Indicators of Cobalamin Status During Pregnancy, Pregnancy Outcome and Long-Term Effects on Offspring Health.

BACKGROUND: Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources. RESULTS: However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring. Low cobalamin status in pregnancy has been associated with similar outcomes as those reported in the Indian studies although the evidence is scant and conflicting. CONCLUSIONS: Consideration should be given to maternal cobalamin status in the context of prevention of adverse pregnancy outcomes as well as cobalamin insufficiency both in the mother and the offspring during lactation. Further attention is now justified with the increasing tendency toward plant-based diets. Reference intervals for cobalamin status during each trimester of pregnancy are needed and further investigation of the long-term conse-quences of low cobalamin status during pregnancy for health and development in the offspring is warranted.

Plain language titleInadequate cobalamin status during critical periods of growth and development can have negative consequences on maternal and childhood health.

The burden of treatment of propranolol for infantile hemangiomas: A mixed methods study.

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one-on-one semi-structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age-based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring.

Perceived Benefit of Active Over Passive Strategies for Pathophysiology Learning and Retention Among Physician Assistant Students.

PURPOSE: This study examines physician assistant (PA) student perceived benefit of active vs. passive studying strategies for learning and retaining physiology and pathophysiology content knowledge. Identifying beneficial studying strategies is crucial to building a strong content knowledge foundation to support PA students' clinical rotations. METHODS: Three cohorts of PA students (n = 64) were anonymously surveyed regarding perceived benefit of studying strategies for learning and retention of physiology and pathophysiology content knowledge. Students also ranked strategies from most to least beneficial. RESULTS: Strategies were identified during survey development pilot study as either active or passive. Physician assistant students rated the active strategies perceived benefit mean as significantly greater than the passive strategies mean for both the learning (t(61) = 9.24, P < .001, d = 1.38) and retention (t(58) = 8.19, P < .001, d = 1.21) conditions. CONCLUSION: This study provides evidence that PA students perceive active studying strategies to be more beneficial than passive strategies for acquiring physiology and pathophysiology content and retaining it into the clinical year.

Ultra-processed food consumption and semen quality parameters in the Led-Fertyl study.

STUDY QUESTION: Is ultra-processed food (UPF) consumption associated with semen quality parameters? SUMMARY ANSWER: Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age. WHAT IS KNOWN ALREADY: The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited. STUDY DESIGN SIZE DURATION: A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023. PARTICIPANTS/MATERIALS SETTING METHODS: UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm concentration (ß: -1.42 × 106 spz./ml; 95% CI: -2.72 to -0.12) and motility (ß: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (ß: -1.50 × 106 spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms. LIMITATIONS REASONS FOR CAUTION: Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out. WIDER IMPLICATIONS OF THE FINDINGS: This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-term designs, these novel findings could provide valuable insights for updating or even designing preventive and interventional programs to address infertility among men of reproductive age. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' [PI21/01447], and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S. gratefully acknowledges the financial support of ICREA under the ICREA Academia program. C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The Differential Translation Capabilities of the Human DHFR2 Gene Indicates a Developmental and Tissue-Specific Endogenous Protein of Low Abundance.

A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level.

Is telomere length a biomarker of sperm quality? A systematic review and meta-analysis of observational studies.

BACKGROUND: Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility. OBJECTIVES: To conduct a systematic review and meta-analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted with studies from Medline-PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross-sectional and case-control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes. RESULTS: Twenty-three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta-analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference [95% confidence interval]: -1.43 [-1.66 to -1.21], p-value <0.001 and -1.67 [-2.02 to -1.31], p-value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (-0.97 [-1.32, -0.61], p-value <0.001). CONCLUSION: The current systematic review and meta-analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis.

Comparative diet-gut microbiome analysis in Crohn's disease and Hidradenitis suppurativa.

Introduction: The chronic inflammatory skin disease Hidradenitis suppurativa (HS) is strongly associated with Crohn's Disease (CD). HS and CD share clinical similarities and similar inflammatory pathways are upregulated in both conditions. Increased prevalence of inflammatory disease in industrialised nations has been linked to the Western diet. However, gut microbiota composition and diet interaction have not been compared in HS and CD. Methods: Here we compared the fecal microbiota (16S rRNA gene amplicon sequencing) and habitual diet of previously reported subjects with HS (n = 55), patients with CD (n = 102) and controls (n = 95). Results and discussion: Patients with HS consumed a Western diet similar to patients with CD. Meanwhile, habitual diet in HS and CD was significantly different to controls. Previously, we detected differences in microbiota composition among patients with HS from that of controls. We now show that 40% of patients with HS had a microbiota configuration similar to that of CD, characterised by the enrichment of pathogenic genera (Enterococcus, Veillonella and Escherichia_Shigella) and the depletion of putatively beneficial genera (Faecalibacterium). The remaining 60% of patients with HS harboured a normal microbiota similar to that of controls. Antibiotics, which are commonly used to treat HS, were identified as a co-varying with differences in microbiota composition. We examined the levels of several inflammatory markers highlighting that growth-arrest specific 6 (Gas6), which has anti-inflammatory potential, were significantly lower in the 40% of patients with HS who had a CD microbiota configuration. Levels of the pro-inflammatory cytokine IL-12, which is a modulator of intestinal inflammation in CD, were negatively correlated with the abundance of health-associated genera in patients with HS. In conclusion, the fecal microbiota may help identify patients with HS who are at greater risk for development of CD.

