Sap flow through partially embolized xylem vessel networks.

Sap is transported through numerous conduits in the xylem of woody plants along the path from the soil to the leaves. When all conduits are functional, vessel lumen diameter is a strong predictor of hydraulic conductivity. As vessels become embolized, sap movement becomes increasingly affected by factors operating at scales beyond individual conduits, creating resistances that result in hydraulic conductivity diverging from diameter-based estimates. These effects include pit resistances, connectivity, path length, network topology, and vessel or sector isolation. The impact of these factors varies with the level and distribution of emboli within the network, and manifest as alterations in the relationship between the number and diameter of embolized vessels with measured declines in hydraulic conductivity across vulnerability to embolism curves. Divergences between measured conductivity and diameter-based estimates reveal functional differences that arise because of species- and tissue-specific vessel network structures. Such divergences are not uniform, and xylem tissues may diverge in different ways and to differing degrees. Plants regularly operate under nonoptimal conditions and contain numerous embolized conduits. Understanding the hydraulic implications of emboli within a network and the function of partially embolized networks are critical gaps in our understanding of plants occurring within natural environments.

Tuberculosis - United States, 2023.

After 27 years of declining U.S. tuberculosis (TB) case counts, the number of TB cases declined considerably in 2020, coinciding with the COVID-19 pandemic. For this analysis, TB case counts were obtained from the National TB Surveillance System. U.S. Census Bureau population estimates were used to calculate rates overall, by jurisdiction, birth origin, race and ethnicity, and age group. Since 2020, TB case counts and rates have increased each year. During 2023, a total of 9,615 TB cases were provisionally reported by the 50 U.S. states and the District of Columbia (DC), representing an increase of 1,295 cases (16%) as compared with 2022. The rate in 2023 (2.9 per 100,000 persons) also increased compared with that in 2022 (2.5). Forty states and DC reported increases in 2023 in both case counts and rates. National case counts increased among all age groups and among both U.S.-born and non-U.S.-born persons. Although TB incidence in the United States is among the lowest in the world and most U.S. residents are at minimal risk, TB continues to cause substantial global morbidity and mortality. This postpandemic increase in U.S. cases highlights the importance of continuing to engage communities with higher TB rates and their medical providers in TB elimination efforts and strengthening the capacity in public health programs to carry out critical disease control and prevention strategies.

Tuberculosis - United States, 2022.

Incidence of reported tuberculosis (TB) decreased gradually in the United States during 1993-2019, reaching 2.7 cases per 100,000 persons in 2019. Incidence substantially declined in 2020 to 2.2, coinciding with the COVID-19 pandemic (1). Proposed explanations for the decline include delayed or missed TB diagnoses, changes in migration and travel, and mortality among persons susceptible to TB reactivation (1). Disparities (e.g., by race and ethnicity) in TB incidence have been described (2). During 2021, TB incidence partially rebounded (to 2.4) but remained substantially below that during prepandemic years, raising concerns about ongoing delayed diagnoses (1). During 2022, the 50 U.S. states and the District of Columbia (DC) provisionally reported 8,300 TB cases to the National Tuberculosis Surveillance System. TB incidence was calculated using midyear population estimates and stratified by birth origin and by race and ethnicity. During 2022, TB incidence increased slightly to 2.5 although it remained lower than during prepandemic years.* Compared with that in 2021, TB epidemiology in 2022 was characterized by more cases among non-U.S.-born persons newly arrived in the United States; higher TB incidence among non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons and persons aged ≤4 and 15-24 years; and slightly lower incidence among persons aged ≥65 years. TB incidence appears to be returning to prepandemic levels. TB disparities persist; addressing these disparities requires timely TB diagnosis and treatment to interrupt transmission and prevention of TB through treatment of latent TB infection (LTBI).

Forest and woodland replacement patterns following drought-related mortality.

Forest vulnerability to drought is expected to increase under anthropogenic climate change, and drought-induced mortality and community dynamics following drought have major ecological and societal impacts. Here, we show that tree mortality concomitant with drought has led to short-term (mean 5 y, range 1 to 23 y after mortality) vegetation-type conversion in multiple biomes across the world (131 sites). Self-replacement of the dominant tree species was only prevalent in 21% of the examined cases and forests and woodlands shifted to nonwoody vegetation in 10% of them. The ultimate temporal persistence of such changes remains unknown but, given the key role of biological legacies in long-term ecological succession, this emerging picture of postdrought ecological trajectories highlights the potential for major ecosystem reorganization in the coming decades. Community changes were less pronounced under wetter postmortality conditions. Replacement was also influenced by management intensity, and postdrought shrub dominance was higher when pathogens acted as codrivers of tree mortality. Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern postdrought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services.

