Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events

BACKGROUND: Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety. AIM: The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV. METHODS: A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher's exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha=0.05). RESULTS: The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p=0.28). CONCLUSION: The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs

Alternative reproductive tactics and evolutionary rescue

Almost all life on earth is facing environmental change, and understanding how populations will respond to these changes is of urgent importance. One factor that is known to affect the speed by which a population can evolve when faced with changes in the environment is strong sexual selection. This increases the adaptive capacity of a population by increasing reproductive skew toward well-adapted (usually) males who will, on average, be best able to compete for matings. This effect could potentially be disrupted when males pursue alternative reproductive tactics (ARTs), whereby males within a species exhibit qualitatively different behaviors in their pursuit of matings. ARTs are diverse, but one common class is those expressed through condition-dependent polyphenism such that high-quality, well-adapted males compete aggressively for mates and low-quality, poorly adapted males attempt to acquire matings via other, nonaggressive behaviors. Here, using an individual-based modeling approach, we consider the possible impacts of ARTs on adaptation and evolutionary rescue. When the ART is simultaneous, meaning that low-quality males not only engage in contests but also pursue other tactics, adaptive capacity is reduced and evolutionary rescue, where a population avoids extinction by adapting to a changing environment, becomes less likely. This is because the use of the ART allows low-quality males to contribute more maladaptive genes to the population than would happen otherwise. When the ART is fixed, however, such that low-quality males will only use the alternative tactic and do not engage in contests, we find the opposite: adaptation happens more quickly and evolutionary rescue when the environment changes is more likely. This surprising effect is caused by an increase in the mating success of the highest quality males who face many fewer competitors in this scenario—counterintuitively, the presence of males pursuing the ART increases reproductive skew toward those males in the best condition

Morph-specific investment in testes mass in a trimorphic beetle, Proagoderus watanabei

When competition between males for mates is intense, it is common to find that some males will adopt alternative tactics for acquiring fertilizations, often involving the use of ‘sneak’ tactics whereby males avoid precopulatory contests. These alternative tactics are sometimes associated with discrete differences in male morphology, with sneak males investing less in weaponry but more in traits such as testes which may give an advantage in sperm competition. In some cases, it appears that males develop into more than two morphs, with a number of examples of tri- and even tetramorphic arthropod species being described. Here, we analyse the scaling relations of the dung beetle species Proagoderus watanabei, which expresses two distinct weapon traits: paired head horns and a pronotal horn. We find that males of this species are trimorphic, with alpha males expressing long head horns and a pronotal horn, beta males with long head horns but no pronotal horn and gamma males with short head horns only. We also find that alpha males invest relatively less in testes than do beta or gamma males, indicating that beta and gamma males in this species probably experience higher risks of sperm competition than do alphas

Development of colonic fermentation in early life

Carbohydrates that escape digestion and absorption in the small intestine enter the colon where they are anaerobically metabohsed by the colonic bacteria. Colonic fermentation of carbohydrates produces short chain fatty acids (SCFA) (Cummings and Englyst, 1987) which are rapidly absorbed which salvages energy and prevents osmotic water loss (Kien et al., 1990). Bacterial colonic fermentation has been well investigated in adults but our knowledge in infants is limited. Neonatal diet and the weaning period are thought to be critical factors to the establishment of the intestinal microflora. The early events m bacterial colonisation of the gut may be critical in establishing the health of the infant as well as determining the properties of the adult flora. It is well established that the flora of breast-fed and formula-fed infants differs (Balmer and Wharton, 1989) and this is reflected in the profile of faecal SCFA (Edwards et al., 1994). However there is no information on the flora and faecal SCFA of infants that receive a mixture of breast milk and formula milk before weaning. As more mothers begin breast-feeding and then do not continue, this 'mixed fed' group are increasingly important in the UK. Little is known about the factors which change the colonic micro flora at weaning when infants are exposed to a wide range of new substrates. If substrates are undigested and unfermented these substrates will pass through the colon unmetabolised causing increased faecal output and possible diarrhoea. Very few studies have investigated the effect of weaning on the faecal flora. Many weaning foods will contain dietary fibre and other complex carbohydrates and it is important to know how easily these will be fermented and the effect these substrates will have on the development of the colonic microflora. We wished to test the hypothesis that neonatal feeding practice determines the rate and pattern of development of the colonic micro flora during weaning. After consideration of fermentation models an in vitro fermentation model (modified from Adiotomre et al., 1990) was chosen to determine the ability of infants to ferment a range of simple and complex carbohydrates. Breast-fed and formula-fed infants were investigated in a cross-sectional pilot study. Faecal samples were collected from infants at different stages during weaning. The cross-sectional study demonstrated that there were differences in the fermentation capacity of breast-fed and formula-fed infants. In formula-fed infants there was no difference between pre-, early and late weaning for any substrate. In breast-fed infants the ability to ferment raftilose increased at early weaning and the ability to ferment soyabean polysaccharide increased at late weaning. In both groups cultures containing soyabean polysaccharide, produced lower total SCFA than adults, even at late weaning. The pilot study indicated the need for a larger number of infants that would be followed longitudinally in order to draw definitive conclusions. The pilot study allowed us to design the longitudinal study which investigated the relative fermentation capacity for a wider range of carbohydrates. Results of the longitudinal study confirmed those of the cross-sectional study. All infant feeding groups were equally able to ferment the simple sugars and oligosaccharides at all development stages. There were significant increases in total SCFA produced in cultures containing the complex carbohydrates at late and very late weaning breastfed infants. In formula-fed infants no differences were seen between any development stage for any substrate, apart from an increase in total SCFA produced between pre- and late weaning. In mixed fed infants total SCFA produced in cultures containing pectin increased significantly at late weaning. With the other complex carbohydrates total SCFA produced increased at early weaning from pre-weaning. In all infant feeding groups, cultures containing complex carbohydrates produced lower levels of total SCFA than adults

