Faecal microbial diversity in a cattle herd infected by Mycobacterium avium subsp. paratuberculosis: a possible effect of production status.

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, or paratuberculosis (PTB) in ruminants, besides having zoonotic potential. It possibly changes the gut microbiome, but no conclusive data are available yet. This study aimed at investigating the influence of MAP on the faecal microbiome of cattle naturally infected with PTB. In a follow up period of 10 months, PTB status was investigated in a herd of dairy cattle with history of clinical cases. Each animal was tested for MAP infection using serum and milk ELISA for MAP anti-bodies and IS900 real-time PCR and recombinase polymerase amplification assays for MAP DNA in the faeces and milk monthly for 4 successive months, then a last one after 6 months. The faecal samples were subjected to 16S rDNA metagenomic analysis using Oxford Nanopore Sequencing Technology. The microbial content was compared between animal groups based on MAP positivity rate and production status. All animals were MAP positive by one or more tests, but two animals were consistently negative for MAP DNA in the faeces. In all animals, the phyla firmicutes and bacteroidetes were highly enriched with a small contribution of proteobacteria, and increased abundance of the families Oscillospiraceae, Planococcaceae, and Streptococcacaceae was noted. Animals with high MAP positivity rate showed comparable faecal microbial content, although MAP faecal positivity had no significant effect (p > 0.05) on the microbiome. Generally, richness and evenness indices decreased with increasing positivity rate. A significantly different microbial content was found between dry cows and heifers (p < 0.05). Particularly, Oscillospiraceae and Rikenellaceae were enriched in heifers, while Planococcaceae and Streptococcaceae were overrepresented in dry cows. Furthermore, abundance of 72 genera was significantly different between these two groups (p < 0.05). Changes in faecal microbiome composition were notably associated with increasing MAP shedding in the faeces. The present findings suggest a combined influence of the production status and MAP on the cattle faecal microbiome. This possibly correlates with the fate of the infection, the concern in disease control, again remains for further investigations.

Characterization of the wild plants in Wadi Degla Protectorate, North Eastern Desert, Egypt.

The present study aimed to evaluate the floristic characteristics of the wild plants in Wadi Degla Protectorate, including taxonomic diversity, life and sex forms, dispersal types, economic potential, threats, and national and global floristic distributions. Field visits were conducted during January and April (2021), and the study area was divided to 185 locations to comprise all the Wadi. From each location, plant and seed specimens were collected. In the present study, 161 plants belonged to 128 genera, and 43 families were recorded. They inhabited three habitats (upstream, midstream, and downstream). Therophytes were the most represented life form. Bisexuals were the most represented sex form. Sarcochores were the most represented dispersal type, followed by desmochores. For small geographic range - national habitat - non-abundant plants were the most represented rarity form. For national scales, the Mediterranean and Sinai regions were the richest wild plants. For global scales, the Saharo-Sindian and Mediterranean regions were the most represented elements. Medicinal plants were the most represented good, while solid wastes were the most represented threat.

Prediction Models Based on Soil Characteristics for Evaluation of the Accumulation Capacity of Nine Metals by Forage Sorghum Grown in Agricultural Soils Treated with Varying Amounts of Poultry Manure.

Predictive models were generated to evaluate the degree to which nine metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) were absorbed by the leaves, stems and roots of forage sorghum in growing media comprising soil admixed with poultry manure concentrations of 0, 10, 20, 30 and 40 g/kg. The data revealed that the greatest contents of the majority of the metals were evident in the roots rather than in the stems and leaves. A bioaccumulation factor (BAF) < 1 was calculated for Cr, Fe, Ni, Pb and Zn; BAF values for Co, Cu, Mn and Cd were 3.99, 2.33, 1.44 and 1.40, respectively, i.e., > 1. Translocation factor values were < 1 for all metals with the exception of Co, Cr and Ni, which displayed values of 1.20, 1.67 and 1.35 for the leaves, and 1.12, 1.23 and 1.24, respectively, for the stems. The soil pH had a negative association with metal tissues in plant parts. A positive relationship was observed with respect to plant metal contents, electrical conductivity and organic matter quantity. The designed models exhibited a high standard of data precision; any variations between the predicted and experimentally observed contents for the nine metals in the three plant tissue components were nonsignificant. Thus, it was concluded that the presented predictive models constitute a pragmatic tool to establish the safety from risk to human well-being with respect to growing forage sorghum when cultivating media fortified with poultry manure.

