Comprehensive encoding of conformational and compositional protein structural ensembles through the mmCIF data structure.

In the folded state, biomolecules exchange between multiple conformational states crucial for their function. However, most structural models derived from experiments and computational predictions only encode a single state. To represent biomolecules accurately, we must move towards modeling and predicting structural ensembles. Information about structural ensembles exists within experimental data from X-ray crystallography and cryo-electron microscopy. Although new tools are available to detect conformational and compositional heterogeneity within these ensembles, the legacy PDB data structure does not robustly encapsulate this complexity. We propose modifications to the macromolecular crystallographic information file (mmCIF) to improve the representation and interrelation of conformational and compositional heterogeneity. These modifications will enable the capture of macromolecular ensembles in a human and machine-interpretable way, potentially catalyzing breakthroughs for ensemble-function predictions, analogous to the achievements of AlphaFold with single-structure prediction.

FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.

The Ser/Thr protein phosphatase 2 A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report the identification of a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor of B55α/PP2A. This motif is necessary for FAM122A binding to B55α, and computational structure prediction suggests the motif, which is helical, blocks substrate docking to the same site. In this model, FAM122A also spatially constrains substrate access by occluding the catalytic subunit. Consistently, FAM122A functions as a competitive inhibitor as it prevents substrate binding and dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. FAM122A deficiency in human cell lines reduces the proliferation rate, cell cycle progression, and hinders G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells attenuates CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a short helical motif (SHeM)-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase.

Glare prediction and mechanism of adaptation following implantation of hydrophilic and hydrophobic intraocular lenses.

Purpose: Glare is a known side effect of intraocular lens (IOL) implantation, affected principally by IOL material and optics, although it is reported subjectively to decrease in impact with time. However, little objective data have been published on changes over time, how these relate to subjective reports, and whether those who will report greater glare symptoms can be predicted prior to IOL implantation. Methods: A total of 32 patients (aged 72.4 ± 8.0 years) with healthy eyes were implanted bilaterally with hydrophilic 600s (Rayner, Worthing, UK) or hydrophobic Acrysof (Alcon, Texas, USA) acrylic IOLs (n = 16 each, randomly assigned). Each patient reported their dysphotopsia symptoms subjectively using the validated forced choice photographic questionnaire for photic phenomena, and halo size resulting from a bright light in a dark environment was quantified objectively in eight orientations using the Aston Halometer. Assessment was performed binocularly pre-operatively and at 1, 2, 3, and 4 weeks after IOL implantation. Setting: The study was carried out at the National Health Service Ophthalmology Department, Queen Elizabeth Hospital, Birmingham, UK. Results: Visual acuity (average 0.37 ± 0.26 logMAR) did not correlate with subjective glare (r = 0.184, p = 0.494) or objective glare (r = 0.294, p = 0.270) pre-surgery. Objective halo size (F = 112.781, p < 0.001) decreased with cataract removal and IOL implantation and continued to decreased over the month after surgery. Subjective dysphotopsia complaints (p < 0.001) were also greater pre-surgery, but did not change thereafter (p = 0.228). In neither case was there a difference with IOL material (p > 0.05). It was not possible to predict post-surgery dysphotopsia from symptoms or a ratio of symptoms to halo size pre-surgery (p > 0.05). Conclusions: Subjective dysphotopsia and objective halos caused by cataracts are greatly reduced by implantation of IOL after cataract removal causing few perceivable symptoms. However, objective measures are able to quantify a further reduction in light scatter over the first month post-IOL implantation, suggesting that any subjective effects over this period are due to the healing process and not due to neuroadaptation.

Mapping MAVE data for use in human genomics applications.

The large-scale experimental measures of variant functional assays submitted to MaveDB have the potential to provide key information for resolving variants of uncertain significance, but the reporting of results relative to assayed sequence hinders their downstream utility. The Atlas of Variant Effects Alliance mapped multiplexed assays of variant effect data to human reference sequences, creating a robust set of machine-readable homology mappings. This method processed approximately 2.5 million protein and genomic variants in MaveDB, successfully mapping 98.61% of examined variants and disseminating data to resources such as the UCSC Genome Browser and Ensembl Variant Effect Predictor.