Calving distribution of the Teshekpuk caribou herd, 1994-2003

Parturient female caribou from the Teshekpuk caribou (Rangifer tarandus granti) herd (TCH) have been observed across the western North Slope, but most cows that were seen with calves during the calving period were in the area surrounding Teshekpuk Lake. During surveys conducted between 1994 and 2003, 155 (91%) of 171 collared cows seen with calves were within an area given protected status in the 1998 Bureau of Land Management Final Integrated Activity Plan/Environmental Impact Statement (IAP/EIS). The percentage of adult collared cows seen with a calf between 1994 and 2003 has ranged from 44% to 86%, with a mean of 66%. The years with the lowest percentage of collared cows seen with calves were 1997 (50%) and 2001 (44%). In 1997 most of the herd migrated much farther south than usual, and in 2001 unusually deep, persistent snow restricted spring migration, resulting in fewer cows returning to the traditional calving area during the calving period. When snowmelt dates were earlier, calving locations were farther north. Average standardized travel rates for parturient cows were significantly greater before they had calves (7.25 km/day) than after 3.89 (km/day). Geographically, protections granted by the 1998 BLM IAP/EIS appear to adequately cover the concentrated calving grounds, allowing for variance in the annual distribution of calving cows

Did a workplace sugar-sweetened beverage sales ban reduce anxiety-related sugar-sweetened beverage consumption during the COVID-19 pandemic?

ObjectiveWorkplace sugar-sweetened beverage (SSB) sales bans can reduce SSB consumption. Because stress and anxiety can promote sugar consumption, we examined whether anxiety among hospital employees during the COVID-19 pandemic was associated with changes in SSB consumption and explored whether this relationship varied by exposure to a workplace SSB sales ban.DesignIn a prospective, controlled trial of workplace SSB sales bans, we examined self-reported anxiety (generalised anxiety disorder-7) and self-reported SSB consumption (fluid ounces/d) before (July 2019) and during (May 2020) the COVID-19 pandemic.SettingHospital sites in two conditions (four with SSB sales bans and three without sales bans) in Northern California.ParticipantsWe sampled 580 participants (hospital employees) from a larger trial of sales bans; all were regular consumers of SSB (minimum 3/week at main trial enrollment). This subsample was chosen based on having appropriately timed data for our study questions.ResultsAcross conditions, participants reduced SSB consumption over the study period. However, participants with higher pandemic-era anxiety scores experienced smaller reductions in SSB consumption after 9 months compared with those with lower anxiety scores (β = 0·65, P < 0·05). When the sample was disaggregated by sales ban condition, this relationship held for participants in the control group (access to SSB at work, β = 0·82, P < 0·05), but not for those exposed to an SSB sales ban (β = 0·42, P = 0·25).ConclusionsSSB sales bans likely reduce SSB consumption through multiple pathways; buffering stress-related consumption may be one mechanism

Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis

Background: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non- susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed. S. mitis-oralis strain 351-D10 was made daptomycin non- susceptible through serial passage in the presence of daptomycin. Background: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non- susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed. S. mitis-oralis strain 351-D10 was made daptomycin non- susceptible through serial passage in the presence of daptomycin. Conclusions: S. mitis-oralis metabolism is altered in daptomycin non-susceptible bacteria relative to the daptomycin susceptible parent strain. As demonstrated in Staphylococcus aureus, inhibiting the metabolic changes that facilitate the transition from a daptomycin susceptible state to a non-susceptible one, inhibits daptomycin non- susceptibility. By preventing these metabolic adaptations in S. mitis-oralis, it should be possible to deter the formation of daptomycin non-susceptibility

