Immune stimulation with short-term exposure to extremely low frequency electromagnetic fields in mice (Mus. musculus)

Thesis (M. Tech. (Biomedical Technology)) -- Central University of technology, Free State, 2013Electromagnetic fields are present wherever electricity is created. The frequency range of these electromagnetic fields is from extremely low to extremely high. The fields present in domestic areas fall within the extremely low frequency range. These fields are created by domestic electrical appliances and telecommunication. There has been much debate on the effect of exposure to these fields on human health. Research has not yet been able to prove adverse effect of these fields on human health. In fact, the benefits of magneto therapy has been recognized and used for several decades. Recently a specific electromagnetic signal has been under investigation for its ability to stimulate the immune response. This signal is produced by a patented generator, called Immunent Activator. Studies performed with the Immunent Activator signal on farm animals revealed increased feed conversion and decreased intestinal lesions of animals with intestinal infections. Most of the research was performed on fish and fowls and evidence of similar findings in mammals is lacking. In the current study, mice were exposed to the Immunent BV signal for seven days, after which immune cell counts were performed and compared to the immune cell counts of a control group of mice which received no electromagnetic exposure. It was found that the T-lymphocyte population of immune cells in the exposed group of mice was statistically significantly higher than that of the control group. The neutrophil count was statistically significantly lower in the exposed group compared to the control group. These findings revealed evidence of immune stimulation in the mice which were exposed to the Immunent Activator signal. Suggestions for further research could be made with regard to specific mechanisms of immune stimulation. The findings of this and other related studies hold benefits for the farming and health industry

Genetic background impacts developmental potential of enteric neural crest-derived progenitors in the Sox10Dom model of Hirschsprung disease

Abnormalities in the development of enteric neural crest-derived progenitors (ENPs) that generate the enteric nervous system (ENS) can lead to aganglionosis in a variable portion of the distal gastrointestinal tract. Cumulative evidence suggests that variation of aganglionosis is due to gene interactions that modulate the ability of ENPs to populate the intestine; however, the developmental processes underlying this effect are unknown. We hypothesized that differences in enteric ganglion deficits could be attributable to the effects of genetic background on early developmental processes, including migration, proliferation, or lineage divergence. Developmental processes were investigated in congenic Sox10Dom mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B6) and C3HeB/FeJ (C3Fe). Immuno-staining on whole-mount fetal gut tissue and dissociated cell suspensions was used to assess migration and proliferation. Flow cytometry utilizing the cell surface markers p75 and HNK-1 was used to isolate live ENPs for analysis of developmental potential. Frequency of ENPs was reduced in Sox10Dom embryos relative to wild-type embryos, but was unaffected by genetic background. Both migration and developmental potential of ENPs in Sox10Dom embryos were altered by inbred strain background with the most highly significant differences seen for developmental potential between strains and genotypes. In vivo imaging of fetal ENPs and postnatal ganglia demonstrates that altered lineage divergence impacts ganglia in the proximal intestine. Our analysis demonstrates that genetic background alters early ENS development and suggests that abnormalities in lineage diversification can shift the proportions of ENP populations and thus may contribute to ENS deficiencies in vivo

