Land Use Influences the Composition and Antimicrobial Effects of Propolis.

Honey bee propolis is a complex, resinous mixture created by bees using plant sources such as leaves, flowers, and bud exudates. This study characterized how cropland surrounding apiaries affects the chemical composition and antimicrobial effects of propolis. The chemical composition and compound abundance of the propolis samples were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) and the antimicrobial effects were analyzed using the 50% minimum inhibitory concentration (MIC50) assay against four relevant bee pathogens, Serratia marcescens, Paenibacillus larvae, Lysinibacillus sphaericus, and Klebsiella pneumoniae. Propolis composition varied significantly with apiary, and cropland coverage predicted mean sum abundance of compounds. The apiary with the highest cropland coverage exhibited significantly higher MIC50 values for S. marcescens and K. pneumoniae compared to other apiaries. These results demonstrate that agricultural land use surrounding honey bee apiaries decreases the chemical quality and antimicrobial effects of propolis, which may have implications for the impacts of land use on hive immunity to potential pathogens.

A proposed service model for early identification of autism spectrum disorder in ethnic communities in Southern Israel.

Early autism spectrum disorder (ASD) detection is a precondition for effective intervention and facilitates significant improvements in functioning. In Israel, toddlers undergo general developmental screening by public health nurses (PHNs) at maternal and child health centres (MCHCs). Nevertheless, there are disparities among ethnic groups in the reported incidence of ASD. By means of an ecological model (EM), we identified strategies that improve ASD detection in the Bedouin community by investigating the social and policy factors that affect diagnosis. We conducted in-depth interviews with 18 policy makers and service providers and three focus groups of PHNs and paediatricians. We mapped the strategies for identifying toddlers with ASD based on the three EM levels. Correlations were established by comparing the codes within and between the EM levels. At the macro-level, the policy makers' strategy for improving ASD detection in the Bedouin community reflected the ideology, values and goals of the PHNs and included the MCHCs as the sole institution involved in detecting ASD. At the meso-level of the service providers, the key elements of the strategy consisted of actualising the professional potential of PHNs and patients' case management. At the micro-level was the population that utilises the services and complies with recommendations. A correlation was established between the PHNs' values and goals and patients' case management. Actualising their professional potential influenced the population's compliance. To reduce gaps in ASD diagnosis between Bedouin communities and the general population, it is necessary to identify and change the policy factors that influence access to services for children with ASD at every EM level while incorporating PHNs from the Bedouin community in future services. Culturally appropriate policies, screening policies and interventions must be developed to serve the needs of Bedouin children.

Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study.

BACKGROUND: On Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths averted by the nationwide vaccination campaign. METHODS: In this retrospective surveillance study, we used national surveillance data routinely collected by the Israeli Ministry of Health from the first 112 days (Dec 20, 2020, up to our data cutoff of April 10, 2021) of Israel's vaccination campaign to estimate the averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalisations, severe or critical hospitalisations, and deaths. As part of the campaign, all individuals aged 16 years and older were eligible for inoculation with the BNT162b2 vaccine in a two-dose schedule 21 days apart. We estimated the direct effects of the immunisation programme for all susceptible individuals (ie, with no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partly vaccinated (at least one dose and at least 14 days of follow-up after the first dose). We estimated the number of SARS-CoV-2 infection-related outcomes averted on the basis of cumulative daily, age-specific rate differences, comparing rates among unvaccinated individuals with those of at least partly vaccinated individuals for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partly vaccinated. FINDINGS: We estimated that Israel's vaccination campaign averted 158 665 (95% CI 144 640-172 690) SARS-CoV-2 infections, 24 597 (18 942-30 252) hospitalisations, 17 432 (12 770-22 094) severe or critical hospitalisations, and 5532 (3085-7982) deaths. 16 213 (65·9%) of 24 597 hospitalisations and 5035 (91·0%) of 5532 of deaths averted were estimated to be among those aged 65 years and older. We estimated 116 000 (73·1%) SARS-CoV-2 infections, 19 467 (79·1%) COVID-19-related hospitalisations, and 4351 (79%) deaths averted were accounted for by the fully vaccinated population. INTERPRETATION: Without the national vaccination campaign, Israel probably would have had triple the number of hospitalisations and deaths compared with what actually occurred during its largest wave of the pandemic to date, and the health-care system might have become overwhelmed. Indirect effects and long-term benefits of the programme, which could be substantial, were not included in these estimates and warrant future research. FUNDING: Israel Ministry of Health and Pfizer.

Effectiveness of BNT162b2 mRNA COVID-19 vaccine against SARS-CoV-2 variant Beta (B.1.351) among persons identified through contact tracing in Israel: A prospective cohort study.

