Unveiling the environmental significance of acetylperoxyl radical: Reactivity quantification and kinetic modeling.

Acetylperoxyl radical (CH3C(O)OO•) is among highly reactive organic radicals which are known to play crucial roles in atmospheric chemistry, aqueous chemistry and, most recently, peracetic acid (PAA)-based advanced oxidation processes. However, fundamental knowledge for its reactivity is scarce and severely hampers the understanding of relevant environmental processes. Herein, three independent experimental approaches were exploited for revelation and quantification of the reaction rates of acetylperoxyl radical. First, we developed and verified laser flash photolysis of biacetyl, ultraviolet (UV) photolysis of biacetyl, and pulse radiolysis of acetaldehyde, each as a clean source of CH3C(O)OO•. Then, using competition kinetics and selection of suitable probe and competitor compounds, the rate constants between CH3C(O)OO• and compounds of diverse structures were determined. The three experimental approaches complemented in reaction time scale and ease of operation, and provided cross-validation of the rate constants. Moreover, the formation of CH3C(O)OO• was verified by spin-trapped electron paramagnetic resonance, and potential influence of other reactive species in the systems was assessed. Overall, CH3C(O)OO• displays distinctively high reactivity and selectivity, reacting especially favorably with naphthyl and diene compounds (k ∼ 107-108 M-1 s-1) but sluggishly with N- and S-containing groups. Significantly, we demonstrated that incorporating acetylperoxyl radical-oxidation reactions significantly improved the accuracy in modeling the degradation of environmental micropollutants by UV/PAA treatment. This study is among the most comprehensive investigation for peroxyl radical reactivity to date, and establishes a robust methodology for investigating organic radical chemistry. The determined rate constants strengthen kinetic databases and improve modeling accuracy for natural and engineered systems.

Examining Introduction of E-consent in the Neurosurgical Caseload: Understanding the Barriers to Implementation.

OBJECTIVE: To evaluate current usage and barriers of electronic consent (e-consent) implementation in neurosurgical practice. E-consent forms provide an alternative method for conducting the informed consent (IC) procedure. IC requires an ability to understand, retain, weigh up, and communicate decisions regarding the proposed procedure. Currently, e-consent has shown promise as a method of improving IC, yet barriers to implementation exist. METHODS: A comparative analysis regarding procedural and consent data was collected over six months in 2 neurosurgical centers with elective and emergency caseloads. These were evaluated for changes over time following e-consent introduction. Clinicians were surveyed for their experience using of e-consenting to understand the barriers to implementation. RESULTS: Over one half (55.6%) of neurosurgical procedures made use of e-consent for IC. Lower rates of e-consent were used in trauma related procedures (38.38%) as compared to elective procedures. This did not increase significantly over the study period. Positive clinician survey feedback indicated e-consenting reduces the time required to perform IC, with 50% of respondents strongly agreeing. Barriers to implementation were reported on free-text entry pertaining largely to difficulties in emergency situations due to form complexity. The inability to create and edit templates for personalized e-consent delivery was a further limitation. CONCLUSIONS: Despite the advantages conferred by e-consent for the administration of IC in neurosurgical procedures, reflected in our survey data, there remains limited use of the technology. Limitations remain relating to ease of access and complexity of use in trauma scenarios.

NONO2P, a novel nitric oxide donor, causes vasorelaxation through NO/sGC/PKG pathway, K+ channels opening and SERCA activation.

BACKGROUND & AIMS: The treatment of cardiovascular diseases (CVD) could greatly benefit from using nitric oxide (NO) donors. This study aimed to investigate the mechanisms of action of NONO2P that contribute to the observed responses in the mesenteric artery. The hypothesis was that NONO2P would have similar pharmacological actions to sodium nitroprusside (SNP) and NO. METHODS: Male Wistar rats were euthanized to isolate the superior mesenteric artery for isometric tension recordings. NO levels were measured using the DAF-FM/DA dye, and cyclic guanosine monophosphate (cGMP) levels were determined using a cGMP-ELISA Kit. RESULTS: NONO2P presented a similar maximum efficacy to SNP. The free radical of NO (NO•) scavengers (PTIO; 100 µM and hydroxocobalamin; 30 µM) and nitroxyl anion (NO-) scavenger (L-cysteine; 3 mM) decreased relaxations promoted by NONO2P. The presence of the specific soluble guanylyl cyclase (sGC) inhibitor (ODQ; 10 µM) nearly abolished the vasorelaxation. The cGMP-dependent protein kinase (PKG) inhibition (KT5823; 1 µM) attenuated the NONO2P relaxant effect. The vasorelaxant response was significantly attenuated by blocking inward rectifying K+ channels (Kir), voltage-operated K+ channels (KV), and large conductance Ca2+-activated K+ channels (BKCa). NONO2P-induced relaxation was attenuated by cyclopiazonic acid (10 µM), indicating that sarcoplasmic reticulum Ca2+-ATPase (SERCA) activation is involved in this relaxation. Moreover, NONO2P increased NO levels in endothelial cells and cGMP production. CONCLUSIONS: NONO2P induces vasorelaxation with the same magnitude as SNP, releasing NO• and NO-. Its vasorelaxant effect involves sGC, PKG, K+ channels opening, and SERCA activation, suggesting its potential as a therapeutic option for CVD.

