Chemical gradients in human enamel crystallites.

Dental enamel is a principal component of teeth1, and has evolved to bear large chewing forces, resist mechanical fatigue and withstand wear over decades2. Functional impairment and loss of dental enamel, caused by developmental defects or tooth decay (caries), affect health and quality of life, with associated costs to society3. Although the past decade has seen progress in our understanding of enamel formation (amelogenesis) and the functional properties of mature enamel, attempts to repair lesions in this material or to synthesize it in vitro have had limited success4-6. This is partly due to the highly hierarchical structure of enamel and additional complexities arising from chemical gradients7-9. Here we show, using atomic-scale quantitative imaging and correlative spectroscopies, that the nanoscale crystallites of hydroxylapatite (Ca5(PO4)3(OH)), which are the fundamental building blocks of enamel, comprise two nanometric layers enriched in magnesium flanking a core rich in sodium, fluoride and carbonate ions; this sandwich core is surrounded by a shell with lower concentration of substitutional defects. A mechanical model based on density functional theory calculations and X-ray diffraction data predicts that residual stresses arise because of the chemical gradients, in agreement with preferential dissolution of the crystallite core in acidic media. Furthermore, stresses may affect the mechanical resilience of enamel. The two additional layers of hierarchy suggest a possible new model for biological control over crystal growth during amelogenesis, and hint at implications for the preservation of biomarkers during tooth development.

Publisher Correction: Chemical gradients in human enamel crystallites.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Uncovering the crystal defects within aragonite CaCO3.

Knowledge of deformation mechanisms in aragonite, one of the three crystalline polymorphs of CaCO3, is essential to understand the overall excellent mechanical performance of nacres. Dislocation slip and deformation twinning were claimed previously as plasticity carriers in aragonite, but crystallographic features of dislocations and twins have been poorly understood. Here, utilizing various transmission electron microscopy techniques, we reveal the atomic structures of twins, partial dislocations, and associated stacking faults. Combining a topological model and density functional theory calculations, we identify complete twin elements, characters of twinning disconnection, and the corresponding twin shear angle (∼8.8°) and rationalize unique partial dislocations as well. Additionally, we reveal an unreported potential energy dissipation mode within aragonite, namely, the formation of nanograins via the pile-up of partial dislocations. Based on the microstructural comparisons of biogenic and abiotic aragonite, we find that the crystallographic features of twins are the same. However, the twin density is much lower in abiotic aragonite due to the vastly different crystallization conditions, which in turn are likely due to the absence of organics, high temperature and pressure differences, the variation in inorganic impurities, or a combination thereof. Our findings enrich the knowledge of intrinsic crystal defects that accommodate plastic deformation in aragonite and provide insights into designing bioengineering materials with better strength and toughness.

Impact of a Public Health Emergency on Behavior, Stress, Anxiety and Glycemic Control in Patients With Pancreas or Islet Transplantation for Type 1 Diabetes.

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (ß-cell Tx; n = 51) to control T1D patients (n = 272). Fear of coronavirus infection was higher in those with ß-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p < 0.001). A previous ß-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with ß-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), p = 0.038). Fewer patients with ß-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with ß-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).

Persistent polyamorphism in the chiton tooth: From a new biomineral to inks for additive manufacturing.

