BACKGROUND: Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only eight documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1.
OBJECTIVE: To provide a comprehensive overview of the clinical and immunological findings of patients with B-cell deficiency attributed to variants in IGLL1.
METHODS: NBS programs reporting using kappa-deleting recombination excision circle assays, the European Society for Immunodeficiencies Registry, and authors of published reports featuring patients with B-cell deficiency linked to IGLL1 variants were contacted. Only patients with (likely) pathogenic variants, reduced CD19+ counts and no alternative diagnosis were included.
RESULTS: The study included 13 patients identified through NBS, two clinically diagnosed patients, and two asymptomatic siblings. All had severely reduced CD19+ B-cells (< 0.1×109/L) on first evaluation, yet subsequent follow-ups indicated residual immunoglobulin production. Specific antibody responses to vaccine antigens varied, with a predominant reduction observed during infancy. Clinical outcomes were favorable with immunoglobulin G substitution. Two patients successfully discontinued substitution without developing susceptibility to infections and maintaining immunoglobulin levels. The pooled incidence of homozygous or compound heterozygous pathogenic IGLL1 variants identified by NBS in Austria, Czechia, and Switzerland was 1.3:100´000, almost double of X-linked agammaglobulinemia.
CONCLUSIONS: B-cell deficiency resulting from IGLL1 variants appears to be more prevalent than initially believed. Despite markedly low B-cell counts, the clinical course in some patients may be milder than reported in the literature so far.

Nature-based Solutions (NbS) are actions that harness nature to help address major societal challenges. The assessment frameworks for NbS proposed in the literature differ in scope and intended use. In 2020, the International Union for Conservation of Nature (IUCN) introduced their Global Standard for NbS as a framework that can be used by anyone working on different types of NbS. Since research on the applicability of the IUCN Standard remains limited, the aim of this paper is to analyse whether the IUCN Standard may be used as an overarching assessment framework for NbS in river flood management applications and to identify the main differences in content with other NbS-frameworks. This was achieved through a comparison with 29 assessment frameworks for NbS, that are applicable to physical interventions for riverine flood risk reduction. The comparisons showed that the IUCN Standard has the largest breadth in scope of application and may therefore be used as an overarching framework. In addition, we identified a distinction between frameworks for the assessment of project processes (process-oriented) and project results (results-oriented), where the IUCN Standard can be characterized as process-oriented. This implies that the IUCN Standard may be used to assess the processes (e.g. stakeholder engagement and adaptive management) of planned, ongoing or completed NbS projects for a wide variety of environmental contexts and societal challenges. This will help persuade policy makers to consider NbS as one of the solutions in flood management issues, next to or in combination with e.g. engineering solutions or changing land use. We also identified that, while the IUCN Standard is straightforward to use and incorporates stakeholder input, the environmental context specificity as well as guidance depth on resources for assessment can be improved.

During the expanded neonatal screening program conducted in 2023, we analyzed samples obtained from 1,227,130 out of 1,256,187 newborns in the Russian Federation in order to detect 5q spinal muscular atrophy (5q SMA). Within the 253-sample risk group formed based on the results of the first screening stage, 5 samples showed a discrepancy between the examination results obtained via various screening methods and quantitative MLPA (used as reference). The discrepancy between the results was caused by the presence of either a c.835-18C>T intronic variant or a c.842G>C p.(Arg281Thr) missense variant in the SMN1 gene, both of which are located in the region complementary to the sequences of annealing probes for ligation and real-time PCR. Three newborns had the c.835-18C>T variant in a compound heterozygous state with a deletion of exons 7-8 of the SMN1 gene, one newborn with two copies of the SMN1 gene had the same variant in a heterozygous state, and one newborn had both variants-c.835-18C>T and c.842G>C p.(Arg281Thr)-in a compound heterozygous state. Additional examination was carried out for these variants, involving segregation analysis in families, carriage analysis in population cohorts, and RNA analysis. Based on the obtained results, according to the ACMG criteria, the c.835-18C>T intronic variant should be classified as likely benign, and the c.842G>C p.(Arg281Thr) missense substitution as a variant of uncertain clinical significance. All five probands are under dynamic monitoring. No 5q SMA symptoms were detected in these newborns neonatally or during a 1-year follow-up period.