The Role and Applications of Artificial Intelligence in the Treatment of Chronic Pain.

PURPOSE OF REVIEW: This review aims to explore the interface between artificial intelligence (AI) and chronic pain, seeking to identify areas of focus for enhancing current treatments and yielding novel therapies. RECENT FINDINGS: In the United States, the prevalence of chronic pain is estimated to be upwards of 40%. Its impact extends to increased healthcare costs, reduced economic productivity, and strain on healthcare resources. Addressing this condition is particularly challenging due to its complexity and the significant variability in how patients respond to treatment. Current options often struggle to provide long-term relief, with their benefits rarely outweighing the risks, such as dependency or other side effects. Currently, AI has impacted four key areas of chronic pain treatment and research: (1) predicting outcomes based on clinical information; (2) extracting features from text, specifically clinical notes; (3) modeling 'omic data to identify meaningful patient subgroups with potential for personalized treatments and improved understanding of disease processes; and (4) disentangling complex neuronal signals responsible for pain, which current therapies attempt to modulate. As AI advances, leveraging state-of-the-art architectures will be essential for improving chronic pain treatment. Current efforts aim to extract meaningful representations from complex data, paving the way for personalized medicine. The identification of unique patient subgroups should reveal targets for tailored chronic pain treatments. Moreover, enhancing current treatment approaches is achievable by gaining a more profound understanding of patient physiology and responses. This can be realized by leveraging AI on the increasing volume of data linked to chronic pain.

Safety evaluation of 8 drug degradants present in over-the-counter cough and cold medications.

Although the United States Food & Drug Administration (FDA) has provided guidance on the control of drug degradants for prescription drugs, there is less guidance on how to set degradant specifications for FDA OTC monograph drugs. Given that extensive impurity testing was not part of the safety paradigm in original OTC monographs, a weight of evidence (WOE) approach to qualify OTC degradants is proposed. This approach relies on in silico tools and read-across approaches alongside standard toxicity testing to determine safety. Using several drugs marketed under 21 CFR 341 as case studies, this research demonstrates the utility of a WOE approach across data-rich and data-poor degradants. Based on degradant levels ranging from 1 to 4% of the maximum daily doses of each case study drug and 10th percentile body weight data for each patient group, children were recognized as having the highest potential exposure relative to adults per body mass. Depending on data availability and relationship to the parent API, margins of safety (MOS) or exposure margins were calculated for each degradant. The findings supported safe use, and indicated that this contemporary WOE approach could be utilized to assess OTC degradants. This approach is valuable to establish specifications for degradants in OTCs.

Post-traumatic Stress Disorder: The Influence of the Environmental Context and Analysis of Oxidative Stress and Inflammatory and Glycemic Markers in Women Living in Kurdistan Regional Government-Iraq.

