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Major-league rules have stipulated since 1950 that the home team always bats last. However, as Gary Belleville relates in a recent Baseball Research Journal article, an exception has been added [...]

Abstract Urban forest soils are complex environments subjected to various stressors that alter chemical and microbial properties. To understand soil chemistry and bacterial community patterns in urban forest soils with respect to site identity and multiflora rose (Rosa multiflora) invasion, soils were collected from beneath R. multiflora, native spice bush (Lindera benzoin), and uncovered ground in three forests in Newark, Delaware. High-throughput sequencing was used to analyze bacterial communities with corresponding soil chemical properties. Soil chemistry and operational taxonomic unit (OTU) communities were explained by site rather than by shrub cover type. Unlike other invasive plant studies, R. multiflora had minimal effects on either soil chemistry or bacterial communities. Phylum level bacterial communities were more uniform under shrub cover versus no cover, indicative of a generalized plant effect shaping soil microbiomes. Correlations between bacterial phyla and soil chemistry varied, with some phyla positively or negatively correlating with the same property at different sites. Filters for bacterial communities differ across forest scales, where sites and sampling location primarily correlate with OTU communities yet shrub presence mediates phylum level organization. Forest soil studies should consider location-based differences in bacterial communities and their correlations with soil chemistry before generalizing outcomes for whole macrosystems.

Summary: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases. Among diseases with type 2 Inflammation, this concept is novel and currently most advanced in asthma. This new paradigm has been developed based on a better understanding of the pathophysiology of type 2 inflammation and the advent of highly effective drugs selectively interfering with type 2 pathways. Here, we review the evolution of the new remission concepts in type 2 inflammatory diseases and discuss associated challenges and future research needs. Funding: None.

BackgroundIndividuals with co-occurring posttraumatic stress disorder (PTSD) and HIV are at high-risk for negative HIV-related outcomes, including low adherence to antiretroviral therapy, faster disease progression, more hospitalizations, and almost twice the rate of death. Despite high rates of PTSD in persons with HIV (PWH) and poor HIV-related health outcomes associated with PTSD, an effective evidence-based treatment for PTSD symptoms in PWH does not exist. ObjectiveThis study aimed to describe the adaptation and theater testing of an evidence-based intervention designed for people with co-occurring PTSD and HIV. MethodsThe Assessment, Decision, Adaptation, Production, Topical experts-integration, Training, and Testing (ADAPT-ITT) framework guided the formative process used to modify an evidence-based PTSD treatment (cognitive processing therapy; CPT) to meet the unique needs of PWH experiencing PTSD. With the integration of Life-Steps for Medication Adherence (Life-Steps), the adapted protocol (CPT-Life-Steps for integration of adherence; CPT-L) targeted HIV-related stigma and HIV medication adherence within a trauma-informed framework. Theater testing was completed with 7 participants to evaluate acceptability of CPT-L for PWH. The qualitative data (N=54 recordings) used to evaluate and adapt CPT-L emerged from individual interviews conducted with participants after each therapy session as well as exit interviews conducted at posttreatment data collection. ResultsAfter challenging stigma-related appraisals, participants expressed feeling less constrained by maladaptive thoughts. These shifts translated to increased self-efficacy with both HIV-related care and mental health. ConclusionsThese results indicate that trauma-informed work with PWH should consider the impact of HIV on trauma-related stuck points, intersecting identities (including living with HIV), and challenging internalized stigma. Findings provide evidence that CPT-L is acceptable and effective in addressing internalized HIV stigma that impacts PTSD symptom maintenance and HIV treatment engagement. Trial RegistrationClinicalTrials.gov; NCT05275842; https://clinicaltrials.gov/study/NCT05275842?id=NCT05275842&rank=1 International Registered Report Identifier (IRRID)RR2-10.1016/j.conctc.2023.101150

