The Natural Products Atlas 2.0: a database of microbially-derived natural products.

Within the natural products field there is an increasing emphasis on the study of compounds from microbial sources. This has been fuelled by interest in the central role that microorganisms play in mediating both interspecies interactions and host-microbe relationships. To support the study of natural products chemistry produced by microorganisms we released the Natural Products Atlas, a database of known microbial natural products structures, in 2019. This paper reports the release of a new version of the database which includes a full RESTful application programming interface (API), a new website framework, and an expanded database that includes 8128 new compounds, bringing the total to 32 552. In addition to these structural and content changes we have added full taxonomic descriptions for all microbial taxa and have added chemical ontology terms from both NP Classifier and ClassyFire. We have also performed manual curation to review all entries with incomplete configurational assignments and have integrated data from external resources, including CyanoMetDB. Finally, we have improved the user experience by updating the Overview dashboard and creating a dashboard for taxonomic origin. The database can be accessed via the new interactive website at https://www.npatlas.org.

Effectiveness of ORSL® Variants as an Adjuvant along with Standard-of-care Treatment in the Restoration of Oral Fluid, Electrolytes, and Energy in Patients with Fever and/or General Weakness in Indian Patients in an Outpatient Setting.

BACKGROUND: Dehydration due to reduced intake or increased losses including insensible losses in patients with acute nondiarrheal diseases may lead to fluid, electrolytes, and energy (FEE) deficits. The impact of oral FEE supplementation adjuvant to standard of care (SOC) treatment on recovery in patients with acute nondiarrheal diseases is yet to be evaluated. AIM: To determine the effectiveness of ORSL® variants (ORSL® Apple Drink and ORSL® PLUS Orange Drink), fruit juice-based electrolyte drinks as an adjuvant along with SOC in the restoration of oral FEE in patients with acute nondiarrheal disease with fever and/or general weakness who attended an outpatient department (OPD). MATERIALS AND METHODS: This was a prospective, interventional, open-label, multicenter, real-world, study conducted at eight sites across India. Patients with fever and/or general weakness due to an acute nondiarrheal illness were given either ORSL® Apple Drink or ORSL® PLUS Orange Drink as an adjuvant along with SOC treatment per physician's discretion. The primary endpoint of the study was to assess improvement from baseline in energy or hydration levels after ORSL® variants consumption at 6, 24, and 48 hours measured by a new aided recovery scale (ARS). Secondary endpoints were to assess the improvement in energy and hydration levels at 20, 40, and 60 minutes, as well as energy levels and hydration levels at 20, 40, and 60 minutes, 6, 24, and 48 hours after the consumption of ORSL® Apple Drink or ORSL® PLUS Orange Drink. The patient's consumption of ORSL® variants and treatment experience, physician's experience of recommending ORSL® variants, and product safety were evaluated. RESULTS: In total, 612 patients were enrolled with mean age 38.3 years, of whom 62.9% were male. The mean baseline level of energy and hydration was 1.59 (range 1.0-2.0) on ARS. Statistically significant (p < 0.0001) improvements were observed in energy or hydration 6 hours after first consumption of ORSL formulations. Furthermore, improvement was observed from 40 minutes, and in levels of energy, hydration, and both energy and hydration from 60 minutes. Patients and physicians reported a positive experience with ORSL® variants. CONCLUSION: ORSL® Apple Drink and ORSL® PLUS Orange Drink are clinically proven to provide hydration and/or energy to patients with fever and/or general weakness.

Comparative Metabologenomics Analysis of Polar Actinomycetes.

Biosynthetic and chemical datasets are the two major pillars for microbial drug discovery in the omics era. Despite the advancement of analysis tools and platforms for multi-strain metabolomics and genomics, linking these information sources remains a considerable bottleneck in strain prioritisation and natural product discovery. In this study, molecular networking of the 100 metabolite extracts derived from applying the OSMAC approach to 25 Polar bacterial strains, showed growth media specificity and potential chemical novelty was suggested. Moreover, the metabolite extracts were screened for antibacterial activity and promising selective bioactivity against drug-persistent pathogens such as Klebsiella pneumoniae and Acinetobacter baumannii was observed. Genome sequencing data were combined with metabolomics experiments in the recently developed computational approach, NPLinker, which was used to link BGC and molecular features to prioritise strains for further investigation based on biosynthetic and chemical information. Herein, we putatively identified the known metabolites ectoine and chrloramphenicol which, through NPLinker, were linked to their associated BGCs. The metabologenomics approach followed in this study can potentially be applied to any large microbial datasets for accelerating the discovery of new (bioactive) specialised metabolites.

