Would plain packaging and health warning labels reduce smoking in the presence of informal markets? A choice experiment in Colombia.

BACKGROUND: Despite progress made by many countries on the adoption of plain tobacco packaging laws over the last years, low- and middle-income countries, with a large supply of loose cigarettes via informal vendors, remain far behind. AIM: To study the potential effectiveness of plain tobacco packaging and dissuasive cigarette sticks, via willingness-to-pay estimates, when illicit cigarette options are available. METHODS: We conducted a discrete choice experiment (DCE) in which respondents chose licit and illicit products with three attributes: packaging (standard vs. plain packaging), stick design (branded stick vs. stick with warning), and price level. The sample, collected on 12/2021, consisted of 1761 respondents from an internet panel involving smokers and nonsmokers. Conditional logit and latent class models were used to estimate the willingness-to-pay (WTP) to avoid restrictive packaging elements. RESULTS: Nonsmokers are willing to pay USD $5.63 for a pack of cigarettes to avoid plain packaging, which is higher than the actual commercial price of illicit cigarettes (USD $2.40). The WTP increases to USD $12.14 in the presence of illicit alternatives. Smokers are also willing to pay to avoid illicit options, which they also deem riskier, and the presence of such options increases the WTP to avoid plain packaging. However, nonsmokers do not perceive the illicit option as riskier. The dissuasive stick (stick with warning) does not affect perceptions of risk and plays a small role in terms of choice for both smokers and nonsmokers. CONCLUSIONS: Even in the presence of illicit tobacco alternatives, plain packaging seems to be as effective in reducing the attractiveness of tobacco products in Colombia as in other countries that have already adopted it. Given conflicting results on the case for dissuasive sticks, there is a need for more research.

Thoracodorsal to long thoracic nerve transfer in a patient with traumatic injury: A case report.

Background: Traumatic injury to the long thoracic nerve causes paralysis of the serratus muscle, clinically expressed as winged scapula and functional impairment of the shoulder girdle. Treatment varies according to the severity of the injury, with a focus on early intervention for best results; however, the therapeutic approach remains a challenge at present. Case Description: We present the case of a 32-year-old male patient, athlete, right-handed, presented with bilateral paresis predominantly in the right arm, associated with paresthesia and changes in the coloring of the upper limbs. After being diagnosed with Thoracic Outlet Syndrome and undergoing surgery, vascular symptoms persisted with a significant loss of strength in the right shoulder. Winged scapula was observed and structural lesions were excluded on magnetic resonance imaging. Electromyographic studies confirmed the presumption of traumatic nerve involvement of the long thoracic nerve. Notwithstanding 6 months of physical therapy, there was no improvement, so a nerve transfer from the thoracodorsal nerve to the right long thoracic nerve was chosen. At 12 months, complete resolution of the winged scapula and functional recovery were observed. The patient also experienced a decrease in preoperative pain from 5/10 to 2/10 on the visual analog scale. Conclusion: Nerve transfer from the thoracodorsal nerve to the long thoracic nerve is a safe and effective technique to treat winged scapula due to long thoracic nerve injury.

Extending the age criteria of lung transplant donors to 70+ years old does not significantly affect recipient survival.

OBJECTIVES: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients. METHODS: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction. RESULTS: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients. CONCLUSIONS: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes.

Conduct and reporting of multivariate network meta-analyses: a scoping review.