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

In 2023, the Australian Government issued ∼250,000 soil carbon credits following a measurement period characterised by high rainfall (Decile 10). The inferred soil organic carbon (SOC) sequestration rates during this period, ranging from ∼2 to 8 t C ha−¹ yr−¹, significantly exceed rates reported in Australian scientific studies (∼0.1 to 1.2 t C ha−¹ yr−¹). Our analysis, incorporating SOC and biomass measurements alongside remote sensing of NDVI, reveals that these SOC gains were largely attributable to above-average rainfall rather than project interventions. Moreover, these gains were not sustained when rainfall returned to average levels, raising concerns about the durability of credited sequestration and its additionality beyond natural climatic variability. Our findings demonstrate that current safeguards within the Soil Carbon Method—such as withholding 25% of credits during the first measurement period—are likely insufficient to account for climatic variability. To strengthen the integrity of the carbon crediting system, we recommend extending the minimum measurement period for credit issuance to at least five years. Additionally, governments should establish science-based ‘reasonable bounds’ for expected long-term SOC gains from management practices to sense-check reported outcomes. These measures will ensure that credited SOC sequestration is more closely tied to management-driven outcomes rather than short-term climate-driven fluctuations.

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

IntroductionMethane production inhibitors included in feed additives are increasingly used to suppress methane production in the rumen. Most products interact with the rumen microbiome and/or component biochemical pathways that scavenge free hydrogen ions (H+) to make methane (CH4 ). The capacity of these agents to inhibit rumen methane production is determined by the ability of the chemical to block methane production pathways, the amount of agent delivered to the rumen (i.e. the dose) and the absorption, distribution, metabolism and excretion (i.e. the pharmacokinetic) characteristics of the chemical that contribute to removal from the site of action (the rumen). The intrinsic inhibitory capacity of an agent determines the maximum rate of methane suppression. This maximal rate may reduce according to pharmacokinetic effects arising from dose rate and frequency. Most studies of additive methane reduction efficacy use total mixed ration (TMR; with the additive included into the ration) feeding systems and estimate methane reduction (absolute or relative) across a 24-hour period. Few studies report critical pharmacokinetic parameters, making it difficult to extrapolate findings into non-TMR systems (such as grazing) where differing doses and dose frequencies apply.MethodsWe consider the likely behaviour of a rumen-acting oral additive to reduce methane production applying basic pharmacokinetic principles to propose an analytical approach to data from multiple field studies employing different dose rates and dose frequencies to estimate methane suppression responses. This is based upon a logistic transformation of relative efficacy (percentage reduction in methane comparing treatment with control groups) as the dependent variable and includes total dose, dose frequency, quadratic and interaction terms between total dose and dose frequency as independent variables that potentially capture any pharmacokinetic effects on performance. The model was tested using simulation and verified against real data (cattle 3-nitrooxypropanol (3-NOP) methane-reduction studies).ResultsGood fit between predicted and observed methane suppression was obtained.DiscussionWe propose use of the general form of this logistic model with dose and dose frequency components included that address basic pharmacological impacts on methane suppression as the standard approach to meta-analysis.

Hexanucleotide repeat expansion (HRE) within C9orf72 is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread derepression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including C9orf72 HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheral C9orf72 expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown. We used FreeSurfer software to assess the effects of C9orf72 HRE and clinical diagnosis (n = 78 individuals, male and female) on atrophy of thalamic nuclei. We also generated a novel, human, whole-blood RNA-sequencing dataset to determine the relationships among peripheral C9orf72 expression, TE activation, thalamic atrophy, and clinical severity (n = 114 individuals, male and female). We confirmed global thalamic atrophy and reduced C9orf72 expression in HRE carriers. Moreover, we identified disproportionate atrophy of the right mediodorsal lateral nucleus in HRE carriers and showed that C9orf72 expression associated with clinical severity, independent of thalamic atrophy. Strikingly, we found global peripheral activation of TEs, including the human endogenous LINE-1 element L1HS L1HS levels were associated with atrophy of multiple pulvinar nuclei, a thalamic region implicated in C9-FTD. Integration of peripheral transcriptomic and neuroimaging data from human HRE carriers revealed atrophy of specific thalamic nuclei, demonstrated that C9orf72 levels relate to clinical severity, and identified marked derepression of TEs, including L1HS, which predicted atrophy of FTD-relevant thalamic nuclei.SIGNIFICANCE STATEMENT Pathogenic repeat expansion in C9orf72 is the most frequent genetic cause of FTD and amyotrophic lateral sclerosis (ALS; C9-FTD/ALS). The clinical, neuroimaging, and pathologic features of C9-FTD/ALS are well characterized, whereas the intersections of transcriptomic dysregulation and brain structure remain largely unexplored. Herein, we used a novel radiogenomic approach to examine the relationship between peripheral blood transcriptomics and thalamic atrophy, a neuroimaging feature disproportionately impacted in C9-FTD/ALS. We confirmed reduction of C9orf72 in blood and found broad dysregulation of transposable elements-genetic elements typically repressed in the human genome-in symptomatic C9orf72 expansion carriers, which associated with atrophy of thalamic nuclei relevant to FTD. C9orf72 expression was also associated with clinical severity, suggesting that peripheral C9orf72 levels capture disease-relevant information.