Engineering structures that bridge between elements with disparate mechanical properties are a significant challenge. Organisms reap synergy by creating complex shapes that are intricately graded. For instance, the wear-resistant cusp of the chiton radula tooth works in concert with progressively softer microarchitectural units as the mollusk grazes on and erodes rock. Herein, we focus on the stylus that connects the ultrahard and stiff tooth head to the flexible radula membrane. Using techniques that are especially suited to probe the rich chemistry of iron at high spatial resolution, in particular synchrotron Mössbauer and X-ray absorption spectroscopy, we find that the upper stylus of Cryptochiton stelleri is in fact a mineralized tissue. Remarkably, the inorganic phase is nano disperse santabarbaraite, an amorphous ferric hydroxyphosphate that has not been observed as a biomineral. The presence of two persistent polyamorphic phases, amorphous ferric phosphate and santabarbaraite, in close proximity, is a unique aspect that demonstrates the level of control over phase transformations in C. stelleri dentition. The stylus is a highly graded material in that its mineral content and mechanical properties vary by a factor of 3 to 8 over distances of a few hundred micrometers, seamlessly bridging between the soft radula and the hard tooth head. The use of amorphous phases that are low in iron and high in water content may be key to increasing the specific strength of the stylus. Finally, we show that we can distill these insights into design criteria for inks for additive manufacturing of highly tunable chitosan-based composites.

Multi-Subunit Repair With the Nasolabial Burow's Advancement Flap.

AIM: We will describe the use of nasolabial Burow's advancement flaps (perialar crescentic advancements) to repair multi subunit defects of the nasal sidewall including the adjacent cheek, dorsum, tip, and ala without the need of additional flaps. METHODS: This retrospective single centre study analyzed 6 month postoperative photographs using the Manchester Scar scale. The operative technique is described in detail. RESULTS: Of 355 cases, 336 were available for analysis. The median Manchester Scar scale was 7 for both sidewall defects and multi-subunit defects. There were low rates of infection or necrosis. CONCLUSIONS: With the correct technique, the nasolabial Burow's advancement alone is suitable to repair even large multi-subunit defects involving the nasal sidewall, cheek, dorsum, tip, and ala with high-level aesthetic and functional results.

Modifiable prognostic factors in uterine fibroid development: a systematic review of literature.

BACKGROUND: Many risk factors in uterine fibroid development have been identified, but women and their physicians are less aware of the influence of lifestyle on uterine fibroid development. The objective of this systematic review is to investigate and summarize modifiable prognostic factors associated with uterine fibroid development. METHODS: Pubmed and Embase were searched for relevant articles according to PRISMA guidelines. References from included articles were screened and when relevant also included. Human in vivo studies on modifiable factors in fibroid development were included. Studies on non-modifiable factors and treatment, in vitro studies and animal studies were excluded. 607 articles were screened and 33 articles were included. Two independent investigators collected data from the report. RESULTS: The strongest risk factor for fibroid development was a high BMI, while the strongest protective factors were a high fruit and vegetable intake and high vitamin D intake. CONCLUSION: More high-quality studies are necessary to better understand the impact of the abovementioned factors as well as the role they play in the growth of already existing fibroids.

Uterine fibroid development is multifactorial. Various non-modifiable and modifiable factors have been linked to uterine fibroid development. Modifiable factors are controllable by patients themselves. We performed a systematic review to investigate these modifiable factors. We screened 607 articles from 2 databases (PubMed and Embase) of which 33 were included in the review. We only included clinical studies on humans. A high body mass index (BMI) is found to be a modifiable risk factor for uterine fibroid development. Protective of uterine fibroid development are high fruit and vegetable intake and high vitamin D intake or sun exposure. More research is needed to investigate the applicability of these findings in clinical practice and to investigate the influence on the growth of already existing uterine fibroids.

eHealth to Improve Psychological Functioning and Self-Management of People With Chronic Kidney Disease: A Randomized Controlled Trial.

