Outcomes and Relapse Patterns in Primary Central Nervous System Lymphoma: Longitudinal Analysis of 559 Patients Diagnosed From 1983-2020.

BACKGROUND: Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow up. METHODS: T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983-2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, other. Progression-free (PFS) and overall (OS) survival was assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. RESULTS: Median follow-up was 7.4 years (N=559). Most (321, 57%) were recursive partitioning analysis class 2 (age≥50, KPS≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs. PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5-years for 351 patients with CR/CRu to consolidation was 80% (95%CI:76-84%) and 46% (95%CI:41-53%), respectively; 1-year cumulative incidence of local vs non-local relapse was 1.8% vs 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local vs non-local relapse was 57% vs 42%, respectively. Deep structure involvement (HR 1.89, 95%CI:1.10-3.27) was associated with local relapse in refractory patients. CONCLUSIONS: We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.

Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn-Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random-effects meta-analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in-hospital mortality, 30-day mortality, and thrombotic events. Low-moderate risk of bias studies were meta-analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty-eight percent of the studies (n = 5) had low-moderate risk and 72% (n = 13) had a high risk of bias. Studies with low-moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15-6.44); one study], lower in-hospital mortality [OR 0.48 (95% CI: 0.38-0.61); three studies], and reduced 30-day mortality [OR 0.49 (95% CI: 0.30-0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01-1.84); 12 studies] and reductions in 30-day mortality [OR 0.53 (95% CI: 0.37-0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low-moderate, high, or combined risk of bias groups. The evidence from low-moderate quality real-world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in-hospital and 30-day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30-day mortality risk remain significantly better with AA versus PCC.

Cost-effectiveness of dietary supplement ingredients versus generic statins for LDL reduction.

Background: While statin therapy is the preferred treatment for hyperlipidemia, literature supports the low-density lipoprotein (LDL) lowering effects associated with red yeast rice, berberine, and Silybum marianum. Dietary supplements may be perceived as a more affordable alternative to prescription medication. Objective: We determined cost-effectiveness of generic pravastatin versus single-ingredient dietary supplements in relation to LDL lowering effect. Methods: Data from meta-analyses and systematic reviews was extracted to calculate pooled weighted mean LDL differences amongst generic pravastatin and single ingredient dietary supplements. The effect was then divided by average 30-day costs and compared amongst agents. Results: The greatest difference was seen in pravastatin 40 mg [MD -57.88 mg/dL (95%CI: - 64.80 to -50.96)], followed by pravastatin 10 mg [MD -41.30 mg/dL (95%CI: 63.30 to - 19.40)], red yeast rice [MD -25.39 (95%CI: -32.98 to -17.81)], berberine [MD -15.13 (95%CI: -21.78 to -8.48)], and Silybum marianum [MD -9.51 mg/dL (95%CI: -22.13 to - 0.10)]. were divided by mean difference to calculate cost per mg/dL reduction in LDL. Cost-effectiveness was greatest for pravastatin 10 mg [$0.66/mg/dL LDL reduction (range: $0.39 to $1.13)], followed by pravastatin 40 mg [$0.74/mg/dL LDL reduction (range: $0.66 to $0.84)], berberine [$0.81/mg/dL LDL reduction (range: $0.56 to $1.44)], red yeast rice [$0.84/mg/dL reduction (range: $0.67 to $1.13)], and Silybum marianum [$0.88/mg/dL LDL reduction (range: $0.38 to $82.02)]. Conclusion: Pravastatin is most cost-effective in each scenario whether or not prescription insurance is utilized.

Effects of a coccidiosis challenge on dietary methionine recommendations in broilers.