Randomized exploratory study to measure ion release from calcium sodium phosphosilicate-containing dentifrice.

This exploratory study investigated salivary concentrations of silicon, calcium, sodium, and phosphorous over a 60-min time period following the use of a calcium sodium phosphosilicate (CSPS)-containing dentifrice. Participants brushed with a dentifrice containing 5% (w/w) or 0% (w/w) CSPS or swilled with a slurry containing 5% (w/w) CSPS/glycerol. Saliva samples were collected before, and 2, 5, 15, and 60 min after, product use and were analysed using inductively coupled plasma optical emission spectroscopy. Intra-oral pH measurements were also taken. Primary analysis was of centrifuged saliva supernatant containing only dissolved material. At most time points, the CSPS-containing dentifrice and slurry generated significantly more salivary silicon than the dentifrice containing 0% CSPS. At 2-15 min after brushing there was significantly more salivary calcium after use of the CSPS-containing dentifrice and slurry, compared with the 0% CSPS dentifrice; a significant reduction, from baseline, in salivary calcium after use of dentifrice containing 0% CSPS; and an increase in salivary sodium after use of dentifrices containing either 5% or 0% CSPS, but no differences between them. Salivary phosphorous concentration decreased significantly with all treatments 2-5 min after use. There were no significant between-treatment differences in intra-oral pH. Products were generally well tolerated. This study establishes that it is possible to measure changes in salivary ionic composition derived through oral retention of CSPS, delivered via a dentifrice.

Condomless Anal Sex Among HIV-Positive Men Who Have Sex with Men: Biomedical Context Matters.

Data from Medical Monitoring Project was used to determine if partner type is associated with condomless anal sex (CAS) and insertive condomless anal sex (ICAS) among HIV-positive men who have sex with men. Participants reported HIV status and PrEP use of up to five anal sex partners. Partner type was categorized as HIV-positive, HIV status unknown, HIV-negative on PrEP or HIV-negative not on PrEP. To account for correlation of multiple observations per participant, generalized estimating equations were used to calculate adjusted prevalence ratios and 95% confidence intervals of CAS and ICAS. Condom use during anal sex and insertive anal sex varied based on partner type. There was a higher prevalence of CAS and ICAS in partnerships with HIV-positive partners or HIV-negative partners on PrEP compared to HIV-negative partners not on PrEP.

A Novel Modeling Approach for Estimating Patterns of Migration into and out of San Francisco by HIV Status and Race among Men Who Have Sex with Men.

In the early 1980s, men who have sex with men (MSM) in San Francisco were one of the first populations to be affected by the human immunodeficiency virus (HIV) epidemic, and they continue to bear a heavy HIV burden. Once a rapidly fatal disease, survival with HIV improved drastically following the introduction of combination antiretroviral therapy in 1996. As a result, the ability of HIV-positive persons to move into and out of San Francisco has increased due to lengthened survival. Although there is a high level of migration among the general US population and among HIV-positive persons in San Francisco, in- and out-migration patterns of MSM in San Francisco have, to our knowledge, never been described. Understanding migration patterns by HIV serostatus is crucial in determining how migration could influence both HIV transmission dynamics and estimates of the HIV prevalence and incidence. In this article, we describe methods, results, and implications of a novel approach for indirect estimation of in- and out-migration patterns, and consequently population size, of MSM by HIV serostatus and race in San Francisco. The results suggest that the overall MSM population and all the MSM subpopulations studied decreased in size from 2006 to 2014. Further, there were differences in migration patterns by race and by HIV serostatus. The modeling methods outlined can be applied by others to determine how migration patterns contribute to HIV-positive population size and output from these models can be used in a transmission model to better understand how migration can impact HIV transmission.

Does a hot drink provide faster absorption of paracetamol than a tablet? A pharmacoscintigraphic study in healthy male volunteers.