Background Internally displaced persons (IDP) camps are still home to a large number of female survivors of the Yazidi genocide carried out in Iraq in 2014 by the Islamic organization known as the Islamic State of Iraq and Syria (ISIS). Many of these women suffer from a persistent form of post-traumatic stress disorder (PTSD), which can last for many years. On the other hand, little is known about the intricate etiology of PTSD. Objectives In this observational cross-sectional study, the biochemical parameters, including inflammatory and oxidative stress (OXS) markers, were evaluated in two groups: the case group (women with newly diagnosed PTSD) and the control group (apparently healthy women). Furthermore, how the environment impacts the biochemical and OXS parameters of people not diagnosed with PTSD but living in IDP camps was also analyzed. Materials and methods The PTSD group (n=55, age=30.0 years) was made up of women survivors of genocide-related events living in IDP camps in the Kurdistan region of Iraq. The studied parameters in the PTSD group have been compared to two healthy control groups: (1) internal control group (n=55, age=28.1 years): healthy women living inside the IDP camps; and (2) external control group (n=55, age=28.3 years): healthy women living outside the IDP camps. The diagnosis of PTSD was conducted using a validated Kurdish version of the PTSD Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) scale. Blood samples were collected to determine the level of glycated hemoglobin (HbA1c) and the concentrations of fasting serum glucose (FSG), C-reactive protein (CRP), ceruloplasmin (CP), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH), malondialdehyde (MDA), protein carbonyls (PC), and catalase (CAT) activity. Results Women with PTSD presented increased values of FSG (4.41%, p<0.05), HbA1c (4.74%, p<0.05), and CRP (114.29%, p<0.05), as well as increased levels of 8-OHdG (185.97%, p<0.001), CP (27.08%, p<0.001), MDA (141.97%, p<0.001), and PC (63.01%, p<0.001), besides increased CAT activity (121.5%, p<0.001), when compared with the control groups. A significant reduction of GSH (-20.33%, p<0.05) was observed in PTSD patients as compared to the external control group. In relation to the internal control group, women diagnosed with PTSD presented significantly increased levels of FSG (3.88%, p<0.05), HbA1c (2.83%, p<0.05), CRP (77.97%, p<0.05), and PC (41.3%, p<0.05), as well as increased levels of 8-OHdG (118.84%, p<0.001), CP (22.72%, p<0.001), MDA (90.67%, p<0.001), and CAT activity (55.31%, p<0.001). Healthy individuals residing in IDP camps, compared with external healthy control, presented significantly elevated levels of 8-OHdG (30.68%, p<0.001), MDA (26.91%, p<0.001), PC (15.37%, p<0.001), and CAT activity (42.62%, p<0.001). Conclusion Our findings indicate that PTSD significantly influences glycemic, inflammatory, oxidant, and antioxidant parameters, as evidenced by increased levels of FSG, HbA1C, CRP, PC, MDA, 8-OHdG, and CP, as well as increased CAT activity and a reduced GSH concentration in the PTSD group in comparison to the external control group. Additionally, our results suggest that the environmental context in IDP camps by itself can potentially affect oxidant and antioxidant parameters, as evidenced by the increased concentrations of 8-OHdG, MDA, and PC and increased CAT activity found in individuals not diagnosed with PTSD but living inside the camps.

The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls.

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

Epidemiological trends of pyogenic spondylodiscitis in Germany: an EANS Spine Section Study.

Pyogenic spondylodiscitis presents significant diagnostic and therapeutic challenges. In Germany, a comprehensive understanding of its epidemiology and inpatient management outcomes is limited, hindering the optimisation of therapeutic strategies. This study aimed to characterise the evolving epidemiological trends of pyogenic spondylodiscitis in Germany, and concurrently evaluate inpatient management strategies and outcomes. We performed a retrospective population-based study of spondylodiscitis cases in Germany from 2005 to 2021, utilising data from the German Federal Statistical Office database. The parameters assessed were incidence trends, demographic characteristics, inpatient management strategies, and inpatient mortality. The study found a significant rise in the population-adjusted incidence of spondylodiscitis in Germany from 2005 to 2021, increasing by 104% from 5.4 to 11.0 cases per 100,000 individuals (p < 0.001). The highest number of diagnoses was recorded in 2019. Age group-adjusted data revealed the largest relative changes in the "90 + " age group, followed by the "80-89" and "70-79" age groups. These increases were not solely attributable to population changes but were also confirmed after calculating the age-group-adjusted incidence rates. Additionally, our statistical analysis demonstrated that both age and year significantly influenced the incidence of spondylodiscitis. Over the same period, inpatient mortality also surged significantly by 347% (p < 0.001), with the highest increase recorded in the 90 + age group, observing a 2450% rise (p < 0.001). The mean length of inpatient stay decreased by 15% (p < 0.05). Concurrently, there was a significant increase in surgical interventions using spinal stabilisation procedures (p < 0.001), which might suggest a shift in the treatment paradigm for spondylodiscitis. The results underscore a concerning rise in spondylodiscitis incidence and mortality in Germany, particularly affecting the ageing population. A notable shift towards surgical intervention was observed. The data highlights the urgent necessity for high-level evidence studies comparing surgical versus conservative treatment, thereby guiding optimised therapeutic strategies.

Methodological and ethical challenges in the use of focused ultrasound for blood-brain barrier disruption in neuro-oncology.

