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Background: α-dystroglycanopathies are congenital muscular dystrophies in which genetic mutations cause the decrease or absence of a unique and complex O-linked glycan called matriglycan. This hypoglycosylation of O-linked matriglycan on the α-dystroglycan (α-DG) protein subunit abolishes or reduces the protein binding to extracellular ligands such as laminins in skeletal muscles, leading to compromised survival of muscle cells after contraction. Methods: Surrogate molecular linkers reconnecting laminin-211 and the dystroglycan β-subunit through bispecific antibodies can be engineered to improve muscle function in the α-dystroglycanopathies. This study reports the metabolic engineering of a novel glycofusion bispecific (GBi) antibody that fuses the mucin-like domain of the α-DG to the light chain of an anti-β-DG subunit antibody. Results: Transient HEK production with the co-transfection of LARGE1, the glycoenzyme responsible for the matriglycan modification, produced the GBi antibody only with a light matriglycan modification and a weak laminin-211 binding activity. However, when a sugar feed mixture of uridine, galactose, and manganese ion (Mn2+) was added to the culture medium, the GBi antibody produced exhibited a dramatically enhanced matriglycan modification and a much stronger laminin-binding activity. Conclusions: Further investigation has revealed that Mn2+ in the sugar feeds played a critical role in increasing the matriglycan modification of the GBi antibody, key for the function of the resulting bispecific antibody.

Abstract Next-generation site-specific cysteine-based antibody–drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation processes, impacting product quality. To overcome this technical challenge, we developed a novel antibody manufacturing process through cysteine (Cys) metabolic engineering in Chinese hamster ovary cells implementing a unique cysteine-capping technology. This development enabled a direct conjugation of drugs after chemoselective-reduction with mild reductant tris(3-sulfonatophenyl)phosphine. This innovative platform produces clinical ADC products with superior quality through a simplified manufacturing process. This technology also has the potential to integrate Cys-based site-specific conjugation with other site-specific conjugation methodologies to develop multi-drug ADCs and exploit multi-mechanisms of action for effective cancer treatments.

Self-association governs the viscosity and solubility of therapeutic antibodies in high-concentration formulations used for subcutaneous delivery, yet it is difficult to reliably identify candidates with low self-association during antibody discovery and early-stage optimization. Here, we report a high-throughput protein engineering method for rapidly identifying antibody candidates with both low self-association and high affinity. We find that conjugating quantum dots to IgGs that strongly self-associate (pH 7.4, PBS), such as lenzilumab and bococizumab, results in immunoconjugates that are highly sensitive for detecting other high self-association antibodies. Moreover, these conjugates can be used to rapidly enrich yeast-displayed bococizumab sub-libraries for variants with low levels of immunoconjugate binding. Deep sequencing and machine learning analysis of the enriched bococizumab libraries, along with similar library analysis for antibody affinity, enabled identification of extremely rare variants with co-optimized levels of low self-association and high affinity. This analysis revealed that co-optimizing bococizumab is difficult because most high-affinity variants possess positively charged variable domains and most low self-association variants possess negatively charged variable domains. Moreover, negatively charged mutations in the heavy chain CDR2 of bococizumab, adjacent to its paratope, were effective at reducing self-association without reducing affinity. Interestingly, most of the bococizumab variants with reduced self-association also displayed improved folding stability and reduced nonspecific binding, revealing that this approach may be particularly useful for identifying antibody candidates with attractive combinations of drug-like properties.Abbreviations: AC-SINS: affinity-capture self-interaction nanoparticle spectroscopy; CDR: complementarity-determining region; CS-SINS: charge-stabilized self-interaction nanoparticle spectroscopy; FACS: fluorescence-activated cell sorting; Fab: fragment antigen binding; Fv: fragment variable; IgG: immunoglobulin; QD: quantum dot; PBS: phosphate-buffered saline; VH: variable heavy; VL: variable light.

