Global health impacts of ambient fine particulate pollution associated with climate variability.

Air pollution is a key global environmental problem raising human health concern. It is essential to comprehensively assess the long-term characteristics of air pollution and the resultant health impacts. We first assessed the global trends of fine particulate matter (PM2.5) during 1980-2020 using a monthly global PM2.5 reanalysis dataset, and evaluated their association with three types of climate variability including El Niño-Southern Oscillation, Indian Ocean Dipole and North Atlantic Oscillation. We then estimated PM2.5-attributable premature deaths using integrated exposure-response functions. Results show a significant increasing trend of ambient PM2.5 during 1980-2020 due to increases in anthropogenic emissions. Ambient PM2.5 caused a total of âˆ¼ 135 million premature deaths globally during the four decades. Occurrence of air pollution episodes was strongly associated with climate variability, which were associated with up to 14 % increase in annual global PM2.5-attributable premature deaths.

Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma.

BACKGROUND: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. METHODS: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). RESULTS: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. CONCLUSION: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Palliative Quad Shot Radiation Therapy with or without Concurrent Immune Checkpoint Inhibition for Head and Neck Cancer.

OBJECTIVES: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. 'QuadShot' (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. MATERIALS AND METHODS: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. RESULTS: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9-77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60-70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073-0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. CONCLUSIONS: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.

Ileal phosphorus digestibility of soybean meal for broiler chickens remains consistent across institutions in a collaborative study regardless of non-phytate phosphorus concentration in the pre-experimental starter diet.

The same experimental protocol was used in 4 institutions to evaluate the impact of non-phytate phosphorus (nPP) concentration in the starter diet on regression method-derived ileal P digestibility of soybean meal (SBM) during the subsequent grower phase. A total of 1,536 Ross 308 male broiler chickens on d 0 post hatching were allotted to 2 pre-experimental starter diets that contained 3.5 or 4.5 g nPP/kg (96 replicate cages per diet, 8 birds per cage) for 18 d. Subsequently, 576 birds from each starter diet were selected and allocated to 3 experimental semi-purified grower diets containing 400, 510, or 620 g SBM/kg (32 replicate cages per diet, 6 birds per cage) for 3 d until collection of ileal digesta. Statistical analysis was conducted as a randomized complete block design with the starter period as whole plot and the grower period as split-plot. The only significant 2-way interaction was between grower diet and experimental institution (P < 0.05) on BW gain and gain to feed ratio. The main effect of institution and grower diet impacted (P < 0.05) feed intake, the digestibility of DM, P, and calcium, and disappearance of inositol hexakisphosphate (InsP6) in the grower diets. Birds fed the 3.5 g nPP/kg starter diet had lower (P < 0.05) BW gain and feed intake during the grower period, but presented higher (P < 0.05) digestibility of P and disappearance of InsP6 compared with the birds that were fed the 4.5 g nPP/kg starter diet. Regression method-derived ileal P digestibility of SBM was determined to be 46 or 42% for the respective 3.5 or 4.5 g nPP/kg pre-experimental starter diet and was not affected by the nPP concentration or by the institution. In conclusion, the experimental protocol used in the current study resulted in similar estimates across multiple institutions and is thus endorsed for future application in studies that aim to expand the database of digestible P content in plant source feed ingredients.

Evaluation of Selected Markers in Kidneys of Cynomolgus Monkey (Macaca fascicularis) with Induced Diabetes during Renal Ischemia-reperfusion Injury.

