Child and adolescent health in Europe: Towards meeting the 2030 agenda.

Background: Childhood and adolescence are critical stages for a healthy life. To support countries in promoting health and development and improving health care for this age group, the WHO Regional Office for Europe developed the European strategy for child and adolescent health 2015-2020, which was adopted by all countries. This paper reports progress in the strategy's implementation until 2020. Methods: A survey was sent to all ministries of health of the 53 Member States of the WHO European Region. Responses were received from 45 Member States. Results are presented in this paper. Results: The European Region made overall progress in recent years, but increasing levels of overweight and obesity among children, adolescent mental health and low breastfeeding rates are recognized as key national challenges. Although forty-one countries adopted a national child and adolescent health strategy, only eight countries involve children in their review, development and implementation stages. Two-thirds of countries have a strategy for health-promoting schools and a school curriculum for health education. One-third of countries do not have legislation against marketing of unhealthy foods and beverages to children. Most countries reported routine assessment for developmental difficulties in children, but less than a quarter collected and reported data on children who are developmentally on track. There are major gaps in data collection for migrant children. Hospitalization rates for young children vary five-fold across the region, indicating over-hospitalization and access problems in some countries. Only ten countries allow minors access to health care without parental consent based on their maturity and only eleven countries allow school nurses to dispense contraceptives to adolescents without a doctor's prescription. Conclusions: This paper shows the progress in child and adolescent health made by countries in Europe until 2020 and key areas where additional work is needed to move the 2030 agenda forward. The survey was undertaken before the COVID-19 pandemic and the war in Ukraine. Both will likely exacerbate many of the observed problems and potentially reverse some gains reported. A renewed commitment is needed.

[The research progress of multimodal imaging for the diagnosis of reticular pseudodrusen].

The emergence and development of multimodal imaging techniques, such as optical coherence tomography, fundus autofluorescence and adaptive optics, make it much easier to differentiate reticular pseudodrusen (RPD) from other fundus lesions. It is of great significance to understand the imaging characteristics of RPD observed with multimodal imaging techniques. This article reviews the formation mechanism and multimodal imaging characteristics of RPD, so as to provide help for better identification of RPD and assessment of the development and prognosis of the disease.

[Supernormal rod response mediated by a novel KCNV2 variant in a cone dystrophy type 3B patient].

The proband was an 8-year-old boy, complaining of progressively decreased vision in both eyes for 3 years. The electroretinogram was characterized by supernormal rod response. While the responses of the rod and cone system were reduced, the amplitudes of dark-adapted electroretinogram responses at a high intensity were supernormal. A homozygous non-frameshift deletion variant c.1002-1004del (p. L335del) in KCNV2 was found by the Next Generation Sequencing using a custom designed panel. His father was a heterozygous carrier of this variant. In silico analysis indicated the variant was harmful. The proband was diagnosed as cone dystrophy type 3B which also known as cone dystrophy with supernormal rod response.

Unusual competition of superconductivity and charge-density-wave state in a compressed topological kagome metal.

Understanding the competition between superconductivity and other ordered states (such as antiferromagnetic or charge-density-wave (CDW) state) is a central issue in condensed matter physics. The recently discovered layered kagome metal AV3Sb5 (A = K, Rb, and Cs) provides us a new playground to study the interplay of superconductivity and CDW state by involving nontrivial topology of band structures. Here, we conduct high-pressure electrical transport and magnetic susceptibility measurements to study CsV3Sb5 with the highest Tc of 2.7 K in AV3Sb5 family. While the CDW transition is monotonically suppressed by pressure, superconductivity is enhanced with increasing pressure up to P1 ≈ 0.7 GPa, then an unexpected suppression on superconductivity happens until pressure around 1.1 GPa, after that, Tc is enhanced with increasing pressure again. The CDW is completely suppressed at a critical pressure P2 ≈ 2 GPa together with a maximum Tc of about 8 K. In contrast to a common dome-like behavior, the pressure-dependent Tc shows an unexpected double-peak behavior. The unusual suppression of Tc at P1 is concomitant with the rapidly damping of quantum oscillations, sudden enhancement of the residual resistivity and rapid decrease of magnetoresistance. Our discoveries indicate an unusual competition between superconductivity and CDW state in pressurized kagome lattice.

The BAPRAS screening tool for reimbursement in a postbariatric population.

INTRODUCTION: Reimbursement of body-contouring surgery (BCS) is a worldwide problem: there is no objective instrument to decide which postbariatric patients should qualify for reimbursement. The British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) has developed a screening tool for this purpose. In this study, we used a modified version of this screening tool in a postbariatric population and describe which patients would qualify for reimbursement using this tool. METHODS: In this cross-sectional study postbariatric patients were asked to fill in an online questionnaire based on the BAPRAS screening tool with questions regarding complaints of overhanging skin and medical history. Weight loss data were extracted from a prospective database. The BODY-Q was added to assess patient-reported outcomes. RESULTS: Patients who wanted to undergo BCS (n = 90) had higher screening tool scores and lower BODY-Q scores compared to patients who did not want BCS (n = 24). In total, 25 patients (26%) qualified for reimbursement, these patients had higher weight loss (33.5% versus 29.2%, p = 0.008), lower BMI (27.3 kg/m2 versus 30.4 kg/m2, p = 0.014) and more medical (4.0 versus 2.0, p = 0.004) and psychological complaints (88% versus 61%, p = 0.009). There was a significant, negative correlation between the screening tool scores and almost all BODY-Q scales. CONCLUSIONS: Patients with a desire for BCS have more complaints of excess skin, which negatively impacts their well-being. With the modified BAPRAS screening tool, patients with the best weight (loss) and most medical and psychological complaints of excess skin qualified for referral and reimbursement of BCS.