Molecular and serological survey of paratuberculosis in cattle in selected districts of Western Uganda.

Knowledge of Mycobacterium avium subsp. paratuberculosis (MAP) herd infection status is important to plan appropriate control and prevention strategies for Paratuberculosis (PTB); however, in Uganda MAP infection status of most herds is unknown. This study aimed at determining the MAP infection status of cattle herds and the associated risk factors for MAP infection in six western districts of Uganda. The survey covered a total of 93 herds where faecal and blood samples were collected from 1814 cattle. A Recombinase Polymerase Amplification (RPA) and an antibody-based (ELISA) assays were used to test for the presence of MAP DNA in faeces and MAP antibodies in serum, respectively. The apparent cow-level prevalence of MAP infection was 3.2 and 2.7% using ELISA and RPA respectively and the true cow-level prevalence using ELISA and RPA was 4.9 and 3% respectively. A herd-level prevalence of 43% (ELISA) and 40.8% (RPA) and a within-herd prevalence of 3.8 ± 2.1% based on ELISA were obtained. Among the risk factors investigated, long dry spells were significantly associated with high MAP infection (p < 0.05). These results indicate that MAP is actively present in most areas where surveillance was carried out. This poses a serious threat to the livestock industry and potentially to public health as MAP is highly suspected to play a role in the pathogenesis of several diseases in humans. Other areas of the country are to be surveyed as well in order to establish full data on MAP infection status to enable interventions for the control and prevention of the disease.

Association with Longevity of Phosphatidylinositol 3-Kinase Regulatory Subunit 1 Gene Variants Stems from Protection against Mortality Risk in Men with Cardiovascular Disease.

INTRODUCTION: Genetic variation in the phosphatidylinositol 3-kinase reregulatory subunit 1 gene (PIK3R1) is associated with longevity. OBJECTIVE: The aim of the study was to determine whether cardiovascular disease (CVD) affects this association. METHODS: We performed a longitudinal study of longevity-associated PIK3R1 single-nucleotide polymorphism rs7709243 genotype by CVD status in 3,584 elderly American men of Japanese ancestry. RESULTS: At baseline (1991-1993), 2,254 subjects had CVD and 1,314 did not. The follow-up until Dec 31, 2019 found that overall, men with a CVD had higher mortality than men without a CVD (p = 1.7 × 10-5). However, survival curves of CVD subjects differed according to PIK3R1 genotype. Those with longevity-associated PIK3R1 TT/CC had survival curves similar to those of subjects without a CVD (p = 0.11 for TT/CC, and p = 0.054 for TC), whereas survival curves for CVD subjects with the CT genotype were significantly attenuated compared with survival curves of subjects without a CVD (p = 0.0000012 compared with TT/CC, and p = 0.0000028 compared with TC). Men without CVD showed no association of longevity-associated genotype with life span (p = 0.58). Compared to subjects without any CVD, hazard ratios for mortality risk were 1.26 (95% CI, 1.14-1.39; p = 0.0000043) for CT subject with CVD and 1.07 (95% CI 0.99-1.17; p = 0.097) for CC/TT subjects with CVD. There was no genotypic effect on life span for 1,007 subjects with diabetes and 486 with cancer. CONCLUSION: Our study provides novel insights into the basis for PIK3R1 as a longevity gene. We suggest that the PIK3R1 longevity genotype attenuates mortality risk in at-risk individuals by protection against cellular stress caused by CVD.

Prediction models based on soil properties for evaluating the heavy metal uptake into Hordeum vulgare L. grown in agricultural soils amended with different rates of sewage sludge.