We previously reported that induced type 1 diabetes mellitus (DM) increases the susceptibility of acute kidney injury in- duced by ischemia-reperfusion injury (IRI) in cynomolgus monkeys. In this follow-up study, we compared the expression of selected markers in the renal tissues of monkeys subjected to bilateral renal IRI with and without diabetes. All tissues were obtained from the original study. Renal biopsies were obtained before and 24 and 48 h after ischemia and were examined for expression of KI-67 (tubular proliferation), Na+ /K+ ATPase (sodium-potassium pump), TNF-α(tumor necrosis factor-α, inflammation), CD31 (microvessels), CD3 (T-cells), 2 fibrotic markers (fibroblast specific protein-1, FSP-1;α-smooth muscle actin,α -SMA), and cleaved caspase 3 (apoptosis). Generally, the expression of these markers differed in monkeys with and without DM. As compared with non-DM monkeys, DM monkeys had more cells that expressed KI-67 during progression of acute kidney injury (AKI). Na+ /K+ ATPase expression was clearly present at baseline in the basolateral tubular areas only in the non-DM monkeys. At 48 h, its expression in the basolateral area was not visible in DM monkeys, but was still present in intercellular junctions of non-DM monkeys. The expression of TNF-αwas higher in DM before and 48 h after ischemia. Before and 24 h after ischemia, the number of CD31-positive capillaries was not different between 2 groups, although more collapsed vessels were found at in DM at 24 h. At 48 h, the number of capillaries was less in DM compared with those from non-DM animals. DM monkeys had more interstitial CD3-positive cells than did non-DM monkeys at 24 and 48 h after ischemia. Finally, FSP-1-stained cells were more abundant in DM than non-DM at 24 and 48 h. Our results show that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting tubular proliferation, capillary density, T cell infil- tration and by altering protein and mRNA expression of various genes involved in ion channel, inflammation, and fibrotic change. The results from this observational study demonstrate that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting multiple events including tubular necrosis, proliferation, function, inflammation and by inducing capillary rarefaction in cynomolgus monkeys.

A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern.

As SARS-CoV-2 variants of concern (VoCs) that evade immunity continue to emerge, next-generation adaptable COVID-19 vaccines which protect the respiratory tract and provide broader, more effective, and durable protection are urgently needed. Here, we have developed one such approach, a highly efficacious, intranasally delivered, trivalent measles-mumps-SARS-CoV-2 spike (S) protein (MMS) vaccine candidate that induces robust systemic and mucosal immunity with broad protection. This vaccine candidate is based on three components of the MMR vaccine, a measles virus Edmonston and the two mumps virus strains [Jeryl Lynn 1 (JL1) and JL2] that are known to provide safe, effective, and long-lasting protective immunity. The six proline-stabilized prefusion S protein (preS-6P) genes for ancestral SARS-CoV-2 WA1 and two important SARS-CoV-2 VoCs (Delta and Omicron BA.1) were each inserted into one of these three viruses which were then combined into a trivalent "MMS" candidate vaccine. Intranasal immunization of MMS in IFNAR1-/- mice induced a strong SARS-CoV-2-specific serum IgG response, cross-variant neutralizing antibodies, mucosal IgA, and systemic and tissue-resident T cells. Immunization of golden Syrian hamsters with MMS vaccine induced similarly high levels of antibodies that efficiently neutralized SARS-CoV-2 VoCs and provided broad and complete protection against challenge with any of these VoCs. This MMS vaccine is an efficacious, broadly protective next-generation COVID-19 vaccine candidate, which is readily adaptable to new variants, built on a platform with a 50-y safety record that also protects against measles and mumps.

Randomized evaluation of an online single-session intervention for minority stress in LGBTQ+ adolescents.

Background: LGBTQ+ youth face myriad adverse health outcomes due to minority stress, creating a need for accessible, mechanism-targeted interventions to mitigate these minority stress-related risk factors. We tested the effectiveness and acceptability of Project RISE, an online single-session intervention designed to ameliorate internalized stigma and improve other outcomes among LGBTQ+ youth. We hypothesized that youth assigned to RISE (versus a control) would report significantly reduced internalized stigma and increased identity pride at post-intervention and at two-week follow-up and would find RISE acceptable. Methods: We recruited adolescents nationally through Instagram advertisements in May 2022 (N = 538; M age = 15.06, SD age = 0.97). Participants were randomly assigned to RISE or an information-only control and completed questionnaires pre-intervention, immediately post-intervention, and two weeks post-intervention. Inclusion criteria included endorsing: (1) LGBTQ+ identity, (2) age 13-16, (3) English fluency (4) Internet access, and (5) subjective negative impact of LGBTQ+ stigma. Results: Relative to participants in the control condition, participants who completed RISE reported significant decreases in internalized stigma (d = -0.49) and increases in identity pride (d = 0.25) from pre- to immediately post-intervention, along with decreased internalized stigma (d = -0.26) from baseline to two-week follow-up. Participants rated both RISE and the information-only control as highly, equivalently acceptable. Conclusions: RISE appears to be an acceptable and useful online SSI for LGBTQ+ adolescents, with potential to reduce internalized stigma in both the short- and longer-term. Future directions include evaluating effects of Project RISE over longer follow-ups and in conjunction with other mental health supports.