OBJECTIVES: Combining multivariate and network meta-analysis methods simultaneously in a multivariate network meta-analysis (MVNMA) provides the methodological framework to analyze the largest amount of evidence relevant to decision-makers (i.e., from indirect evidence and correlated outcomes). The objectives of this scoping review were to summarize the characteristics of MVNMAs published in the health sciences literature and map the methodological guidance available for MVNMA. STUDY DESIGN AND SETTING: We searched MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature from inception to 28 August 2023, along with citations of included studies, for quantitative evidence syntheses that applied MVNMA and articles addressing MVNMA methods. Pairs of reviewers independently screened potentially eligible studies. Collected data included bibliographic, methodological, and analytical characteristics of included studies. We reported results as total numbers, frequencies, and percentages for categorical variables and medians and interquartile ranges for continuous variables that were not normally distributed. RESULTS: After screening 1,075 titles and abstracts, and 112 full texts, we included 38 unique studies, of which, 10 were quantitative evidence syntheses that applied MVNMA and 28 were articles addressing MVNMA methods. Among the 10 MVNMAs, the first was published in 2013, four used studies identified from already published systematic reviews, and eight addressed pharmacological interventions, which were the most common interventions. They evaluated interventions for metastatic melanoma, colorectal cancer, prostate cancer, oral hygiene, disruptive behavior disorders, rheumatoid arthritis, narcolepsy, type 2 diabetes, and overactive bladder syndrome. Five MVNMAs analyzed two outcomes simultaneously, and four MVNMAs analyzed three outcomes simultaneously. Among the articles addressing MVNMA methods, the first was published in 2007 and the majority provided methodological frameworks for conducting MVNMAs (26/28, 93%). One study proposed criteria to standardize reporting of MVNMAs and two proposed items relevant to the quality assessment of MVNMAs. Study authors used data from 18 different illnesses to provide illustrative examples within their methodological guidance. CONCLUSIONS: The application of MVNMA in the health sciences literature is uncommon. Many methodological frameworks are published; however, standardization and specific criteria to guide reporting and quality assessment are lacking. This overview of the current landscape may help inform future conduct of MVNMAs and research on MVNMA methods.

Nonlinear T-Wave Time Warping-Based Sensing Model for Non-Invasive Personalised Blood Potassium Monitoring in Hemodialysis Patients: A Pilot Study.

BACKGROUND: End-stage renal disease patients undergoing hemodialysis (ESRD-HD) therapy are highly susceptible to malignant ventricular arrhythmias caused by undetected potassium concentration ([K+]) variations (Δ[K+]) out of normal ranges. Therefore, a reliable method for continuous, noninvasive monitoring of [K+] is crucial. The morphology of the T-wave in the electrocardiogram (ECG) reflects Δ[K+] and two time-warping-based T-wave morphological parameters, dw and its heart-rate corrected version dw,c, have been shown to reliably track Δ[K+] from the ECG. The aim of this study is to derive polynomial models relating dw and dw,c with Δ[K+], and to test their ability to reliably sense and quantify Δ[K+] values. METHODS: 48-hour Holter ECGs and [K+] values from six blood samples were collected from 29 ESRD-HD patients. For every patient, dw and dw,c were computed, and linear, quadratic, and cubic fitting models were derived from them. Then, Spearman's (ρ) and Pearson's (r) correlation coefficients, and the estimation error (ed) between Δ[K+] and the corresponding model-estimated values (Δ^[K+]) were calculated. RESULTS AND DISCUSSIONS: Nonlinear models were the most suitable for Δ[K+] estimation, rendering higher Pearson's correlation (median 0.77 ≤r≤ 0.92) and smaller estimation error (median 0.20 ≤ed≤ 0.43) than the linear model (median 0.76 ≤r≤ 0.86 and 0.30 ≤ed≤ 0.40), even if similar Spearman's ρ were found across models (median 0.77 ≤ρ≤ 0.83). CONCLUSION: Results support the use of nonlinear T-wave-based models as Δ[K+] sensors in ESRD-HD patients.

Prophylaxis against covid-19: living systematic review and network meta-analysis.

UPDATES: This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity. OBJECTIVE: To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis (NMA). DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022. STUDY SELECTION: Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. RESULTS: The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation­risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence. CONCLUSIONS: Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).

Conventional compared to network meta-analysis to evaluate antibiotic prophylaxis in patients with cancer and haematopoietic stem cell transplantation recipients.