Rapidly producing drug-like antibody therapeutics for lead molecule discovery and candidate optimization is typically accomplished by large-scale transient gene expression technologies (TGE) with cultivated mammalian cells. The TGE methodologies have been extensively developed over the past three decades, yet produce significantly lower yields than the stable cell line approach, facing the technical challenge of achieving universal high expression titers for a broad range of antibodies and therapeutics modalities. In this study, we explored various parameters for antibody production in the TGE cell host Expi293FTM and ExpiCHO-STM with the transfection reagents ExpiFectamineTM and polyethylenimine. We discovered that there are significant differences between Expi293FTM and ExpiCHO-STM cells with regards to DNA complex formation time and ratio, complex formation buffers, DNA complex uptake trafficking routes, responses to dimethyl sulfoxide and cell cycle inhibitors, as well as light-chain isotype expression preferences. This investigation mechanistically dissected the TGE processes and provided a new direction for future transient antibody production optimization.

Abstract GDF15 is a distant TGF-β family member that induces anorexia and weight loss. Due to its function, GDF15 has attracted attention as a potential therapeutic for the treatment of obesity and its associated metabolic diseases. However, the pharmacokinetic and physicochemical properties of GDF15 present several challenges for its development as a therapeutic, including a short half-life, high aggregation propensity, and protease susceptibility in serum. Here, we report the design, characterization and optimization of GDF15 in an Fc-fusion protein format with improved therapeutic properties. Using a structure-based engineering approach, we combined knob-into-hole Fc technology and N-linked glycosylation site mutagenesis for half-life extension, improved solubility and protease resistance. In addition, we identified a set of mutations at the receptor binding site of GDF15 that show increased GFRAL binding affinity and led to significant half-life extension. We also identified a single point mutation that increases p-ERK signaling activity and results in improved weight loss efficacy in vivo. Taken together, our findings allowed us to develop GDF15 in a new therapeutic format that demonstrates better efficacy and potential for improved manufacturability.

Summary: Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose. GDF15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. Similarly, in GDF15 knockout mice, the LPS effect on appetite and survival was comparable with that observed in wild-type controls. Therefore, effective inhibition of circulating active GDF15 via an antibody or via gene knockout demonstrated that survival in the LPS acute inflammation model was independent of GDF15.

We report here the discovery and optimization of a novel T cell retargeting anti-GUCY2C x anti-CD3ε bispecific antibody for the treatment of solid tumors. Using a combination of hybridoma, phage display and rational design protein engineering, we have developed a fully humanized and manufacturable CD3 bispecific antibody that demonstrates favorable pharmacokinetic properties and potent in vivo efficacy. Anti-GUCY2C and anti-CD3ε antibodies derived from mouse hybridomas were first humanized into well-behaved human variable region frameworks with full retention of binding and T-cell mediated cytotoxic activity. To address potential manufacturability concerns, multiple approaches were taken in parallel to optimize and de-risk the two antibody variable regions. These approaches included structure-guided rational mutagenesis and phage display-based optimization, focusing on improving stability, reducing polyreactivity and self-association potential, removing chemical liabilities and proteolytic cleavage sites, and de-risking immunogenicity. Employing rapid library construction methods as well as automated phage display and high-throughput protein production workflows enabled efficient generation of an optimized bispecific antibody with desirable manufacturability properties, high stability, and low nonspecific binding. Proteolytic cleavage and deamidation in complementarity-determining regions were also successfully addressed. Collectively, these improvements translated to a molecule with potent single-agent in vivo efficacy in a tumor cell line adoptive transfer model and a cynomolgus monkey pharmacokinetic profile (half-life>4.5 days) suitable for clinical development. Clinical evaluation of PF-07062119 is ongoing.

For an antibody to be a successful therapeutic many competing factors require optimization, including binding affinity, biophysical characteristics, and immunogenicity risk. Additional constraints may arise from the need to formulate antibodies at high concentrations (>150 mg/ml) to enable subcutaneous dosing with reasonable volume (ideally