Red-faced lies: a qualitative analysis of online misinformation and conspiracy theories in rosacea.

Rosacea is a common chronic inflammatory skin disease with a complex aetiology and major psychological impact, rendering patients susceptible to misinformation. We aimed to assess the content of rosacea-related misinformation online. A formal review of PubMed was performed, using the terms 'rosacea' AND 'misinformation' OR 'disinformation' OR 'conspiracy theory', along with informal Google searches using combinations of these terms, and further targeted searches on Twitter, Facebook, Instagram and TikTok. Key areas of misinformation identified in the search included mislabelling of rosacea as adult acne; falsehoods about rosacea only occurring in older adults or in individuals with lightly pigmented skin; incorrect causes of rosacea such as makeup or diet; and misleading 'cures', some of which may lead to exacerbation of the underlying rosacea. Dermatologists must be aware of the large amount of rosacea misinformation trending online and be prepared to counteract them with evidence to optimize patient care.

Exploring progressive mental model representation of core physiology concepts in physician assistant students through word frequency and association analyses.

A well-developed mental model is crucial for effectively studying physiology core concepts. However, mental models can be difficult for students to represent and for instructors to evaluate and correct. Systems modeling as a visualization cognitive tool may facilitate mental model development. On the other hand, evidence of mental model development may also be represented verbally, in writing, and therefore, be evaluated. In this study, analysis of writing prompt completions illustrated progress in physician assistant student mental model formation of physiology core concepts, such as homeostasis and cell-cell communication, over time. Two cohorts of physician assistant students were invited to voluntarily submit completions of writing prompts five times over 16 months. Sessions included submissions pre- and post-small group systems modeling participation. Word frequency and word association cluster dendrogram analyses were conducted on submissions using the tm text mining package in R to provide insight into progressive changes in core concepts of word use and associations. Students demonstrated expanded core concepts systems thinking over time. This was apparent through the increased use of systems process terms, such as homeostasis, in submissions immediately following systems modeling activities. Students also increasingly included terms and associations emphasizing cell-cell communication and systems integration. The inclusion of these concepts within student mental models was demonstrably enhanced by participation in systems modeling activities.NEW & NOTEWORTHY This study applies text mining, an artificial intelligence form of natural language processing, to evaluate a series of physiology student-written prompt completions. Text mining of student writing in physiology has not yet been reported in the literature. Through the application of this technique, longitudinal trends in student development of mental models of core concepts were identified and visualized through word frequency distributions and cluster dendrograms.

Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21.

Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.

Crying Wolf: A Qualitative Review of Misinformation and Conspiracy Theories in Lupus Erythematosus.

BACKGROUND: Lupus comprises a complex group of inflammatory disorders including cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). The issue of health misinformation is increasingly problematic, although the content of misinformation related to lupus available online has not been deeply explored. This study aimed to qualitatively assess the type of misinformation related to lupus available online. METHODS: A literature search on PubMed was conducted, using search terms "cutaneous lupus" OR "discoid lupus" OR "lupus" AND "misinformation" OR "conspiracy" OR "disinformation." Further searches were also performed on Google, YouTube, Twitter, Facebook, Instagram, and TikTok. RESULTS: Published literature describing lupus-related misinformation was minimal, with only three manuscripts identified. Conversely, a variety of points of misinformation were identified online and on social media. Key themes identified in online content included suggestion of incorrect causes such as infection or aspartame consumption, false risk assessments such as lupus never developing in males, false claims about conventional treatments, and promotion of alternative treatments or "cures" without evidence. CONCLUSION: Dermatologists, rheumatologists, and all clinicians treating patients with lupus play an essential role in dispelling the pervasive misinformation surrounding the disease and its treatments, encouraging patients to seek reliable sources of information, and advocating for evidence-based guidance.

Pooling the evidence: A review of swimming and atopic dermatitis.