Our purpose was to compare conventional meta-analysis and network meta-analysis to evaluate the efficacy of different prophylactic systemic antibiotic classes in patients undergoing chemotherapy or haematopoietic stem cell transplant (HSCT). We included randomised trials if patients had cancer or were HSCT recipients and the intervention was systemic antibacterial prophylaxis. Three types of control groups were used: (1) placebo, no antibiotic and non-absorbable antibiotic separately; (2) placebo and no antibiotic combined; and (3) all three combined. These gave different network geometries. Strategies synthesised were fluoroquinolone, trimethoprim-sulfamethoxazole, cephalosporin and parenteral glycopeptide versus control groups. In total 113 trials met the eligibility criteria. Where treatment effects could be estimated with both conventional and network meta-analysis, values were generally similar. However, where events were sparse, network meta-analysis could be more precise. For example, trimethoprim-sulfamethoxazole versus placebo for infection-related mortality showed a relative risk ratio (RR) of 0.55, 95% CI (0.21 to 1.44) with conventional, and RR 0.43, 95% credible region (0.20 to 0.82) with network meta-analysis. Cephalosporin versus fluoroquinolone was comparable only indirectly using the network approach and yielded RR 0.59, 95% credible region (0.28 to 1.20) to reduce bacteraemia. Incoherence (difference between direct and indirect estimates raising concerns about network meta-analysis validity) was observed with network geometry where control groups were separated, but not where control groups were combined. In this situation, conventional and network meta-analysis yielded similar results in general. Network meta-analysis results could be more precise when events were rare. Some analysis could only be performed with the network approach. These results identify scenarios in which network meta-analysis may be advantageous.

Drug treatments for covid-19: living systematic review and network meta-analysis

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty). CONCLUSION: Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is publicly available in the supplementary material. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Automatic Detection of Slow Conducting Channels during Substrate Ablation of Scar-Related Ventricular Arrhythmias.

BACKGROUND: Voltage mapping allows identifying the arrhythmogenic substrate during scar-related ventricular arrhythmia (VA) ablation procedures. Slow conducting channels (SCCs), defined by the presence of electrogram (EGM) signals with delayed components (EGM-DC), are responsible for sustaining VAs and constitute potential ablation targets. However, voltage mapping, as it is currently performed, is time-consuming, requiring a manual analysis of all EGMs to detect SCCs, and its accuracy is limited by electric far-field. We sought to evaluate an algorithm that automatically identifies EGM-DC, classifies mapping points, and creates new voltage maps, named "Slow Conducting Channel Maps" (SCC-Maps). METHODS: Retrospective analysis of electroanatomic maps (EAM) from 20 patients (10 ischemic, 10 with arrhythmogenic right ventricular dysplasia/cardiomyopathy) was performed. EAM voltage maps were acquired during sinus rhythm and used for ablation. Preprocedural contrast-enhanced cardiac magnetic resonance (Ce-CMR) imaging was available for the ischemic population. Three mapping modalities were analysed: (i) EAM voltage maps using standard (EAM standard) or manual (EAM screening) thresholds for defining core and border zones; (ii) SCC-Maps derived from the use of the novel SCC-Mapping algorithm that automatically identify EGM-DCs measuring the voltage of the local component; and (iii) Ce-CMR maps (when available). The ability of each mapping modality in identifying SCCs and their agreement was evaluated. RESULTS: SCC-Maps and EAM screening identified a greater number of SCC entrances than EAM standard (3.45 ± 1.61 and 2.95 ± 2.31, resp., vs. 1.05 ± 1.10; p < 0.01). SCC-Maps and EAM screening highly correlate with Ce-CMR maps in the ischemic population when compared to EAM standard (Lin's correlation = 0.628 and 0.679, resp., vs. 0.212, p < 0.01). CONCLUSION: The SCC-Mapping algorithm allows an operator-independent analysis of EGM signals showing better identification of the arrhythmogenic substrate characteristics when compared to standard voltage EAM.