OBJECTIVE: Psychological distress is common among patients with chronic kidney disease and can interfere with disease self-management. We assessed the effectiveness of the personalized E-GOAL electronic health care pathway with screening and cognitive-behavioral therapy including self-management support, aimed to treat psychological distress and facilitate self-management among people with chronic kidney disease not on dialysis ( N = 121). METHODS: Primary outcome of the open two-arm parallel randomized controlled trial in four Dutch hospitals was psychological distress at posttest directly after the intervention and at 3-month follow-up. Secondary outcomes were physical and mental health-related quality of life, self-efficacy, chronic disease self-management, and personalized outcomes, that is, perceived progress compared with the previous time point on functioning (e.g., mood or social functioning) and self-management (e.g., dietary or medication adherence) outcomes that were prioritized by each individual. RESULTS: Linear mixed-effects analyses showed no significant time-by-group interaction effects for psychological distress, health-related quality of life, self-efficacy, and chronic condition self-management, whereas analyses of covariance showed significantly more perceived progress in the intervention group at posttest on personally prioritized areas of functioning ( b = 0.46, 95% confidence interval = 0.07-0.85) and self-management ( b = 0.55, 95% confidence interval = 0.16-0.95), with Cohen d values of 0.46 and 0.54 (medium effects), respectively. Effects on personalized outcomes were maintained at follow-up. CONCLUSIONS: Compared with regular care only, the electronic health intervention did not reduce psychological distress, whereas personalized outcomes did improve significantly after intervention. Future studies could consider personalized outcomes that reflect individually relevant areas and treatment goals, matching person-tailored treatments. TRIAL REGISTRATION: Registered at the Netherlands Trial Register with study number NTR7555 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7555 ).

Age and gender differences in symptom experience and health-related quality of life in kidney transplant recipients: a cross-sectional study.

BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience. METHODS: Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups. RESULTS: A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7-22), with a burden of 20 (8-37; range 0-244). Per extra symptom, physical and mental HRQOL decreased [-0.41 (-0.50; -0.31) and -0.51 (-0.59; -0.42), respectively, P < .001]. Most occurring symptoms were bruises, tiredness, lack of energy, urge to urinate at night and dry skin. Sexual problems were considered most burdensome. Female KTRs reported more symptoms than men. Amongst others, younger KTRs experienced more (18-50 > 50-65 ≥65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance. CONCLUSION: KRTs' symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL.

A vision of 14 T MR for fundamental and clinical science.

OBJECTIVE: We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set. RESEARCH FIELDS: The 14 Tesla system can be considered a 'mesocope': a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes. CONCLUSIONS: The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR.

Self-Monitoring and Self-Efficacy in Patients with Chronic Kidney Disease During Low-Sodium Diet Self-Management Interventions: Secondary Analysis of the ESMO and SUBLIME Trials.

BACKGROUND: Patients with chronic kidney disease are often requested to engage in self-monitoring sodium (i.e. salt) intake, but it is currently unknown how self-monitoring would empower them. This study aims to assess: (1) how frequent self-monitoring tools are being used during low-sodium diet self-management interventions; (2) whether self-efficacy (i.e. trust in own capability to manage the chronic disease) is associated with self-monitoring frequency; and (3) whether higher self-monitoring frequency is associated with an improvement in self-efficacy over time. METHOD: Data from two multicenter randomized controlled trials (ESMO [n = 151] and SUBLIME [n = 99]) among adult Dutch patients with chronic kidney disease (eGFR ≥ 20-25 mL/min/1.73 m2) were used. In both studies, routine care was compared to a 3-month low-sodium diet self-management intervention with several self-monitoring tools (online food diary, home blood pressure monitor, and urinary sodium measurement device [only ESMO]). Data was collected on usage frequency of self-monitoring tools. Frequencies during the interventions were compared between low and high baseline self-efficacy groups using the Mann-Whitney U test and T-test and associated with changes in self-efficacy during the interventions using Spearman correlation coefficients. RESULTS: Large variations in self-monitoring frequency were observed. In both interventions, usage of self-monitoring tools was highest during the first month with sharp drops thereafter. The online food diary was the most frequently used tool. In the ESMO intervention, low baseline self-efficacy was associated with a higher usage frequency of self-monitoring tools. This finding was not confirmed in the SUBLIME intervention. No significant associations were found between usage frequency of self-monitoring tools and changes in self-efficacy over time. CONCLUSION: Patients with low self-efficacy might benefit most from frequent usage of self-monitoring tools when sufficient guidance and support is provided.