Broilers are commonly exposed to coccidiosis infections, and the use of dietary strategies to reduce losses in growth performance has practical implications for the poultry industry. Methionine (Met) is typically the first limiting amino acid for broilers and is involved in metabolic and immunological pathways; however, literature is conflicting on how dietary Met requirements are affected by environmental stressors. Our objective was to assess how the Met requirement changes during coccidiosis based on results of growth performance, carcass traits, and health outcomes. Two trials were conducted using 780 male Ross 308 broiler chicks in floor pens randomly assigned to 1 of 12 experimental treatments. All birds received common starter (d 0-10) and finisher (d 24-35, Trial 2 only) diets, and only differed based on their assigned experimental grower diet (d 10-24). Trial 1 experimental grower diets ranged from 2.61 to 6.21 g/kg digestible Met. Trial 2 experimental grower diets were formulated to contain 15% below, at, or 15% above the Met requirement determined in Trial 1. Birds were exposed to a coccidiosis challenge on d 11, with blood and tissue collection (1 bird/pen) on d 18 and carcass processing on d 35 (2 birds/pen) in Trial 2. Data were analyzed using a 1- or 2-way ANOVA. A non-linear regression analysis was conducted in Trial 1 to determine the Met requirement of 4.32 g of digestible Met/kg of diet using BW gain. Coccidiosis infection reduced (P < 0.05) growth performance during the experimental grower and overall study periods in Trial 2. Increasing dietary Met from below requirement to meeting requirement during the grower period improved (P < 0.001) BW gain and feed conversion ratio (FCR), but this effect was only significant between treatments below and above the requirement for the overall study period. There was an interactive effect (P = 0.038) on FCR for the overall study period. These findings provide evidence that the Met requirement is likely increased during coccidiosis based on growth performance outcomes.

Roadmap for the expression of canonical and extended endocannabinoid system receptors and metabolic enzymes in peripheral organs of preclinical animal models.

The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold-standard behavioral tests. However, the potential for lack of clinical translation to non-human primates and humans is high as cross-species comparisons of the endocannabinoid system have not been evaluated. To bridge this gap in knowledge, we evaluate the relative gene expression of 14 canonical and extended endocannabinoid receptors in seven peripheral organs of C57/BL6 mice, Sprague-Dawley rats, and non-human primate rhesus macaques. Notably, we identify species- and organ-specific heterogeneity in endocannabinoid receptor distribution where there is surprisingly limited overlap among the preclinical models. Importantly, we determined there were no receptors with identical expression patterns among mice (three males and two females), rats (six females), and rhesus macaques (four males). Our findings demonstrate a critical, yet previously unappreciated, contributor to challenges of rigor and reproducibility in the cannabinoid field, which has implications in hampering progress in understanding the complexity of the endocannabinoid system and development of cannabinoid-based therapies.

Eye Drop Quality Issues: Can the FDA See This One Through?

The Food and Drug Administration (FDA) has long suffered from a lack of resources limiting their inspection capacity. They have fallen behind on proactive surveillance inspections of foreign manufacturing sites, relying instead on for-cause inspections after a problem has been discovered. Over-the-counter (OTC) products are especially vulnerable because the FDA considers them lower priority. This issue recently made big news after improperly manufactured OTC eye drops harmed users across the country, in some cases causing blindness. To prevent future harm to Americans, it is imperative that the FDA receives enough resources to keep up with their routine inspections.

Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived.

In this month's Annals of Pharmacotherapy, the largest observational study assessing the early versus later use of vasopressin has been published. When this new study is combined with the other available observational studies, there are 2 important outcomes to focus on. When all the observational studies are pooled together, no reduction in new onset arrhythmias is seen (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.41-1.95) with early versus late vasopressin use while the reduction in renal replacement therapy just missed statistical significance (OR = 0.56, 95% CI = 0.32-1.00). Early vasopressin likely does not reduce new onset arrhythmias versus later use but might reduce the need for renal replacement therapy.

Impact of Berberine or Berberine Combination Products on Lipoprotein, Triglyceride and Biological Safety Marker Concentrations in Patients with Hyperlipidemia: A Systematic Review and Meta-Analysis.

