Respiratory Infection- and Asthma-prone, Low Vaccine Responder Children Demonstrate Distinct Mononuclear Cell DNA Methylation Pathways.

Background: Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunisations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripharal immune cells from respiratory infection allergy/asthma prone (IAP) infants were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fishers Exact p-value = 0.01). Results: An endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPLA), a TLR agonist, partially reversing this signature at a subset of CpGs, suggesting the potential for epigenetic remodelling. Conclusions: This proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for furture investigation.

Intraductal magnetic resonance imaging of cholangiocarcinoma - a practical possibility.

Intraductal T2 mapping based on a catheter receiver is proposed as a method of visualizing the extent of intraductal and periductal cholangiocarcinoma (CCA). Compared to external receivers, internal receivers provide locally enhanced signal-to-noise ratios by virtue of their lower field-of-view for body noise, allowing smaller voxels and higher resolution. However, inherent radial sensitivity variation and segmentation for patient safety both distort image brightness. We discuss simulated T2 weighted images and T2 maps, and in vitro images obtained using a thin film catheter receiver of a freshly resected liver specimen containing a polypoid intraductal tumor from a patient with CCA. T2 mapping provides a simple method of compensating non-uniform signal reception patterns of catheter receivers, allowing the visualization of tumor extent without contrast enhancement and potentially quantitative tissue characterization. Potential advantages and disadvantages of in vivo intraductal imaging are considered.

Bioisosteric analogs of MDMA with improved pharmacological profile.

3,4-Methylenedioxymethamphetamine (MDMA, ' ecstasy' ) is re-emerging in clinical settings as a candidate for the treatment of specific psychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. In vitro methods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubation with isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry. In silico methods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin and dopamine transporters (hSERT and hDAT, respectively) but decreased activity at 5-HT 2A/2B/2C receptors. Regarding their hepatic metabolism, they differed from MDMA, with N -demethylation being the only metabolic route shared, and without forming phase II metabolites. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA analogs might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT and hDAT, but displaying a reduced activity at 5-HT 2A/2B/2C receptors and reduced hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.

MR-based Bony 3D models enable radiation-free preoperative patient-specific analysis and 3D printing for SCFE patients.

Objectives: Slipped capital femoral epiphyses (SCFE) is a common pediatric hip disease with the risk of osteoarthritis and impingement deformities, and 3D models could be useful for patient-specific analysis. Therefore, magnetic resonance imaging (MRI) bone segmentation and feasibility of 3D printing and of 3D ROM simulation using MRI-based 3D models were investigated. Methods: A retrospective study involving 22 symptomatic patients (22 hips) with SCFE was performed. All patients underwent preoperative hip MR with pelvic coronal high-resolution images (T1 images). Slice thickness was 0.8-1.2 mm. Mean age was 12 ± 2 years (59% male patients). All patients underwent surgical treatment. Semi-automatic MRI-based bone segmentation with manual corrections and 3D printing of plastic 3D models was performed. Virtual 3D models were tested for computer-assisted 3D ROM simulation of patients with knee images and were compared to asymptomatic contralateral hips with unilateral SCFE (15 hips, control group). Results: MRI-based bone segmentation was feasible (all patients, 100%, in 4.5 h, mean 272 ± 52 min). Three-dimensional printing of plastic 3D models was feasible (all patients, 100%) and was considered helpful for deformity analysis by the treating surgeons for severe and moderate SCFE. Three-dimensional ROM simulation showed significantly (p < 0.001) decreased flexion (48 ± 40°) and IR in 90° of flexion (-14 ± 21°, IRF-90°) for severe SCFE patients with MRI compared to control group (122 ± 9° and 36 ± 11°). Slip angle improved significantly (p < 0.001) from preoperative 54 ± 15° to postoperative 4 ± 2°. Conclusion: MRI-based 3D models were feasible for SCFE patients. Three-dimensional models could be useful for severe SCFE patients for preoperative 3D printing and deformity analysis and for ROM simulation. This could aid for patient-specific diagnosis, treatment decisions, and preoperative planning. MRI-based 3D models are radiation-free and could be used instead of CT-based 3D models in the future.

Analytical and behavioral characterization of 1-dodecanoyl-LSD (1DD-LSD).