Swimming is an excellent form of aerobic exercise and is an essential life skill. Many children with atopic dermatitis (AD) are advised not to swim because of concerns about negative impacts on their skin disease, and some children with AD do not swim because they are self-conscious about the appearance of their skin. We aimed to perform a narrative review of the available literature on swimming and AD and scientifically analyze the potential impact of all components of swimming in AD-water, skin barrier, swimming gear, and exercise. Studies examined the impact of swimming on the skin barrier and the relative contraindications to swimming. Constituents of water which may affect AD include hardness, pH, temperature, antiseptics, and other chemicals. Potential interventions to reduce damage included emollient application, special swim gear, and showering post-submersion. The benefits of swimming as a form of exercise in AD included reduced sweating, cardiorespiratory fitness, and maintenance of healthy weight. Drawbacks of swimming as a form of exercise in AD included the limited benefit on bone mineral density. Future research should examine the impact of swimming on flares of AD using noninvasive biomarkers as well as clinical severity assessment and assess the role for different types of emollient as an intervention for optimal eczema control. This review highlights gaps in the scientific literature on swimming and AD and provides evidence-based guidance on interventions to minimize deleterious effects on skincare and maximize opportunities for children with AD to swim.

Think zinc: Transient nutritional deficiency related to novel maternal SLC30A2 mutation potentially precipitated by antenatal proton pump inhibitor exposure.

A second-born breastfed infant presented with zinc deficiency. His mother had a novel heterozygous mutation in SLC30A2. A previous baby did not have zinc deficiency but the mother had taken a proton pump inhibitor (PPI) during the second pregnancy. Antenatal PPI exposure may plausibly contribute to transient infantile zinc deficiency.

Oral health in patients with severe inflammatory dermatologic and rheumatologic disease.

Background: Poor oral health (OH) is a risk factor for systemic disease and lower quality of life (QoL). Patients with inflammatory dermatologic/rheumatologic diseases report more oral discomfort, dry mouth, and periodontal disease than controls. Medications used to treat these conditions can also adversely affect OH. Objectives: The aim was to assess the OH of patients with chronic inflammatory dermatologic/rheumatologic diseases treated with systemic/biologic therapy, compared to controls. Methods: Patients with chronic inflammatory dermatologic/rheumatologic diseases treated with systemic/biologic therapy were recruited from outpatient clinics across two university hospitals. All patients had a standardized World Health Organisation OH assessment performed consisting of an OH exam and questionnaire. Age- and sex-matched controls without chronic inflammatory disease were recruited from a pigmented lesion clinic. Charts of patients with chronic inflammatory dermatologic/rheumatologic diseases were reviewed to assess OH documentation. Results: One hundred patients were examined (50 cases and 50 controls). Patients with inflammatory dermatologic/rheumatologic diseases (cases) had poorer periodontal status (mean loss of attachment 6.9 mm vs. 1.9 mm controls, p = 0.01), more missing teeth (mean 7.7 vs. 4.4 controls, p = 0.029), more dry mouth (82% vs. 20% controls, p = 0.001), and less frequent tooth brushing (60% vs. 80% controls, p = 0.037). Of 250 patient charts which were reviewed, 98.4% (n = 246) had no documentation of OH. Conclusion: Patients with severe inflammatory dermatologic/rheumatologic conditions have poorer OH and OH-related QoL. Clinicians should appreciate the risk of poor OH in this cohort and have a low threshold for involving OH professionals in care pathways for severe inflammatory disease.

#corticophobia: a review on online misinformation related to topical steroids.

Misinformation in healthcare is at crisis level worldwide, with the internet as primary source of prevarication. Topical corticosteroids (TCS) are a safe and effective treatment used in multiple dermatological conditions. Nonadherence to prescribed TCS can be due to phobia secondary to misinformation. TCS phobia is a complex multifaceted phenomenon that exploits patients with skin disease, creates cognitive dissonance and can obstruct successful treatment. This study aimed to examine the content of TCS-related misinformation available online. A formal review of PubMed was performed using the terms 'topical corticosteroids' AND 'misinformation' OR 'disinformation' OR 'conspiracy theory, along with an informal Google search using combinations of these terms and further targeted searches on social media applications including Facebook™, Twitter™, Instagram™ and TikTok™. 'Topical steroid withdrawal', 'red skin syndrome' or 'TCS addiction' is a particularly prevalent myth currently being propagated on social media, with most content suggesting that eczema is due to a 'leaky gut' or food intolerance and not to skin inflammation. The risks of potential adverse effects such as skin thinning and stunted growth/development are often exaggerated. Multiple websites promoting misinformation were frequently endorsed by companies advertising consultations or testing to identify 'underlying causes', or 'natural' products as alternative treatments, including 'herbal' remedies, which can contain significant quantities of corticosteroids or other potent ingredients. The dermatology community should be vigilant of the type of TCS-related misinformation online and be active in attempts to counteract it with evidence-based advice.