The overuse and misuse of antibiotics have accelerated the selection of antibiotic-resistant bacteria, significantly impacting human, animal, and environmental health. As aquatic environments are vulnerable to antibiotic resistance, suitable management practices should be adopted to tackle this phenomenon. Here we show an effective, nature-based solution for reducing antibiotic resistance from actual wastewater. We utilize a bioreactor that relies on benthic (biofilms) and planktonic microbial communities to treat secondary effluent from a small urban wastewater treatment plant (<10,000 population equivalent). This treated effluent is eventually released into the local aquatic ecosystem. We observe high removal efficiency for genes that provide resistance to commonly used antibiotic families, as well as for mobile genetic elements that could potentially aid in their spread. Importantly, we notice a buildup of sulfonamide (sul1 and sul2) and tetracycline (tet(C), tet(G), and tetR) resistance genes specifically in biofilms. This advancement marks the initial step in considering this bioreactor as a nature-based, cost-effective tertiary treatment option for small UWWTPs facing antibiotic resistance challenges.

BACKGROUND: New York (NY) State implemented a new cystic fibrosis (CF) newborn screen (NBS) algorithm in December 2017 with improvement in positive predictive value and unanticipated increased identification of infants with cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS). Repeat sweat testing is recommended in infants with CRMS. During the COVID-19 pandemic infants with CRMS were lost to follow up. With this quality improvement (QI) initiative, we aimed to perform repeat sweat testing in 25% of infants lost to follow up. We also describe consensus recommendations for CRMS from the NY CF NBS Consortium.
METHODS: Our QI team identified the primary drivers contributing to absent follow up, outreached to families, and created a questionnaire to evaluate parental understanding of CRMS using QI-based strategies.
RESULTS: Of 350 infants diagnosed with CRMS during the study period, 179 (51.1%) infants were lost to follow up. A total of 31 (17.3%) were scheduled for repeat sweat tests and followed up at CF Centers. Families reported high satisfaction with the CRMS knowledge questionnaire.
CONCLUSIONS: With this QI-based approach, we effectively recaptured infants with CRMS previously lost to follow up during the COVID-19 pandemic. Ongoing concerns about infection risk and lack of understanding on the part of families and pediatricians likely contributed to patients with CRMS lost to follow up. Consensus recommendations for CRMS include annual visits with repeat sweat testing until 2-6 years of age and education for adolescents about clinical and reproductive implications of CRMS.

Maximizing treatment efficacy and forecasting patient prognosis in cancer necessitates the strategic use of targeted therapy, coupled with the prompt precise detection of malignant tumors. Theutilizationof gaseous systems as an adaptable platform for creating nanobubbles (NBs) has garnered significant attention as theranostics, which involve combining contrast chemicals typically used for imaging with pharmaceuticals to diagnose and treattumorssynergistically in apersonalizedmanner for each patient. This review specifically examines the utilization of oxygen NBsplatforms as a theranostic weapon in the field of oncology. We thoroughly examine the key factors that impact the effectiveness of NBs preparations and the consequences of these treatment methods. This review extensively examines recent advancements in composition schemes, advanced developments in pre-clinical phases, and other groundbreaking inventions in the area of NBs. Moreover, this review offers a thorough examination of the optimistic future possibilities, addressing prospective methods for improvement and incorporation into widely accepted therapeutic practices. As we explore the ever-changing field of cancer theranostics, the incorporation of oxygen NBs appears as a promising development, providing new opportunities for precision medicine and marking a revolutionary age in cancer research and therapy.

The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1β), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1β, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1β, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse.