Assessing the impact of health information exchange on hospital data breach risk.

OBJECTIVE: Widespread electronic health information exchange (HIE) across hospitals remains an important policy goal for reducing costs and improving the quality of care. Meanwhile, cybersecurity incidents are a growing threat to hospitals. The relationship between the electronic sharing of health information and cybersecurity incidents is not well understood. The objective of this study was to empirically examine the impact of hospitals' HIE engagement on their data breach risk. MATERIALS AND METHODS: A balanced panel dataset included 4,936 US community hospitals spanning the period 2010-2017, which was assembled by linking the American Hospital Association annual survey database and the Information Technology (IT) supplement, and the Department of Health and Human Services reports of health data breaches. The relationship between HIE engagement and hospital data breaches was modeled using a difference-in-differences specification controlling for time-varying hospital characteristics. RESULTS: The percentage of hospitals electronically exchanging information has more than tripled (from 18% to 68%) from 2010 to 2017. Hospital data breaches increased concurrently, largely due to the rise in hacking and unauthorized access. HIE engagement was associated with a 0.672 percentage point increase in the probability of an IT breach three years after the engagement. Hospitals actively engaging in a health information organization and exchanging data with outside providers were associated with a higher risk of IT related breaches in the long run; however, hospitals actively engaging in HIE and exchanging data with inside providers were not associated with any significant risk of IT related breaches. DISCUSSION: Over time, the increasing amount and complexity of patient information being exchanged can create challenges for cybersecurity if data protection is not up to date. Additionally, data security depends on the weakest link of HIE, and providers with fewer resources for data governance and infrastructure are more vulnerable to data breaches. CONCLUSION: Moving toward widespread health information exchange has important cybersecurity implications that can significantly impact both patients and healthcare organizations.

Understanding patient-level costs of weekly isoniazid-rifapentine (3HP) among people living with HIV in Uganda.

BACKGROUND: Twelve weeks of weekly isoniazid and rifapentine (3HP) prevents TB disease among people with HIV (PWH), but the costs to people of taking TB preventive treatment is not well described.METHODS: We surveyed PWH who initiated 3HP at a large urban HIV/AIDS clinic in Kampala, Uganda, as part of a larger trial. We estimated the cost of one 3HP visit from the patient perspective, including both out-of-pocket costs and estimated lost wages. Costs were reported in 2021 Ugandan shillings (UGX) and US dollars (USD; USD1 = UGX3,587)RESULTS: The survey included 1,655 PWH. The median participant cost of one clinic visit was UGX19,200 (USD5.36), or 38.5% of the median weekly income. Per visit, the cost of transportation was the largest component (median: UGX10,000/USD2.79), followed by lost income (median: UGX4,200/USD1.16) and food (median: UGX2,000/USD0.56). Men reported greater income loss than women (median: UGX6,400/USD1.79 vs. UGX3,300/USD0.93), and participants who lived further than a 30-minute drive to the clinic had higher transportation costs than others (median: UGX14,000/USD3.90 vs. UGX8,000/USD2.23).CONCLUSION: Patient-level costs to receive 3HP accounted for over one-third of weekly income. Patient-centered approaches to averting or defraying these costs are needed.

Using molecular straps to engineer conjugated porous polymer growth, chemical doping, and conductivity.