The current study aims at forming new prediction models to be employed in the approximating the possible uptake of a range of 10 heavy metals (HMs) (Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb and Zn) by Hordeum vulgare tissues including roots, shoots and grains following its growth in soil amended with sewage sludge (SS) using conditions employed in greenhouses. The present study determined an insignificant difference between the actual and predicted quantities of the HMs in the three tissues using t values. The majority of the predicted quantities of the HMs were acceptable with the exception of Cd in the shoots, Cu in grains and Pb in roots. Consequently, it is possible to use these models in assessing the cultivation of barley plants in soil amended with SS in a safe way, while simultaneously monitoring any potential risks to the health of humans.

Selective and sensitive turn on fluorescence cyanide recognition in aqueous medium based on Zn(II)-hydrazone metal complex chemosensor.

Detection and quantification of the cyanide ion (CN- ) has attracted considerable attention because of its extreme toxicity. A novel Zn(II)-complex, applicable as a fluorescent chemosensor for CN- recognition, was synthesized in excellent yields from the reaction of zinc sulfate with the novel hydrazone: 3-(amino-9H-purin-yl)-N'-(hydroxybenzylidene) propanehydrazide. The structures of the hydrazone (L) and the zinc-hydrazone complex (L.Zn) were characterized by ultraviolet-visible spectrophotometry, Fourier-transform infrared spectrometry, mass spectrometry, proton- and carbon-13-nuclear magnetic resonance. The sensing performance of the proposed chemosensors, L and L.Zn, towards common ions was investigated via naked-eye studies as well as absorption and emission spectral analysis. Hydrazone (L) efficiently functioned as a fluorescence sensor for aluminum ions (Al3+ ) and zinc ions (Zn2+ ) with large binding constants, and exhibited colorimetric and fluorometric responses for several basic anions: OH- , CO3 2- , HCO3 - , HSO3 - , CH3 COO- and CN- . However, L.Zn showed quick, sensitive and specific enhancement of fluorescence intensity towards CN- anion, and a linear relationship was observed as the concentration of CN- varied from 1 to 14 µM. The detection limit was determined to be 0.14 µM, which is lower than the 1.9 µM maximum value recommended by the World Health Organization for drinking water. The practical performance of the sensor was successfully demonstrated using various environmental water samples spiked with cyanide ion.

Evaluation of uptake of eight metals by Sorghum bicolor grown in arable soil combined with sewage sludge based on prediction models.

Prediction models were developed to estimate the extent to which aluminium, chromium, copper, iron, manganese, nickel, lead, and zinc were absorbed in the grains, leaves, stems, and roots of Sorghum bicolor cultivated in soil with various amendment rate of sewage sludge (0, 10, 20, 30, 40, and 50 g/kg) under greenhouse conditions. It was found that, aside from lead, all the examined metals occurred in significantly higher content in the roots compared to aerial tissues. Furthermore, the r-values were significantly negative between the bioconcentration factors of all metals, apart from aluminium and lead, and soil pH, whereas they were significantly positive between the bioconcentration factors, apart from lead, and soil organic matter content (OM). The r-values were typically significantly positive between the levels of all eight metals in the investigated tissues and in the soil. Moreover, the content of all the eight metals in the tissues exhibited a significant negative r-value with soil pH but a significant positive r-value with soil OM. The eight metal contents in the tissues given by the prediction models were quite similar to the real values, suggesting that the created models performed well, as shown by t-tests. It was thus concluded that prediction models were a viable option for evaluating how safe it was to grow S. bicolor in soils with sewage sludge content and at the same time for keeping track of possible human health hazards.

Temporal Potential of Phragmites australis as a Phytoremediator to Remove Ni and Pb from Water and Sediment in Lake Burullus, Egypt.