Relationships of self-reported opioid and benzodiazepine use with health-related quality of life among adults with spinal cord injury.

BACKGROUND: There is limited understanding of the relationships between prescription opioid and benzodiazepine use and indices of health-related quality of life (HRQOL) among those with spinal cord injuries (SCI). OBJECTIVE: To identify the relationships between self-reported prescription opioid and benzodiazepine use and two indicators of HRQOL, number of days in poor physical health and poor mental health in the past 30 days among adults with SCI. METHODS: A cross-sectional cohort study of 918 adults with chronic (>1 year), traumatic SCI living in the Southeastern United States was conducted. Participants completed a self-report assessment (SRA). RESULTS: In the preliminary model, both opioid and benzodiazepine use were associated with a greater number of days in poor physical health and poor mental health in the past month. After controlling for health conditions (pain intensity, spasticity, anxiety and perceived sleep insufficiency), opioid use was associated with 2.04 (CI = 0.69; 3.39) additional poor physical health days in the past 30 days, and benzodiazepine use was associated with 2.18 (CI = 0.70; 3.64) additional days of poor mental health. Age was associated with greater number of poor physical health days and fewer poor mental health days. Lower income was associated with poor mental health days. Most of the health conditions were significantly related to the number of past month poor physical and mental health days. CONCLUSIONS: Opioid and benzodiazepine use are associated with poor physical and mental HRQOL, even after controlling for health conditions. Treatment strategies should consider potential unanticipated negative consequences of pharmacological interventions.

Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery.

BACKGROUND: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as "genetic constraint". Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. METHODS: We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. RESULTS: We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. CONCLUSIONS: Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation.

Improving Pediatric Hypertension Screening in an Academic Primary Care Setting.

Introduction: Adherence to the American Academy of Pediatrics clinical practice guidelines for screening and managing high blood pressure (BP) is low. This team sought to improve recognition and documentation of relevant diagnoses in patients aged 13-20 years who presented to general pediatric clinics. Methods: The primary outcome measure was the proportion of office visits for patients ages 13-20 with a BP ≥ 120/80 with a visit or problem list diagnosis of hypertension or elevated BP. Secondary measures included (1) the proportion of patients who had their BP measured in the right arm, (2) the proportion of patients who had a mid-arm circumference measurement recorded, and (3) the proportion of patients who had a second BP reading measured at the visit. Interventions addressed key drivers for evidence-based high BP screening: standard BP measurement, electronic health record clinical decision support, and clinical pathway adoption. Data were collected over a twenty-seven-month period and plotted using the Laney p' chart. Results: Provider documentation of elevated BP or hypertension improved from a baseline mean of 24% in April 2020 through January 2022 to 41% in February 2021 through June 2022. All secondary outcome measures also demonstrated significant improvement. Conclusions: This project demonstrates the feasibility of improving adherence to best practices of BP measurement in primary care clinics through education, acquisition of resources, and implementation of electronic health record flags for abnormal values.

Indications and Outcomes of Emergency Keratoplasty in a Major New Zealand Eye Tertiary Referral Center, 2000 to 2021.

PURPOSE: To report the indications and outcomes of emergency keratoplasty over a 21-year period in Greenlane Clinical Centre, the major tertiary eye referral center in Auckland, New Zealand (Aotearoa). METHODS: A retrospective review of medical records of all emergency keratoplasties performed in Greenlane Clinical Centre from January 2000 to September 2021 was conducted. Demographic, preoperative, intraoperative, and 1-year postoperative data were collected. RESULTS: Emergency keratoplasty was performed in 102 eyes of 97 patients (54 men), comprising 5.6% of transplants performed (N = 1830) in this period. The mean age was 53 years (range = 4-95 years, SD = 20). Patients of Maori ethnicity were overrepresented (31%). Corneal perforation was present in 90% of eyes, and microbial keratitis was the most common indication. Bacteria were the most commonly isolated organisms (38%). The mean preoperative and 12-month postoperative best potential corrected distance visual acuity was 1.6 and 1.2 (logMAR), respectively. All cases of therapeutic keratoplasty achieved initial therapeutic success, with no eyes lost or requiring repeat emergency keratoplasty. Complications included nonhealing epithelial defects (19%), cataract (19%), glaucoma (15%), allograft rejection (13%), and corneal melting (5%). Fifteen cases (15%) had documented graft failure at 12 months. Multivariate analysis revealed that younger age was the only statistically significant factor associated with failure at 12 months. CONCLUSIONS: Emergency keratoplasty was the indication for 5.6% of keratoplasties performed. Our results compare favorably with those in the literature, possibly because of early intervention and lower incidence of fungal keratitis. The reported overrepresentation of Maori has important implications for health access and delivery in New Zealand.