BACKGROUND: Focused ultrasound (FUS) shows promise for enhancing drug delivery to the brain by temporarily opening the blood-brain barrier (BBB), and it is increasingly used in the clinical setting to treat brain tumours. It remains however unclear whether FUS is being introduced in an ethically and methodologically sound manner. The IDEAL-D framework for the introduction of surgical innovations and the SYRCLE and ROBINS-I tools for assessing the risk of bias in animal studies and non-randomized trials, respectively, provide a comprehensive evaluation for this. OBJECTIVES AND METHODS: A comprehensive literature review on FUS in neuro-oncology was conducted. Subsequently, the included studies were evaluated using the IDEAL-D framework, SYRCLE, and ROBINS-I tools. RESULTS: In total, 19 published studies and 12 registered trials were identified. FUS demonstrated successful BBB disruption, increased drug delivery, and improved survival rates. However, the SYRCLE analysis revealed a high risk of bias in animal studies, while the ROBINS-I analysis found that most human studies had a high risk of bias due to a lack of blinding and heterogeneous samples. Of the 15 pre-clinical stage 0 studies, only six had formal ethical approval, and only five followed animal care policies. Both stage 1 studies and stage 1/2a studies failed to provide information on patient data confidentiality. Overall, no animal or human study reached the IDEAL-D stage endpoint. CONCLUSION: FUS holds promise for enhancing drug delivery to the brain, but its development and implementation must adhere to rigorous safety standards using the established ethical and methodological frameworks. The complementary use of IDEAL-D, SYRCLE, and ROBINS-I tools indicates a high risk of bias and ethical limitations in both animal and human studies, highlighting the need for further improvements in study design for a safe implementation of FUS in neuro-oncology.

Disinfection of Phi6, MS2, and Escherichia coli by Natural Sunlight on Healthcare Critical Surfaces.

Ultraviolet (UV) radiation systems, commonly used to disinfect surfaces, drinking water, and air, stem from historical practice to use sunlight to disinfect household items after contagious illness. Currently, it is still recommended in viral outbreak contexts such as COVID-19, Ebola, and Marburg to expose soft surfaces to sunlight after washing with detergent or disinfecting with chlorine. However, sunlight that reaches the Earth's surface is in the UVA/UVB wavelengths, whereas UV disinfection systems typically rely on biocidal UVC. Our goal was to fill the evidence gap on the efficacy of sunlight disinfection on surface materials common in low-resource healthcare settings by seeding four surfaces (stainless steel, nitrile, tarp, cloth) with three microorganisms (viral surrogate bacteriophages Phi6 and MS2 and Escherichia coli bacteria), with and without soil load, and exposing to three sunlight conditions (full sun, partial sun, cloudy). We conducted 144 tests in triplicate and found: solar radiation averaged 737 W/m2 (SD = 333), 519 W/m2 (SD = 65), and 149 W/m2 (SD = 24) for full sun, partial sun, and cloudy conditions; significantly more surfaces averaged ≥ 4 log10 reduction value (LRV) for Phi6 than MS2 and E. coli (P < 0.001) after full sun exposure, and no samples achieved ≥ 4 LRV for partial sun or cloudy conditions. On the basis of our results, we recommend no change to current protocols of disinfecting materials first with a 0.5% chlorine solution then moving to sunlight to dry. Additional field-based research is recommended to understand sunlight disinfection efficacy against pathogenic organisms on healthcare relevant surfaces during actual outbreak contexts.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Updated systematic assessment of human, animal and mechanistic evidence demonstrates lack of human carcinogenicity with consumption of aspartame.

Aspartame has been studied extensively and evaluated for its safety in foods and beverages yet concerns for its potential carcinogenicity have persisted, driven primarily by animal studies conducted at the Ramazzini Institute (RI). To address this controversy, an updated systematic review of available human, animal, and mechanistic data was conducted leveraging critical assessment tools to consider the quality and reliability of data. The evidence base includes 12 animal studies and >40 epidemiological studies reviewed by the World Health Organization which collectively demonstrate a lack of carcinogenic effect. Assessment of >1360 mechanistic endpoints, including many guideline-based genotoxicity studies, demonstrate a lack of activity associated with endpoints grouped to key characteristics of carcinogens. Other non-specific mechanistic data (e.g., mixed findings of oxidative stress across study models, tissues, and species) do not provide evidence of a biologically plausible carcinogenic pathway associated with aspartame. Taken together, available evidence supports that aspartame consumption is not carcinogenic in humans and that the inconsistent findings of the RI studies may be explained by flaws in study design and conduct (despite additional analyses to address study limitations), as acknowledged by authoritative bodies.