Terapia de presión negativa como tratamiento alternativo en el manejo de una úlcera vascular arterial de miembros inferiores / Negative- pressure therapy as an alternative treatment for managing arterial vascular ulcer of the lower limbs

Resumen Objetivo: Reportar un caso sobre el uso de la terapia de presión negativa como tratamiento alternativo en el manejo de una úlcera vascular arterial de miembros inferiores. Métodos: Por medio de la historia clínica, se revisó los registros previos de una paciente en un centro de atención médica de tercer nivel en Popayán, Colombia. Posteriormente, se realizó una revisión sistemática bibliográfica a través de las bases de datos de Pubmed, ScienceDirect y Scielo. Resultados: La terapia de presión negativa favoreció el proceso de cicatrización, permitiendo el cierre de la herida. Conclusiones: Actualmente, este sistema se considera un apoyo fundamental en el tratamiento de las heridas complejas, las cuales suponen un reto terapéutico importante.

Abstract Objective: To report a case about the use of the Negative-pressure wound therapy as an alternative treatment for arterial vascular ulcers presented in the lower limbs. Methods: The patient's records were reviewed based on her medical history in a tertiary referral care center in Popayan, Colombia. Subsequently, a systematic literature review was conducted through the Pubmed database, ScienceDirect, and Scielo. Results: The use of Negative-pressure wound therapy favored the lesion healing process. Conclusions: Nowadays, this system is considered as an essential treatment for complex wounds, which represent a major therapeutic challenge.

Effect of TNF-inhibitor therapy on spinal structural progression in ankylosing spondylitis patients: A systematic review and meta-analysis.

To review the effect of tumor necrosis factor-alpha inhibitor (TNFi) therapies on radiographic progression in ankylosing spondylitis (AS) patients as evaluated by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from inception to August 2019. All comparative and non-comparative studies that evaluated the clinical effectiveness of TNFi on radiographic progression as assessed by mSASSS change at a minimum follow-up of 1 year were included. The Newcastle-Ottawa Scale and Cochrane Collaboration Risk of Bias Tool were utilized to assess the methodological quality. Pooled analysis was performed for continuous and binomial variables where appropriate. Inter-rater reliability of mSASSS status and change scores were assessed with intra-class coefficients (ICC). Twenty-one studies were identified with a total of 4460 patients (mean age: 40.4 years [range 25.3-50 years]; 76% male; mean baseline mSASSS: 12.7 units [range 5.5-19.8 units]). All studies (3 randomized and 18 observational studies) were considered to have moderate-to-high methodological quality. The inter-rater reliability of mSASSS status and change scores from 14 of the 21 studies were excellent (ICC ranges, 0.91-0.99) and moderate-to-excellent (ICC ranges, 0.58-0.90), respectively. From the 21 studies, 11/21 (50%) demonstrated a delayed effect in mSASSS in AS patient administered TNFi. When stratifying these studies into those with ≤4 years of follow-up and >4 years follow-up, 3/11 (27%) and 8/10 (80%) studies respectively indicated a delayed effect of mSASSS with TNFi in AS patients. Pooling for meta-analysis from 3 studies (1159 patients) with study durations ranging 4-8 years, indicated that TNFi-treated patients had reduced odds of structural progression (odds ratio 0.81; 95% CI 0.68-0.96; P = .01; I2  = 0%). Mean rate of mSASSS change from 16 studies ranged from -0.15 to 7.3 mSASSS units for all AS patients. Meta-analysis indicated a numerical, but statistically non-significant, reduction in the rate of mSASSS change with TNFi treatment (7 studies [1438 patients]; mean difference, -0.24; 95% CI, -0.49-0.01; P = .06; I2  = 0%). This systematic review and meta-analysis indicated that >4 years of TNFi usage was associated with delayed structural progression by mSASSS. The narrative analysis of the data from 21 studies further confirmed that studies with >4 years of follow-up had delayed structural progression with TNFi use in AS patients. The systematic review also confirmed that mSASSS has good-to-excellent inter-rater reliability in AS.

Joint trajectories of disease activity, and physical and mental health-related quality of life in an inception lupus cohort.