PURPOSE: To investigate the hypothesis that paracetamol is absorbed faster from a hot drink than from a standard tablet using simultaneous scintigraphic imaging and pharmacokinetic sampling. METHODS: Twenty-five healthy male volunteers received both paracetamol formulations in a randomised manner. The formulation administered in the first treatment arm was radiolabelled to allow scintigraphic monitoring. In both treatment arms, blood samples were taken for assessing paracetamol absorption. RESULTS: Following the hot drink, paracetamol absorption was both significantly faster and greater over the first 60 min post-dose compared with the tablet, as evidenced by the median time to reach t0.25 µg/mL of 4.6 and 23.1 min, respectively, and AUC0-60 of 4668.00 and 1331.17 h*ng/mL, respectively. In addition, tmax was significantly shorter for the hot drink (median time = 1.50 h) compared with the tablet (1.99 h). However, Cmax was significantly greater following the tablet (9,077 ng/mL) compared with the hot drink (8,062 ng/mL). Onset of gastric emptying after the hot drink was significantly faster than after the standard tablet (7.9 versus 54.2 min), as confirmed scintigraphically. CONCLUSIONS: Compared with a standard tablet, a hot drink provides faster absorption of paracetamol potentially due to more rapid gastric emptying.

People fifty years or older now account for the majority of AIDS cases in San Francisco, California, 2010.

People aged 50 and older are an increasing proportion of the population of persons living with AIDS (PLWA) in the USA. We used San Francisco's population-based HIV/AIDS surveillance registry to examine trends in the age distribution of people diagnosed and living with AIDS in San Francisco, California. AIDS case reporting is highly complete. Death ascertainment is complete through 2009 and 95% complete for 2010. At the end of 2010, 9796 persons were living with AIDS in San Francisco. Of these, more than half (5112 or 52%) were 50-years old or older. This proportion has steadily increased since 1990 in San Francisco. Our data also indicate that age at AIDS diagnosis has increased in San Francisco during the years 1990-2010. The proportion of PLWA who are aged 50 years or older is now a majority among PLWA in San Francisco. We believe that San Francisco is the first local jurisdiction in the USA to reach this milestone. The growing population of older persons with AIDS presents new challenges for research, medical care and support services.

Trends in Time Spent Viremic Among Persons Newly Diagnosed With HIV in San Francisco.

OBJECTIVE: To examine trends in time spent viremic and initiation into antiretroviral treatment (ART) among persons newly diagnosed with HIV in San Francisco. METHODS: Using HIV surveillance data, we included persons diagnosed with HIV during 2012-2020, a San Francisco resident at HIV diagnosis, alive 12 months after HIV diagnosis, and had ≥2 viral load tests within 12 months after diagnosis. Percent person-time spent (pPT) >200, pPT >1500, and pPT >10,000 copies per milliliter was calculated during the 12 months after HIV diagnosis. Multivariate regression models assessed the year of diagnosis and time spent above each viral threshold and year of diagnosis and ART initiation within 0-7 days (rapid), 8-365 days (delayed), or no ART initiation. RESULTS: Of 2471 new HIV diagnoses in San Francisco from 2012 to 2020, 1921 (72%) were included. Newly diagnosed persons spent a mean of 40.4% pPT >200, 32.4% pPT >1,500%, and 23.4% pPT >10,000 copies per milliliter; 33.8% had rapid ART initiation, 57.3% delayed, and 9% had no ART initiation. After adjustment, persons diagnosed in years 2014-2015, 2016-2017, 2018-2019, and 2020 were associated with less time spent above all viral thresholds and lower risk of delayed or no ART initiation compared with those diagnosed in 2012-2013. Greater time above thresholds correlated with injection drug use, ages 25-29 and 30-39 years, and homelessness. CONCLUSIONS: Percent time spent above each viremic level decreased significantly, whereas rapid ART initiation increased among newly diagnosed persons from 2014 through 2020 compared with 2012-2013. Population differences in time spent unsuppressed highlight the need for targeted interventions to reduce new HIV infections and improve health.

Hepatitis C prevalence among HIV-positive MSM in San Francisco: 2004 and 2008.

Recent reports suggest the potential for an epidemic of Hepatitis C among nonintravenous drug-using HIV-positive men who have sex with men. HIV-positive specimens from surveillance surveys in 2004 and 2008 were tested for HCV antibodies. Among noninjection drug using men who have sex with men, HCV prevalence was 8.7% and 4.5% in 2004 and 2008, respectively. There was no evidence of a change in HCV prevalence between 2004 and 2008.

Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics.