BACKGROUND: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Beta. We estimated BNT162b2 vaccine effectiveness (VE) against Beta infections in Israel, a country with high vaccine uptake. METHODS: The Ministry of Health (MoH) identified Beta cases through mandatory reporting of SARS-CoV-2 cases and whole genome sequencing (WGS) of specimens from vaccination-breakthrough infections, reinfections, arriving international travelers, and a selection of other infected persons. A cohort analysis was conducted of exposure events of contacts of primary Beta cases. WGS was conducted on available PCR-positive specimens collected from contacts. VE estimates with 95% confidence intervals (CIs) against confirmed and probable Beta infections were determined by comparing infection risk between unvaccinated and fully-vaccinated (≥7 days after the second dose) contacts, and between unvaccinated and partially-vaccinated (<7 days after the second dose) contacts. FINDINGS: MoH identified 310 Beta cases through Jun 27, 2021. During the study period (Dec 11, 2020 - Mar 25, 2021), 164 non-institutionalized primary Beta cases, with 552 contacts aged ≥16 years, were identified. 343/552 (62%) contacts were interviewed and tested. 71/343 (21%) contacts were PCR-positive. WGS was performed on 7/71 (10%) PCR-positive specimens; all were Beta. Among SARS-CoV-2-infected contacts, 48/71 (68%) were symptomatic, 10/71 (14%) hospitalized, and 2/71 (3%) died. Fully-vaccinated VE against confirmed or probable Beta infections was 72% (95% CI -5 - 97%; p=0·04) and against symptomatic confirmed or probable Beta infections was 100% (95% CI 19 - 100%; p=0·01). There was no evidence of protection in partially-vaccinated contacts. INTERPRETATION: In a prospective observational study, two doses of BNT162b2 were effective against confirmed and probable Beta infections. Through the end of June 2021, introductions of Beta did not interrupt control of the pandemic in Israel. FUNDING: Israel Ministry of Health and Pfizer.

Waning Immunity after the BNT162b2 Vaccine in Israel.

BACKGROUND: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. METHODS: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. RESULTS: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. CONCLUSIONS: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.

BACKGROUND: Following the emergency use authorisation of the Pfizer-BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) in Israel, the Ministry of Health (MoH) launched a campaign to immunise the 6·5 million residents of Israel aged 16 years and older. We estimated the real-world effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine. METHODS: We used national surveillance data from the first 4 months of the nationwide vaccination campaign to ascertain incident cases of laboratory-confirmed SARS-CoV-2 infections and outcomes, as well as vaccine uptake in residents of Israel aged 16 years and older. Vaccine effectiveness against SARS-CoV-2 outcomes (asymptomatic infection, symptomatic infection, and COVID-19-related hospitalisation, severe or critical hospitalisation, and death) was calculated on the basis of incidence rates in fully vaccinated individuals (defined as those for whom 7 days had passed since receiving the second dose of vaccine) compared with rates in unvaccinated individuals (who had not received any doses of the vaccine), with use of a negative binomial regression model adjusted for age group (16-24, 25-34, 35-44, 45-54, 55-64, 65-74, 75-84, and ≥85 years), sex, and calendar week. The proportion of spike gene target failures on PCR test among a nationwide convenience-sample of SARS-CoV-2-positive specimens was used to estimate the prevelance of the B.1.1.7 variant. FINDINGS: During the analysis period (Jan 24 to April 3, 2021), there were 232 268 SARS-CoV-2 infections, 7694 COVID-19 hospitalisations, 4481 severe or critical COVID-19 hospitalisations, and 1113 COVID-19 deaths in people aged 16 years or older. By April 3, 2021, 4 714 932 (72·1%) of 6 538 911 people aged 16 years and older were fully vaccinated with two doses of BNT162b2. Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95·3% (95% CI 94·9-95·7; incidence rate 91·5 per 100 000 person-days in unvaccinated vs 3·1 per 100 000 person-days in fully vaccinated individuals) against SARS-CoV-2 infection, 91·5% (90·7-92·2; 40·9 vs 1·8 per 100 000 person-days) against asymptomatic SARS-CoV-2 infection, 97·0% (96·7-97·2; 32·5 vs 0·8 per 100 000 person-days) against symptomatic COVID-19, 97·2% (96·8-97·5; 4·6 vs 0·3 per 100 000 person-days) against COVID-19-related hospitalisation, 97·5% (97·1-97·8; 2·7 vs 0·2 per 100 000 person-days) against severe or critical COVID-19-related hospitalisation, and 96·7% (96·0-97·3; 0·6 vs 0·1 per 100 000 person-days) against COVID-19-related death. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. 8006 of 8472 samples tested showed a spike gene target failure, giving an estimated prevalence of the B.1.1.7 variant of 94·5% among SARS-CoV-2 infections. INTERPRETATION: Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic. FUNDING: None.