Tuberculosis - United States, 2021.

During 1993-2019, the incidence of tuberculosis (TB) in the United States decreased steadily; however, during the later years of that period the annual rate of decline slowed (1) until 2020 when a substantial decline (19.9%) was observed. This sharp decrease in TB incidence might have been related to multiple factors coinciding with the COVID-19 pandemic, including delayed or missed TB diagnoses or a true reduction in TB incidence related to pandemic mitigation efforts and changes in immigration and travel (2). During 2021, a total of 7,860 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC). National incidence of reported TB (cases per 100,000 persons) rose 9.4% during 2021 (2.37) compared with that in 2020 (2.16) but remained 12.6% lower than the rate during 2019 (2.71).* During 2021, TB incidence increased among both U.S.-born and non-U.S.-born persons. The increased TB incidence observed during 2021 compared with 2020 might be partially explained by delayed diagnosis of cases in persons with symptom onset during 2020; however, the continued, substantial reduction from prepandemic levels raises concern for ongoing underdiagnosis. TB control and prevention services, including early diagnosis and complete treatment of TB and latent TB infection, should be maintained and TB awareness promoted to achieve elimination in the United States.

Tuberculosis - United States, 2020.

Tuberculosis (TB) disease incidence has decreased steadily since 1993 (1), a result of decades of work by local TB programs to detect, treat, and prevent TB disease and transmission. During 2020, a total of 7,163 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC), a relative reduction of 20%, compared with the number of cases reported during 2019.* TB incidence per 100,000 persons was 2.2 during 2020, compared with 2.7 during 2019. Since 2010, TB incidence has decreased by an average of 2%-3% annually (1). Pandemic mitigation efforts and reduced travel might have contributed to the reported decrease. The magnitude and breadth of the decrease suggest potentially missed or delayed TB diagnoses. Health care providers should consider TB disease when evaluating patients with signs and symptoms consistent with TB (e.g., cough of >2 weeks in duration, unintentional weight loss, and hemoptysis), especially when diagnostic tests are negative for SARS-CoV-2, the virus that causes COVID-19. In addition, members of the public should be encouraged to follow up with their health care providers for any respiratory illness that persists or returns after initial treatment. The steep, unexpected decline in TB cases raises concerns of missed cases, and further work is in progress to better understand factors associated with the decline.

Reduced viscosity mutants of Trichoderma reesei with improved industrial fermentation characteristics.

Morphological mutants of Trichoderma reesei were isolated following chemical or insertional mutagenesis. The mutant strains were shown to have reduced viscosity under industrially relevant fermentation conditions and to have maintained high specific productivity of secreted protein. This allowed higher biomass concentration to be maintained during the production phase and, consequently, increased volumetric productivity of secreted protein. The causative mutations were traced to four individual genes (designated sfb3, ssb7, seb1, and mpg1). We showed that two of the morphological mutations could be combined in a single strain to further reduce viscosity and enable a 100% increase in volumetric productivity.

Tuberculosis - United States, 2019.

Since 1989, the United States has pursued a goal of eliminating tuberculosis (TB) through a strategy of rapidly identifying and treating cases and evaluating exposed contacts to limit secondary cases resulting from recent TB transmission (1). This strategy has been highly effective in reducing U.S. TB incidence (2), but the pace of decline has significantly slowed in recent years (2.2% average annual decline during 2012-2017 compared with 6.7% during 2007-2012) (3). For this report, provisional 2019 data reported to CDC's National Tuberculosis Surveillance System were analyzed to determine TB incidence overall and for selected subpopulations and these results were compared with those from previous years. During 2019, a total of 8,920 new cases were provisionally reported in the United States, representing a 1.1% decrease from 2018.* TB incidence decreased to 2.7 cases per 100,000 persons, a 1.6% decrease from 2018. Non-U.S.-born persons had a TB rate 15.5 times greater than the rate among U.S.-born persons. The U.S. TB case count and rate are the lowest ever reported, but the pace of decline remains slow. In recent years, approximately 80% of U.S. TB cases have been attributed to reactivation of latent TB infection (LTBI) acquired years in the past, often outside the United States (2). An expanded TB elimination strategy for this new decade should leverage existing health care resources, including primary care providers, to identify and treat persons with LTBI, without diverting public health resources from the continued need to limit TB transmission within the United States. Partnerships with health care providers, including private providers, are essential for this strategy's success.

Tuberculosis - United States, 2017.