With more than 156,000 described species, eukaryotic algae (both macro- and micro-algae) are a rich source of biological diversity, however their chemical diversity remains largely unexplored. Specialised metabolites with promising biological activities have been widely reported for seaweeds, and more recently extracts from microalgae have exhibited activity in anticancer, antimicrobial, and antioxidant screens. However, we are still missing critical information on the distinction of chemical profiles between macro- and microalgae, as well as the chemical space these metabolites cover. This study has used an untargeted comparative metabolomics approach to explore the chemical diversity of seven seaweeds and 36 microalgal strains. A total of 1390 liquid chromatography-mass spectrometry (LC-MS) features were detected, representing small organic algal metabolites, with no overlap between the seaweeds and microalgae. An in-depth analysis of four Dunaliella tertiolecta strains shows that environmental factors may play a larger role than phylogeny when classifying their metabolomic profiles.

The challenge of contributing to policy making in primary care: the gendered experiences and strategies of nurses.

This paper explores nurses' experiences as members of primary care organisations set up to develop and commission health services for local communities. Nurses, alongside GPs and other health professionals, were given a place on the governing bodies (boards) of Local Health Groups - a move widely welcomed by the nursing profession as long overdue recognition of the important contribution nurses and nursing could bring to the policy arena. Nurse board members faced a number of challenges in their attempts to contribute to and influence local health policy. This ethnographic study (which involved non-participant observation of 33 board meetings and interviews with 29 board members including nurses) suggests that medical authority and control, and hierarchical power relations between doctors and nurses on the board, were seen by nurses as significant obstacles to their participation in this new policy arena. In response to their perceived lack of power and subordinate status, nurses employed a number of strategies to negotiate their participation as board members - these included 'getting it right', 'achieving the right balance', 'self-presentation' and 'unassertiveness'. These strategies reflected and reproduced gendered identities and relations of power and raise important questions regarding the influence of nurses and nursing within policy making.

"Is a Bird in the Hand Worth 5 in the Bush?": A Comparison of 3 Data-to-Care Referral Strategies on HIV Care Continuum Outcomes in San Francisco.

BACKGROUND: Health departments utilize HIV surveillance data to identify people with HIV (PWH) who need re-linkage to HIV care as part of an approach known as Data to Care (D2C.) The most accurate, effective, and efficient method of identifying PWH for re-linkage is unknown. METHODS: We evaluated referral and care continuum outcomes among PWH identified using 3 D2C referral strategies: health care providers, surveillance, and a combination list derived by matching an electronic medical record registry to HIV surveillance. PWH who were enrolled in the re-linkage intervention received short-term case management for up to 90 days. Relative risks and 95% confidence intervals were calculated to compare proportions of PWH retained and virally suppressed before and after re-linkage. Durable viral suppression was defined as having suppressed viral loads at all viral load measurements in the 12 months after re-linkage. RESULTS: After initial investigation, 233 (24%) of 954 referrals were located and enrolled in navigation. Although the numbers of surveillance and provider referrals were similar, 72% of enrolled PWH were identified by providers, 16% by surveillance, and 12% by combination list. Overall, retention and viral suppression improved, although relative increases in retention and viral suppression were only significant among individuals identified by surveillance or providers. Seventy percent of PWH who achieved viral suppression after the intervention remained durably virally suppressed. CONCLUSIONS: PWH referred by providers were more likely to be located and enrolled in navigation than PWH identified by surveillance or combination lists. Overall, D2C re-linkage efforts improved retention, viral suppression, and durable viral suppression.

A health management competency framework for Australia.

Objective This study examined whether the management competency framework for health service managers developed in the Victorian healthcare context is applicable to managers in other Australian states. Methods An online questionnaire survey of senior and middle-level health service managers in both community health services and hospitals was conducted in New South Wales and Queensland. Results The study confirmed that the essential tasks for senior and middle-level managers are consistent across health and social care sectors, as well as states. Core competencies for health services managers identified in the Victorian healthcare context are relevant to other Australian states. In addition, two additional competencies were incorporated into the framework. Conclusion The Management Competency Assessment Program competency framework summarises six competencies and associated behaviours that may be useful for guiding performance management and the education and training development of health service managers in Australia. What is known about the topic? The evidence suggests that competency-based approaches can enhance performance and talent management, and inform education and training needs, yet there has been no validated competency framework for Australian health service managers. What does the paper add? This paper explains the process of the finalisation of the first management competency framework for guiding the identification of the training and development needs of Australian health service managers and the management of their performance. What are the implications for practice? The Management Competency Assessment Program competency framework can guide the development of the health service management workforce in three Australian states, and may be applicable to other jurisdictions. Further studies are required in the remaining jurisdictions to improve the external validity of the framework.

Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells.

UNLABELLED: The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in approximately 20% of multiple myeloma (MM) patients. In this study, we investigated whether the therapeutic effect of bortezomib is associated with FGFR3 expression. MATERIALS AND METHODS: Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U266 cells and compared to U266 cells overexpressing FGFR3 wild-type (T-U266), or Y373C (Y-U266) or K650E (K-U266) mutant FGFR3. RESULTS: Our results suggested cell survival decreases in a dose-dependent manner. Interestingly, expression of FGFR3 protein was similarly dose dependent on bortezomib. It is confirmed the bortezomib-induced apoptotic death is correlated with FGFR3 expression. Furthermore, increased expression of p-STAT3, Mcl-1 and VEGF suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through p-STAT3 signaling. CONCLUSION: Our data indicates that Y373C mutation and wild-type FGFR3 may be associated with bortezomib-related treatment resistance in multiple myeloma.

Modern Innovative Solutions to Improve Outcomes in Severe Asthma: Protocol for a Mixed Methods Observational Comparison of Clinical Outcomes in MISSION Versus Current Care Delivery.

BACKGROUND: Asthma that is poorly controlled and undertreated can progress to more severe disease that is associated with high levels of unscheduled care that requires high-cost therapy, leading to a significant health economic burden. The identification and appropriate referral to a specialist asthma service is also often delayed by several months or years because of poor recognition and understanding of symptom severity. Current severe asthma services may take several months to provide a comprehensive multidisciplinary assessment, often necessitating multiple hospital visits and costing up to £5000 per patient. OBJECTIVE: This study aims to evaluate whether a new service model could identify poorly controlled and potentially severe asthma much earlier in the patient pathway, and then compare clinical outcomes between this new care model with standard care. METHODS: Modern Innovative Solutions to Improve Outcomes in (MISSION) Severe Asthma is a novel service model developed by asthma specialists from Portsmouth and Southampton severe asthma services. MISSION Severe Asthma identified patients with poorly controlled disease from general practice databases who had not been under secondary outpatient care in the last 12 months or who were not known to secondary care. In 1- or 2-stop assessments, a thorough review of diagnosis, disease phenotype, and control is undertaken, and clinical outcomes collected at baseline. RESULTS: A variety of clinical outcomes will be collected to assess the service model. The results will be reported in February 2020. CONCLUSIONS: This protocol outlines a mixed methods study to assess the impact on disease control, unscheduled health care usage, and quality of life in patients seen in the MISSION clinic compared with a closely matched cohort who declined to attend. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/9585.

Methods to include persons living with HIV not receiving HIV care in the Medical Monitoring Project.

The Medical Monitoring Project (MMP) is an HIV surveillance system that provides national estimates of HIV-related behaviors and clinical outcomes. When first implemented, MMP excluded persons living with HIV not receiving HIV care. This analysis will describe new case-surveillance-based methods to identify and recruit persons living with HIV who are out of care and at elevated risk for mortality and ongoing HIV transmission. Stratified random samples of all persons living with HIV were selected from the National HIV Surveillance System in five public health jurisdictions from 2012-2014. Sampled persons were located and contacted through seven different data sources and five methods of contact to collect interviews and medical record abstractions. Data were weighted for non-response and case reporting delay. The modified sampling methodology yielded 1159 interviews (adjusted response rate, 44.5%) and matching medical record abstractions for 1087 (93.8%). Of persons with both interview and medical record data, 264 (24.3%) would not have been included using prior MMP methods. Significant predictors were identified for successful contact (e.g., retention in care, adjusted Odds Ratio [aOR] 5.02; 95% Confidence Interval [CI] 1.98-12.73), interview (e.g. moving out of jurisdiction, aOR 0.24; 95% CI: 0.12-0.46) and case reporting delay (e.g. rural residence, aOR 3.18; 95% CI: 2.09-4.85). Case-surveillance-based sampling resulted in a comparable response rate to existing MMP methods while providing information on an important new population. These methods have since been adopted by the nationally representative MMP surveillance system, offering a model for public health program, research and surveillance endeavors seeking inclusion of all persons living with HIV.