computer susceptibilities, with nearly all outbreaks initially over-affecting the tail of the distribution, then collapsing quickly once this tail is depleted. This mechanism restricts the correlation between an epidemic’s initial growth rate and its total reach, thus preventing the majority of epidemics, including initially fast-growing outbreaks, from reaching a macroscopic fraction of the population. The few pervasive malwares distinguish themselves early on via the following key trait: they avoid infecting the tail, while preferentially targeting computers unaffected by typical malware.

På skidor i kulturella gränsland: Samiska spår i skidsportens historia

The aim of this compilation thesis is to shed light on the Sámi history of ski sport in Sweden from an organizational and cultural history perspective where concepts like nation and ethnicity fill an important function. The Sámi are an indigenous people living in Sápmi, a land area extending across the North Calotte region and including parts of Norway, Sweden, Finland and Russia. The thesis contains six separate articles which together comprise a research period extending between 1879 and 1990. The articles have been studied from different points of view with the focus on how skis as sport equipment have been historically charged with cultural expressions created by the individual skiers as well as by the general public’s interest in skiing. These cultural expressions have also been internalized as collective identification objects positioning the mutual relations between groups and collectives. By historical links to kings, heroic myths and polar expeditions, the sport of skiing has, for example, become associated with a national Swedish identity. By pinpointing its Sámi origins in the light of history, the ski sport is in this thesis instead viewed as a culturally heterogeneous phenomenon. In three of the articles of the thesis, the Sámi history of Swedish ski sport is studied. The focus of these studies lies on how ”Sáminess” and ”Swedishness”, viewed as cultural identities, were constructed in connection with the early rise and development of ski sport from the late 19th century to the interwar period (Articles I and II) as well as with the sporting career of downhill skier Bengt-Erik Grahn in the 1960s (Article V). The studies illustrate that, at its rise and early development, cross-country skiing in Sweden was regarded as a Sámi sport. In the early 20th century, however, an ethnic borderline was created between what was Sámi and what was Swedish, which gradually invisibilized the Sámi link to ski sport. Instead, cross-country skiing acquired the inofficial character of being the Swedish national sport. The three remaining studies investigate the separately organized Sámi sport movement from its rise in 1948 through the year 1990 (Articles III, IV and VI). The origin of this movement derives from the Sámi Championships, a winter event whose original contests include skiing and other sports with a background in reindeer husbandry. The articles clarify the importance of ski sport in creating contrastive ethnic identities between Sáminess and Swedishness (Articles I–V). Similarly, these constructed cultural markers of Sáminess and Swedishness have been interwoven to symbolize an overarching ethnic national identity (Articles IV–V). In addition, the way ski sport has been operated within the separately organized Sámi sport movement has carried weight in the creation of Sápmi as a crossborder nation (Article VI).

The Early Rise of Social Security in China: Ideas and Reforms, 1911–1949

Applying the editor’s “onion skin model” of social policy ideas, this chapter analyses the early rise of social security ideas and policies in Republican China (1911–1949). Facing imperialism, Chinese elites turned to Western social ideas to “save the nation”. They accepted organic concepts of society, leading to a concern for societal stability and harmony. The Guomindang (GMD) state reinforced this trend in the 1930s when the party-state incorporated Confucianism into its ideology. The GMD state, thus, adopted collectivist notions of social policy, emphasising class harmonisation and productivism. During the Sino-Japanese war, Chinese elites were attracted to the idea of universal social security, which led to an intense development of social security policies. In the entire process, however, Chinese elites emphasised China’s special situation.

Hepatocytes trap and silence coxsackieviruses, protecting against systemic disease in mice

Previous research suggests that hepatocytes catabolize chemical toxins but do not remove microbial agents, which are filtered out by other liver cells (Kupffer cells and endothelial cells). Here we show that, contrary to current understanding, hepatocytes trap and rapidly silence type B coxsackieviruses (CVBs). In genetically wildtype mice, this activity causes hepatocyte damage, which is alleviated in mice carrying a hepatocyte-specific deletion of the coxsackievirus-adenovirus receptor. However, in these mutant mice, there is a dramatic early rise in blood-borne virus, followed by accelerated systemic disease and increased mortality. Thus, wild type hepatocytes act similarly to a sponge for CVBs, protecting against systemic illness at the expense of their own survival. We speculate that hepatocytes may play a similar role in other viral infections as well, thereby explaining why hepatocytes have evolved their remarkable regenerative capacity. Our data also suggest that, in addition to their many other functions, hepatocytes might be considered an integral part of the innate immune system.

Multiscale model of heart growth during pregnancy: Integrating mechanical and hormonal signaling

Pregnancy stands at the interface of mechanics and biology. The growing fetus continuously loads the maternal organs as circulating hormone levels surge, leading to significant changes in mechanical and hormonal cues during pregnancy. In response to these cues, maternal soft tissues undergo remarkable growth and remodeling to support both mother and baby for a healthy pregnancy. We focus here on the maternal left ventricle, which increases its cardiac output and mass during pregnancy. The objective of this study is to build a multiscale cardiac growth model for pregnancy to understand how mechanical and hormonal cues interact to drive this growth process. Towards this objective, we coupled a cell signaling network model that predicts cell-level hypertrophy in response to hormones and stretch, to a compartmental model of the rat heart and circulation that predicts organ-level growth in response to hemodynamic changes. Since pregnancy is associated with a volume overloaded state and elevated hormones, we first calibrated the coupled, multiscale model to data from experimental volume overload (VO) and hormonal infusion of angiotensin 2 (AngII), estrogen (E2), and progesterone (P4). We then validated the ability of our model to capture interactions between inputs by comparing model predictions against published observations for the combinations of VO+E2 and AngII+E2. Finally, we simulated pregnancy-induced changes in hormones and hemodynamics to predict heart growth during pregnancy. Our multiscale model produced realistic heart growth consistent with experimental data. Overall, our analysis suggests that much of heart growth during pregnancy is driven by the early rise in P4, particularly during the first half of gestation. We conclude with suggestions for future experimental studies that will provide a better understanding of how hormonal and mechanical cues interact to drive pregnancy-induced heart growth.

Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial

Context Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. Design A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. Interventions and Outcome A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. Results Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126–129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24. Conclusion FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.