1-Acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52) was first synthesized in the 1950s and found to produce psychedelic effects similar to those of LSD. Evidence suggests that ALD-52 serves as a prodrug in vivo and hydrolysis to LSD is likely responsible for its activity. Extension of the N1-alkylcarbonyl chain gives rise to novel lysergamides, which spurred further investigations into their structure-activity relationships. At the same time, ALD-52 and numerous homologues have emerged as recreational drugs ("research chemicals") that are available from online vendors. In the present study, 1-dodecanoyl-LSD (1DD-LSD), a novel N1-acylated LSD derivative, was subjected to analytical characterization and was also tested in the mouse head-twitch response (HTR) assay to assess whether it produces LSD-like effects in vivo. When tested in C57BL/6J mice, 1DD-LSD induced the HTR with a median effective dose (ED50) of 2.17 mg/kg, which was equivalent to 3.60 µmol/kg. Under similar experimental conditions, LSD has 27-fold higher potency than 1DD-LSD in the HTR assay. Previous work has shown that other homologues such as ALD-52 and 1-propanoyl-LSD also have considerably higher potency than 1DD-LSD in mice, which suggests that hydrolysis of the 1-dodecanoyl moiety may be comparatively less efficient in vivo. Further investigations are warranted to determine whether the increased lipophilicity of 1DD-LSD causes it to be sequestered in fat, thereby reducing its exposure to enzymatic hydrolysis in plasma and tissues. Further clinical studies are also required to assess its activity in humans and to test the prediction that it could potentially serve as a long-acting prodrug for LSD.

2024 Australia-New Zealand Expert Consensus Statement on Cardiac Amyloidosis.

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA.

A survey of practice in the anesthetic management of adolescent idiopathic scoliosis spine fusion by the North American Pediatric Spine Anesthesiologists Collaborative.

BACKGROUND: Adolescent Idiopathic Scoliosis (AIS) affects 2%-4% of the general pediatric population. While surgical correction remains one of the most common orthopedic procedures performed in pediatrics, limited consensus exists on the perioperative anesthetic management. AIMS: To examine the current state of anesthetic management of typical AIS spine fusions at institutions which have a dedicated pediatric orthopedic spine surgeon. METHODS: A web-based survey was sent to all members of the North American Pediatric Spine Anesthesiologists (NAPSA) Collaborative. This group included 34 anesthesiologists at 19 different institutions, each of whom has a Harms Study Group surgeon performing spine fusions at their hospital. RESULTS: Thirty-one of 34 (91.2%) anesthesiologists completed the survey, with a missing response rate from 0% to 16.1% depending on the question. Most anesthesia practices (77.4%; 95% confidence interval [CI], 67.7-93.4) do not have patients come for a preoperative visit prior to the day of surgery. Intravenous induction was the preferred method (74.2%; 95% CI 61.3-89.9), with the majority utilizing two peripheral IVs (93.5%; 95% CI 90.3-100) and an arterial line (100%; 95% CI 88.8-100). Paralytic administration for intubation and/or exposure was divided (51.6% rocuronium/vecuronium, 45.2% no paralytic, and 3.2% succinylcholine) amongst respondents. While tranexamic acid was consistently utilized for reducing blood loss, dosing regimens varied. When faced with neuromonitoring signal issues, 67.7% employ a formal protocol. Most anesthesiologists (93.5%; 95% CI 78.6-99.2) extubate immediately postoperatively with patients admitted to an inpatient floor bed (77.4%; 95% CI 67.7-93.3). CONCLUSION: Most anesthesiologists (87.1%; 95% CI 80.6-99.9) report the use of some form of an anesthesia-based protocol for AIS fusions, but our survey results show there is considerable variation in all aspects of perioperative care. Areas of agreement on management comprise the typical vascular access required, utilization of tranexamic acid, immediate extubation, and disposition to a floor bed. By recognizing the diversity of anesthetic care, we can develop areas of research and improve the perioperative management of AIS.

The loss of the PDIM/PGL virulence lipids causes differential secretion of ESX-1 substrates in Mycobacterium marinum.