Actinomycotic Osteomyelitis and Myiasis in Oroantral Communication: Clinicopathological and Tomographic Findings

Actinomycotic osteomyelitis of the maxilla presenting with oroantral communication is very rare, herein we report the first case of this condition in association with myiasis. A 50-year-old man reported chronic sinusopathy and a non-healing maxillary lesion, with 30 years of evolution, presenting occasional nasal and intraoral purulent discharge, with foul smell, and recurrent episodes of larvae presence. Cone beam computed tomography showed a large hyperdense image inside the left maxillary sinus, with focal areas with soft tissue density, and extensive discontinuity of the maxillary sinus floor, confirming the oroantral fistula. The necrotic tissue curetted during surgery presented hard consistency, and dark greenish color, and was submitted for histopathological analysis. Microscopically, necrotic bone, masses of filamentous bacteria colonie s, compatible with actinomycosis, and large rhomboidal structures surrounded by eosinophilic capsule - suggestive of larvae, were observed. The diagnosis of actinomycotic osteomyelitis with presence of structures compatible with larvae was established.

La osteomielitis actinomicótica del maxilar que se presenta con comunicación oroantral es poco frequente. En este trabajo reportamos el primer caso de esta condición en asociación con miasis. Un hombre de 50 años que refiere sinusopatía crónica y lesión maxilar que no cicatriza, de 30 años de evolución, presenta secreción ocasional purulenta nasal e intraoral, con mal olor y episodios recurrentes de presencia de larvas. La tomografía computarizada de haz cónico mostró una gran imagen hiperdensa en el interior del seno maxilar izquierdo, con áreas focales con densidad de partes blandas y una extensa discontinuidad del piso del seno maxilar, lo que confirma la fístula oroantral. El tejido necrótico legrado durante la cirugía presentó consistencia dura, coloración verdosa oscura, y fue remitido para análisis histopatológico. Microscópicamente se observó hueso necrótico, masas de colonias de bacterias filamentosas compatibles con actinomicosis y grandes estructuras romboidales rodeadas de cápsula eosinofílica sugestiva de larvas. Se estableció el diagnóstico de osteomielitis actinomicótica con presencia de estructuras compatibles con larvas.

7-Hydroxycoumarin Induces Vasorelaxation in Animals with Essential Hypertension: Focus on Potassium Channels and Intracellular Ca2+ Mobilization.

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 µM-300 µM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200-300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K+-channels (KATP, BKCa, and, to a lesser extent, Kv) activation and also on Ca2+ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery's responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation.

A Simplified Sanger Sequencing Method for Detection of Relevant SARS-CoV-2 Variants.

Molecular surveillance of the new coronavirus through new genomic sequencing technologies revealed the circulation of important variants of SARS-CoV-2. Sanger sequencing has been useful in identifying important variants of SARS-CoV-2 without the need for whole-genome sequencing. A sequencing protocol was constructed to cover a region of 1000 base pairs, from a 1120 bp product generated after a two-step RT-PCR assay in samples positive for SARS-CoV-2. Consensus sequence construction and mutation identification were performed. Of all 103 samples sequenced, 69 contained relevant variants represented by 20 BA.1, 13 delta, 22 gamma, and 14 zeta, identified between June 2020 and February 2022. All sequences found were aligned with representative sequences of the variants. Using the Sanger sequencing methodology, we were able to develop a more accessible protocol to assist viral surveillance with a more accessible platform.

Benefit-risk of coffee consumption and all-cause mortality: A systematic review and disability adjusted life year analysis.