Organized professional baseball began in the 1870s with three independent entities. The first was the National Association, which operated from 1871 to 1875. This was followed in 1876 by the [...]

Niniejsza aktualizacja i rewizja międzynarodowych wytycznych dotyczących pokrzywki została opracowana zgodnie z metodami zalecanymi przez Cochrane i grupę roboczą Grading of Recommendations Assessment, Development and Evaluation (GRADE). Jest to wspólna inicjatywa Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), Global Allergy and Asthma European Network (GA2LEN) i jej Urticaria and Angioedema Centers of Reference and Excellence (UCAREs i ACAREs), European Dermatology Forum (EDF; EuroGuiDerm) oraz Asia Pacific Association of Allergy, Asthma and Clinical Immunology z udziałem 64 delegatów z 50 towarzystw krajowych i międzynarodowych z 31 krajów. Konferencja uzgodnieniowa odbyła się 3 grudnia 2020 r. Niniejsze wytyczne zostały uznane i zaakceptowane przez European Union of Medical Specialist s (UEMS). Pokrzywka jest częstą chorobą, w której pośredniczą komórki tuczne, objawiającą się bąblami, obrzękiem naczynioruchowym lub obydwoma tymi objawami. Częstość występowania ostrej pokrzywki w ciągu życia wynosi około 20%. Przewlekła pokrzywka spontaniczna lub indukowalna powoduje niesprawność, pogarsza jakość życia oraz wpływa na aktywność w pracy i w szkole. Ta zaktualizowana wersja międzynarodowych wytycznych dotyczących pokrzywki obejmuje definicję i klasyfikację pokrzywki oraz przedstawia opracowane przez ekspertów i oparte na dowodach metody diagnostyki i leczenia w przypadku różnych podtypów pokrzywki.

Key Clinical Message After ingestion rubber gloves harden and can produce dangerous complications. Therefore the choice of treatment is of utmost importance. Aside from a surgical approach, endoscopy should also be considered as a treatment option on a case‐to‐case basis or if not applicable as a useful diagnostic tool.

The phyllosphere (aerial plant surfaces colonized by microorganisms) remains an understudied ecosystem in terms of bacterial biogeography, particularly at intermediate or local spatial scales. This study characterized the phyllosphere bacterial community on the leaves of 87 Magnolia grandiflora trees sampled throughout a small town, encompassing an area of approximately 60 km2. Sequencing of the 16S ribosomal RNA gene revealed the dominant bacterial phyla to be Alphaproteobacteria, Bacteroidetes, and Acidobacteria, consistent with other studies of the phyllosphere. There was a small but significant relationship between the phyllosphere community similarity and the distance between the trees (i.e., trees further apart were more likely to have dissimilar bacterial communities). There was also a relationship between the assigned categories of tree height (low, medium, high) and the phyllosphere bacterial community composition, with the trees in the high category having more diverse bacterial communities on their leaves than the shorter trees. This study provides insight into the relationship between phyllosphere community composition and host tree characteristics and shows that the distance between M. grandiflora trees has a significant, albeit low, influence on bacterial composition. These findings contribute to a deeper understanding of phyllosphere microbiome biogeography, highlighting how individual tree characteristics and spatial proximity shape phyllosphere bacterial communities.

At its 1876 founding, the National League presented the nascent professional baseball community with a business model radically different from that of its predecessor: the National Association of 1871-75. The [...]