The mycobacterial cell envelope is a major virulence determinant in pathogenic mycobacteria. Specific outer lipids play roles in pathogenesis, modulating the immune system and promoting the secretion of virulence factors. ESX-1 (ESAT-6 system-1) is a conserved protein secretion system required for mycobacterial pathogenesis. Previous studies revealed that mycobacterial strains lacking the outer lipid PDIM have impaired ESX-1 function during laboratory growth and infection. The mechanisms underlying changes in ESX-1 function are unknown. We used a proteo-genetic approach to measure phthiocerol dimycocerosate (PDIM)- and phenolic glycolipid (PGL)-dependent protein secretion in M. marinum, a non-tubercular mycobacterial pathogen that causes tuberculosis-like disease in ectothermic animals. Importantly, M. marinum is a well-established model for mycobacterial pathogenesis. Our findings showed that M. marinum strains without PDIM and PGL showed specific, significant reductions in protein secretion compared to the WT and complemented strains. We recently established a hierarchy for the secretion of ESX-1 substrates in four (I-IV) groups. Loss of PDIM differentially impacted secretion of Group III and IV ESX-1 substrates, which are likely the effectors of pathogenesis. Our data suggest that the altered secretion of specific ESX-1 substrates is responsible for the observed ESX-1-related effects in PDIM-deficient strains.IMPORTANCEMycobacterium tuberculosis, the cause of human tuberculosis, killed an estimated 1.3 million people in 2022. Non-tubercular mycobacterial species cause acute and chronic human infections. Understanding how these bacteria cause disease is critical. Lipids in the cell envelope are essential for mycobacteria to interact with the host and promote disease. Strains lacking outer lipids are attenuated for infection, but the reasons are unclear. Our research aims to identify a mechanism for attenuation of mycobacterial strains without the PDIM and PGL outer lipids in M. marinum. These findings will enhance our understanding of the importance of lipids in pathogenesis and how these lipids contribute to other established virulence mechanisms.

A New Family of High Oxidation State Antiperovskite Nitrides: La3MN5 (M = Cr, Mn and Mo).

Three new nitrides La3MN5 (M = Cr, Mn, and Mo) have been synthesized using a high pressure azide route. These are the first examples of ternary Cs3CoCl5-type nitrides, and show that this (MN4)NLa3 antiperovskite structure type may be used to stabilise high oxidation-state transition metals in tetrahedral molecular [MN4]n- nitridometallate anions. Magnetic measurements confirm that Cr and Mo are in the M6+ state, but the M = Mn phase has an anomalously small paramagnetic moment and large cell volume. Neutron powder diffraction data are fitted using an anion-excess La3MnN5.30 model (space group I4/mcm, a = 6.81587(9) Å and c = 11.22664(18) Å at 200 K) in which Mn is close to the +7 state. Excess-anion incorporation into Cs3CoCl5-type materials has not been previously reported, and this or other substitution mechanisms may enable many other high oxidation state transition metal nitrides to be prepared.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

SARS-CoV-2 infection is associated with self-reported post-acute neuropsychological symptoms within six months of follow-up.

BACKGROUND: Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype. METHODS: The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores. RESULTS: The study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, p<0.001), fatigue (20.1% vs 8.0%, p<0.001), impaired cognitive function (15.7% vs 8.6%, p<0.001), and impaired cognitive function abilities (24.3% vs 16.3%, p<0.001). In multivariable models, SARS-CoV-2 positive participants, assessed at an average of 2.7 months after infection, had increased risk of moderate to severe depression (RR: 1.44, 95% CI 1.12-1.84), fatigue (RR: 2.07, 95% CI 1.62-2.65), impaired cognitive function (RR: 1.64, 95% CI 1.27-2.11), and impaired cognitive function abilities (RR: 1.41, 95% CI 1.15-1.71); MPFP/E was not significant. CONCLUSIONS: Participants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.

Evaluation of respondent-driven sampling in seven studies of people who use drugs from rural populations: findings from the Rural Opioid Initiative.

BACKGROUND: Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. METHODS: RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. RESULTS: Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. CONCLUSIONS: RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.

Bioengineered Salivary Gland Microtissues─A Review of 3D Cellular Models and their Applications.