In the current work, we investigated the concentration of Ni and Pb in different organs of Phragmites australis to evaluate its potential application as a phytoremediator to remove these two metals from contaminated water and sediment in Lake Burullus (a Ramsar site in Egypt). Above- and below-ground biomass of P. australis, water and sediment were sampled monthly for 1 year at six sites of Lake Burullus (three sites represent each of the northern and southern parts of the lake) using six randomly distributed quadrats (each of 0.5 × 0.5 m) at each sampling site. Significant variation was detected for Ni and Pb concentrations in the sediments and waters between the northern and southern sites of the lake. The biomass of P. australis in the southern sites was greater than that in the northern sites; in addition, the above-ground biomass was higher than the below-ground biomass. The above-ground organs accumulated higher concentrations of Ni and Pb than the below-ground organs. The Ni and Pb standing stocks data indicated that the organs of P. australis extracted higher amounts of Ni and Pb per its area from the southern rather than the northern sites. In the current study, the Ni and Pb above-ground standing stocks increased from the early growing season (February) and reached its peak during August and then decreased. The highest monthly Ni and Pb standing stock (18.2 and 18.4 g m- 2, respectively) was recorded in the above-ground organs of plants in the southern sites in August. The bioaccumulation factor of Ni was 157.6 and 153.4 in the northern and southern sites, respectively, whereas that of Pb was 175.3 and 158.3. The translocation factor of Ni and Pb from the below- to above-ground organs was generally > 1. Thus, this reed species is a potential candidate for Ni and Pb phytoextraction. Based on our results, P. australis could be used for the extraction of Ni and Pb to reduce the pollution in Lake Burullus, if the above-ground biomass is harvested at its maximum value in August, as was the case regarding the maximum standing stock of Ni and Pb.

Genome-wide epigenetic analyses in Japanese immigrant plantation workers with Parkinson's disease and exposure to organochlorines reveal possible involvement of glial genes and pathways involved in neurotoxicity.

BACKGROUND: Parkinson's disease (PD) is a disease of the central nervous system that progressively affects the motor system. Epidemiological studies have provided evidence that exposure to agriculture-related occupations or agrichemicals elevate a person's risk for PD. Here, we sought to examine the possible epigenetic changes associated with working on a plantation on Oahu, HI and/or exposure to organochlorines (OGC) in PD cases. RESULTS: We measured genome-wide DNA methylation using the Illumina Infinium HumanMethylation450K BeadChip array in matched peripheral blood and postmortem brain biospecimens in PD cases (n = 20) assessed for years of plantation work and presence of organochlorines in brain tissue. The comparison of 10+ to 0 years of plantation work exposure detected 7 and 123 differentially methylated loci (DML) in brain and blood DNA, respectively (p < 0.0001). The comparison of cases with 4+ to 0-2 detectable levels of OGCs, identified 8 and 18 DML in brain and blood DNA, respectively (p < 0.0001). Pathway analyses revealed links to key neurotoxic and neuropathologic pathways related to impaired immune and proinflammatory responses as well as impaired clearance of damaged proteins, as found in the predominantly glial cell population in these environmental exposure-related PD cases. CONCLUSIONS: These results suggest that distinct DNA methylation biomarker profiles related to environmental exposures in PD cases with previous exposure can be found in both brain and blood.

Prediction models for evaluating heavy metal uptake by Pisum sativum L. in soil amended with sewage sludge.

The present study aims to develop prediction models for estimating the potential uptake of 10 heavy metals (HMs) (cadmium, Cd; cobalt, Co; chromium, Cr; copper, Cu; iron, Fe; manganese, Mn; molybdenum, Mo; nickel, Ni; lead, Pb; zinc, Zn) by the tissues of Pisum sativum (root, shoot and pod) grown in soil amended with sewage sludge (SS) under greenhouse conditions. Soil organic matter (OM) was estimated by loss-on-ignition at 550 °C for 2 h. The pH was determined by shaking the soil and pure water at a 1:5 ratio. For HM quantifications, 0.5-1.0 g of each soil or plant sample was digested using a tri-acid mixture digestion method. The quantities of selected HMs were estimated by means of inductively coupled plasma optical emission spectrometry. Bio-concentration (BCF) and translocation (TF) factors were <1 for most of the HMs. In addition, simple linear correlations were significantly negative between the BCF of all studied HMs and soil pH, except for Pb, Mn and Ni, whereas significant positive correlations were observed between BCFs and soil OM, except for Mn, Ni and Zn. The accumulation of the 10 HMs in P. sativum tissues was predicted using regression models based on the values of the same HM in the soil as well as its pH and OM. The calculated prediction models performed well for most HMs in P. sativum tissues (except Ni in the pod, Cd in the shoot and Mn in the root). All measured soil factors (HM, pH and OM) consistently contributed to HM concentrations in the three tissues of the studied plants. These models may help to evaluate the safe cultivation of this species in soil amended with SS.

