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Significance of Primary Stability in Non-Immediate Loaded Dental Implants: A Systematic Review & Meta-Analysis
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Consultations, prescribed topical treatments and disease severity in children with eczema in primary care: analysis of electronic medical records in the BATHE study.
Get PDFBACKGROUND: In countries with well-resourced primary care, most children with eczema are managed by their General Practitioner (GP) but we know little about how often they are seen or how they are treated. OBJECTIVES: To describe patterns of consultations and prescribing by eczema severity for children with eczema. METHODS: Analysis of electronic medical record data from 422/483 participants in the BATHE study. We used descriptive statistics to compare participants characteristics, consultation and prescribing patterns. We explored associations with eczema severity (POEM), age and gender using Poisson and linear regression models. RESULTS: Mean (SD) age 4.8 (2.9) years and POEM 10.0 (5.8). Over 12 months, 386 children had a median (IQR) of 4.0 (2-7) consultations. Of 2049 encounters, 1421 (69.4%) were for an eczema flare. Emollients were the most commonly prescribed item, with a mean of 4.6 prescriptions (507.9 g/ml) per child, yet 32.0% were not prescribed any. On average, children were prescribed 1.3 different emollient-types, with cream being most common (79.5% children, 66.5% prescriptions). 51.4% were prescribed a topical corticosteroid (TCS) with a mean of 2.8 prescriptions (50.6 g) per child and a mean of 1.4 different TCS potency-types (mild being the most common 73.3% children, 56.7% prescriptions). Number of consultations but not quantity of emollients and TCS prescribed were associated to age and eczema severity. CONCLUSIONS: Children with eczema are seen frequently in primary care but are prescribed less emollient and TCS than might be appropriate for age and severity
C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis.
No full textBACKGROUND: Sepsis is a life-threatening condition and a major cause of mortality in intensive care units worldwide, a clear unmet medical need. CNP (C-type natriuretic peptide) regulates inflammation and cardiovascular homeostasis, but its involvement in sepsis pathogenesis is not fully elucidated. This study investigated the intrinsic role of CNP, and therapeutic potential of the peptide, in offsetting the pathogenesis of sepsis. METHODS: Plasma concentrations of CNP, and its N-terminal cleavage product NT-proCNP (N-terminal pro-CNP), were measured in sepsis patients. Cardiac function, vascular hemodynamics, endothelial integrity, and biomarkers of inflammation were analyzed in wild-type, endothelium-restricted (ecCNP-/-), or cardiomyocyte-restricted (cmCNP-/-) CNP knockout animals, or global NPR (natriuretic peptide receptor)-C-/- deficient mice, in etiologically distinct models of sepsis. CNP (0.2 mg/kg per d) was infused to rescue any adverse phenotype and probe therapeutic potential. RESULTS: Circulating (NT-proCNP) increased in sepsis patients and was associated with reduced disease severity. ecCNP-/- mice exhibited an aggravated phenotype compared with wild-type mice in experimental sepsis, exemplified by impaired microcirculatory flow, edema, and increased expression of inflammatory biomarkers. In addition, cmCNP-/- animals showed overt cardiac dysfunction following lipopolysaccharide treatment. This worsened phenotype was mirrored in NPR-C-/- mice, implying that this cognate NPR subtype underpins the salutary actions of endogenous CNP. Pharmacological CNP administration improved microvascular perfusion, cardiac output, and inflammation in wild-type and ecCNP-/-, but not NPR-C-/-, mice. CONCLUSIONS: Endogenous CNP plays a protective role in sepsis by preserving microvascular perfusion, reducing inflammation, maintaining endothelial integrity, and sustaining cardiac function via NPR-C. Pharmacologically targeting CNP signaling warrants further evaluation as a potential therapeutic opportunity in sepsis
European Code Against Cancer 5th edition: 14 ways you can help prevent cancer.
Get PDFDespite the growing cancer burden in the European Union, public awareness of effective prevention is low. In response, Europe's Beating Cancer Plan has supported the development of the 5th edition of the European Code Against Cancer (ECAC5). Using a transparent, stepwise decision-making process, around 80 experts reviewed the latest scientific evidence on cancer prevention and used modern communication strategies to update the previous edition. An innovation in ECAC5 is the inclusion of population-level recommendations, aiming to structurally influence the systems that shape individual choices and improve environmental conditions to which all citizens are involuntarily exposed. ECAC5 includes 14 actionable, evidence-based recommendations for individuals to reduce their cancer risk alongside their respective policy recommendations. All are presented through equity lens, with attention to co-benefits for preventing other non-communicable diseases and tailoring messages to diverse audiences. Clear evidence-based statements on cancer risks factors and effective preventive interventions will empower citizens to make healthier choices, call policymakers to act, foster public support for effective policies, and contribute to more effective cancer prevention
Single-cell atlas of the developing Down syndrome brain cortex.