Monoclonal antibody Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors reduce total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (TG). We assessed the ability of berberine, a natural PCSK9 inhibitor, to reduce lipid concentrations either alone or combined with other nutraceuticals. We searched PubMed, Scopus and EMBASE from inception to September 30th, 2022 for randomized controlled trials (RCTs) assessing 8-18 wk of berberine therapy on. A total of 41 RCTs with 4,838 patients met our inclusion criteria. Berberine containing products significantly reduced TC (MD -17.42 mg/dL [95%CI: -22.91 to -11.93]), LDL (MD -14.98 mg/dL [95%CI: -20.67 to -9.28]), and TG (MD -18.67 mg/dL [95%CI: -25.82 to -11.51]) while raising HDL (MD 1.97 mg/dL [95%CI: 1.16 to 2.78]) versus control (I2 > 72% for all analyses). Products with berberine alone had less robust effects on TC (MD -12.08 mg/dL [95%CI: -21.79 to -2.37]), LDL (MD -9.26 mg/dL [95%CI: -20.31 to 1.78]), and HDL (MD 1.38 mg/dL [95%CI: -1.27 to 4.03]) but TG effects were similar (MD -17.40 mg/dL [95%CI: -32.57 to -2.23]). Berberine along with red yeast rice reduced TC (MD -19.62 mg/dL [95%CI: -28.56 to -10.68]) and LDL (MD -18.79 mg/dL [95%CI: -28.03 to -9.54]) as did combination therapy with Silybum maranium for TC (MD -31.81 mg/dL [95%CI: -59.88 to -3.73]) and LDL (MD -30.82 mg/dL [95%CI: -56.48 to -5.16]). Berberine, alone or with other nutraceuticals, can provide a modest positive impact on lipid concentrations.

The impact of psychedelics on patients with alcohol use disorder: a systematic review with meta-analysis.

OBJECTIVES: Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder. METHODS: A systematic literature search of PubMed was completed from 1960 to 9/9/2023. We pooled randomized controlled trials comparing psychedelics to control therapy for the treatment of alcohol use disorder. RESULTS: At the first recorded follow-up, LSD [n = 3, Odds Ratio (OR) 1.99 (95% Confidence interval (CI): 1.10 to 3.61)] and any psychedelic [n = 4, OR 2.16 (95%CI: 1.26 to 3.69)] enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol versus placebo in randomized, double-blind, placebo-controlled trials. When the inclusion criteria were relaxed to include controlled trials without double-blinding or placebo control, LSD [n = 5, OR 1.79 (95%CI: 1.36 to 2.34)] and any psychedelic therapy [n = 6, OR 1.89 (95%CI: 1.42 to 2.50)] still enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol. Four of 6 trials had high risk of bias and other methodological issues. One trial found an instance of suicidal ideation as well as transient increases in blood pressure that requires further exploration before the balance of benefits to harms can be determined. CONCLUSIONS: The use of psychedelics to treat alcohol use disorder is promising, but the weaknesses in the literature base preclude making definitive statements about its value. Future trials with greater methodological rigor are needed.

Lysergic acid diethylamine (LSD) and psilocybin (hallucinogenic mushrooms) are psychedelics that have been studied in patients with alcohol use disorder (chronic issue with heavy or problem drinking). When all the studies are pooled together in a meta-analysis, the odds of being able to refrain from drinking alcohol or to substantially reduce the amount of alcohol consumed was enhanced by 89%. This is a promising finding that if bore out in additional studies, especially those with higher study quality, would be a major advance in patients with alcohol use disorder. We cannot make more definitive conclusions because all the LSD studies were published between 1966 and 1970 which may not reflect contemporary practice and most of the studies had methodological weaknesses that reduce confidence in the studies to prove the benefits. It is heartening that the single psilocybin trial from 2022 was of higher methodological quality, reflected contemporary practice, and still showed positive effects.

The Impact of Ketamine for Treatment of Post-Traumatic Stress Disorder: A Systematic Review With Meta-Analyses.