Salivary glands (SGs) play a vital role in maintaining oral health through the production and release of saliva. Injury to SGs can lead to gland hypofunction and a decrease in saliva secretion manifesting as xerostomia. While symptomatic treatments for xerostomia exist, effective permanent solutions are still lacking, emphasizing the need for innovative approaches. Significant progress has been made in the field of three-dimensional (3D) SG bioengineering for applications in gland regeneration. This has been achieved through a major focus on cell culture techniques, including soluble cues and biomaterial components of the 3D niche. Cells derived from both adult and embryonic SGs have highlighted key in vitro characteristics of SG 3D models. While still in its first decade of exploration, SG spheroids and organoids have so far served as crucial tools to study SG pathophysiology. This review, based on a literature search over the past decade, covers the importance of SG cell types in the realm of their isolation, sourcing, and culture conditions that modulate the 3D microenvironment. We discuss different biomaterials employed for SG culture and the current advances made in bioengineering SG models using them. The success of these 3D cellular models are further evaluated in the context of their applications in organ transplantation and in vitro disease modeling.

Four Years Since COVID-19 Day Zero: A Time to Evaluate Past and Future Pandemic Control Policies and Practices in Sub-Saharan Africa?

Four years after the first case of COVID-19, the world is still determining how best to prevent and control the long-term effects of SARS-CoV-2 infection. Non-pharmaceutical interventions (NPIs) were employed at the start of the pandemic as the only available options, prior to effective vaccines and antiviral agents. The World Health Organization recommended dual vaccination for 70% worldwide as the threshold for a return to "normal" community life. Immunization rates needed to increase in all global regions, irrespective of socioeconomic status, necessitating more equitable access. During the pandemic, wealthier countries hoarded vaccine supplies even when their citizens were immunized. This highlights the already enormous difficulties in healthcare provision faced by low-income sub-Saharan African countries, which remain at risk as industrialized nations have progressed to a post-pandemic era. Thus, in addition to redoubling vaccination efforts public health policymakers should consider ongoing and future use of NPIs. In this narrative account, we advocate that various NPI practices should not be shelved; rather, more research is needed to evaluate their impact in parallel with booster vaccination. This especially applies to so-called "long COVID". Lessons learned from implementing best practices in resource-limited settings should be incorporated into preparedness guidelines for future infectious disease outbreaks.

Geographical discrimination of Paw San rice cultivated in different regions of Myanmar using near-infrared spectroscopy, headspace-gas chromatography-ion mobility spectrometry and chemometrics.

Paw San rice, also known as "Myanmar pearl rice", is considered the highest quality rice in Myanmar. There are considerable differences in terms of the premium commercial value of Paw San rice, which is an incentive for fraud, e.g. adulteration with cheaper rice varieties or mislabelling its geographical origin. Shwe Bo District is one of the most popular rice growing areas in the Sagaing region of Myanmar which produces the most valued and highly priced Paw San rice (Shwe Bo Paw San). The verification of the geographical origin of Paw San rice is not readily undertaken in the rice supply chain because the existing analytical approaches are time-consuming and expensive. Therefore, there is a need for rapid, robust and cost-effective analytical techniques for monitoring the authenticity and geographical origin of Paw San rice. In this 4-year study, two rapid screening techniques, Fourier-transform near-infrared (FT-NIR) spectroscopy and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), coupled with chemometric modelling, were applied and compared for the regional differentiation of Paw San rice. In addition, low-level fusion of the FT-NIR and HS-GC-IMS data was performed and its effect on the discriminative power of the chemometric models was assessed. Extensive model validation, including the validation using independent samples from a different production year, was performed. Furthermore, the effect of the sample preparation technique (grinding versus no sample preparation) on the performance of the discriminative model, obtained with FT-NIR spectral data, was assessed. The study discusses the suitability of FT-NIR spectroscopy, HS-GC-IMS and the combination of both approaches for rapid determination of the geographical origin of Paw San rice. The results demonstrated the excellent potential of the FT-NIR spectroscopy as well as HS-GC-IMS for the differentiation of Paw San rice cultivated in two distinct geographical regions. The OPLS-DA model, built using FT-NIR data of rice from 3 production years, achieved 96.67% total correct classification rate of an independent dataset from the 4th production year. The DD-SIMCA model, built using FT-NIR data of ground rice, also demonstrated the highest performance: 94% sensitivity and 97% specificity. This study has demonstrated that FT-NIR spectroscopy can be used as an accessible, rapid and cost-effective screening tool to discriminate between Paw San rice cultivated in the Shwe Bo and Ayeyarwady regions of Myanmar.

N-terminal proteomics of Mycobacterium marinum using bottom-up label-free quantitative analysis in data-dependent acquisition mode on a timsTOF Pro mass spectrometer.