Controlling network growth and architecture of 3D-conjugated porous polymers (CPPs) is challenging and therefore has limited the ability to systematically tune the network architecture and study its impact on doping efficiency and conductivity. We have proposed that π-face masking straps mask the π-face of the polymer backbone and therefore help to control π-π interchain interactions in higher dimensional π-conjugated materials unlike the conventional linear alkyl pendant solubilizing chains that are incapable of masking the π-face. Herein, we used cycloaraliphane-based π-face masking strapped monomers and show that the strapped repeat units, unlike the conventional monomers, help to overcome the strong interchain π-π interactions, extend network residence time, tune network growth, and increase chemical doping and conductivity in 3D-conjugated porous polymers. The straps doubled the network crosslinking density, which resulted in 18 times higher chemical doping efficiency compared to the control non-strapped-CPP. The straps also provided synthetic tunability and generated CPPs of varying network size, crosslinking density, dispersibility limit, and chemical doping efficiency by changing the knot to strut ratio. For the first time, we have shown that the processability issue of CPPs can be overcome by blending them with insulating commodity polymers. The blending of CPPs with poly(methylmethacrylate) (PMMA) has enabled them to be processed into thin films for conductivity measurements. The conductivity of strapped-CPPs is three orders of magnitude higher than that of the poly(phenyleneethynylene) porous network.

Application of Phytogenic Liquid Supplementation in Soil Microbiome Restoration in Queensland Pasture Dieback.

Pasture production is vital in cattle farming as it provides animals with food and nutrients. Australia, as a significant global beef producer, has been experiencing pasture dieback, a syndrome of deteriorating grassland that results in the loss of grass and the expansion of weeds. Despite two decades of research and many remediation attempts, there has yet to be a breakthrough in understanding the causes or mechanisms involved. Suggested causes of this phenomenon include soil and plant microbial pathogens, insect infestation, extreme heat stress, radiation, and others. Plants produce a range of phytomolecules with antifungal, antibacterial, antiviral, growth-promoting, and immunostimulant effects to protect themselves from a range of environmental stresses. These products are currently used more in human and veterinary health than in agronomy. In this study, we applied a phytogenic product containing citric acid, carvacrol, and cinnamaldehyde, to investigate its ability to alleviate pasture dieback. The phytogenic liquid-based solution was sprayed twice, one week apart, at 5.4 L per hectare. The soil microbial community was investigated longitudinally to determine long-term effects, and pasture productivity and plant morphometric improvements were explored. The phytogenic liquid significantly improved post-drought recovery of alpha diversity and altered temporal and spatial change in the community. The phytogenic liquid reduced biomarker genera associated with poor and polluted soils and significantly promoted plant and soil beneficial bacteria associated with plant rhizosphere and a range of soil benefits. Phytogenic liquid application produced plant morphology improvements and a consistent enhancement of pasture productivity extending beyond 18 months post-application. Our data show that phytogenic products used in the livestock market as an alternative to antibiotics may also have a beneficial role in agriculture, especially in the light of climate change-related soil maintenance and remediation.

Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

Humate application alters microbiota-mineral interactions and assists in pasture dieback recovery.

Pasture dieback is a rapidly expanding decaying pasture syndrome that affects millions of hectares of agricultural land in Queensland, Australia, making it useless for the cattle industry and decimating farmers' income and welfare. Since the syndrome was first identified in the early 1990s, farmers and agronomists have tried various methods for pasture recovery, including slashing, burning, ploughing and resowing grass, fertilising, destocking, and overstocking. In most cases, after a minimal initial improvement, the grass reverts to dieback within a few weeks. Here, we present an application of potassium humate, a well-known plant growth stimulator, as a possible long-term recovery option. Humate was applied once at the rate of 12 ml per m2. Humate application did not alter the alpha or beta diversity of soil bacterial communities, nor did it change the mineral profile in the soil. However, humate application altered soil microbiota-mineral temporal interactions and introduced subtle changes in the microbial community that could assist pasture recovery. A single humate application increased paddock plant biomass significantly up to 20 weeks post-application. Eleven months after the single application, the paddock was grazed to the ground by the cattle just before the rainfall season. After pasture regrowth, the humate-treated plots significantly improved root morphometric indicators for both grass and dicots and increased the ratio of grass/weeds by 27.6% compared to the water-treated control. While this treatment will not resolve the dieback syndrome, our results invite more research to optimise the use of humate for maximum economic benefit in paddock use under pasture dieback syndrome conditions.

Phytogenic Blend Improves Intestinal Health and Reduces Obesity, Diabetes, Cholesterol and Cancers: A Path toward Customised Supplementation.