BACKGROUND: Ketamine has been used in anesthesia, pain management, and major depressive disorder. It has recently been studied in patients with post-traumatic stress disorder (PTSD). OBJECTIVE: To determine the impact of ketamine on PTSD symptomatology and depression scores. METHODS: We conducted a literature search of Medline 1960 to May 20, 2023, and found 6 randomized controlled trials that met our inclusion criteria. We extracted data on the Clinician-Administered PTSD (CAPS), PTSD Checklist (PCL), or Montgomery-Asberg Depression Rating (MADRS) scales. RESULTS: The use of ketamine significantly reduced CAPS scores (n = 5, MD: -10.63 [95% CI -14.95 to -6.32]), PCL scores (n = 3, MD: -6.13 [95% CI -8.61 to -3.64]), and MADRS scores (n = 3, MD: -6.33 [95% CI -8.97 to -3.69]) at the maximal follow-up times versus control. Significant benefits were found at day 1 and weeks 1, 2, and 4 for CAPS and PCL scores as well as MADRS scores at day 1, week 1, and week 4 for ketamine versus control. The time to PTSD relapse was prolonged in the patients receiving ketamine versus control (n = 2, 15.74 days [95% CI 3.57 to 29.91 days]). More dry mouth (n = 2, OR 5.85 [95% CI 1.32 to 25.95]), dizziness (n = 2, OR 3.83 [95% CI 1.28 to 11.41]), and blurred vision (n = 2, OR 7.57 [1.00 to 57.10]) occurred with ketamine than control therapy. CONCLUSIONS AND RELEVANCE: Ketamine modestly reduced PTSD and depression scores as early as 1 day of therapy, but the longevity of effect needs to be determined. Given similar magnitude of benefit with SSRIs and venlafaxine, ketamine would not supplant these traditional options for chronic use.

Whanau Maori and Pacific peoples' knowledge, perceptions, expectations and solutions regarding antibiotic treatment of upper respiratory tract infections: a qualitative study.

INTRODUCTION: The rate of community antibiotic use is high in Aotearoa New Zealand (NZ) when compared to other nations, and in NZ, as in most other nations, antibiotics are very commonly prescribed for self-limiting upper respiratory tract infections (URTIs). Resources that build knowledge, perceptions and understanding can potentially reduce unnecessary antibiotic consumption. METHODS: To inform the content of educational resources, we conducted an in-depth qualitative study with 47 participants via 6 focus groups of the knowledge, attitudes, and expectations of whanau Maori and Pacific peoples about antibiotics and URTIs. RESULTS: Focus groups with 47 participants identified four themes: Knowledge that might influence expectations to receive antibiotics for URTIs; Perceptions - the factors that influence when and why to seek medical care for URTI; Expectations - the features of successful medical care for URTI; Solutions - how to build community knowledge about URTI and their treatment and prevention. Knowledge that might reduce expectations to receive antibiotics for URTI included confidence in the use of alternative remedies, knowledge that URTI are usually caused by viruses, and concerns about antibiotic adverse effects. Participants commonly reported that they would confidently accept their doctor's recommendation that an antibiotic was not necessary for an URTI, provided that a thorough assessment had been performed and that treatment decisions were clearly communicated. CONCLUSION: These findings suggest that building patients' knowledge and skills about when antibiotics are necessary, and increasing doctors' confidence and willingness not to prescribe an antibiotic for patients with an URTI, could significantly reduce inappropriate antibiotic prescribing in NZ.

Roadmap For The Expression Of Canonical and Extended Endocannabinoid System Receptors and Proteins in Peripheral Organs of Preclinical Animal Models.

The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold-standard behavioral tests. However, the potential for lack of clinical translation to non-human primates and humans is high as cross-species comparisons of the endocannabinoid system has not been evaluated. To bridge this gap in knowledge, we evaluate the relative gene expression of 14 canonical and extended endocannabinoid receptors in seven peripheral organs of C57/BL6 mice, Sprague-Dawley rats, and non-human primate rhesus macaques. Notably, we identify species- and organ-specific heterogeneity in endocannabinoid receptor distribution where there is surprisingly limited overlap among the preclinical models. Importantly, we determined there were only five receptors (CB2, GPR18, GPR55, TRPV2, and FAAH) that had identical expression patterns in mice, rats, and rhesus macaques. Our findings demonstrate a critical, yet previously unappreciated, contributor to challenges of rigor and reproducibility in the cannabinoid field, which has profound implications in hampering progress in understanding the complexity of the endocannabinoid system and development of cannabinoid-based therapies.

Wildlife health surveillance: gaps, needs and opportunities.