The role of brain-derived neurotrophic factor (BDNF) signaling in chronic pain has been well documented. Given the important central role of BDNF in long term plasticity and memory, we sought to engineer a high affinity, peripherally-restricted monoclonal antibody against BDNF to modulate pain. BDNF shares 100% sequence homology across human and rodents; thus, we selected chickens as an alternative immune host for initial antibody generation. Here, we describe the affinity optimization of complementarity-determining region-grafted, chicken-derived R3bH01, an anti-BDNF antibody specifically blocking the TrkB receptor interaction. Antibody optimization led to the identification of B30, which has a > 300-fold improvement in affinity based on BIAcore, an 800-fold improvement in potency in a cell-based pERK assay and demonstrates exquisite selectivity over related neurotrophins. Affinity improvements measured in vitro translated to in vivo pharmacological activity, with B30 demonstrating a 30-fold improvement in potency over parental R3bH01 in a peripheral nerve injury model. We further demonstrate that peripheral BDNF plays a role in maintaining the plasticity of sensory neurons following nerve damage, with B30 reversing neuron hyperexcitability associated with heat and mechanical stimuli in a dose-dependent fashion. In summary, our data demonstrate that effective sequestration of BDNF via a high affinity neutralizing antibody has potential utility in modulating the pathophysiological mechanisms that drive chronic pain states.

Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART®) bispecific molecule against P-cadherin and CD3 that demonstrates antibody-like properties. Using phage display, we identified anti-P-cadherin single chain Fv (scFv) that were subsequently affinity-optimized to picomolar affinity using stringent phage selection strategies, resulting in low picomolar potency in cytotoxic T lymphocyte (CTL) killing assays in the DART format. The crystal structure of this disulfide-constrained diabody shows that it forms a novel compact structure with the two antigen binding sites separated from each other by approximately 30 Å and facing approximately 90° apart. We show here that introduction of the human Fc domain in PF-06671008 has produced a molecule with an extended half-life (-4.4 days in human FcRn knock-in mice), high stability (Tm1 > 68 °C), high expression (>1 g/L), and robust purification properties (highly pure heterodimer), all with minimal impact on potency. Finally, we demonstrate in vivo anti-tumor efficacy in a human colorectal/human peripheral blood mononuclear cell (PBMC) co-mix xenograft mouse model. These results suggest PF-06671008 is a promising new bispecific for the treatment of patients with solid tumors expressing P-cadherin.

Review of / Reseña de: Guirao Mirón, Cristina. Transgresoras. Una historia cultural de las mujeres. Madrid: Catarata, 2024. 109 pp. ISBN: 978-84-1067-045-7

IntroductionAdvancements in machine learning (ML) algorithms that make predictions from data without being explicitly programmed and the increased computational speeds of graphics processing units (GPUs) over the last decade have led to remarkable progress in the capabilities of ML. In many fields, including agriculture, this progress has outpaced the availability of sufficiently diverse and high-quality datasets, which now serve as a limiting factor. While many agricultural use cases appear feasible with current compute resources and ML algorithms, the lack of reusable hardware and software components, referred to as cyberinfrastructure (CI), for collecting, transmitting, cleaning, labeling, and training datasets is a major hindrance toward developing solutions to address agricultural use cases. This study focuses on addressing these challenges by exploring the collection, processing, and training of ML models using a multimodal dataset and providing a vision for agriculture-focused CI to accelerate innovation in the field.MethodsData were collected during the 2023 growing season from three agricultural research locations across Ohio. The dataset includes 1 terabyte (TB) of multimodal data, comprising Unmanned Aerial System (UAS) imagery (RGB and multispectral), as well as soil and weather sensor data. The two primary crops studied were corn and soybean, which are the state's most widely cultivated crops. The data collected and processed from this study were used to train ML models to make predictions of crop growth stage, soil moisture, and final yield.ResultsThe exercise of processing this dataset resulted in four CI components that can be used to provide higher accuracy predictions in the agricultural domain. These components included (1) a UAS imagery pipeline that reduced processing time and improved image quality over standard methods, (2) a tabular data pipeline that aggregated data from multiple sources and temporal resolutions and aligned it with a common temporal resolution, (3) an approach to adapting the model architecture for a vision transformer (ViT) that incorporates agricultural domain expertise, and (4) a data visualization prototype that was used to identify outliers and improve trust in the data.DiscussionFurther work will be aimed at maturing the CI components and implementing them on high performance computing (HPC). There are open questions as to how CI components like these can best be leveraged to serve the needs of the agricultural community to accelerate the development of ML applications in agriculture.