Uptake Prediction of Ten Heavy Metals by Eruca sativa Mill. Cultivated in Soils Amended with Sewage Sludge.

This study was carried out to develop mathematical regression equations for predicting the uptake of ten heavy metals (HMs) (cadmium, Cd; cobalt, Co; chromium, Cr; copper, Cu; iron, Fe; manganese, Mn; molybdenum, Mo; nickel, Ni; lead, Pb; zinc, Zn) by a vegetable species (Eruca sativa Mill.) in the Abha region (Saudi Arabia) based on the concentration of these HMs in soils amended with sewage sludge, organic matter (OM) content and soil pH. The resultant regression equations indicated that the three soil factors were significant predictors for the uptake of the ten HMs in the plant tissues. By applying a t test, we found that there are no significant differences between the actual and predicted values of the ten HMs in the E. sativa roots and leaves (P > 0.05), which reflects the goodness of fit of these equations for predicting the uptake of these HMs. Such types of equations may be helpful for evaluating the risk of cultivation of E. sativa plants in soils amended with sewage sludge.

Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology.

BACKGROUND: Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study. METHODS: Organochlorines were measured in frozen occipital or temporal lobes in 705 brains using gas chromatography with mass spectrometry. Lewy pathology was identified using hematoxylin and eosin- and α-synuclein immunochemistry-stained sections from multiple brain regions. RESULTS: The prevalence of Lewy pathology was nearly doubled in the presence versus the absence of heptachlor epoxide (30.1% versus 16.3%, P < 0.001). Although associations with other compounds were weaker, hexachlorobenzene (P = 0.003) and α-chlordane (P = 0.007) were also related to Lewy pathology. Most of the latter associations, however, were a result of confounding from heptachlor epoxide. Neither compound was significantly related to Lewy pathology after adjustment for heptachlor epoxide. In contrast, the association of heptachlor epoxide with Lewy pathology remained significant after adjustments for hexachlorobenzene (P = 0.013) or α-chlordane (P = 0.005). Findings were unchanged after removal of cases of PD and adjustment for age and other characteristics. CONCLUSIONS: Organochlorine pesticides are associated with the presence of Lewy pathology in the brain, even after exclusion of PD cases. Although most of the association is through heptachlor epoxide, the role of other organochlorine compounds is in need of clarification. © 2018 International Parkinson and Movement Disorder Society.

Novel triazine-based pyrimidines suppress glomerular mesangial cells proliferation and matrix protein accumulation through a ROS-dependent mechanism in the diabetic milieu.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes worldwide. It is depicted as the leading cause of end-stage renal disease. Oxidative stress plays a key role in hyperglycemia-induced DN. The preparation and characterization of novel mono-, di-, and trisubstituted-s-triazines endowed with uracil and/or thymine are described in this paper. The synthesis of the title compounds was realized through selective nucleophilic substitution reactions of cyanuric chloride with the corresponding hydrazide nucleobases. In this study, we assessed the effects of these derivatives on the progression of diabetic nephropathy. Our results show that trisubstituted-s-triazines endowed with acylhydrazides attenuate high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. Notably, these derivatives also display anti-oxidative properties. This suggests that the novel trisubstituted-s-triazine derivatives provide renal protection through a reactive oxygen species (ROS)-dependent mechanism. Our data provide evidence that these derivatives may serve as potential therapeutic candidates in the treatment of DN.

Spectroscopic Evaluation of Novel Adenine/Thymine-Conjugated Naphthalenediimides: Preference of Adenine-Adenine over Thymine-Thymine Intermolecular Hydrogen Bonding in Adenine- and Thymine-Functionalized Naphthalenediimides.