N-terminal acetylation in Mycobacterium tuberculosis is correlated with pathogenic activity. We used genomics and bottom-up proteomics to identify protein Emp1 as the sole acetyltransferase responsible for acetylation of EsxA, a known virulence factor. Using custom data analysis, we screened the proteome to identify 22 additional putative substrates of Emp1.

Circulating total 25(OH)D and calculated free 25(OH)D in professional academy footballers at a northerly latitude in the UK.

There is limited data on the vitamin D status of UK-based professional academy footballers. Therefore, the objective of this study was to report total 25(OH)D, free 25(OH)D and free 1, 25(OH)2D at the end of the winter (March) and summer periods (October) in a cohort (n = 27) of professional academy footballers in northern England. Blood samples were collected to measure total 25(OH)D, parathyroid hormone, vitamin D binding protein, albumin and calcium. Free 25(OH)D and 1, 25(OH)2D were calculated. Dietary vitamin D intake and retrospective summer sunlight exposure were also collected. At the end of winter, 2/27 (7.4%) players were vitamin D deficient (25(OH)D < 30 nmol/l) and 11/27 (40.7%) were insufficient (25(OH)D > 30 nmol/l < 50 nmol/l). By the end of summer, none were deficient but 3/14 (21.4%) were still insufficient. Median total 25(OH)D (82.2 nmol/l [IQR: 50.3-90.2] vs. 54.2 nmol/l [IQR: 36.8-71.9]; P = .02), free 25(OH)D (25.8 pmol/l [IQR: 15.1-33.1] vs. 13.2 pmol/l [IQR: 9.0-14.9]; P = .005) and free 1, 25(OH)2D (389 fmol/l [IQR: 209-594] vs. 212 fmol/l [IQR: 108-278]; P = .034) were significantly higher at the end of summer than the end of winter. At the end of winter, free 25(OH)D was lower (P = .003) in those vitamin D insufficient (8.8 pmol/l [IQR: 5.5-11.8]) vs. sufficient (13.7 pmol/l [IQR: 12.0-17.0]). There was a high prevalence of vitamin D insufficiency at the end of the winter. Free 25(OH)D was also lower at the winter timepoint and in players that were insufficient vs. sufficient.

COVID-19 post-pandemic reflections from sub-Saharan Africa: what we know now that we wish we knew then.

The commonly heard aphorism about history repeating itself suggests an endless cycle of recurring events. However, George Santayana offered a similar sentiment when he said, "Those who do not learn from history are doomed to repeat it". This emphasises that the responsibility for the recurrence of events lies not with history itself, but with humanity. It underscores that if we desire change, it is our responsibility to initiate it, rather than attributing it to external forces such as fate, luck, or time. With this thought in mind, here we offer a narrative view from sub-Saharan Africa, focusing primarily on our own experiences in Nigeria and Uganda, on what harsh lessons can be learnt from the COVID-19 pandemic regarding emergency preparedness to respond effectively to the next major infectious disease outbreak. Four strategies are suggested, the implementation of which may contribute substantially to safeguarding against an experience similar to the catastrophic public health, social and economic costs borne by African nations during COVID-19 and in its immediate aftermath.

Towards Precision Ophthalmology: The Role of 3D Printing and Bioprinting in Oculoplastic Surgery, Retinal, Corneal, and Glaucoma Treatment.

In the forefront of ophthalmic innovation, biomimetic 3D printing and bioprinting technologies are redefining patient-specific therapeutic strategies. This critical review systematically evaluates their application spectrum, spanning oculoplastic reconstruction, retinal tissue engineering, corneal transplantation, and targeted glaucoma treatments. It highlights the intricacies of these technologies, including the fundamental principles, advanced materials, and bioinks that facilitate the replication of ocular tissue architecture. The synthesis of primary studies from 2014 to 2023 provides a rigorous analysis of their evolution and current clinical implications. This review is unique in its holistic approach, juxtaposing the scientific underpinnings with clinical realities, thereby delineating the advantages over conventional modalities, and identifying translational barriers. It elucidates persistent knowledge deficits and outlines future research directions. It ultimately accentuates the imperative for multidisciplinary collaboration to enhance the clinical integration of these biotechnologies, culminating in a paradigm shift towards individualized ophthalmic care.