In 2017, a total of 9,093 new cases of tuberculosis (TB) were provisionally* reported in the United States, representing an incidence rate of 2.8 cases per 100,000 population. The case count decreased by 1.8% from 2016 to 2017, and the rate declined by 2.5% over the same period. These decreases are consistent with the slight decline in TB seen over the past several years (1). This report summarizes provisional TB surveillance data reported to CDC's National Tuberculosis Surveillance System for 2017 and in the last decade. The rate of TB among non-U.S.-born persons in 2017 was 15 times the rate among U.S.-born persons. Among non-U.S.-born persons, the highest TB rate among all racial/ethnic groups was among Asians (27.0 per 100,000 persons), followed by non-Hispanic blacks (blacks; 22.0). Among U.S.-born persons, most TB cases were reported among blacks (37.1%), followed by non-Hispanic whites (whites; 29.5%). Previous studies have shown that the majority of TB cases in the United States are attributed to reactivation of latent TB infection (LTBI) (2). Ongoing efforts to prevent TB transmission and disease in the United States remain important to continued progress toward TB elimination. Testing and treatment of populations most at risk for TB disease and LTBI, including persons born in countries with high TB prevalence and persons in high-risk congregate settings (3), are major components of this effort.

Epidemiology of Pediatric Multidrug-Resistant Tuberculosis in the United States, 1993-2014.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global public health threat, but accurate estimates of MDR-TB burden among children are lacking. METHODS: We analyzed demographic, clinical, and laboratory data for newly diagnosed pediatric (age <15 years) TB cases reported to the US National TB Surveillance System during 1993-2014. MDR-TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential underestimation of pediatric MDR-TB, we surveyed high-burden states for clinically diagnosed cases treated for MDR-TB. RESULTS: Of 20789 pediatric TB cases, 5162 (24.8%) had bacteriologically confirmed TB. Among 4826 (93.5%) with drug susceptibility testing, 82 (1.7%) had MDR-TB. Most pediatric MDR-TB cases were female (n = 51 [62%]), median age was 5 years (interquartile range, 1-12 years), one-third were Hispanic (n = 28 [34%]), and two-thirds (n = 55 [67%]) were born in the United States. Most cases had additional resistance to ≥1 other first-line drug (n = 66 [81%]) and one-third had resistance to ≥1 second-line drug (24/73 tested). Of 77 who started treatment prior to 2013, 66 (86%) completed treatment and 4 (5%) died. Among the 4 high-TB-burden states/jurisdictions surveyed, there was 42%-55% underestimation of pediatric MDR-TB cases when using only culture-confirmed case definitions. CONCLUSIONS: Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR-TB burden in the United States using strictly bacteriologic criteria. Better estimates of pediatric MDR-TB burden in the United States are needed and should include clinical diagnoses based on epidemiologic criteria.

Tuberculosis - United States, 2016.

In 2016, a total of 9,287 new tuberculosis (TB) cases were reported in the United States; this provisional* count represents the lowest number of U.S. TB cases on record and a 2.7% decrease from 2015 (1). The 2016 TB incidence of 2.9 cases per 100,000 persons represents a slight decrease compared with 2015 (-3.4%) (Figure). However, epidemiologic modeling demonstrates that if similar slow rates of decline continue, the goal of U.S. TB elimination will not be reached during this century (2). Although current programs to identify and treat active TB disease must be maintained and strengthened, increased measures to identify and treat latent TB infection (LTBI) among populations at high risk are also needed to accelerate progress toward TB elimination.

Human Tuberculosis Caused by Mycobacterium bovis in the United States, 2006-2013.

BACKGROUND: Using genotyping techniques that have differentiated Mycobacterium bovis from Mycobacterium tuberculosis since 2005, we review the epidemiology of human tuberculosis caused by M. bovis in the United States and validate previous findings nationally. METHODS: All tuberculosis cases with a genotyped M. tuberculosis complex isolate reported during 2006-2013 in the United States were eligible for analysis. We used binomial regression to identify characteristics independently associated with M. bovis disease using adjusted prevalence ratios (aPRs) and corresponding 95% confidence intervals (CIs). RESULTS: During 2006-2013, the annual percentages of tuberculosis cases attributable to M. bovis remained consistent nationally (range, 1.3%-1.6%) among all tuberculosis cases (N = 59 273). Compared with adults 25-44 years of age, infants aged 0-4 years (aPR, 1.9 [95% CI, 1.4-2.8]) and children aged 5-14 years (aPR, 4.0 [95% CI, 3.1-5.3]) had higher prevalences of M. bovis disease. Patients who were foreign-born (aPR, 1.4 [95% CI, 1.2-1.7]), Hispanic (aPR, 3.9 [95% CI, 3.0-5.0]), female (aPR, 1.4 [95% CI, 1.3-1.6]), and resided in US-Mexico border counties (aPR, 2.0 [95% CI, 1.7-2.4]) also had higher M. bovis prevalences. Exclusively extrapulmonary disease (aPR, 3.7 [95% CI, 3.3-4.2]) or disease that was both pulmonary and extrapulmonary (aPR, 2.4 [95% CI, 2.1-2.9]) were associated with a higher prevalence of M. bovis disease. CONCLUSIONS: Children, foreign-born persons, Hispanics, and females are disproportionately affected by M. bovis, which was independently associated with extrapulmonary disease. Targeted prevention efforts aimed at Hispanic mothers and caregivers are warranted.