The synthesis and spectroscopic characterization of novel nucleobase (adenine/thymine)-conjugated naphthalenediimides (NDIs), namely, NDI-AA, NDI-TT, and NDI-AT have been successfully achieved. NDI-AA, NDI-TT and NDI-AT have similar absorption in the 300-400 nm region. The effect of solvent on the absorption spectrum indicates aggregation, either through intermolecular π-σ interaction among the main chromophore or through intermolecular hydrogen bonding between adenine and adenine group. Addition of water does not assist hydrogen bond formation between thymine-thymine, rather increasing the polarity of the solvent encourages π-σ interaction among NDI-TTs. No spectral change for NDI-TT with increasing temperature confirms hydrogen bonding is not playing a crucial role in NDI-TT. A fluorescence study on NDI-AA also establishes excimer formation along with ground state aggregation. As the water content in the solvent mixture increases, aggregation of NDI-AA is discouraged due to adenine-adenine hydrogen bonding in accordance with earlier results. At the same time, the NDI-TT emission spectrum does not shift to the blue region and the intensity of the peak around 535 nm increases at the expense of fluorescence in 411 nm. Thus, increasing water content in the solvent mixture facilitates aggregation through π-σ interaction in NDI-TT as thymine-thymine hydrogen bonding is less pronounced.

Effect of the conversion of mangroves into shrimp farms on carbon stock in the sediment along the southern Red Sea coast, Saudi Arabia.

The conservation of coastal ecosystems and specially mangroves ''blue carbon'' is receiving more attention as consequence of their recognition as high ecosystem carbon stocks and for the fact that these areas are undergoing land conversion. The aim of the present study is to evaluate the impact of land use changes due to conversion of mangroves to shrimp farms on the bulk density (SBD), organic carbon (SOC) concentration, and SOC stock in the sediments along the southern Saudi Arabian Red Sea coast. Shrimp farms and mangrove locations showed significant (P < 0.001) differences in SBD with high mean values in the sediments of shrimp farms. Shrimp farms and mangrove locations showed significant (P < 0.001) SOC concentration differences with high mean values in the sediments of mangroves. Considering the whole depth of sediment interval (0-100 cm), the highest value of SOC stock was recorded at mangroves (29.2 kg C m-2) and the lowest was identified at the locations of shrimp farms (19.9 kg C m-2). The results show that SOC stock of mangroves is 147% higher than that of shrimp farms confirming the fact that anthropogenic factors contributed significantly to SOC stock decrease. The mean cumulative potential carbon dioxide (CO2) emission due to loss soil carbon stock from mangrove conversion to the shrimp ponds was 34.9 kg CO2 m-2. In conclusion, the conversion of mangroves into shrimp farms contributed to the loss of SOC stock, therefore, the preservation of mangrove areas has an important value especially in arid areas such as Saudi Arabia.

Bioaccumulation and translocation of nine heavy metals by Eichhornia crassipes in Nile Delta, Egypt: perspectives for phytoremediation.

The current research was carried out to estimate the potential of water hyacinth (WH) for removal of nine heavy metals (HMs) from three irrigation canals in Nile Delta. Sampling was achieved in monospecific and homogeneous WH stands at three irrigation canals in the study area, and WH biomass was sampled at monthly intervals from April 2014 to November 2014 using five randomly distributed quadrats (each 0.5 × 0.5 m) at each canal. All HM concentrations were significantly higher in the roots compared with the other WH organs. The WH was recognized by a bioaccumulation factor >1.0 for all HMs. The WH was recognized by translocation factor <1.0 for all HMs (except Pb). In many cases, the concentrations of the HMs in the different organs of WH were correlated with the same HMs in the water. Such correlations indicate that WH reflects the cumulative influences of environmental pollution from the water, and thereby suggesting its potential use in the bio-monitoring of most examined HMs. In conclusion, WH is a promising macrophyte for remediation of irrigation canals polluted with Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn.

Proton-Based Ultrafast Magic Angle Spinning Solid-State NMR Spectroscopy.