The prevalence of serious mental illness is higher in healthcare professionals than in the general population. Mental health issues are associated with more lost workdays than any other chronic condition within the NHS. For healthcare professionals, disclosure of mental health condition can lead to stigmatisation and devaluation as a professional. The aim of this study was to investigate the experiences of living with a mental health condition as a healthcare professional and access to support. The study used qualitative methods combining data from semi-structured interviews (n = 10) and textual data from Twitter threads (n = 51). Purposeful sampling was used to achieve maximum variation in terms of serious mental illness experience, health care professions, and location of work. Search criteria for identifying relevant twitter threads followed the same sampling criteria. The data was analysed using thematic analysis. Three themes were identified: importance of support and advice, need to tackle stigmatisation, and challenges to improve mental well-being. Emotional validation of living with a mental health condition as a health care professional was an important factor for feeling supported. Organisational mismanagement and negative attitudes about mental illnesses were considered as key reasons for persistent stigmatisation. Challenges included disparities in support between the professions, high expectations by self and others, and fearing to disclose suicidal thoughts and ideation. Organisational changes are needed to better support healthcare professionals living with serious mental health conditions. Barriers to seeking support could be addressed by providing better training and toolkits for managers and colleagues.

Abstract Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity ( ≥ five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05–29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63–18.29]) of these serious outcomes compared to those with high antibody levels.

Introduction Strabismus influences health-related quality of life. Individuals may have functional and psychosocial consequences of strabismus that impact their well-being. As strabismus is prevalent in all age groups, patients are seen in varied specialties in healthcare organizations. Therefore, healthcare professionals need to be aware of the psychosocial consequences when caring for strabismic individuals. Objective To describe strabismic adults’ experiences of the psychosocial influence of strabismus. Methods Twelve strabismic adults participated in face-to-face or online semistructured individual interviews to share their experiences of the psychosocial influence of strabismus. The participants were selected purposefully. The data were analyzed using inductive content analysis. Results The participating adults described challenges with social environments, which showed stress in social situations and pressure in interactions. Strabismic adults had experienced staring from others, avoided social situations, and were uncomfortable with photography. They hid their strabismus, avoided eye contact, and struggled with intimate relationships. They also expressed struggles with mental well-being, which were emotional and psychological burdens. The adults described feeling negative emotions, worry, and irritation due to their condition. Struggles with self-confidence, difficulties with acceptance, negative thoughts about their appearance, experiences of bullying, and dealing with being different were described. Conclusion Strabismic adults experience psychosocial consequences of strabismus, influencing their psychosocial health-related quality of life. Further studies should focus on how healthcare professionals could support strabismic individuals’ psychosocial well-being.

Introduction Transition of care for a patient between hospital and home can cause disruption to normal routines, increasing the risk of medicines-related harm. The transition from hospital to home is more complex when a patient does not self-manage their medicines but relies on an informal or unpaid carer (eg, spouse, family member or friend) to provide support. Given the day-to-day medicines-related support provided by informal carers, there is a need to understand how informal carers manage the transition of care from hospital to home; what aspects of hospital discharge act as barriers and facilitators to their involvement and when, how and why these impact patients.Methods and analysis A realist review will be undertaken to develop a programme theory. The programme theory will theorise which medicines-related interventions are useful to carers, and how they are useful. It will outline what aspects of those interventions are the most useful and why, and how context influences engagement and medicine-related outcomes. The review will be reported in line with the Realist and Meta-narrative Evidence Syntheses: Evolving Standards guidelines. Data will be selected, screened and extracted based on defined inclusion and exclusion criteria and relevance to the developing programme theory with the involvement of at least two authors acting independently. Inclusion criteria relate to the relevance to hospital discharge where patients move back to their home, where a carer is involved and where interventions relate to medicines use. Searches will be conducted in PubMed, CINAHL (via EBSCOhost) and EMBASE databases (see supplementary materials for a draft search strategy).Patients and public, participation, involvement and engagement (PPIE) will be incorporated into all stages of the review through iterative engagement and discussion with patient, carers and representatives from carer organisations. The review will follow four steps: (1) development of the initial programme theory, (2) evidence search, (3) selection, extracting, and organising data and (4) synthesising evidence and drawing conclusions.Informal carer involvement in transitions of care is a complex and varied phenomena. The programme theory will be shaped by sustained PPIE reflecting the priorities and experiences of lived experience. The realist review be progressively focused so we can develop a better understanding of carer involvement in patient transitions when moving from hospital to home relating to medicines use.Ethics and dissemination Ethical approval is not required. The findings of the review will be disseminated via journal articles and through patient and public facing resources such as a visual patient–public-carer focused summary.PROSPERO registration number CRD42021262827.