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee

State of the climate in 2017

In 2017, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-reached new record highs. The annual global average carbon dioxide concentration at Earth's surface for 2017 was 405.0 ± 0.1 ppm, 2.2 ppm greater than for 2016 and the highest in the modern atmospheric measurement record and in ice core records dating back as far as 800 000 years. The global growth rate of CO2 has nearly quadrupled since the early 1960s. With ENSO-neutral conditions present in the central and eastern equatorial Pacific Ocean during most of the year and weak La Niña conditions notable at the start and end, the global temperature across land and ocean surfaces ranked as the second or third highest, depending on the dataset, since records began in the mid-to-late 1800s. Notably, it was the warmest non-El Niño year in the instrumental record. Above Earth's surface, the annual lower tropospheric temperature was also either second or third highest according to all datasets analyzed. The lower stratospheric temperature was about 0.2°C higher than the record cold temperature of 2016 according to most of the in situ and satellite datasets. Several countries, including Argentina, Uruguay, Spain, and Bulgaria, reported record high annual temperatures. Mexico broke its annual record for the fourth consecutive year. On 27 January, the temperature reached 43.4°C at Puerto Madryn, Argentina-the highest temperature recorded so far south (43°S) anywhere in the world. On 28 May in Turbat, western Pakistan, the high of 53.5°C tied Pakistan's all-time highest temperature and became the world-record highest temperature for May. In the Arctic, the 2017 land surface temperature was 1.6°C above the 1981-2010 average, the second highest since the record began in 1900, behind only 2016. The five highest annual Arctic temperatures have all occurred since 2007. Exceptionally high temperatures were observed in the permafrost across the Arctic, with record values reported in much of Alaska and northwestern Canada. In August, high sea surface temperature (SST) records were broken for the Chukchi Sea, with some regions as warm as +11°C, or 3° to 4°C warmer than the longterm mean (1982-present). According to paleoclimate studies, today's abnormally warm Arctic air and SSTs have not been observed in the last 2000 years. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 7 March, sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, covering 8% less area than the 1981-2010 average. The Arctic sea ice minimum on 13 September was the eighth lowest on record and covered 25% less area than the long-term mean. Preliminary data indicate that glaciers across the world lost mass for the 38th consecutive year on record; the declines are remarkably consistent from region to region. Cumulatively since 1980, this loss is equivalent to slicing 22 meters off the top of the average glacier. Antarctic sea ice extent remained below average for all of 2017, with record lows during the first four months. Over the continent, the austral summer seasonal melt extent and melt index were the second highest since 2005, mostly due to strong positive anomalies of air temperature over most of the West Antarctic coast. In contrast, the East Antarctic Plateau saw record low mean temperatures in March. The year was also distinguished by the second smallest Antarctic ozone hole observed since 1988. Across the global oceans, the overall long-term SST warming trend remained strong. Although SST cooled slightly from 2016 to 2017, the last three years produced the three highest annual values observed; these high anomalies have been associated with widespread coral bleaching. The most recent global coral bleaching lasted three full years, June 2014 to May 2017, and was the longest, most widespread, and almost certainly most destructive such event on record. Global integrals of 0-700-m and 0-2000-m ocean heat content reached record highs in 2017, and global mean sea level during the year became the highest annual average in the 25-year satellite altimetry record, rising to 77 mm above the 1993 average. In the tropics, 2017 saw 85 named tropical storms, slightly above the 1981-2010 average of 82. The North Atlantic basin was the only basin that featured an above-normal season, its seventh most active in the 164-year record. Three hurricanes in the basin were especially notable. Harvey produced record rainfall totals in areas of Texas and Louisiana, including a storm total of 1538.7 mm near Beaumont, Texas, which far exceeds the previous known U.S. tropical cyclone record of 1320.8 mm. Irma was the strongest tropical cyclone globally in 2017 and the strongest Atlantic hurricane outside of the Gulf of Mexico and Caribbean on record with maximum winds of 295 km h-1. Maria caused catastrophic destruction across the Caribbean Islands, including devastating wind damage and flooding across Puerto Rico. Elsewhere, the western North Pacific, South Indian, and Australian basins were all particularly quiet. Precipitation over global land areas in 2017 was clearly above the long-term average. Among noteworthy regional precipitation records in 2017, Russia reported its second wettest year on record (after 2013) and Norway experienced its sixth wettest year since records began in 1900. Across India, heavy rain and flood-related incidents during the monsoon season claimed around 800 lives. In August and September, above-normal precipitation triggered the most devastating floods in more than a decade in the Venezuelan states of Bolívar and Delta Amacuro. In Nigeria, heavy rain during August and September caused the Niger and Benue Rivers to overflow, bringing floods that displaced more than 100 000 people. Global fire activity was the lowest since at least 2003; however, high activity occurred in parts of North America, South America, and Europe, with an unusually long season in Spain and Portugal, which had their second and third driest years on record, respectively. Devastating fires impacted British Columbia, destroying 1.2 million hectares of timber, bush, and grassland, due in part to the region's driest summer on record. In the United States, an extreme western wildfire season burned over 4 million hectares; the total costs of $18 billion tripled the previous U.S. annual wildfire cost record set in 1991