We utilized a blend of replica exchange and event-chain Monte Carlo techniques to generate candidate configurations, aiming for a maximal packing fraction of hard disks within a circular enclosure. Our investigation encompassed systems comprising N particles, with N ranging from 300 to 720. Through our analysis, we identified 108 novel maximal packings, with some surpassing existing configurations by over 0.001 in packing fraction. As such, Monte Carlo methods demonstrate their efficacy in tackling optimization challenges of this nature. [ABSTRACT FROM AUTHOR]

Abstract Background Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. Main text 10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. Conclusion The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival.

Ruminant production systems in the arid and semi-arid regions of Sub-Saharan Africa confront severe challenges due to recurring droughts and the intensifying effects of climate change (CC). These systems grapple with numerous stress factors, including poor animal nutrition, water scarcity, gastrointestinal (GIT) parasite burdens, and heat stress, which contribute to below optimal animal productivity and a high environmental footprint. Addressing these issues urgently, by creating livestock systems resilient to CC that also promote better animal health, enhanced productivity, and reduced environmental impact, is paramount to safeguarding the livelihoods of the rural population. This 50-day study aimed to evaluate the effects of improved feeding and nutritional management in sheep, focusing on GIT parasite infections, feed intake and digestibility, liveweight (LW) gain, and enteric methane (CH4) emissions. We investigated the legume forage tree, Calliandra (Calliandra calothyrsus), as a high-quality feed source because of its rich crude protein content and its potential as a remedy for gastrointestinal tract (GIT) parasite infections, attributed to its high condensed tannin (CT) content. Twenty-eight Dorper lambs underwent random allocation across four treatments, each consisting of seven lambs. These treatments combined either a trickle infection or no infection with Haemonchus contortus with a supplementation (40% of diet on a dry matter basis or lack thereof) of the basal diet (Rhodes grass hay) with dried Calliandra leaflets. The treatments were: UnHay (uninfected, fed on hay-only), InHay (infected, fed on hay-only), InHay+Cal (infected, fed on hay plus Calliandra), and InHay+Cal+PEG [infected, fed on hay, Calliandra, and polyethylene glycol (PEG)]. The latter was to evaluate the potential effects of Calliandra’s condensed tannins. The results show that lambs in the InHay+Cal treatment exhibited a higher packed cell volume (PCV) and lower faecal egg counts (FEC) compared to the InHay group. No effects of infection on the other measured variables were observed in unsupplemented lambs. Calliandra supplementation increased total feed dry matter intake (DMI) by 20% (61.8 vs. 51.7 g DM/kg LW0.75) (InHay+Cal vs. InHay) and enhanced LW gain (7.2 g/d) in the InHay+Cal group, whereas the unsupplemented infected group (InHay) experienced LW loss (-26.6 g/d). Calliandra supplementation to infected lambs reduced daily CH4 emission by 15% (13.9 vs. 16.2 g/d) and CH4 yield (g/kg DMI) by 30% (18.7 vs. 26.5 g/kg DMI), compared to emissions from unsupplemented infected lambs. Nonetheless, Calliandra supplementation decreased the digestibility of crude protein and fibre and raised the faecal nitrogen (N) output to N intake (FN/NI) ratio. The effects of PEG supplementation on CT activity remained inconclusive. The study concludes that a 40% replacement of a protein-deficient basal diet with Calliandra may be excessive. However, the findings underscore the considerable advantages of integrating Calliandra into farming systems. Such nature-based solution control GIT parasite infections and their lifecycle, bolster the nutritional value of a deficient basal diet, improve animal productivity cost-effectively, and mitigate enteric methane emissions both in absolute terms and intensity.

Abstract The field of health promotions faces considerable ethical and programmatic challenge – and we believe opportunity – in addressing the relative normativity of the concept(s) of health and its professional handling. To date, distinctions of objective and subjective indicants of “health” have fostered normative tension(s) within the utilitarian ethics of health promotions, which we opine to be anathema to the ultimate goal(s) of attaining and sustaining healthy individuals and societies. Objective and subjective metrics and values should be reconciled, as reciprocal and complementary on both idiosyncratic and systemic levels. In this light, we propose that a philosophical and ethical approach, based primarily upon Schmitz’s New Phenomenology and its specific understanding of subjectivity could afford epistemological bases for non-normative engagement of health promotion within a structural–functional framework of ethics. We dialectically address its potential benefit, limitations and value for health promotion and health care ethics and present an approach which points towards a more substantial encouragement of diversity through the legitimation of subjectivity.