Lichen sclerosus (LS) is a chronic inflammatory condition predominantly affecting the anogenital region of postmenopausal women. It is associated with considerable aesthetic and functional impairments and an increased risk of squamous cell carcinoma. While high-potency topical corticosteroids remain the cornerstone of treatment, therapeutic options for patients with refractory LS are scarce. Fractional CO2 laser therapy has emerged as a potential second-line intervention aiming to mitigate symptoms and improve quality of life. This prospective observational study investigated the short-term efficacy and safety of fractional CO2 laser therapy in 75 women with refractory LS who underwent four treatment sessions between January 2022 and February 2024. Sixty-nine patients completed the protocol, demonstrating significant reductions in key symptoms, including pruritus (VAS score from 7.53 ± 3.02 to 4.08 ± 3.07), pain (5.83 ± 3.84 to 2.42 ± 2.85), and dyspareunia (8.26 ± 2.82 to 6.34 ± 3.30). Quality of life, sexual function, and psychological well-being also improved, as evidenced by reductions in Dermatology Life Quality Index (DLQI) scores (10.72 ± 7.25 to 5.94 ± 5.16), enhancements in sexual function (FSFI scores from 10.48 ± 8.46 to 15.52 ± 9.59), and decreased depression severity (BDI scores from 16.66 ± 12.64 to 5.94 ± 5.16). Importantly, no adverse effects were reported during the study period. Although these findings highlight the potential of fractional CO2 laser therapy as a safe and effective adjunct for refractory LS, it is essential to acknowledge the study’s limitations, particularly the relatively short follow-up period. Longer-term studies are warranted to confirm sustained benefits and to evaluate the broader applicability of this approach.

Introduction Here we present the Scottish Linked Pregnancy and Baby Dataset (SLiPBD), a new national data resource held by Public Health Scotland (PHS). Methods SLiPBD comprises a population-based e-cohort of all fetuses and births (babies) from pregnancies to women in Scotland from 2000 onwards. It is updated monthly by linking and reconciling the following national datasets: antenatal booking records; general and maternity hospital discharge records; termination of pregnancy notifications; and statutory live and stillbirth registrations. Results Key information included on all babies in SLiPBD includes estimated date of conception, end of pregnancy date, gestation, multiple pregnancy status, pregnancy outcome, and maternal sociodemographic characteristics. For live births, additional information on the birth, the baby's sociodemographic characteristics, and subsequent infant deaths is included. Following the cohort refresh in January 2024, SLiPBD contained 1,770,226 babies from 1,750,830 pregnancies to 898,161 women. Of the 1,770,226 babies, 1,284,461 (73%) were live births, 5,731 (0.3%) stillbirths, and 316,897 (18%) and 114,840 (6%) came from a pregnancy ending a termination or early spontaneous loss respectively. 22,414 (1%) had an unknown pregnancy outcome, and for 25,883 (1%) the pregnancy was still ongoing. Data completeness for key sociodemographic characteristics except for ethnicity was very high, and variables showed expected patterns. Ethnicity data completeness is poor on historical records but improving over time. Completeness of unique patient identifiers was very high. External validation to source datasets was reassuring. Conclusion SLiPBD can be analysed standalone or linked to other national vital event and health datasets held by PHS. It supports longitudinal and intergenerational analyses, enabling epidemiological and health service surveillance and research on maternal and child health. Researchers interested in accessing pseudonymised extracts of SLiPBD through the Scottish NHS safe haven facility should contact Research Data Scotland. PHS will continue to refine SLiPBD as source datasets improve. Key Features • The Scottish Linked Pregnancy and Baby Dataset (SLiPBD) is a new national data resource created and maintained by Public Health Scotland to facilitate epidemiological and health service analyses focused on maternal and child health. • SLiPBD comprises a population-based e-cohort of all fetuses and births (babies) from pregnancies to women in Scotland from 2000 onwards. At least 68,000 babies (of which at least 46,000 are live births) are included annually. • SLiPBD is updated on a monthly basis by linking and reconciling records relating to ongoing and completed pregnancies from the following existing national datasets: antenatal booking records; general and maternity hospital discharge records; termination of pregnancy notifications; and statutory live and stillbirth registrations. • Key information included on all babies in SLiPBD includes estimated date of conception, end of pregnancy date, gestation, multiple pregnancy status, pregnancy outcome, and maternal sociodemographic characteristics. For live births, additional information on the birth, the baby’s sociodemographic characteristics, and any subsequent infant deaths is included. • Inclusion of unique personal identifiers for the mother and (where applicable) baby used within the health service and on statutory birth registration records ensures SLiPBD provides a core intergenerational spine record, allowing linkage between mothers and babies, and to other national datasets. • Subject to governance approvals, researchers can access pseudonymised extracts of SLiPBD (linked to other national datasets as required) through the Scottish NHS safe haven facility, which is supported by Public Health Scotland. Interested researchers should submit an initial enquiry form to Research Data Scotland (https://www.researchdata.scot/accessing-data/).