Ethnic Disparities in the Diagnosis of Autism in Southern Israel.

The prevalence of autism spectrum disorder (ASD) is continuously rising worldwide, with remarkable differences in ASD rates being reported across ethnic and socioeconomic groups. We conducted a prospective cohort study to identify the reasons for differences in ASD rates between the Bedouin and Jewish populations in southern Israel. Screening, referral, and diagnosis of toddlers aged 16-36 months were compared between Bedouin and Jewish populations. ASD screening was conducted at 35 randomly selected mother and child health centers (MCHCs) by trained nurses using the Modified Checklist for Autism in Toddlers with follow-up (M-CHAT/F) instrument. Toddlers screened positive at the MCHCs were monitored throughout the referral and diagnosis process at a single medical center until a diagnosis was determined by a physician specialist using DSM-5 criteria. The study cohort comprised 3,343 toddlers (996 Jewish and 2,347 Bedouin). Bedouin toddlers, compared to Jewish toddlers, were less likely to screen positive with M-CHAT/F (3.0% vs. 3.9%; P = 0.165), were significantly less likely to begin the hospital diagnosis process (HR = 0.38, 95% CI: 0.14-1.08; P = 0.068), and had a higher rates of loss-to-follow-up during the hospital diagnosis process (42.9% vs. 15.6%, respectively; P = 0.001). The results suggest that ethnic-specific barriers in the diagnosis process of ASD contribute to under-diagnosis of ASD in the Bedouin population. Facilitating the diagnosis process for Bedouin families will help to identify more children with ASD at earlier ages and consequently close the ethnic gap in ASD rates. LAY SUMMARY: We followed Bedouin and Jewish toddlers aged 16-36 months from southern Israel through their autism spectrum disorder (ASD) screening referral and diagnosis to identify the reasons for the differences in ASD prevalence between these ethnic groups. Jewish and Bedouin toddlers were equally identified in the ASD screening. However, Bedouin toddlers were less likely to complete the diagnosis process due to higher rates of loss-to-follow-up and slower diagnosis process. Facilitating ASD diagnosis for the Bedouin population will help identifying more toddlers with ASD.

Tdap vaccination during pregnancy interrupts a twenty-year increase in the incidence of pertussis.

Pertussis incidence in developed countries, including Israel, has increased over the past two decades despite the addition of two booster doses in children. However, as pertussis is characterized by a multi-annual periodicity, and since clinical diagnosis can miss cases, determining disease trends at the population level is challenging. To bridge this gap, we developed a simple statistical model to capture the temporal patterns of pertussis incidence in Israel. Our model was calibrated and tested using laboratory-confirmed cases of pertussis for the Israeli population between 1998 and 2019. The model identifies a clear four-year periodicity of pertussis incidence over the past two decades that is identical to the one observed in the pre-vaccine era. Accounting for this periodicity, the model shows a 325% increase in pertussis incidence from 2002 to 2014. These multi-year trends were interrupted shortly after the introduction of routine immunization of Tdap vaccine in pregnancy in 2015, after which we found a 59.7% (95% CI: 57.7-61.6%)decline in pertussis incidence and a 49.5% (36.0-61.6%) decline in hospitalizations compared to the model's projection. While this sharp decline cannot be fully attributed to the newly introduced vaccination policy, sharper reductions of 71.2% (65.6-76.1%) in incidence and 58.4% (39.6-72.7%) in hospitalizations, have been observed in infants of age two months and below - young infants that have yet to become vaccinated and are more likely to be protected by maternal vaccination. Our work suggests that Tdap vaccination during pregnancy is a promising policy for controlling pertussis. Furthermore, due to the stable periodicity of pertussis, public health decision-makers should invest continuous efforts in the implementation of this strategy with additional reinforcement in expected peak years.

A Comparison Between Two Screening Approaches for ASD Among Toddlers in Israel.