Mind the gap: TB trends in the USA and the UK, 2000-2011.

BACKGROUND: TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. METHODS: We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. FINDINGS: A total of 259,609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100,000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100,000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p<0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p<0.01). INTERPRETATION: To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years.

Weak tradeoff between xylem safety and xylem-specific hydraulic efficiency across the world's woody plant species.

The evolution of lignified xylem allowed for the efficient transport of water under tension, but also exposed the vascular network to the risk of gas emboli and the spread of gas between xylem conduits, thus impeding sap transport to the leaves. A well-known hypothesis proposes that the safety of xylem (its ability to resist embolism formation and spread) should trade off against xylem efficiency (its capacity to transport water). We tested this safety-efficiency hypothesis in branch xylem across 335 angiosperm and 89 gymnosperm species. Safety was considered at three levels: the xylem water potentials where 12%, 50% and 88% of maximal conductivity are lost. Although correlations between safety and efficiency were weak (r(2)  < 0.086), no species had high efficiency and high safety, supporting the idea for a safety-efficiency tradeoff. However, many species had low efficiency and low safety. Species with low efficiency and low safety were weakly associated (r(2)  < 0.02 in most cases) with higher wood density, lower leaf- to sapwood-area and shorter stature. There appears to be no persuasive explanation for the considerable number of species with both low efficiency and low safety. These species represent a real challenge for understanding the evolution of xylem.

Leveling of Tuberculosis Incidence - United States, 2013-2015.

After 2 decades of progress toward tuberculosis (TB) elimination with annual decreases of ≥0.2 cases per 100,000 persons (1), TB incidence in the United States remained approximately 3.0 cases per 100,000 persons during 2013-2015. Preliminary data reported to the National Tuberculosis Surveillance System indicate that TB incidence among foreign-born persons in the United States (15.1 cases per 100,000) has remained approximately 13 times the incidence among U.S.-born persons (1.2 cases per 100,000). Resuming progress toward TB elimination in the United States will require intensification of efforts both in the United States and globally, including increasing U.S. efforts to detect and treat latent TB infection, strengthening systems to interrupt TB transmission in the United States and globally, accelerating reductions in TB globally, particularly in the countries of origin for most U.S.

Tuberculosis trends--United States, 2014.

In 2014, a total of 9,412 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0* cases per 100,000 persons, a decrease of 2.2% from 2013. Although overall numbers of TB cases and rates continue to decline, the percentage decrease in rate is the smallest decrease in over a decade (1). This report summarizes provisional TB surveillance data reported to CDC's National Tuberculosis Surveillance System for 2014. TB cases and rates decreased among U.S.-born persons, and although the case rate also decreased among foreign-born persons, there was an increase in total number of cases among foreign-born persons. The rate among foreign-born persons in the United States in 2014 was 13.4 times higher than among U.S.-born persons. Racial/ethnic minorities continue to be disproportionately affected by TB within the United States. Asians continue to be the racial/ethnic group with the largest number of TB cases. Compared with non-Hispanic whites, the TB rate among Asians was 28.5 times higher, whereas rates among non-Hispanic blacks and Hispanics were each eight times higher. Four states (California, Texas, New York, and Florida), representing approximately one third of the U.S. population, accounted for half of all TB cases reported in 2014. Continued progress toward TB elimination in the United States will require focused TB control efforts among populations and in geographic areas with disproportionate burdens of TB.

Trends in tuberculosis - United States, 2013.