Background: In various social-emotional situations, it is desirable to use emotional information in a flexible, goal-directed manner. When testing this flexibility in an endogenous spatial cueing task, in which threat-related facial expressions served as informative cues, socially anxious individuals showed a deficit in using the cues for task-relevant attention orienting (Folyi, Rohr, & Wentura, 2023). The present study investigated the scope of the social anxiety-related deficit in endogenous cueing by testing whether it is specifically related to threat-relevant emotions or extends to non-threat-relevant emotional faces. Methods: First, we assessed social anxiety; second, participants with low or high social anxiety were invited to the experiment. In a block-balanced design, we presented threat-relevant (i.e., anger and fear) or non-threat-relevant (i.e., sadness and joy) expression cues to test if reduced cueing in high compared to low social anxiety extends to non-threat-relevant cues. Results: Whereas participants with low social anxiety showed a significant cueing effect, participants with high social anxiety had no significant effect. This pattern extended to all emotional faces. However, the significant group difference was limited to the first of the two task blocks, possibly due to extensive practice and carry-over effects. Limitations: Identifying the exact processes that hinder the flexible usage of emotional information remains an important question for future research. Conclusions: Our results suggest that prepotent responses to social-emotional stimuli in general can hinder their goal-directed use in socially anxious individuals. Such an imbalance may have clinical implications, as it may interfere with overcoming rigid emotional responses to social-emotional stimuli.

ABSTRACT Increasing soybean yield in the MATOPIBA region can be attributed to fertility management, which is crucial to achieving maximum agronomic efficiency. Therefore, the proper management begins with the assessment of plant nutrition. This study aimed to evaluate soybean nutritional status in western Bahia using the Diagnosis and Recommendation Integrated System (DRIS). Database comprised 153 samples from commercial fields located in the research area. To carry out the evaluation using the DRIS method, the database contained information on nutritional levels and leaf productivity of the sampled areas. Database was divided into high-productivity populations (reference population) and low-productivity populations, based on the inflection point value of the cumulative cubic function of yield. The DRIS method allowed for evaluating the potential response to fertilization; however, this method was inefficient in recommending fertilizer doses in both subpopulations. For the sufficiency levels proposed by DRIS, the nutrients N, K, Ca, Mg and S had their maximum and minimum limits reduced, while Cu, Fe and Zn had their ranges of sufficiency expanded, when compared with ranges proposed by other authors. In addition, Zn and Mn were more limiting due to lack for the high-yield subpopulation, and P and Mn for the low-yield subpopulation. The most limiting nutrients due to excess were P and Zn for the high-yield, while K and S were limiting for the low yield subpopulation.