Systematic screening of autism spectrum disorder (ASD) can improve early diagnosis of ASD. We compared the efficacy of two ASD screening methods, the Global Developmental Screening (GDS), and the Modified Checklist for Autism in Toddlers-Revised, with Follow-Up (M-CHAT/F) in 1591 toddlers of ages 18-36 months from 35 government-funded clinics in south Israel. The M-CHAT/F performed better than the GDS in detecting toddlers with ASD (sensitivity: 70.0% vs. 50.0%, and specificity: 98.2% vs. 96.6% respectively). Both methods had an equivalent performance in detecting other forms of developmental delays (sensitivity = 63%; and specificity ~ 98%). In addition, remarkable inter-nurse variation was observed in the GDS referral decisions. Thus, employment of the M-CHAT/F in the Israeli health system may improve early detection of ASD among toddlers.

Outbreak of human leptospirosis linked to contaminated water bodies in Northern Israel, June to August 2018.

We report preliminary findings of a large outbreak of human leptospirosis with 36 confirmed/probable and 583 suspected cases from June-August 2018, linked to contaminated water bodies in Northern Israel. There was a travel-associated case in Germany; additional cases are being investigated in other countries. The presumed chain of transmission, implicating wild boar and cattle, raises multiple challenges for risk assessment, risk management and risk communication currently being addressed by a public health response team.

Ongoing mumps outbreak in Israel, January to August 2017.

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected.

Control of a Mycoplasma pneumoniae Outbreak in an Institutional Setting Using Azithromycin Prophylaxis.

BACKGROUND: Mycoplasma pneumoniae is a major cause of respiratory infection of varying severity. Outbreaks of M. pneumoniae infection commonly occur in closed or semi-closed communities and settings. The control of such outbreaks is challenging, owing to delayed detection, long incubation period, and paucity of infection control guidelines. METHODS: Between May and July 2015, a residential facility for adults with developmental disabilities in Southern Israel witnessed an outbreak of acute respiratory infection, subsequently diagnosed as associated with M. pneumoniae. All relevant data were collected as a part of a formal outbreak investigation. Strict infection control procedures were implemented, and azithromycin prophylaxis was provided to all residents. RESULTS: Out of 215 residents, there were 29 suspected cases, 23 of which were confirmed as M. pneumoniae infection by serology or nucleic acid testing, for an attack rate of 11%. There were no cases of severe or fatal illness. An infection control strategy, including implementation of strict case isolation, enforcement of hygiene measures, a high index of suspicion for case detection, and use of azithromycin prophylaxis for all residents, led to rapid cessation of the outbreak. DISCUSSION: The use of azithromycin prophylaxis may be worthwhile in closed institutional settings in which M. pneumoniae infections are documented. The dynamics of this outbreak suggest that if spread between wards is anticipated, expanding prophylaxis beyond immediate contacts of affected individuals should be considered.

A Short Profile of Hypnotherapy Licensure in Israel.

In Israel, only physicians, dentists, and psychologists who complete an accredited licensing process may practice hypnosis. This study examines the characteristics of hypnotherapists compared to nonhypnotherapists in the same discipline. All hypnotherapists in Israel were compared to nonhypnotherapist health professionals. There are more subspecialists among hypnotists, and the most common specialties were psychiatry, pediatric dentistry, and clinical psychology. These findings imply self-sorting of hypnotists as a result of the regulation in Israel. Licensure of hypnotherapists could be useful in other countries by comprehensive follow-up of all licensed hypnotists and by improving public and health professional perceptions of the field and its relevance to clinical practice.

Use of vaccination in a large outbreak of primary varicella in a detention setting for African immigrants.

BACKGROUND: Primary varicella (PV) presents a public health risk for adults in closed residential settings, especially for immigrants from tropical areas where infection during childhood is less likely. METHODS: In this study, an outbreak of PV at a detention facility for illegal immigrants from Eritrea and Sudan in southern Israel is described. Basic demographic information and clinical course for all cases were obtained. RESULTS: One hundred and nine cases of PV, all in young adult men aged 18-40 years, were diagnosed over a 7-month period (June to December 2012). Diagnosed patients were placed in quarantine until the resolution of illness without other public health measures being implemented. The Israeli Ministry of Health was notified of the outbreak in early December and recommended two doses of varicella vaccine for all susceptible detainees and staff. Within 2 weeks of completion of the first dose of vaccine, there was only one additional case in a detainee immunized 13 days prior to diagnosis. The effectiveness of vaccination in halting the outbreak was immediate, despite the fact that 15.6% of detainees refused to be immunized. CONCLUSIONS: The possible roles of vaccination or natural infection in achieving herd immunity and thereby ending the outbreak in this population are discussed. We recommend considering early vaccination for all when an outbreak or a series of connected cases is detected in a closed-residential setting such as the detention facility described here.

Switchgrass PviCAD1: understanding residues important for substrate preferences and activity.