Disease emergence represents a global threat to public health, economy and biological conservation. Most emerging zoonotic diseases have an animal origin, most commonly from wildlife. To prevent their spread and to support the implementation of control measures, disease surveillance and reporting systems are needed, and due to globalisation, these activities should be carried out at the global level. To define the main gaps affecting the performance of wildlife health surveillance and reporting systems globally, the authors analysed data from a questionnaire sent to National Focal Points of the World Organisation for Animal Health that inquired on structure and limits of wildlife surveillance and reporting systems in their territories. Responses from 103 Members, covering all areas of the globe, revealed that 54.4% have a wildlife disease surveillance programme and 66% have implemented a strategy to manage disease spread. The lack of dedicated budget affected the possibility of outbreak investigations, sample collection and diagnostic testing. Although most Members maintain records relating to wildlife mortality or morbidity events in centralised databases, data analysis and disease risk assessment are reported as priority needs. The authors' evaluation of surveillance capacity found an overall low level, with marked variability among Members that was not restricted to a specific geographical area. Increased wildlife disease surveillance globally would help in understanding and managing risks to animal and public health. Moreover, consideration of the influence of socio-economic, cultural and biodiversity aspects could improve disease surveillance under a One Health approach.

L'émergence de maladies représente une menace pour la santé publique, l'économie et la conservation de la biodiversité au niveau mondial. La plupart des maladies émergentes sont d'origine animale et proviennent de la faune sauvage. Afin de prévenir leur propagation et de soutenir la mise en oeuvre de mesures de contrôle, une surveillance des maladies et des systèmes de notification sont nécessaires - et ce à l'échelle internationale, en raison de la mondialisation. En vue de définir les lacunes principales affectant les performances de la surveillance et de la notification sanitaire relative à la faune sauvage au niveau mondial, les auteurs ont analysé les données d'un questionnaire envoyé aux Points focaux nationaux de l'Organisation mondiale de la santé animale et traitant de la structure et des limites des systèmes de surveillance et de notification applicables à la faune sauvage sur leur territoire. Selon les réponses des 103 Membres, qui représentaient toutes les régions du monde, 54,4 % disposent d'un programme de surveillance et 66 % ont mis en oeuvre une stratégie visant à gérer la propagation de maladies. L'absence de budgets dédiés affecte la possibilité d'enquêter sur l'apparition d'épidémies, de prélever des échantillons et d'effectuer des tests diagnostiques. Bien que la majorité des Membres consignent dans des bases de données centralisées les événements de mortalité et de morbidité affectant la faune sauvage, l'analyse des données et l'évaluation des risques sanitaires ont été mentionnées comme étant des besoins prioritaires. Les auteurs ont évalué les capacités de surveillance qui se situent, selon eux, à un niveau faible et se caractérisent par une grande variabilité entre les Membres, indépendamment des zones géographiques dont il s'agit. Une meilleure surveillance sanitaire de la faune sauvage au niveau mondial permettrait d'améliorer la compréhension et la gestion des risques pour la santé animale et publique. Par ailleurs, une réflexion sur l'influence des aspects socio-économiques, culturels et liés à la biodiversité améliorerait la surveillance sanitaire mise en place dans le cadre de l'approche Une seule santé.