OBJECTIVES: To examine for latent patterns of SLE disease activity trajectories that associate with specific latent patterns of health-related quality of life (HRQoL; Medical Outcomes Study Short Form-36), and to determine baseline predictors of class membership. METHODS: In this retrospective longitudinal inception cohort of 222 SLE adults over 10 years, trajectories of three outcomes were studied jointly: Short Form-36 physical (PCS) and mental (MCS) component summaries and adjusted mean SLEDAI-2000 (AMS). Group-based joint trajectory modelling was used to model latent classes; univariable and multivariable analyses were used to identify predictors of class membership. RESULTS: Four latent classes were identified: Class 1 (C1) (24%) had moderate AMS, and persistently low PCS and MCS; C2 (26%) had low AMS, moderate PCS and improved then worsened MCS; C3 (38%) had moderate AMS, and persistently high PCS and MCS; and C4 (11%) had high AMS, moderate-low PCS and improving MCS. Baseline older age was associated with lower HRQoL trajectories. Higher AMS trajectories did not associate with a particular pattern of HRQoL trajectory. A higher prevalence of fibromyalgia (44% in C1) was associated with worse HRQoL trajectories. Disease manifestations, organ damage and cumulative glucocorticoid were not differentially distributed across the latent classes. CONCLUSION: High disease activity did not necessarily associate with low HRQoL. More patients with worse HRQoL trajectories had fibromyalgia. Older age at diagnosis increased the probability of belonging to a class with low HRQoL trajectories. The care of SLE patients may be improved through addressing fibromyalgia in addition to disease activity.

Effectiveness of Electronic Medication Packaging Devices on Medication Adherence: A Scoping Review.

Poor adherence to complex medication regimens is a global problem that affects the treatment of chronic diseases, which involves polypharmacy and requires long-term administration of medications. The most significant barrier to medication adherence in older adults is patient-related factors. The purpose of this study was to find evidence from the current literature to evaluate the effectiveness of electronic medication packaging (EMP) devices on improving medication adherence in older patients. MEDLINE and EMBASE databases were searched based on inclusion/exclusion criteria, focusing on medication adherence and EMP devices with specific technological features. Search results included studies with experiences of patients with four different devices and various medical conditions. Study results indicated that EMP devices may improve medication adherence in older patients. However, due to insufficient evidence that supports their effectiveness specifically in the aging population, further clinical validation in older adults is recommended to draw strong conclusions. [Journal of Gerontological Nursing, 46(3), 27-36.].

Thyroid Function Reference Values in Healthy Iodine-Sufficient Pregnant Women and Influence of Thyroid Nodules on Thyrotropin and Free Thyroxine Values.