Ultranarrow plasmon resonances from annealed nanoparticle lattices.

This paper reports how the spectral linewidths of plasmon resonances can be narrowed down to a few nanometers by optimizing the morphology, surface roughness, and crystallinity of metal nanoparticles (NPs) in two-dimensional (2D) lattices. We developed thermal annealing procedures to achieve ultranarrow surface lattice resonances (SLRs) with full-width at half-maxima linewidths as narrow as 4 nm from arrays of Au, Ag, Al, and Cu NPs. Besides annealing, we developed a chemical vapor deposition process to use Cu NPs as catalytic substrates for graphene growth. Graphene-encapsulated Cu NPs showed the narrowest SLR linewidths (2 nm) and were stable for months. These ultranarrow SLR nanocavity modes supported even narrower lasing emission spectra and high nonlinearity in the input-output light-light curves.

Governance of a Blockchain-Enabled IoT Ecosystem: A Variable Geometry Approach.

The proliferation of Internet of Things (IoT) applications is rapidly expanding, generating increased interest in the incorporation of blockchain technology within the IoT ecosystem. IoT applications enhance the efficiency of our daily lives, and when blockchain is integrated into the IoT ecosystem (commonly referred to as a blockchain-IoT system), it introduces crucial elements, like security, transparency, trust, and privacy, into IoT applications. Notably, potential domains where blockchain can empower IoT applications include smart logistics, smart health, and smart cities. However, a significant obstacle hindering the widespread adoption of blockchain-IoT systems in mainstream applications is the absence of a dedicated governance framework. In the absence of proper regulations and due to the inherently cryptic nature of blockchain technology, it can be exploited for nefarious purposes, such as ransomware, money laundering, fraud, and more. Furthermore, both blockchain and the IoT are relatively new technologies, and the absence of well-defined governance structures can erode confidence in their use. Consequently, to fully harness the potential of integrating blockchain-IoT systems and ensure responsible utilization, governance plays a pivotal role. The implementation of appropriate regulations and standardization is imperative to leverage the innovative features of blockchain-IoT systems and prevent misuse for malicious activities. This research focuses on elucidating the significance of blockchain within governance mechanisms, explores governance tailored to blockchain, and proposes a robust governance framework for the blockchain-enabled IoT ecosystem. Additionally, the practical application of our governance framework is showcased through a case study in the realm of smart logistics. We anticipate that our proposed governance framework will not only facilitate but also promote the integration of blockchain and the IoT in various application domains, fostering a more secure and trustworthy IoT landscape.

Effects of the Encapsulation Membrane in Operando Scanning Transmission Electron Microscopy.

Nanoscale tailoring of catalytic materials and Li-battery alternatives has elevated the importance of in situ gas-phase electron microscopy. Such advanced techniques are often performed using an environmental cell inserted into a conventional S/TEM setup, as this method facilitates concurrent electrochemical and temperature stimulations in a convenient and cost-effective manner. However, these cells are made by encapsulating gas between two insulating membranes, which introduces additional electron scattering. We have evaluated strengths and limitations of the gas-phase E-cell S/TEM technique, both experimentally and through simulations, across a variety of practical parameters. We reveal the degradation of image quality in an E-cell setup from various components and explore opportunities to improve imaging quality through intelligent choice of experimental parameters. Our results underscore the benefits of using an E-cell STEM technique, due to its versatility and excellent ability to suppress the exotic contributions from the membrane device.

Recurrence and survival after laparoscopy versus laparotomy without lymphadenectomy in early-stage endometrial cancer: Long-term outcomes of a randomised trial.

BACKGROUND: Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively. METHODS: Follow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined. RESULTS: In total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31-1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30-1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23-1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable. CONCLUSION: Disease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer.

Volumetric microsampling for simultaneous remote immunosuppressant and kidney function monitoring in outpatient kidney transplant recipients.