Poultry production is among the most challenging industries for pathogen control. High animal density and abundance of faecal material demand strict biosecurity measures and continual vigilance in monitoring animal health parameters. Despite this vigilance, dealing with disease outbreaks is a part of farmers' routines. Phytogenic feed additives comprised of herbs, spices, essential oils, and oleoresins have potent antimicrobial and anti-inflammatory actions. Related studies are gaining substantial interest in human and animal health worldwide. In this study, a commercial blend phytogenic feed additive was supplemented to layers in an industrial free-range production system with 20,000 birds in both control and treatment groups. At the end of the trial, the ileum tissue was sampled for RNAseq transcriptomic analysis to study the host reaction to the supplement. Phytogenic supplement significantly inhibited four cholesterol-related pathways and reduced the Arteriosclerosis disease category towards improved cardiovascular health. The supplemented birds exhibited reduced disease susceptibility for 26 cancer categories with p-values in the range from 5.23 × 10-4 to 1.02 × 10-25. Major metabolic shifts in Lipid metabolism in combination with Carbohydrate metabolism have resulted in a decrease in the Obesity category, altering the ratio of fat and carbohydrate metabolism toward lower fat storage.

Phytogen Improves Performance during Spotty Liver Disease by Impeding Bacterial Metabolism and Pathogenicity.

A range of antibiotic alternative products is increasingly studied and manufactured in the current animal agriculture, particularly in the poultry industry. Phytogenic feed additives are known for their remarkable ability to suppress pathogens such as Clostridium spp., Escherichia coli, and Salmonella. Other than enhancing biosecurity, improvements in productivity and performance were also observed. However, clear mechanisms for these improvements were not established. In this study, 20,000 Lohman-Brown layers were provided with phytogenic supplement from 16 to 40 weeks of age, and performance parameters were assessed against the same number of unsupplemented control birds. The performance results showed that the birds with phytogenic supplementation presented consistently reduced mortality, increased rate of lay, and increased average egg weight. Functional analysis through shotgun sequencing of cecal metagenomes confirmed a substantial functional shift in the microbial community, showing that phytogen significantly reduced the range of microbial functions, including the production of essential vitamins, cofactors, energy, and amino acids. Functional data showed that phytogen supplementation induced a phenotypic shift in intestinal bacteria LPS phenotype toward the less pathogenic form. The study corroborates the use of phytogenic products in antibiotic-free poultry production systems. The productivity improvements in the number and weight of eggs produced during Spotty Liver Disease justify further optimizing phytogenic alternatives for use in high-risk open and free-range poultry systems. IMPORTANCE The present study establishes the beneficial effects of the continuous phytogenic supplementation reflected in reduced diarrhea and mortality and higher egg productivity under normal conditions and during a natural outbreak of Spotty Liver Disease. Our data points to the importance of phytogen-driven alteration of microbial pathogenicity and fitness-related functional capabilities revealed on the commercial layer farm. Phytogenic product showed an ability to improve the bird's welfare and sustainability in free-range poultry production systems.

Molecular dynamics simulations of the secondary-binding site in disaccharide-modified glycopeptide antibiotics.

Oritavancin is a semisynthetic glycopeptide antibiotic used to treat severe infections by multidrug-resistant Gram-positive pathogens. Oritavancin is known to be a thousand times more potent than vancomycin against Gram-positive bacteria due to the additional interactions with bacterial peptidoglycan (PG) facilitated by a secondary-binding site. The presence of this secondary-binding site is evident in desleucyl-oritavancin, an Edman degradation product of oritavancin, still retaining its potency against Gram-positive bacteria, whereas desleucyl-vancomycin is devoid of any antimicrobial activities. Herein, using explicit solvent molecular dynamics (MD) simulations, steered MD simulations, and umbrella sampling, we show evidence of a secondary-binding site mediated by the disaccharide-modified hydrophobic sidechain of oritavancin interactions with the pentaglycyl-bridge segment of the PG. The interactions were characterized through comparison to the interaction of PG with chloroeremomycin, vancomycin, and the desleucyl analogs of the glycopeptides. Our results show that the enhanced binding of oritavancin to PG over the binding of the other complexes studied is due to an increase in the hydrophobic effect, electrostatic and van der Waals interactions, and not the average number of hydrogen bonds. Our ranking of the binding interactions of the biomolecular complexes directly correlates with the order based on their experimental minimum inhibitory concentrations. The results of our simulations provide insight into the modification of glycopeptides to increase their antimicrobial activities or the design of novel antibiotics against pathogenic Gram-positive bacteria.