La aparición de enfermedades representa una amenaza de dimensión mundial para la salud pública, la economía y la conservación de los recursos biológicos. La mayor parte de las enfermedades zoonóticas tienen un origen animal, por lo general localizado en la fauna silvestre. Para evitar que estas enfermedades se propaguen y apoyar la aplicación de medidas de lucha hacen falta sistemas de vigilancia y notificación de enfermedades, sistemas que, teniendo en cuenta las dinámicas de la mundialización, deben declinarse a escala planetaria. Con objeto de determinar las principales carencias que lastran el buen funcionamiento de los sistemas de vigilancia y notificación de enfermedades de la fauna silvestre a escala mundial, los autores analizaron datos extraídos de un cuestionario distribuido entre los puntos focales nacionales de la Organización Mundial de Sanidad Animal, en el cual se les preguntaba por la estructura y los límites que presentaban en su territorio dichos sistemas. Las respuestas recibidas de 103 Miembros de todas las zonas del globo pusieron de relieve que un 54,4% de ellos cuenta con un programa de vigilancia sanitaria de la fauna silvestre y que un 66% tiene implantada una estrategia para contener la propagación de enfermedades. La falta de un presupuesto asignado específicamente a estas tareas limita la posibilidad de investigar eventuales brotes, obtener muestras y practicar pruebas de diagnóstico. Aunque la mayoría de los Miembros lleva un registro de los episodios de mortalidad y morbilidad de animales salvajes en bases de datos centralizadas, el análisis de datos y la determinación del riesgo de enfermedad son dos de los aspectos mencionados como necesidad prioritaria. La evaluación de la capacidad de vigilancia realizada por los autores puso de manifiesto un nivel en general bajo, con una marcada heterogeneidad entre los Miembros que no se circunscribía a una zona geográfica en particular. Una mayor vigilancia de las enfermedades de la fauna silvestre a escala mundial ayudaría a aprehender y manejar mejor los riesgos que estas presentan para la sanidad animal y la salud pública. Además, el hecho de tener en cuenta la influencia de factores socioeconómicos, culturales y ligados a la diversidad biológica podría traducirse en una más eficaz vigilancia sanitaria en clave de Una sola salud.

Effects of UV radiation on natural and synthetic materials.

The deleterious effects of solar ultraviolet (UV) radiation on construction materials, especially wood and plastics, and the consequent impacts on their useful lifetimes, are well documented in scientific literature. Any future increase in solar UV radiation and ambient temperature due to climate change will therefore shorten service lifetimes of materials, which will require higher levels of stabilisation or other interventions to maintain their lifetimes at the present levels. The implementation of the Montreal Protocol and its amendments on substances that deplete the ozone layer, controls the solar UV-B radiation received on Earth. This current quadrennial assessment provides a comprehensive update on the deleterious effects of solar UV radiation on the durability of natural and synthetic materials, as well as recent innovations in better stabilising of materials against solar UV radiation-induced damage. Pertinent emerging technologies for wood and plastics used in construction, composite materials used in construction, textile fibres, comfort fabric, and photovoltaic materials, are addressed in detail. Also addressed are the trends in technology designed to increase sustainability via replacing toxic, unsustainable, legacy additives with 'greener' benign substitutes that may indirectly affect the UV stability of the redesigned materials. An emerging class of efficient photostabilisers are the nanoscale particles that include oxide fillers and nanocarbons used in high-performance composites, which provide good UV stability to materials. They also allow the design of UV-shielding fabric materials with impressive UV protection factors. An emerging environmental issue related to the photodegradation of plastics is the generation of ubiquitous micro-scale particles from plastic litter exposed to solar UV radiation.

Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues.

Serial multi-omic analysis of proteome, phosphoproteome, and acetylome provides insights into changes in protein expression, cell signaling, cross-talk and epigenetic pathways involved in disease pathology and treatment. However, ubiquitylome and HLA peptidome data collection used to understand protein degradation and antigen presentation have not together been serialized, and instead require separate samples for parallel processing using distinct protocols. Here we present MONTE, a highly sensitive multi-omic native tissue enrichment workflow, that enables serial, deep-scale analysis of HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome from the same tissue sample. We demonstrate that the depth of coverage and quantitative precision of each 'ome is not compromised by serialization, and the addition of HLA immunopeptidomics enables the identification of peptides derived from cancer/testis antigens and patient specific neoantigens. We evaluate the technical feasibility of the MONTE workflow using a small cohort of patient lung adenocarcinoma tumors.

The Impact of Psychedelic Drugs on Anxiety and Depression in Advanced Cancer or other Life-threatening Disease: A Systematic Review With Meta-analysis.