AIMS: Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden as compared to conventional venous sampling at the clinic. We developed a liquid chromatography-tandem mass spectrometry assay to quantify tacrolimus, mycophenolic acid (MPA), creatinine and iohexol in dried blood spot (DBS), and volumetric absorptive microsample (VAMS) samples. METHODS: The assay was successfully validated analytically for all analytes. Clinical validation was conducted by direct comparison of paired DBS, VAMS and venous reference samples from 25 kidney transplant recipients. Patients received iohexol 5-15 minutes before immunosuppressant intake and were sampled 0, 1, 2 and 3 hours thereafter, enabling tacrolimus and MPA area under the concentration-time curve (AUC) and creatinine-based and iohexol-based glomerular filtration rate (GFR) estimation. Method agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and the percentages of values within 15-30% of the reference (P15 -P30 ) with a P20 acceptance threshold of 80%. RESULTS: For DBS samples, method agreement was excellent for tacrolimus trough concentrations (n = 25, P15  = 92.0%) and AUCs (n = 25; P20  = 95.8%) and adequate for creatinine-based GFR trend monitoring (n = 25; P20  = 80%). DBS-based MPA AUC assessment showed suboptimal agreement (n = 16; P20  = 68.8%), but was considered acceptable given its P30 of 100%. The assay performed inadequately for DBS-based iohexol GFR determination (n = 24; P20  = 75%). The VAMS technique generally showed inferior performance, but can be considered for certain situations. CONCLUSION: The assay was successfully validated for tacrolimus, MPA and creatinine quantification in DBS samples, enabling simultaneous remote kidney function trend monitoring and immunosuppressant therapeutic drug monitoring in kidney transplant recipients.

Employment and ability to work after kidney transplantation in the Netherlands: The impact of preemptive versus non-preemptive kidney transplantation.

BACKGROUND: Work can have a major positive impact on health and wellbeing. Employment of kidney transplant recipients (KTR) of working age is much lower than in the general population. The first aim of this study was to examine the impact of a preemptive kidney transplantation (PKT) on employment, in addition to other possible influencing factors. The second aim was to explore differences in work ability, absenteeism and work performance among employed KTR with different types of transplantations. METHODS: A cross-sectional survey study was conducted between 2018 and 2019 in nine Dutch hospitals. PKT as potential predictor of employment was examined. Furthermore, work ability, absenteeism and loss of work performance were compared between employed preemptive recipients with a living donor (L-PKT) and non-preemptive recipients with a living donor (L-nPKT) and with a deceased donor (D-nPKT). RESULTS: Two hundred and twenty four KTR participated; 71% reported having paid work. Paid work was more common among PKT recipients (82% vs. 65% in L-nPKT and 55% in D-nPKT) and recipients who were younger (OR .950, 95%CI .913-.989), had no comorbidities (1 comorbidity: OR .397, 95%CI .167-.942; 2 comorbidities: OR .347, 95%CI .142-.844), had less fatigue (OR .974, 95%CI .962-.987) and had mentally demanding work tasks (only in comparison with physically demanding tasks, OR .342, 95%CI .145-.806). If recipients were employed, D-nPKT recipients worked fewer hours (mean 24.6±11.3 vs. PKT 31.1±9.6, L-nPKT 30.1±9.5) and D-nPKT and L-nPKT recipients received more often supplemental disability benefits (32 and 33.3%, respectively) compared to PKT recipients (9.9%). No differences were found for self-reported ability to work, sick leave (absenteeism) and loss of work performance with the exception of limitations in functioning at work. CONCLUSIONS: Preemptive kidney transplantation recipients with a kidney from a living donor are employed more often, work more hours per week (only in comparison with D-nPKT) and have a partial disability benefit less often than nPKT recipients. More knowledge regarding treatments supporting sustainable participation in the labor force is needed as work has a positive impact on recipients' health and wellbeing and is also beneficial for society as a whole.