Medical image registration via neural fields.

Image registration is an essential step in many medical image analysis tasks. Traditional methods for image registration are primarily optimization-driven, finding the optimal deformations that maximize the similarity between two images. Recent learning-based methods, trained to directly predict transformations between two images, run much faster, but suffer from performance deficiencies due to domain shift. Here we present a new neural network based image registration framework, called NIR (Neural Image Registration), which is based on optimization but utilizes deep neural networks to model deformations between image pairs. NIR represents the transformation between two images with a continuous function implemented via neural fields, receiving a 3D coordinate as input and outputting the corresponding deformation vector. NIR provides two ways of generating deformation field: directly output a displacement vector field for general deformable registration, or output a velocity vector field and integrate the velocity field to derive the deformation field for diffeomorphic image registration. The optimal registration is discovered by updating the parameters of the neural field via stochastic mini-batch gradient descent. We describe several design choices that facilitate model optimization, including coordinate encoding, sinusoidal activation, coordinate sampling, and intensity sampling. NIR is evaluated on two 3D MR brain scan datasets, demonstrating highly competitive performance in terms of both registration accuracy and regularity. Compared to traditional optimization-based methods, our approach achieves better results in shorter computation times. In addition, our methods exhibit performance on a cross-dataset registration task, compared to the pre-trained learning-based methods.

Cyanotoxin accumulation and growth patterns of biocrust communities under variable environmental conditions.

Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a(S) (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient. In contrast to previous work, we showed that hydration had an overall positive effect on growth and toxin accumulation, that nitrogen was not correlated with growth or toxin production, and that phosphorus enrichment negatively affected AEG and BMAA concentrations. Excess illumination positively correlated with AEG, and negatively correlated with all other toxins and growth. Basic pH negatively affected only the accumulation of BMAA. Anatoxin-a(S) (guanitoxin) was not correlated with any tested variables, while microcystins were not detected in any of the samples. Concerning toxin pools, AEG and BMAA were good predictors of the presence of one another. In a newly conceptualized scheme, we integrate aspects of biocrust growth and toxin pool accumulations with arid-relevant desertification drivers.

Discovery of a Series of Orally Bioavailable Androgen Receptor Degraders for the Treatment of Prostate Cancer.

Androgen receptor (AR) signaling plays a key role in the progression of prostate cancer. This study describes the discovery and optimization of a novel series of AR PROTAC degraders that recruit the Cereblon (CRBN) E3 ligase. Having identified a series of AR ligands based on 4-(4-phenyl-1-piperidyl)-2-(trifluoromethyl)benzonitrile, our PROTAC optimization strategy focused on linker connectivity and CRBN ligand SAR to deliver potent degradation of AR in LNCaP cells. This work culminated in compounds 11 and 16 which demonstrated good rodent oral bioavailability. Subsequent SAR around the AR binding region brought in an additional desirable feature, degradation of the important treatment resistance mutation L702H. Compound 22 (AZ'3137) possessed an attractive profile showing degradation of AR and L702H mutant AR with good oral bioavailability across species. The compound also inhibited AR signaling in vitro and tumor growth in vivo in a mouse prostate cancer xenograft model.

Pharmacokinetic evaluation of ibrexafungerp for the treatment of vulvovaginal candidiasis and beyond.