Fishers who rely on mangroves: Modelling and mapping the global intensity of mangrove-associated fisheries

Mangroves are critical nursery habitats for fish and invertebrates, providing livelihoods for many coastal communities. Despite their importance, there is currently no estimate of the number of fishers engaged in mangrove associated fisheries, nor of the fishing intensity associated with mangroves at a global scale. We address these gaps by developing a global model of mangrove associated fisher numbers and mangrove fishing intensity. To develop the model, we undertook a three-round Delphi process with mangrove fisheries experts to identify the key drivers of mangrove fishing intensity. We then developed a conceptual model of intensity of mangrove fishing using those factors identified both as being important and for which appropriate global data could be found or developed. These factors were non-urban population, distance to market, distance to mangroves and other fishing grounds, and storm events. By projecting this conceptual model using geospatial datasets, we were able to estimate the number and distribution of mangrove associated fishers and the intensity of fishing in mangroves. We estimate there are 4.1 million mangrove associated fishers globally, with the highest number of mangrove fishers found in Indonesia, India, Bangladesh, Myanmar, and Brazil. Mangrove fishing intensity was greatest throughout Asia, and to a lesser extent West and Central Africa, and Central and South America

Controlled trial of a workplace sales ban on sugar-sweetened beverages

Abstract Objective: To examine the effectiveness of a workplace sugar-sweetened beverage (SSB) sales ban on reducing SSB consumption in employees, including those with cardiometabolic disease risk factors. Design: A controlled trial of ethnically diverse, full-time employees who consumed SSB heavily (sales ban n 315; control n 342). Outcomes included standardised measures of change in SSB consumption in the workplace (primary) and at home between baseline and 6 months post-sales ban. Setting: Sutter Health, a large non-profit healthcare delivery system in Northern California. Participants: Full-time employees at Sutter Health screened for heavy SSB consumption. Results: Participants were 66·1 % non-White. On average, participants consumed 34·7 ounces (about 1 litre) of SSB per d, and the majority had an elevated baseline BMI (mean = 29·5). In adjusted regression analyses, those exposed to a workplace SSB sales ban for 6 months consumed 2·7 (95 % CI –4·9, –0·5) fewer ounces of SSB per d while at work, and 4·3 (95 % CI –8·4, –0·2) fewer total ounces per d, compared to controls. Sales ban participants with an elevated BMI or waist circumference had greater post-intervention reductions in workplace SSB consumption. Conclusions: Workplace sales bans can reduce SSB consumption in ethnically diverse employee populations, including those at higher risk for cardiometabolic disease

Promoter methylation regulates cyclooxygenase expression in breast cancer

INTRODUCTION: Overexpression of cyclooxygenase (COX-2) is commonly observed in human cancers. In a murine model of metastatic breast cancer, we observed that COX-2 expression and enzyme activity were associated with enhanced tumorigenic and metastatic potential. In contrast to the high COX-2 expression in metastatic tumors, transplantation of poorly tumorigenic tumor cell lines to syngeneic mice results in less COX-2 expression and less COX-2 activity in vivo. Aberrant CpG island methylation, and subsequent silencing of the COX-2 promoter, has been observed in human cancer cell lines and in some human tumors of the gastrointestinal tract. METHODS: Using bisulfite modification and a methylation-specific PCR, we examined the methylation status of the COX-2 promoter in a series of four closely-related murine mammary tumors differing in COX-2 expression and metastatic potential. RESULTS: We showed that line 410, which does not express COX-2 in vivo, exhibited evidence of promoter methylation. Interestingly, the metastatic counterpart of this cell (line 410.4) displayed only the unmethylated COX-2 promoter, as did two additional cell lines (lines 66.1 and 67). The methylation patterns observed in vitro were maintained when these murine mammary tumor lines were transplanted to syngeneic mice. Treatment with the DNA demethylating agent 5-aza-deoxycytidine increased COX-2 mRNA, increased protein and increased enzyme activity (prostaglandin synthesis). CONCLUSIONS: These results indicate that COX-2 promoter methylation may be one mechanism by which tumor cells regulate COX-2 expression. Upregulation of COX-2 expression in closely related metastatic lesions versus nonmetastatic lesions may represent a shift towards the unmethylated phenotype