In 2013, a total of 9,588 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population, a decrease of 4.2% from 2012. This report summarizes provisional TB surveillance data reported to CDC in 2013. Although case counts and incidence rates continue to decline, certain populations are disproportionately affected. The TB incidence rate among foreign-born persons in 2013 was approximately 13 times greater than the incidence rate among U.S.-born persons, and the proportion of TB cases occurring in foreign-born persons continues to increase, reaching 64.6% in 2013. Racial/ethnic disparities in TB incidence persist, with TB rates among non-Hispanic Asians almost 26 times greater than among non-Hispanic whites. Four states (California, Texas, New York, and Florida), home to approximately one third of the U.S. population, accounted for approximately half the TB cases reported in 2013. The proportion of TB cases occurring in these four states increased from 49.9% in 2012 to 51.3% in 2013. Continued progress toward TB elimination in the United States will require focused TB control efforts among populations and in geographic areas with disproportionate burdens of TB.

Progress Toward Tuberculosis Elimination and Tuberculosis Program Performance - National Tuberculosis Indicators Project, 2016-2022.

Problem/Condition: Elimination of tuberculosis (TB) is defined as reducing TB disease incidence in the United States to less than 1 case per million persons per year. In 2022, TB incidence in the United States was 2.5 TB cases per 100,000 persons. CDC's TB program developed a set of national TB indicators to evaluate progress toward TB elimination through monitoring performance of state and city TB program activities. Examining TB indicator data enables state- and city-level TB programs to identify areas for program evaluation and improvement activities. These data also help CDC identify states and cities that might benefit from technical assistance. Period Covered: The 5-year period for which the most recent data were available for each of five indicators: 1) overall TB incidence (2018-2022), 2) TB incidence among non-U.S.-born persons (2018-2022), 3) percentage of persons with drug susceptibility results reported (2018-2022), 4) percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment (2017-2021), and 5) percentage of patients with completion of TB therapy within 12 months (2016-2020). Description of System: The National TB Indicators Project (NTIP) is a web-based performance monitoring tool that uses national TB surveillance data reported through the National TB Surveillance System and the Aggregate Reports for TB Program Evaluation. NTIP was developed to facilitate the use of existing data to help TB program staff members prioritize activities, monitor progress, and focus program improvement efforts. The following five indicators were selected for this report because of their importance in Federal TB funding allocation and in accelerating the decline in TB cases: 1) overall TB incidence in the United States, 2) TB incidence among non-U.S.-born persons, 3) percentage of persons with drug susceptibility results reported, 4) percentage of contacts to sputum AFB smear-positive TB cases who completed treatment for LTBI, and 5) percentage of patients with completion of TB therapy within 12 months. For this report, 52 TB programs (50 states, the District of Columbia, and New York City) were categorized into terciles based on the 5-year average number of TB cases reported to National TB Surveillance System. This grouping allows comparison of TB programs that have similar numbers of TB cases and allocates a similar number of TB programs to each category. The following formula was used to calculate the relative change by TB program for each indicator: [(% from year 5 - % from year 1 ÷ % from year 1) × 100]. Results: During the 5-year period for which the most recent data were available, most TB programs had improvements in reducing overall TB incidence (71.2%) and increasing the percentage of contacts receiving a diagnosis of LTBI who completed LTBI treatment (55.8%); the majority of programs (51.0%) also had improvements in reducing incidence among non-U.S.-born persons. The average percentage of persons with drug susceptibility results reported in most jurisdictions (28 of 52, [53.9%]) met or exceeded the 5-year national average of 97% (2018-2022). The percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment increased in 29 of 52 (55.8%) jurisdictions from 2017 to 2021, signifying that, for most jurisdictions, steps have been taken to enhance performance in this area. The average percentage of patients with completion of TB therapy within 12 months was at or above the national average of 89.7% in approximately two-thirds (32 of 52 [61.5%]) of jurisdictions. Interpretation: This report is the first to describe a 5-year relative change for TB program performance. These results suggest that TB programs are making improvements in activities that help identify persons with TB and LTBI and ensure patients complete treatment in a timely manner. Public Health Action: Use of NTIP data from individual TB programs enables a more detailed examination of trends in program performance and identification of areas for program improvement. Assessing indicator trends by TB program provides an opportunity to gain a better understanding of program performance in comparison to other programs. It can also facilitate communication between programs regarding successes and challenges in program improvement. This information is valuable for TB programs to allocate resources effectively and provide additional context on TB control for public health policymakers.

Hepatitis E virus infection.

Hepatitis resulting from viral infection is common worldwide and is associated with significant morbidity and mortality. Caused by a group of unrelated viruses that target the liver, hepatitis E virus is not well understood and is consequently often perceived in many countries as unimportant. This article describes the main features of hepatitis E virus and reviews global patterns of transmission, endemicity and the variable clinical outcomes of infection, especially in pregnant women and anyone who is immunocompromised. Infection prevention measures are also discussed.

Fatty acid amide hydrolase inhibitors. 3: tetra-substituted azetidine ureas with in vivo activity.

We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.