Abstract Understanding the impact of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy on neonatal and maternal outcomes informs clinical decision-making. Here we report a national, population-based, matched cohort study to investigate associations between SARS-CoV-2 infection and, separately, COVID-19 vaccination just before or during pregnancy and the risk of adverse neonatal and maternal outcomes among women in Scotland with a singleton pregnancy ending at ≥20 weeks gestation. Neonatal outcomes are stillbirth, neonatal death, extended perinatal mortality, preterm birth (overall, spontaneous, and provider-initiated), small-for-gestational age, and low Apgar score. Maternal outcomes are admission to critical care or death, venous thromboembolism, hypertensive disorders of pregnancy, and pregnancy-related bleeding. We use conditional logistic regression to derive odds ratios adjusted for socio-demographic and clinical characteristics (aORs). We find that infection is associated with an increased risk of preterm (aOR=1.36, 95% Confidence Interval [CI] = 1.16–1.59) and very preterm birth (aOR = 1.90, 95% CI 1.20–3.02), maternal admission to critical care or death (aOR=1.72, 95% CI = 1.39–2.12), and venous thromboembolism (aOR = 2.53, 95% CI = 1.47–4.35). We find no evidence of increased risk for any of our outcomes following vaccination. These data suggest SARS-CoV-2 infection during pregnancy is associated with adverse neonatal and maternal outcomes, and COVID-19 vaccination remains a safe way for pregnant women to protect themselves and their babies against infection.

Background: Our Burn center has used the Parkland formula (4 ml/kg/TBSA%) adjusted by physiological parameters to guide fluid resuscitation in burn patients. Our main objective was to examine fluid resuscitation in patients with major burn injury and its effect on mortality, need for renal replacement therapy (RRT) and the length of stay (LOS) in the Intensive Care Unit (ICU). Further aims were to determine which factors were associated with fluid resuscitation volumes during the first 24 h, and whether these fluid volumes had an association with the volumes infused during the next 48 h. Methods: This retrospective observational study accrued patients (N = 46) admitted to the Helsinki Burn Center between 2016 and 2018 with burn injuries ≥ 20% TBSA. The national intensive care registry and the electronic patient record system provided data on fluid infusions, urine output, laboratory measurements, presence of inhalation injury, surgical procedures within 72 h from injury, patient demographics, need for renal replacement therapy and mortality. Patients were divided into groups based on infused fluid volumes and univariate regressions were performed to identify factors associated with fluid volumes. Results: 48% of the patients received fluids more than 6 ml/kg/TBSA% during the first 24 h. 35% of the patients received fluid volumes exceeding the Ivy index (250 ml/kg/d) and was associated with higher TBSA%, SOFA and SAPS scores as well as increased mortality and need for RRT. Higher lactate and lower base excess were associated with higher fluid volumes. Urine output had no association with the resuscitation volumes. Larger resuscitation volumes during the first 24 h were associated with larger fluid volumes given also during the next 48 h. Higher cumulative fluid volume in 0–72 h resulted in increased need of RRT and higher ICU mortality. Conclusion: Using the Parkland formula and adjusting the infusion based on physiological parameters leads to over resuscitation in many of the patients. It seems that the more fluids are given during the initial resuscitation phase, the more fluids are also administered during the subsequent phase. Higher cumulative fluid volumes are associated with RRT requirements and higher mortality. We postulate that starting fluid resuscitation with a lower infusion rate could be beneficial, as it may lead to smaller cumulative fluid volumes during the first 72 h, leading to reduced mortality and kidney injury.

ObjectivesSocial prescribing is an approach that enables the referral of patients to non-clinical support and places a focus on holistic care. This study explored views of community pharmacists regarding social prescribing in pharmacies.Study designA qualitative phenomenological approach was used.MethodsA convenience sample of eleven community pharmacists from Northern England were recruited via social media (Twitter, Facebook) and took part in a semi-structured, one-to-one qualitative interviews that asked about their knowledge of social prescribing, the advantages of community pharmacist involvement and any barriers they predicted to its implementation. Interviews were transcribed verbatim and thematically analysed.ResultsThe sample included largely male pharmacists (63.3%) with less than five years' experience (45.5%) and included pharmacists working as employees (63.6%), locums (27.3%) and owners (9%) in both chain (36%) and independent stores (54.5%). The main findings indicate an enthusiasm for but limited understanding of social prescribing. Factors which appeared to influence involvement were training requirements and time available to complete an additional service in busy pharmacies. Opportunities centred on the broader pharmacy team's role to optimise health outcomes.ConclusionsThe findings indicate pharmacists may be an underused resource due to a poor understanding of the full scale and scope of social prescribing beyond health promotion, lifestyle interventions. Further work is needed to explore the transferability of the findings to the broader pharmacy workforce to understand how social prescribing can be positioned within pharmacy practice.