Protons are vastly abundant in a wide range of exciting macromolecules and thus can be a powerful probe to investigate the structure and dynamics at atomic resolution using solid-state NMR (ssNMR) spectroscopy. Unfortunately, the high signal sensitivity, afforded by the high natural-abundance and high gyromagnetic ratio of protons, is greatly compromised by severe line broadening due to the very strong 1H-1H dipolar couplings. As a result, protons are rarely used, in spite of the desperate need for enhancing the sensitivity of ssNMR to study a variety of systems that are not amenable for high resolution investigation using other techniques including X-ray crystallography, cryo-electron microscopy, and solution NMR spectroscopy. Thanks to the remarkable improvement in proton spectral resolution afforded by the significant advances in magic-angle-spinning (MAS) probe technology, 1H ssNMR spectroscopy has recently attracted considerable attention in the structural and dynamics studies of various molecular systems. However, it still remains a challenge to obtain narrow 1H spectral lines, especially from proteins, without resorting to deuteration. In this Account, we review recent proton-based ssNMR strategies that have been developed in our laboratory to further improve proton spectral resolution without resorting to chemical deuteration for the purposes of gaining atomistic-level insights into molecular structures of various crystalline solid systems, using small molecules and peptides as illustrative examples. The proton spectral resolution enhancement afforded by the ultrafast MAS frequencies up to 120 kHz is initially discussed, followed by a description of an ensemble of multidimensional NMR pulse sequences, all based on proton detection, that have been developed to obtain in-depth information from dipolar couplings and chemical shift anisotropy (CSA). Simple single channel multidimensional proton NMR experiments could be performed to probe the proximity of protons for structure determination using 1H-1H dipolar couplings and to evaluate the changes in chemical environments as well as the relative orientation to the external magnetic field using proton CSA. Due to the boost in signal sensitivity enabled by proton detection under ultrafast MAS, by virtue of high proton natural abundance and gyromagnetic ratio, proton-detected multidimensional experiments involving low-γ nuclei can now be accomplished within a reasonable time, while the higher dimension also offers additional resolution enhancement. In addition, the application of proton-based ssNMR spectroscopy under ultrafast MAS in various challenging and crystalline systems is also presented. Finally, we briefly discuss the limitations and challenges pertaining to proton-based ssNMR spectroscopy under ultrafast MAS conditions, such as the presence of high-order dipolar couplings, friction-induced sample heating, and limited sample volume. Although there are still a number of challenges that must be circumvented by further developments in radio frequency pulse sequences, MAS probe technology and approaches to prepare NMR-friendly samples, proton-based ssNMR has already gained much popularity in various research domains, especially in proteins where uniform or site-selective deuteration can be relatively easily achieved. In addition, implementation of the recently developed fast data acquisition approaches would also enable further developments in the design and applications of proton-based ultrafast MAS multidimensional ssNMR techniques.

Organizational Leadership and Adaptive Reserve in Blood Pressure Control: The Heart Health NOW Study.

PURPOSE: Our purpose was to assess whether a practice's adaptive reserve and high leadership capability in quality improvement are associated with population blood pressure control. METHODS: We divided practices into quartiles of blood pressure control performance and considered the top quartile as the benchmark for comparison. Using abstracted clinical data from electronic health records, we performed a cross-sectional study to assess the association of top quartile hypertension control and (1) the baseline practice adaptive reserve (PAR) scores and (2) baseline practice leadership scores, using modified Poisson regression models adjusting for practice-level characteristics. RESULTS: Among 181 practices, 46 were in the top quartile, which averaged 68% or better blood pressure control. Practices with higher PAR scores compared with lower PAR scores were not more likely to reside in the top quartile of performance (prevalence ratio [PR] = 1.92 for highest quartile; 95% CI, 0.9-4.1). Similarly, high quality improvement leadership capability compared with lower capability did not predict better blood pressure control performance (PR = 0.94; 95% CI, 0.57-1.56). Practices with higher proportions of commercially insured patients were more likely than practices with lower proportions of commercially insured patients to have top quartile performance (37% vs 26%, P =.002), whereas lower proportions of the uninsured (8% vs 14%, P =.055) were associated with better performance. CONCLUSIONS: Our findings show that adaptive reserve and leadership capability in quality improvement implementation are not statistically associated with achieving top quartile practice-level hypertension control at baseline in the Heart Health NOW project. Our findings, however, may be limited by a lack of patient-related factors and small sample size to preclude strong conclusions.