OBJECTIVES: Life-threatening cancer or other diseases can induce anxiety and depressive symptoms. We performed a systematic review with meta-analyses of randomized controlled trials assessing patients with cancer or other life-threatening diseases using validated anxiety and depression scales. METHODS: PubMed was searched up to November 15, 2022 and citations were applied to prespecified inclusion criteria. Disease rating scales for anxiety or depression included the State-Trait Anxiety Inventory (STAI) (STAI Trait [STAI-T], STAI-State [STAI-S]), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS) (HADS-Anxiety [HADS-A]; HADS-Depression [HADS-D]), Profile of Mood States (POMS), and the Hamilton Rating Scale for Depression (HAM-D or GRID-HAM-D-17). Safety outcomes included assessments of blood pressure and heart rate. RESULTS: Five trials, predominantly in cancer patients, had data assessing anxiety and depressive symptoms. These trials found promising results for psychedelics versus placebo in several anxiety and depression scales but increases in blood pressure and heart rate also occurred. There were some concerns of risk of bias because it is difficult to truly randomize a psychedelic trial and there was a high percentage of patients in the trials who had used psychedelics in the past. There was high heterogeneity for all analyses that we could not explain. CONCLUSIONS: Although the results are promising, future trials are needed to assess the optimal psychedelic, dose, number of sessions required, and how psychedelic naïve patients would respond both psychologically and hemodynamically before this therapy can be considered for widescale clinical use.

The Impact of Sedative Hypnotic Drugs on Hallucinated Sexual Assault or Sexual Fantasies Involving Health Professionals: A Systematic Review.

This article discusses the rare but serious occurrence of sedative hypnotic drug-induced sexual thoughts. We searched PubMed from the earliest date to February 7, 2023. Articles were selected if they provided data on sexual assault hallucinations or sexual fantasies associated with the use of sedative hypnotic drugs including benzodiazepines, propofol, nitric oxide, ether, chloroform, ketamine, or esketamine. Twenty-two citations provided useful information, including 87 cases of hallucinations about sexual assault or sexual fantasy. In several of the cases, the environment and monitoring made the actual occurrence of sexual assault unlikely, but there was still significant anguish for the patients and the accused clinicians. In many of the cases, the places of the body where procedures were conducted coincided with the area of the body where the patients perceived the sexual assault or fantasy occurred. The higher the dose of sedative hypnotic administered, the greater the risk of experiencing a hallucination about sexual assault or sexual fantasy. The US Food and Drug Administration Adverse Events Reporting System has numerous occurrences in which "excessive sexual fantasies" and "abnormal dreams" were associated with the use of sedative hypnotic medication but also occurrences of "sexual abuse." While sexual assault hallucinations or fantasies associated with sedative hypnotics are rare, it is imperative that health care providers take the necessary precautions and follow recommendations to provide safety for themselves and their patients.

Psychedelics for Patients With Cancer: A Comprehensive Literature Review.

OBJECTIVE: To assess the role of psychedelics in the treatment of anxiety or depression among patients with cancer. DATA SOURCES: PubMed search from inception to March 11, 2022, using the terms anxiety, depression, psychedelics, psilocybin, lysergic acid, methylenedioxymethamphetamine, or ayahuasca. STUDY SELECTION AND DATA EXTRACTION: Studies assessing patients with cancer receiving psychedelics for the treatment of anxiety or depression. DATA SYNTHESIS: Five unique randomized, double-blind, placebo-controlled trials were conducted. Significant reductions were found in 2 trials with 2 anxiety scales (State-Trait Anxiety Inventory-State, State-Trait Anxiety Inventory-Trait) and in 1 trial with 2 additional anxiety scales (Hamilton Rating Scale-Anxiety, Hospital Anxiety and Depression Scale-Anxiety). Significant reductions were found in 2 trials in 2 depression scales (Hospital Anxiety and Depression Scale-Depression, Beck Depression Inventory) and in 1 trial with an additional depression scale (Hamilton Rating Scale-Depression). Two studies assessed for clinically relevant reductions in anxiety and depression scores, and they occurred much more commonly in psychedelic-treated patients than those given placebo. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: There is a new potential option for treating patients with anxiety and depression along with cancer, which is important given the generally lackluster benefits with traditional antidepressants. Only a few sessions may also provide benefits extending out for 6 to 12 months and possibly beyond that. However, the studies were small, had many methodological limitations, and there were increases in blood pressure and heart rate. CONCLUSIONS: Psychedelics have a unique mechanism of action that might be well suited for treating anxiety and depression associated with cancer. This offers new promise for patients who are not being sufficiently treated with current antianxiety or antidepressant medications.