State of the climate in 2017

In 2017, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-reached new record highs. The annual global average carbon dioxide concentration at Earth's surface for 2017 was 405.0 ± 0.1 ppm, 2.2 ppm greater than for 2016 and the highest in the modern atmospheric measurement record and in ice core records dating back as far as 800 000 years. The global growth rate of CO2 has nearly quadrupled since the early 1960s. With ENSO-neutral conditions present in the central and eastern equatorial Pacific Ocean during most of the year and weak La Niña conditions notable at the start and end, the global temperature across land and ocean surfaces ranked as the second or third highest, depending on the dataset, since records began in the mid-to-late 1800s. Notably, it was the warmest non-El Niño year in the instrumental record. Above Earth's surface, the annual lower tropospheric temperature was also either second or third highest according to all datasets analyzed. The lower stratospheric temperature was about 0.2°C higher than the record cold temperature of 2016 according to most of the in situ and satellite datasets. Several countries, including Argentina, Uruguay, Spain, and Bulgaria, reported record high annual temperatures. Mexico broke its annual record for the fourth consecutive year. On 27 January, the temperature reached 43.4°C at Puerto Madryn, Argentina-the highest temperature recorded so far south (43°S) anywhere in the world. On 28 May in Turbat, western Pakistan, the high of 53.5°C tied Pakistan's all-time highest temperature and became the world-record highest temperature for May. In the Arctic, the 2017 land surface temperature was 1.6°C above the 1981-2010 average, the second highest since the record began in 1900, behind only 2016. The five highest annual Arctic temperatures have all occurred since 2007. Exceptionally high temperatures were observed in the permafrost across the Arctic, with record values reported in much of Alaska and northwestern Canada. In August, high sea surface temperature (SST) records were broken for the Chukchi Sea, with some regions as warm as +11°C, or 3° to 4°C warmer than the longterm mean (1982-present). According to paleoclimate studies, today's abnormally warm Arctic air and SSTs have not been observed in the last 2000 years. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 7 March, sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, covering 8% less area than the 1981-2010 average. The Arctic sea ice minimum on 13 September was the eighth lowest on record and covered 25% less area than the long-term mean. Preliminary data indicate that glaciers across the world lost mass for the 38th consecutive year on record; the declines are remarkably consistent from region to region. Cumulatively since 1980, this loss is equivalent to slicing 22 meters off the top of the average glacier. Antarctic sea ice extent remained below average for all of 2017, with record lows during the first four months. Over the continent, the austral summer seasonal melt extent and melt index were the second highest since 2005, mostly due to strong positive anomalies of air temperature over most of the West Antarctic coast. In contrast, the East Antarctic Plateau saw record low mean temperatures in March. The year was also distinguished by the second smallest Antarctic ozone hole observed since 1988. Across the global oceans, the overall long-term SST warming trend remained strong. Although SST cooled slightly from 2016 to 2017, the last three years produced the three highest annual values observed; these high anomalies have been associated with widespread coral bleaching. The most recent global coral bleaching lasted three full years, June 2014 to May 2017, and was the longest, most widespread, and almost certainly most destructive such event on record. Global integrals of 0-700-m and 0-2000-m ocean heat content reached record highs in 2017, and global mean sea level during the year became the highest annual average in the 25-year satellite altimetry record, rising to 77 mm above the 1993 average. In the tropics, 2017 saw 85 named tropical storms, slightly above the 1981-2010 average of 82. The North Atlantic basin was the only basin that featured an above-normal season, its seventh most active in the 164-year record. Three hurricanes in the basin were especially notable. Harvey produced record rainfall totals in areas of Texas and Louisiana, including a storm total of 1538.7 mm near Beaumont, Texas, which far exceeds the previous known U.S. tropical cyclone record of 1320.8 mm. Irma was the strongest tropical cyclone globally in 2017 and the strongest Atlantic hurricane outside of the Gulf of Mexico and Caribbean on record with maximum winds of 295 km h-1. Maria caused catastrophic destruction across the Caribbean Islands, including devastating wind damage and flooding across Puerto Rico. Elsewhere, the western North Pacific, South Indian, and Australian basins were all particularly quiet. Precipitation over global land areas in 2017 was clearly above the long-term average. Among noteworthy regional precipitation records in 2017, Russia reported its second wettest year on record (after 2013) and Norway experienced its sixth wettest year since records began in 1900. Across India, heavy rain and flood-related incidents during the monsoon season claimed around 800 lives. In August and September, above-normal precipitation triggered the most devastating floods in more than a decade in the Venezuelan states of Bolívar and Delta Amacuro. In Nigeria, heavy rain during August and September caused the Niger and Benue Rivers to overflow, bringing floods that displaced more than 100 000 people. Global fire activity was the lowest since at least 2003; however, high activity occurred in parts of North America, South America, and Europe, with an unusually long season in Spain and Portugal, which had their second and third driest years on record, respectively. Devastating fires impacted British Columbia, destroying 1.2 million hectares of timber, bush, and grassland, due in part to the region's driest summer on record. In the United States, an extreme western wildfire season burned over 4 million hectares; the total costs of $18 billion tripled the previous U.S. annual wildfire cost record set in 1991