OBJECTIVE: We aimed to summarise and critically appraise the available evidence for the effect of age on responsiveness to non-invasive brain stimulation (NBS) paradigms delivered to the primary motor cortex.
METHODS: Four databases (Medline, Embase, PsycINFO and Scopus) were searched from inception to February 7, 2023. Studies investigating age group comparisons and associations between age and neuroplasticity induction from NBS paradigms were included. Only studies delivering neuroplasticity paradigms to the primary motor cortex and responses measured via motor-evoked potentials (MEPs) in healthy adults were considered.
RESULTS: 39 studies, encompassing 40 experiments and eight NBS paradigms were included: paired associative stimulation (PAS; n = 12), repetitive transcranial magnetic stimulation (rTMS; n = 2), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct and alternating current stimulation ((tDCS; n = 7; tACS; n = 2)), quadripulse stimulation (QPS; n = 1) and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1). Pooled findings from PAS paradigms suggested older adults have reduced post-paradigm responses, although there was considerable heterogeneity. Mixed results were observed across all other NBS paradigms and post-paradigm timepoints.
CONCLUSIONS: Whilst age-dependent reduction in corticospinal excitability is possible, there is extensive inter- and intra-individual variability both within and between studies, making it difficult to draw meaningful conclusions from pooled analyses.

This paper examines the socio-ecological resilience within China\'s Northeast National Forest Region (NNFR), focusing on the implications of climate change for forest management and carbon sequestration. It offers a critical assessment of the Natural Forest Protection Program (NFPP) and the associated logging ban policy, recognizing their pivotal contributions to forest conservation but also identifying the shortcomings of a one-size-fits-all approach. Integrating panarchy theory, the study proposes sustainable management practices that align ecological dynamics with societal needs, emphasizing nature-based solutions. The overarching aim is to bolster the long-term resilience and enhance the carbon sequestration potential of the NNFR\'s forests. It aims to inform global environmental strategy with lessons from the NNFR, advocating for integrated approaches that ensure both ecological sustainability and community prosperity. This approach seeks to provide a comprehensive and effective strategy for addressing environmental challenges, ensuring both ecological integrity and community well-being.

Biodiversity loss and climate change have severely impacted ecosystems and livelihoods worldwide, compromising access to food and water, increasing disaster risk, and affecting human health globally. Nature-based Solutions (NbS) have gained interest in addressing these global societal challenges. Although much effort has been directed to NbS in urban and terrestrial environments, the implementation of NbS in marine and coastal environments (blue NbS) lags. The lack of a framework to guide decision-makers and practitioners through the initial planning stages appears to be one of the main obstacles to the slow implementation of blue NbS. To address this, we propose an integrated conceptual framework, built from expert knowledge, to inform the selection of the most appropriate blue NbS based on desired intervention objectives and social-ecological context. Our conceptual framework follows a four incremental steps structure: Step 1 aims to identify the societal challenge(s) to address; Step 2 highlights ecosystem services and the underlying biodiversity and ecological functions that could contribute to confronting the societal challenge(s); Step 3 identify the specific environmental context the intervention needs to be set within (e.g. the spatial scale the intervention will operate within, the ecosystem\'s vulnerability to stressors, and its ecological condition); and Step 4 provides a selection of potential blue NbS interventions that would help address the targeted societal challenge(s) considering the context defined through Step 3. Designed to maintain, enhance, recover, rehabilitate, or create ecosystem services by supporting biodiversity, the blue NbS intervention portfolio includes marine protection (i.e., fully, highly, lightly, and minimally protected areas), restorative activities (i.e., active, passive, and partial restoration; rehabilitation of ecological function and ecosystem creation), and other management measures (i.e., implementation and enforcement of regulation). Ultimately, our conceptual framework guides decision-makers toward a versatile portfolio of interventions that cater to the specific needs of each ecosystem rather than imposing a rigid, one-size-fits-all model. In the future, this framework needs to integrate socio-economic considerations more comprehensively and be kept up-to-date by including the latest scientific information.