BACKGROUND: Recommendations and guidance from scientific bodies do not provide clear messages about potential health risks or benefits of coffee consumption. Numerous studies have demonstrated inverse (beneficial) effects of coffee consumption for many adverse outcomes such as cancer and cardiovascular disease; fewer studies demonstrate risks. However, the risk-benefit relationship has not yet been fully assessed using quantitative metrics preferred by policy makers (disability-adjusted life years [DALYs]). OBJECTIVE: Conduct a quantitative analysis of the risk-benefit for coffee consumption and all-cause mortality using the Benefit-Risk Analysis for Foods (BRAFO) framework and the DALY as a quantitative metric. METHOD: A systematic search and appraisal of meta-analyses investigating coffee consumption and all-cause mortality was conducted. Using the BRAFO framework, evidence was assessed in context of potential risks or benefits associated with the reference scenario - coffee consumption (assessed by varying the consumption level in three analyses) in adults aged 15+ versus the alternative scenario of no coffee consumption. DALYs were used to quantify risks and benefits based on risk ratios from meta-analyses with populations from the United States. RESULTS: Meta-analyses consistently report an inverse (beneficial) relationship between coffee consumption and all-cause mortality; subsequently, even while varying consumption amounts and prevalence of coffee consumption, DALYs calculated consistently demonstrated findings in the direction of prevention of healthy years of life lost with variable magnitude. More than 3.5 million DALYs, or ∼3.35% of estimated years of healthy life lost could be prevented by consuming one cup of coffee per day, up to 4.7% of estimated years of healthy life lost could be prevented at current consumption rates ranging from 1 to 8 cups/day, and even more benefit could be seen (prevention of an estimated 6% of years of healthy life lost) if consumers all drank 3 cups of coffee per day. IMPACT: Policy that directs consumers to avoid drinking coffee may be a detriment to the overall health of the population given the substantial potential benefits of coffee consumption on all-cause mortality for adults.

Chlorine efficacy against bacteriophage Phi6, a surrogate for enveloped human viruses, on porous and non-porous surfaces at varying temperatures and humidity.

While efficacy of chlorine against Phi6, a widely-used surrogate for pathogenic enveloped viruses, is well-documented, surfaces common to low-resource contexts are under-researched. We evaluated seven surfaces (stainless steel, plastic, nitrile, tarp, cloth, concrete, wood) and three environmental conditions-temperature (4, 25, 40 °C), relative humidity (RH) (23, 85%), and soiling-to determine Phi6 recoverability and the efficacy of disinfection with 0.5% NaOCl. Overall, Phi6 recovery was >4 log10 PFU/mL on most surfaces after drying 1 hour at all temperature/humidity conditions. After disinfection, all non-porous test conditions (48/48) achieved ≥4 LRV at 1 and 5 minutes of exposure; significantly more non-porous surfaces met ≥4 LRV than porous (p < 0.001). Comparing porous surfaces, significantly fewer wood samples met ≥4 LRV than cloth (p < 0.001); no differences were observed between concrete and either wood (p = 0.083) or cloth (p = 0.087). Lastly, no differences were observed between soil and no-soil conditions for all surfaces (p = 0.712). This study highlights infectious Phi6 is recoverable across a range of surfaces and environmental conditions, and confirms the efficacy of chlorine disinfection. We recommend treating all surfaces with suspect contamination as potentially infectious, and disinfecting with 0.5% NaOCl for the minimum contact time required for the target enveloped virus (e.g. Ebola, SARS-CoV-2).

Passive In-Line Chlorination for Drinking Water Disinfection: A Critical Review.

The world is not on track to meet Sustainable Development Goal 6.1 to provide universal access to safely managed drinking water by 2030. Removal of priority microbial contaminants by disinfection is one aspect of ensuring water is safely managed. Passive chlorination (also called in-line chlorination) represents one approach to disinfecting drinking water before or at the point of collection (POC), without requiring daily user input or electricity. In contrast to manual household chlorination methods typically implemented at the point of use (POU), passive chlorinators can reduce the user burden for chlorine dosing and enable treatment at scales ranging from communities to small municipalities. In this review, we synthesized evidence from 27 evaluations of passive chlorinators (in 19 articles, 3 NGO reports, and 5 theses) conducted across 16 countries in communities, schools, health care facilities, and refugee camps. Of the 27 passive chlorinators we identified, the majority (22/27) were solid tablet or granular chlorine dosers, and the remaining devices were liquid chlorine dosers. We identified the following research priorities to address existing barriers to scaled deployment of passive chlorinators: (i) strengthening local chlorine supply chains through decentralized liquid chlorine production, (ii) validating context-specific business models and financial sustainability, (iii) leveraging remote monitoring and sensing tools to monitor real-time chlorine levels and potential system failures, and (iv) designing handpump-compatible passive chlorinators to serve the many communities reliant on handpumps as a primary drinking water source. We also propose a set of reporting indicators for future studies to facilitate standardized evaluations of the technical performance and financial sustainability of passive chlorinators. In addition, we discuss the limitations of chlorine-based disinfection and recognize the importance of addressing chemical contamination in drinking water supplies. Passive chlorinators deployed and managed at-scale have the potential to elevate the quality of existing accessible and available water services to meet "safely managed" requirements.