Ileum transcriptional response to prolonged supplementation with phytogenic product containing menthol, carvacrol and carvone.

Pathogen control is a critical issue in the layer industry. Plant-based natural products are firmly replacing the undesirable use of antibiotics in animal production. The poultry industry embraced the opportunity to distance itself from the negative public perception of antibiotic use. In this study, we investigated the effects of a phytogenic product comprising of menthol, carvacrol and carvone on ileum gene expression profile in layers after 16 weeks of continual supplementation. Phytogen supplementation increased endocytosis and autophagy while showing significant predicted cardiovascular protective effects. Statistical comparison with over 100,000 manually curated and comparably reanalysed public datasets suggests that the phytogen effects are highly significantly comparable with transcriptomic effects of clinical antibiotics doxycycline and geldanamycin, and that phytogen can reverse transcriptomic effects of a range of viral diseases and malaria. Our data confirmed the hypothesis that similarly to the original essential oil type antimicrobial constituents of phytogenic products, there may be a range of benefits unrelated to their critical antimicrobial action, contributing to improved bird welfare.

Risk of stroke with antivenom usage after venomous snakebite in Taiwan: a population-based cohort study.

BACKGROUND AND PURPOSE: Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study. METHODS: This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors. RESULTS: The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41-5.26). CONCLUSION: Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.

The relationship between cybersecurity ratings and the risk of hospital data breaches.

OBJECTIVE: We investigated the progression of healthcare cybersecurity over 2014-2019 as measured by external risk ratings. We further examined the relationship between hospital data breaches and cybersecurity ratings. MATERIALS AND METHODS: Using Fortune 1000 firms as a benchmark, time trends in hospital cybersecurity ratings were compared using linear regression. Further, the relationship between hospital data breaches and cybersecurity ratings was modeled using logistic regression. Hospital breach data were collected from US HHS, and cybersecurity ratings were provided by BitSight. The resulting study sample yielded 3528 hospital-year observations. RESULTS: In aggregate, we found that hospitals had significantly lower cybersecurity ratings than Fortune 1000 firms, however, hospitals have closed the gap in recent years. We also found that hospitals with the low security ratings were associated with significant risk of a data breach, with the probability of a breach in a given year ranging from 14% to 33%. DISCUSSION: Recent cyber-attacks in healthcare continue to illustrate the need to better secure information systems. While hospitals have reduced cyber risk over the past decade, they remain statistically more vulnerable than the Fortune 1000 firms against botnets, spam, and malware. CONCLUSION: Policy makers should continue encouraging acute-care hospitals to proactively invest in security controls that reduce cyber risk. Best practices from other sectors like the financial services sector could provide useful guides and benchmarks for improvement.

Current Stimulation of the Midbrain Nucleus in Pigeons for Avian Flight Control.

A number of research attempts to understand and modulate sensory and motor skills that are beyond the capability of humans have been underway. They have mainly been expounded in rodent models, where numerous reports of controlling movement to reach target locations by brain stimulation have been achieved. However, in the case of birds, although basic research on movement control has been conducted, the brain nuclei that are triggering these movements have yet to be established. In order to fully control flight navigation in birds, the basic central nervous system involved in flight behavior should be understood comprehensively, and functional maps of the birds' brains to study the possibility of flight control need to be clarified. Here, we established a stable stereotactic surgery to implant multi-wire electrode arrays and electrically stimulated several nuclei of the pigeon's brain. A multi-channel electrode array and a wireless stimulation system were implanted in thirteen pigeons. The pigeons' flight trajectories on electrical stimulation of the cerebral nuclei were monitored and analyzed by a 3D motion tracking program to evaluate the behavioral change, and the exact stimulation site in the brain was confirmed by the postmortem histological examination. Among them, five pigeons were able to induce right and left body turns by stimulating the nuclei of the tractus occipito-mesencephalicus (OM), nucleus taeniae (TN), or nucleus rotundus (RT); the nuclei of tractus septo-mesencephalicus (TSM) or archistriatum ventrale (AV) were stimulated to induce flight aviation for flapping and take-off with five pigeons.