Get PDFDown syndrome (DS), caused by trisomy of chromosome 21, is the leading genetic cause of intellectual disability, yet the mechanisms disrupting fetal brain development remain unclear. We performed single-cell transcriptomic and chromatin accessibility profiling of approximately 250,000 cells from 15 DS and 15 control human fetal cortices (10-20 weeks post-conception). Our analysis revealed a subtype-specific reduction in RORB/FOXP1-expressing excitatory neurons and widespread disruption of neurodevelopmental transcriptional programs. Chromosome 21 transcription factors (TFs) BACH1, PKNOX1, and GABPA emerged as dosage-sensitive hubs regulating genes linked to intellectual disability. Antisense oligonucleotide-mediated normalization of these TFs in human neural progenitors in vitro partially rescued target gene expression. Benchmarking a humanized in vivo model captured additional molecular and cellular signatures of DS, complementing the in vitro model. Together, we present a resource defining the gene-regulatory landscape underlying cortical development in DS and highlight molecular pathways for further investigation
Oocyte cryo-preservation for fertility preservation: a comparative study of efficacy and cost-effectiveness between progestin-primed and antagonist ovarian stimulation protocol.
Get PDFSuppression of an LH surge is fundamental to successful oocyte retrieval after controlled ovarian stimulation. This study evaluates the efficacy and cost-effectiveness of progestin-primed ovarian stimulation (PPOS) using oral medroxyprogesterone acetate in fertility preservation cycles. The design is a retrospective single-centre study (January 2022-August 2023) comparing two ovarian stimulation protocols: PPOS and the gonadotrophin-releasing hormone antagonist (GnRHant) protocols. Cycles began at any time of the menstrual cycle. The primary outcome was the number of metaphase II oocytes retrieved. Secondary outcomes included total oocytes retrieved, maturity ratio, stimulation duration, incidence of premature LH rise/ovulation events, and the cost of medication used to prevent ovulation. The study included 125 fertility preservation cycles: 54 in the PPOS group and 71 in the GnRHant group. Median body mass index, antral follicle count, and anti-Mullerian hormone levels were comparable between the two groups. The median age was younger in the PPOS group; 28 years vs. 32 years, p = 0.03. Mature oocyte retrieval was similar; mean 9.33 [SD 5.87] vs. 8.97 [SD 5.44], p = 0.73. No premature LH rises occurred in either group. Secondary outcomes showed no significant differences, except for the cost of medication used to prevent ovulation. The PPOS protocol was considerably more cost-effective, by achieving a 98.06% cost reduction (medroxyprogesterone acetate, mean £4.38 [SD, £1.10] vs cetrorelix acetate £226.2 [SD £64.36], p= <0.0001. PPOS is a practical, cost-effective strategy for fertility preservation. Its appeal lies in its patient-centric focus, with a less invasive injection-based administration, while maintaining comparable effectiveness and significant cost reduction compared with the GnRH antagonist ovarian stimulation protocol
Burn Selection: How Fire Injury Shaped Human Evolution.
No full textThe mastery of fire transformed human evolution through advantages spanning diet, behavior, physiology, and ecology. While these benefits are well established, here we highlight a previously overlooked cost - and selective pressure - unique to humans: high-temperature burn injury. Unlike other species, humans and their hominin ancestors have faced increased lifetime risk of burns, which we argue has driven genetic adaptation. Drawing on comparative genomic evidence across primates, we suggest that genes associated with burn injury response - relating to wound healing and inflammation - show signs of accelerated evolution in humans. We propose that recurrent exposure to burns acted as a selective force in our lineage, helping to explain both beneficial adaptations and paradoxical maladaptive responses to severe injury. By framing burns as an evolutionary pressure, the Burn Selection Hypothesis invites a re-evaluation of how fire shaped human biology and offers new perspectives for understanding both the evolutionary past and modern burn care