Cinnamyl alcohol dehydrogenase (CAD) catalyzes the final step in monolignol biosynthesis. Although plants contain numerous genes coding for CADs, only one or two CADs appear to have a primary physiological role in lignin biosynthesis. Much of this distinction appears to reside in a few key residues that permit reasonable catalytic rates on monolignal substrates. Here, several mutant proteins were generated using switchgrass wild type (WT) PviCAD1 as a template to understand the role of some of these key residues, including a proton shuttling HL duo in the active site. Mutated proteins displayed lowered or limited activity on cinnamylaldehydes and exhibited altered kinetic properties compared to the WT enzyme, suggesting that key residues important for efficient catalysis had been identified. We have also shown that a sorghum ortholog containing EW, instead of HL in its active site, displayed negligible activity against monolignals. These results indicate that lignifying CADs require a specific set of key residues for efficient activity against monolignals.

Risk Factors and Outcomes for Vancomycin-Resistant Enterococcus Bloodstream Infection in Children.

Background and objective. Enterococcal bloodstream infections (BSIs) cause morbidity and mortality in children. This study aims to describe the epidemiological characteristics of enterococcal BSI, to determine the risk factors for vancomycin-resistant Enterococcus (VRE) BSI, and to compare outcomes of VRE BSI and vancomycin-susceptible Enterococcus (VSE) BSI in this population. Methods. A retrospective cohort study at a 418-bed tertiary care children's hospital in Philadelphia, Pennsylvania, examined the epidemiological characteristics of children hospitalized with enterococcal BSI during the period from 2001 through 2006. A nested case-control study compared patients with VRE BSI with control patients with VSE BSI. Analysis included regression modeling to identify independent risk factors for VRE BSI. Results. We identified 339 patients with enterococcal BSI during the study period, including 39 patients with VRE infection. Fifty-three patients (16%) died before hospital discharge. Risk factors for VRE included long-term receipt of mechanical ventilation (adjusted odds ratio [OR], 5.40 [95% confidence interval {CI}, 1.28-6.48]), receipt of immunosuppressive medications during the preceding 30 days (adjusted OR, 2.88 [95% CI, 1.40-20.78]), use of vancomycin during the 2 weeks before onset of bacteremia (adjusted OR per day of vancomycin use, 1.25 [95% CI, 1.14-1.38]), and older age (adjusted OR, 1.08 [95% CI, 1.03-1.14]). VRE BSI was not associated with an increased length of stay after onset of bacteremia (0.77 days [95% CI, 0.55-1.07 days]). Mortality was higher for VRE BSI, but the difference was not statistically significant (adjusted OR, 1.94 [95% CI, 0.78-4.8]). Conclusion. Most enterococcal BSI in children was caused by VSE. Risk factors for VRE BSI included receipt of vancomycin, long-term receipt of mechanical ventilation, immunosuppression, and older age. Differences in length of stay and mortality were not detected.

A nonsense mutation in a cinnamyl alcohol dehydrogenase gene is responsible for the Sorghum brown midrib6 phenotype.

Brown midrib6 (bmr6) affects phenylpropanoid metabolism, resulting in reduced lignin concentrations and altered lignin composition in sorghum (Sorghum bicolor). Recently, bmr6 plants were shown to have limited cinnamyl alcohol dehydrogenase activity (CAD; EC 1.1.1.195), the enzyme that catalyzes the conversion of hydroxycinnamoyl aldehydes (monolignals) to monolignols. A candidate gene approach was taken to identify Bmr6. Two CAD genes (Sb02g024190 and Sb04g005950) were identified in the sorghum genome based on similarity to known CAD genes and through DNA sequencing a nonsense mutation was discovered in Sb04g005950 that results in a truncated protein lacking the NADPH-binding and C-terminal catalytic domains. Immunoblotting confirmed that the Bmr6 protein was absent in protein extracts from bmr6 plants. Phylogenetic analysis indicated that Bmr6 is a member of an evolutionarily conserved group of CAD proteins, which function in lignin biosynthesis. In addition, Bmr6 is distinct from the other CAD-like proteins in sorghum, including SbCAD4 (Sb02g024190). Although both Bmr6 and SbCAD4 are expressed in sorghum internodes, an examination of enzymatic activity of recombinant Bmr6 and SbCAD4 showed that Bmr6 had 1 to 2 orders of magnitude greater activity for monolignol substrates. Modeling of Bmr6 and SbCAD4 protein structures showed differences in the amino acid composition of the active site that could explain the difference in enzyme activity. These differences include His-57, which is unique to Bmr6 and other grass CADs. In summary, Bmr6 encodes the major CAD protein involved in lignin synthesis in sorghum, and the bmr6 mutant is a null allele.