Illness Perceptions and Medication Nonadherence to Immunosuppressants After Successful Kidney Transplantation: A Cross-Sectional Study.

Background: Medication nonadherence to immunosuppressants is a well-known risk factor for suboptimal health outcomes in kidney transplant recipients (KTRs). This study examined the relationship between illness perceptions and medication nonadherence in prevalent Dutch KTRs and whether this relationship depended on post-transplant time. Methods: Eligible KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. The illness perceptions and medication nonadherence were measured via validated questionnaires. Associations between illness perceptions and medication nonadherence were investigated using multivariable logistic regression models. Results: For the study, 627 participating KTRs were analyzed. 203 (32.4%) KTRs were considered nonadherent to their immunosuppressants with "taking medication more than 2 h from the prescribed dosing time" as the most prevalent nonadherent behaviour (n = 171; 27.3%). Three illness perceptions were significantly associated with medication nonadherence: illness identity (adjusted odds ratio [ORadj] = 1.07; 95% confidence interval [CI], 1.00-1.14), concern (ORadj = 1.07; 95%CI,1.00-1.14), and illness coherence (ORadj = 1.11; 95%CI,1.01-1.22). The relationships between illness perceptions and medication nonadherence did not differ depending on post-transplant time (p-values ranged from 0.48 to 0.96). Conclusion: Stronger negative illness perceptions are associated with medication nonadherence to immunosuppressants. Targeting negative illness perceptions by means of psychoeducational interventions could optimize medication adherence and consequently improve health outcomes in KTRs.

Artificial intelligence in the detection of skin cancer.

Recent advances in artificial intelligence (AI) in dermatology have demonstrated the potential to improve the accuracy of skin cancer detection. These capabilities may augment current diagnostic processes and improve the approach to the management of skin cancer. To explain this technology, we discuss fundamental terminology, potential benefits, and limitations of AI, and commercial applications relevant to dermatologists. A clear understanding of the technology may help to reduce physician concerns about AI and promote its use in the clinical setting. Ultimately, the development and validation of AI technologies, their approval by regulatory agencies, and widespread adoption by dermatologists and other clinicians may enhance patient care. Technology-augmented detection of skin cancer has the potential to improve quality of life, reduce health care costs by reducing unnecessary procedures, and promote greater access to high-quality skin assessment. Dermatologists play a critical role in the responsible development and deployment of AI capabilities applied to skin cancer.

A review of the evidence for Mohs micrographic surgery. Part 2: basal cell carcinoma.

Mohs micrographic surgery (MMS) is considered the gold-standard treatment for basal cell carcinoma (BCC) particularly for sites with a high-risk of incomplete excision such as the central face, for tumours with an aggressive growth pattern and consequent unpredictable subclinical extension and for recurrent tumours. However, the process is more time-consuming than for standard excision (SE), and the magnitude of benefit is uncertain. This article aims to provide a more complete picture of current evidence, including a review of cosmetic outcomes, tissue-sparing ability and cost-effectiveness of MMS. Although robust evidence is lacking, there is a large volume of observational data supporting a low recurrence rate after MMS. The risk of incomplete excision and higher recurrence rate of standard excision favours the use of MMS at high-risk sites. There is some low-certainty evidence that MMS results in a smaller defect size compared with SE, and that incomplete excision with SE results in larger defects. Larger defects may affect cosmetic outcome but there is no direct evidence that MMS improves cosmetic outcome compared with SE. There is conflicting evidence regarding the cost of MMS compared with SE, as some studies consider MMS less expensive than SE and others consider it more expensive, which may reflect the healthcare setting. A multicentre 10-year randomized controlled trial comparing MMS and SE in the treatment of high-risk BCC would be desirable, but is unlikely to be feasible or ethical. Collection of robust registry data capturing both MMS and SE outcomes would provide additional long-term outcomes.