INTRODUCTION: Ibrexafungerp is a new triterpenoid antifungal agent with activity against a variety of fungal species, including Aspergillus spp. and echinocandin-resistant Candida spp. AREAS COVERED: This evaluation will summarize currently available clinical evidence on the use of ibrexafungerp in the treatment/prevention of vulvovaginal candidiasis (VVC) and detail the mechanism of action, pharmacokinetic/pharmacodynamic parameters, and ongoing/latest research involving ibrexafungerp. EXPERT OPINION: The evidence involving the utilization of ibrexafungerp for the treatment of VVC shows that it is superior when compared to placebo and has comparable clinical cure rates when compared with fluconazole. Ibrexafungerp demonstrates reliable coverage against several Candida spp. including echinocandin-resistant strains, Candida auris, and Aspergillus spp. For VVC, a dose of 300 mg (two 150 mg tablets) twice daily is recommended and does not require dose adjustments based on renal or hepatic function. The use of ibrexafungerp outside of VVC is currently under study with several ongoing trials showing promising interim data.

Evaluating surgical expertise with AI-based automated instrument recognition for robotic distal gastrectomy.

Introduction: Complexities of robotic distal gastrectomy (RDG) give reason to assess physician's surgical skill. Varying levels in surgical skill affect patient outcomes. We aim to investigate how a novel artificial intelligence (AI) model can be used to evaluate surgical skill in RDG by recognizing surgical instruments. Methods: Fifty-five consecutive robotic surgical videos of RDG for gastric cancer were analyzed. We used Deeplab, a multi-stage temporal convolutional network, and it trained on 1234 manually annotated images. The model was then tested on 149 annotated images for accuracy. Deep learning metrics such as Intersection over Union (IoU) and accuracy were assessed, and the comparison between experienced and non-experienced surgeons based on usage of instruments during infrapyloric lymph node dissection was performed. Results: We annotated 540 Cadiere forceps, 898 Fenestrated bipolars, 359 Suction tubes, 307 Maryland bipolars, 688 Harmonic scalpels, 400 Staplers, and 59 Large clips. The average IoU and accuracy were 0.82 ± 0.12 and 87.2 ± 11.9% respectively. Moreover, the percentage of each instrument's usage to overall infrapyloric lymphadenectomy duration predicted by AI were compared. The use of Stapler and Large clip were significantly shorter in the experienced group compared to the non-experienced group. Conclusions: This study is the first to report that surgical skill can be successfully and accurately determined by an AI model for RDG. Our AI gives us a way to recognize and automatically generate instance segmentation of the surgical instruments present in this procedure. Use of this technology allows unbiased, more accessible RDG surgical skill.

Inferior vena cava ultrasound to predict hypotension after general anesthesia induction: a systematic review and meta-analysis of observational studies.

PURPOSE: Hypotension after induction of general anesthesia is common and is associated with significant adverse events. Identification of patients at high risk can inform the use of preoperative mitigation strategies. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the inferior vena cava collapsibility index (IVC-CI) and maximal diameter (dIVCmax) in predicting postinduction hypotension and to identify their predictive performance across different threshold ranges. METHODS: We searched MEDLINE, PubMed®, and Embase from inception to March 2023 for prospective observational studies exploring the performance of IVC-CI and dIVCmax in predicting postinduction hypotension in adults presenting for elective surgery under general anesthesia. We excluded studies reporting on IVC parameters predicting postinduction hypotension in the obstetric patient population or exclusively in patients with obesity. Trials screening and data extraction were conducted independently. We performed meta-analyses to identify the performance of IVC parameters in predicting postinduction hypotension, followed by subgroup analyses that sought the IVC-CI range with the highest hierarchical summary receiver-operating characteristic area under the curve (HSROC-AUC). We used a bivariate random effects model to calculate summary estimates. We evaluated study quality using Newcastle-Ottawa scores and certainty of evidence using the GRADE framework. RESULTS: We included 14 studies involving 1,166 patients. Pooled sensitivity and specificity of the IVC-CI to predict postinduction hypotension was 0.68 (95% confidence interval [CI], 0.55 to 0.79; coverage probability, 0.91) and 0.78 (95% CI, 0.69 to 0.85; coverage probability, 0.9), respectively, with an HSROC-AUC of 0.80 (95% CI, 0.68 to 0.85, high quality of evidence). An IVC-CI threshold range of 40-45% had an HSROC-AUC of 0.86 (95% CI, 0.69 to 0.93, high quality of evidence). CONCLUSIONS: Preoperative IVC-CI is a strong predictor of postinduction hypotension. We recommend that future studies use an IVC-CI threshold of 40-45% (low certainty of evidence). Future studies are needed to establish whether ultrasound-guided preoperative optimization improves outcomes in high-risk patients. STUDY REGISTRATION: PROSPERO ( CRD42022316140 ); first submitted 10 March 2022.