BACKGROUND: Thyroid function assessment in pregnancy requires specific reference intervals stratified by gestational age and according to each laboratory method. Thyroid nodules may influence thyroid function in pregnant women. The aims of this study were to define the reference values of thyrotropin (TSH) and free thyroxine (fT4) in the three pregnancy trimesters in iodine-sufficient pregnant women, and to analyze the influence of thyroid nodules on thyroid function during pregnancy. METHODS: This was a prospective, longitudinal study comprising 400 pregnant women with no history of thyroid disease and no medication influencing thyroid function. TSH, fT4, antithyroglobulin, and antithyroid peroxidase antibodies were measured each trimester by chemiluminescent immunoassays. Urinary iodine concentration was measured in the first trimester when a thyroid echography was also performed. Women with multiple gestation pregnancies, positive thyroid autoimmunity, TSH values >5 or <0.1 mIU/L with a simultaneous fT4 level above the general population reference value in the first trimester, or clinically significant thyroid nodules (nodules ≥1 cm and/or multiple nodules) were excluded to establish TSH and fT4 reference values. RESULTS: Reference intervals in the first, second, and third trimesters were 0.13-4.16, 0.31-3.73, and 0.58-4.36 mIU/L, respectively, for TSH, and 0.85-1.24, 0.82-1.20, and 0.67-1.06 ng/dL, respectively, for fT4. The total prevalence of thyroid nodules was 28.8% [95% confidence interval (CI) 24.4-33.5%], and 6.0% of the participants showed clinically significant nodules. Pregnant women with thyroid nodules (n = 115) showed consistently lower TSH values during all pregnancy stages (first trimester: median 1.14 mIU/L [interquartile range (IQR) 0.53-1.75 mIU/L] vs. 1.48 mIU/L [IQR 0.94-2.19 mIU/L], p < 0.001; second trimester: 1.22 mIU/L [IQR 0.66-1.77 mIU/L] vs. 1.45 mIU/L [1.04-2.05 mIU/L], p = 0.001; third trimester: 1.74 mIU/L [IQR 1.08-2.36 mIU/L] vs. 1.93 mIU/L [IQR 1.37-2.58 mIU/L], p = 0.041) and higher fT4 values in the first trimester (M ± SD = 1.08 ± 0.14 ng/dL vs. 1.03 ± 0.12, p < 0.001) compared to those without nodules (n = 285). Both pregnant women with clinically significant thyroid nodules and those with nonsignificant ones had lower TSH values than women without nodules. CONCLUSIONS: TSH/fT4 reference intervals in pregnant women from the authors' geographical area will thyroid dysfunction in pregnancy to be appropriately diagnosed. The prevalence of thyroid nodules is high in iodine-sufficient pregnant women, and is associated with low TSH values across pregnancy.

Intrinsic fluorescence and mechanical testing of articular cartilage in human patients with osteoarthritis.

The degeneration of articular cartilage is the main cause of osteoarthritis (OA), a common cause of disability among elderly patients. The aim of this study is to understand the correlation between intrinsic fluorescence of articular cartilage and its biomechanical properties in patients with osteoarthritis. Cylindrical samples of articular cartilage 6 mm in diameter were extracted via biopsy punch from the femoral condyles of 6 patients with advanced OA undergoing knee replacement surgery. The mechanical stiffness and fluorescence of each cartilage plug were measured by indentation test and spectrofluorometry. Maps of fluorescence intensity, at excitation/emission wavelengths of 240-520/290-530 nm, were used to identify wavelengths of interest. The mechanical stiffness and fluorescence intensity were correlated using a Spearman analysis. The excitation/emission maps demonstrated three fluorescence peaks at excitation/emission wavelength pairs 330/390, 350/430 and 370/460 nm. The best correlation between the fluorescence intensity and stiffness of cartilage was obtained for the 330 nm excitation band [R=0.82, p=0.04]. The intrinsic fluorescence of articular cartilage may have application in optically assessing the state of cartilage in patients with osteoarthritis.

Infantile myofibromatosis

Abstract: Infantile myofibromatosis is a mesenchymal disorder characterized by the fibrous proliferation of the skin, bone, muscle and viscera. It is the most common fibrous tumor in childhood. We present a newborn with skin and bone disease without visceral involvement, who showed good response to vinblastine and methotrexate. Clinical features, etiology, diagnosis, and treatment are reviewed.

Phosphorus deficiency modifies As translocation in the halophyte plant species Atriplex atacamensis.

Most arsenic in surface soil and water exists primarily in its oxidized form, as arsenate (As(V); AsO43-), which is an analog of phosphate (PO43-). Arsenate can be taken up by phosphate transporters. Atriplex atacamensis Phil. is native to northern Chile (Atacama Desert), and this species can cope with high As concentrations and low P availability in its natural environment. To determine the impact of P on As accumulation and tolerance in A. atacamensis, the plants were cultivated in a hydroponic system under four treatments: no As(V) addition with 323µM phosphate (control); 1000µM As(V) addition with 323µM phosphate; no As(V) and no phosphate; 1000µM As(V) addition and no phosphate. Phosphate starvation decreased shoot fresh weight, while As(V) addition reduced stem and root fresh weights. Arsenate addition decreased the P concentrations in both roots and leaves, but to a lesser extent than for P starvation. Phosphorus starvation increased the As concentrations in roots, but decreased it in shoots, which suggests that P deficiency reduced As translocation from roots to shoots. Arsenate addition increased total glutathione, but P deficiency decreased oxidized and reduced glutathione in As(V)-treated plants. Arsenate also induced an increase in S accumulation and nonprotein thiol and ethylene synthesis, and a decrease in K concentrations, effects that were similar for the P-supplied and P-starved plants. In contrast, in As(V)-treated plants, P starvation dramatically decreased total soluble protein content and increased lipid peroxidation, compared to plants supplied with P. Phosphorus nutrition thus appears to be an important component of A. atacamensis response to As toxicity.