RéSUMé: OBJECTIF: L'hypotension après l'induction de l'anesthésie générale est fréquente et est associée à des effets indésirables importants. L'identification des patient•es à haut risque peut éclairer l'utilisation de stratégies préopératoires d'atténuation. Nous avons réalisé une revue systématique et une méta-analyse pour évaluer la précision diagnostique de l'indice de collapsibilité de la veine cave inférieure (IC-VCI) et du diamètre maximal (dVCImax) pour prédire l'hypotension post-induction et identifier leurs performances prédictives dans différentes plages de seuils. MéTHODE: Nous avons fait des recherches dans les bases de données MEDLINE, PubMed® et Embase de leur création jusqu'en mars 2023 pour en extraire les études observationnelles prospectives explorant les performances de l'IC-VCI et du dVCImax pour la prédiction de l'hypotension post-induction chez des adultes se présentant pour une chirurgie non urgente sous anesthésie générale. Nous avons exclu les études rapportant des paramètres de VCI prédisant l'hypotension post-induction dans la population obstétricale ou exclusivement chez des personnes obèses. Le tri des études et l'extraction des données ont été menés indépendamment. Nous avons réalisé des méta-analyses pour identifier la performance des paramètres de VCI dans la prédiction de l'hypotension post-induction, suivies d'analyses de sous-groupes qui ont recherché la plage d'IC-VCI avec le plus haut niveau de hiérarchie de l'aire sous la courbe de la courbe ROC (HSROC-AUC). Nous avons utilisé un modèle bivarié à effets aléatoires pour calculer des estimations sommaires. Nous avons évalué la qualité des études à l'aide des scores de Newcastle-Ottawa et la certitude des données probantes à l'aide de l'outil GRADE. RéSULTATS: Quatorze études portant sur 1166 patient·es ont été incluses. La sensibilité et la spécificité combinées de l'IC-VCI pour prédire l'hypotension post-induction étaient de 0,68 (intervalle de confiance [IC] à 95 %, 0,55 à 0,79; probabilité de couverture, 0,91) et 0,78 (IC 95 %, 0,69 à 0,85; probabilité de couverture, 0,9), respectivement, avec une HSROC-AUC de 0,80 (IC 95 %, 0,68 à 0,85, données probantes de haute qualité). Une plage de seuils d'IC-VCI de 40 à 45 % avait une HSROC-AUC de 0,86 (IC 95 %, 0,69 à 0,93, haute qualité des données probantes). CONCLUSION: L'IC-VCI préopératoire est un bon prédicteur de l'hypotension post-induction. Nous recommandons que les études futures utilisent un seuil d'IC-VCI de 40 à 45 % (faible certitude des données probantes). De futures études sont nécessaires pour déterminer si l'optimisation préopératoire échoguidée améliore les devenirs chez la patientèle à risque élevé. ENREGISTREMENT DE L'éTUDE: PROSPERO ( CRD42022316140 ); première soumission le 10 mars 2022.

Remotely sensed crown nutrient concentrations modulate forest reproduction across the contiguous United States.

Global forests are increasingly lost to climate change, disturbance, and human management. Evaluating forests' capacities to regenerate and colonize new habitats has to start with the seed production of individual trees and how it depends on nutrient access. Studies on the linkage between reproduction and foliar nutrients are limited to a few locations and few species, due to the large investment needed for field measurements on both variables. We synthesized tree fecundity estimates from the Masting Inference and Forecasting (MASTIF) network with foliar nutrient concentrations from hyperspectral remote sensing at the National Ecological Observatory Network (NEON) across the contiguous United States. We evaluated the relationships between seed production and foliar nutrients for 56,544 tree-years from 26 species at individual and community scales. We found a prevalent association between high foliar phosphorous (P) concentration and low individual seed production (ISP) across the continent. Within-species coefficients to nitrogen (N), potassium (K), calcium (Ca), and magnesium (Mg) are related to species differences in nutrient demand, with distinct biogeographic patterns. Community seed production (CSP) decreased four orders of magnitude from the lowest to the highest foliar P. This first continental-scale study sheds light on the relationship between seed production and foliar nutrients, highlighting the potential of using combined Light Detection And Ranging (LiDAR) and hyperspectral remote sensing to evaluate forest regeneration. The fact that both ISP and CSP decline in the presence of high foliar P levels has immediate application in improving forest demographic and regeneration models by providing more realistic nutrient effects at multiple scales.

Occupational Contact Dermatitis in Construction Workers: A Retrospective Analysis of the North American Contact Dermatitis Group Data, 2001-2020.

Background: Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Objective: Determine the prevalence of occupational allergic CD and characterize common occupational allergens in CWs referred for patch testing in the United States and Canada. Methods: Retrospective cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group from 2001 to 2020. Results: Of 47,843 patch-tested patients, 681 (1.4%) were CWs. Compared with non-CWs, CWs were more likely to be male (91.0% vs 30.9%) have occupational skin disease (36.9% vs 11.4%) and have hand involvement (37.2% vs 22.5%) (all P < 0.0001). Of 681 CWs, 60.1% (411) had clinically relevant positive patch test reactions, and nearly 1/3 of CWs (128) had occupationally relevant reactions. Most common occupationally relevant allergens were potassium dichromate 0.25% pet. (30.5%, 39/128), bisphenol A epoxy resin 1% pet. (28.1%, 36/128), carba mix 3% pet. (14.8%, 19/128), cobalt (ii) chloride hexahydrate 1% pet. (14.1%, 18/128), and thiuram mix 1% pet. (14.1%, 18/128). Top sources of occupationally relevant allergens were cement/concrete/mortar (20.4%, 46/225), gloves (15.1%, 34/225), and coatings (paint/lacquer/shellac/varnish/stains) (9.8%, 22/225). Conclusions: Occupational CD in North American CWs is common. In this group, frequently identified etiological sources of occupational allergic CD included metals, epoxy resin, and rubber.

Impact of Self-Monitoring Blood Glucose on Glycaemic Control Among Insulin-Treated Patients With Diabetes Mellitus in Northeastern Tanzania: A Randomised Controlled Trial.

Introduction: Tracking of blood glucose levels by patients and care providers remains an integral component in the management of diabetes mellitus (DM). Evidence, primarily from high-income countries, has illustrated the effectiveness of self-monitoring of blood glucose (SMBG) in controlling DM. However, there is limited data on the feasibility and impact of SMBG among patients in the rural regions of sub-Saharan Africa. This study is aimed at assessing SMBG, its adherence, and associated factors on the effect of glycaemic control among insulin-treated patients with DM in northeastern Tanzania. Materials and Methods: This was a single-blinded, randomised clinical trial conducted from December 2022 to May 2023. The study included patients with DM who had already been on insulin treatment for at least 3 months. A total of 85 participants were recruited into the study and categorised into the intervention and control groups by a simple randomization method using numbered envelopes. The intervention group received glucose metres, test strips, logbooks, and extensive SMBG training. The control group received the usual care at the outpatient clinic. Each participant was followed for a period of 12 weeks, with glycated haemoglobin (HbA1c) and fasting blood glucose (FBG) being checked both at the beginning and at the end of the study follow-up. The primary and secondary outcomes were adherence to the SMBG schedule, barriers associated with the use of SMBG, and the ability to self-manage DM, logbook data recording, and change in HbA1c. The analysis included descriptive statistics, paired t-tests, and logistic regression. Results: Eighty participants were analysed: 39 in the intervention group and 41 in the control group. In the intervention group, 24 (61.5%) of patients displayed favourable adherence to SMBG, as evidenced by tests documented in the logbooks and glucometer readings. Education on SMBG was significantly associated with adherence. Structured SMBG improved glycaemic control with a HbA1c reduction of -1.01 (95% confidence interval (CI) -1.39, -0.63) in the intervention group within 3 months from baseline compared to controls of 0.18 (95% CI -0.07, 0.44) (p < 0.001). Conclusion: Structured SMBG positively impacted glycaemic control among insulin-treated patients with DM in the outpatient clinic. The results suggest that implementing a structured testing programme can lead to significant reductions in HbA1c and FBG levels. Trial Registration: Pan African Clinical Trials Registry identifier: PACTR202402642155729.