Inhibition of ethylene synthesis reduces salt-tolerance in tomato wild relative species Solanum chilense.

Exposure to salinity induces a burst in ethylene synthesis in the wild tomato halophyte plant species Solanum chilense. In order to gain information on the role of ethylene in salt adaptation, plants of Solanum chilense (accession LA4107) and of cultivated glycophyte Solanum lycopersicum (cv. Ailsa Craig) were cultivated for 7days in nutrient solution containing 0 or 125mM NaCl in the presence or absence of the inhibitor of ethylene synthesis (aminovinylglycine (AVG) 2µM). Salt-induced ethylene synthesis in S. chilense occurred concomitantly with an increase in stomatal conductance, an efficient osmotic adjustment and the maintenance of carbon isotope discrimination value (Δ13C). In contrast, in S. lycopersicum, salt stress decreased stomatal conductance and Δ13C values while osmotic potential remained higher than in S. chilense. Inhibition of stress-induced ethylene synthesis by AVG decreased stomatal conductance and Δ13C in S. chilense and compromised osmotic adjustment. Solanum chilense behaved as an includer and accumulated high amounts of Na in the shoot but remained able to maintain K nutrition in the presence of NaCl. This species however did not stimulate the expression of genes coding for high-affinity K transport but genes coding for ethylene responsive factor ERF5 and JREF1 were constitutively more expressed in S. chilense than in S. lycopersicum. It is concluded that ethylene plays a key role in salt tolerance of S. chilense.

Infantile myofibromatosis.

Infantile myofibromatosis is a mesenchymal disorder characterized by the fibrous proliferation of the skin, bone, muscle and viscera. It is the most common fibrous tumor in childhood. We present a newborn with skin and bone disease without visceral involvement, who showed good response to vinblastine and methotrexate. Clinical features, etiology, diagnosis, and treatment are reviewed.

Salicylic acid differently impacts ethylene and polyamine synthesis in the glycophyte Solanum lycopersicum and the wild-related halophyte Solanum chilense exposed to mild salt stress.

This study aimed to determine the effects of exogenous application of salicylic acid (SA) on the toxic effects of salt in relation to ethylene and polyamine synthesis, and to correlate these traits with the expression of genes involved in ethylene and polyamine metabolism in two tomato species differing in their sensitivity to salt stress, Solanum lycopersicum cv Ailsa Craig and its wild salt-resistant relative Solanum chilense. In S. chilense, treatment with 125 mM NaCl improved plant growth, increased production of ethylene, endogenous salicylic acid and spermine. The production was related to a modification of expression of genes involved in ethylene and polyamine metabolism. In contrast, salinity decreased plant growth in S. lycopersicum without affecting endogenous ethylene, salicylic or polyamine concentrations. Exogenous application of salicylic acid at 0.01 mM enhanced shoot growth in both species and affected ethylene and polyamine production in S. chilense. Concomitant application of NaCl and salicylic acid improved osmotic adjustment, thus suggesting that salt and SA may act in synergy on osmolyte synthesis. However, the beneficial impact of exogenous application of salicylic acid was mitigated by salt stress since NaCl impaired endogenous SA accumulation in the shoot and salicylic acid did not improve plant growth in salt-treated plants. Our results thus revealed that both species respond differently to salinity and that salicylic acid, ethylene and polyamine metabolisms are involved in salt resistance in S. chilense.