High expression of carbonic anhydrase 12 (CA12) is associated with good prognosis in breast cancer.

The purpose of this research was to explore whether the expression of carbonic anhydrase 12 (CA12) and the prognosis had a significant relationship in breast cancer patients. A total of 262 breast cancer specimens and 75 normal breast tissue specimens were recruited in this study. The expression of CA12 was detected by immunohistochemistry (IHC), and its correlation with the clinicopathological characteristics of breast cancer patients and their prognosis were further analyzed through standard statistical algorithms. The result of immunohistochemical staining showed that CA12 was detected in both normal breast tissue and breast cancer tissue. Compared to normal breast tissue, CA12 was significant higher expressing in cancer tissues (P=0.009). Statistical analysis showed that the high expression of CA12 in breast cancer tissue was related to estrogen receptor expression level (P<0.001). The follow-up of 262 cases of breast cancer patients within 5 years showed that patients with high expression of CA12 had significant better outcome in DFS (P=0.020) and OS (P=0.019) than patients with low expression of CA12. Univariate analysis of DFS showed that lymph node metastasis (P=0.034) and CA12 (P=0.024) are prognostic indicators. Multivariate analysis manifested that the expression of CA12 (P=0.025) and lymph node metastasis (P=0.024) are two independent factors affecting the prognosis of breast cancer. Conclusion: In breast cancer patients, CA12 can be seen as a new prognostic indicator and even a new target for treatment.

Discrete Superconducting Phases in FeSe-Derived Superconductors.

A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.

Antiferromagnetic Order in Epitaxial FeSe Films on SrTiO_{3}.

Single monolayer FeSe film grown on a Nb-doped SrTiO_{3}(001) substrate shows the highest superconducting transition temperature (T_{C}∼100 K) among the iron-based superconductors (iron pnictides), while the T_{C} value of bulk FeSe is only ∼8 K. Although bulk FeSe does not show antiferromagnetic order, calculations suggest that the parent FeSe/SrTiO_{3} films are antiferromagnetic. Experimentally, because of a lack of a direct probe, the magnetic state of FeSe/SrTiO_{3} films remains mysterious. Here, we report direct evidence of antiferromagnetic order in the parent FeSe/SrTiO_{3} films by the magnetic exchange bias effect measurements. The magnetic blocking temperature is ∼140 K for a single monolayer film. The antiferromagnetic order disappears after electron doping.

Efficacy and safety of three adefovir-based combination therapies in HBeAg-positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy.

Although high potent nucleos(t)ide analogues are strongly recommended as first-line therapy for chronic hepatitis B (CHB) in China, some patients are still being treated with adefovir disoproxil (ADV), especially those low-income patients whose health insurance could not reimburse the drug cost. Therefore, the management of patients who have failed ADV therapy or who sustained renal damage during ADV therapy remains an important clinical problem in China. This retrospective study aimed to compare the efficacy and safety of lamivudine (LAM), telbivudine (LdT) or entecavir (ETV) add-on strategies to optimize the treatment of patients with prior suboptimal response to ADV monotherapy. A total of 277 eligible patients were included in this study, and the baseline characteristics were similar among the LAM + ADV (n = 116), LdT + ADV (n = 72) and ETV + ADV (n = 89) groups. At week 96, both the proportion of undetectable HBV DNA (81.03% for LAM + ADV, 84.72% for LdT + ADV and 88.76% for ETV + ADV; P = .317) and ALT elevation (5.17% for LAM + ADV, 4.17% for LdT + ADV and 4.49% for ETV + ADV; P = 1.000) were similar among the three groups; also, a significant decline in liver stiffness was observed in each group from baseline to week 96. At week 96, the rate of HBeAg seroconversion was significantly higher in LdT + ADV than in LAM + ADV (26.39% vs 13.79%, P = .031) and ETV + ADV (26.39% vs 10.11%, P = .007). During the 96 weeks, no obvious renal injury was reported in any of the three groups, but an improvement in eGFR was found in LdT + ADV compared with LAM + ADV and ETV + ADV. In summary, all three combination strategies provide good control of virus replication, but the LdT + ADV combination therapy may yield better HBeAg seroconversion and eGFR improvement.

Structure similarity-guided image binarization for automatic segmentation of epidermis surface microstructure images.

Partitioning epidermis surface microstructure (ESM) images into skin ridge and skin furrow regions is an important preprocessing step before quantitative analyses on ESM images. Binarization segmentation is a potential technique for partitioning ESM images because of its computational simplicity and ease of implementation. However, even for some state-of-the-art binarization methods, it remains a challenge to automatically segment ESM images, because the grey-level histograms of ESM images have no obvious external features to guide automatic assessment of appropriate thresholds. Inspired by human visual perceptual functions of structural feature extraction and comparison, we propose a structure similarity-guided image binarization method. The proposed method seeks for the binary image that best approximates the input ESM image in terms of structural features. The proposed method is validated by comparing it with two recently developed automatic binarization techniques as well as a manual binarization method on 20 synthetic noisy images and 30 ESM images. The experimental results show: (1) the proposed method possesses self-adaption ability to cope with different images with same grey-level histogram; (2) compared to two automatic binarization techniques, the proposed method significantly improves average accuracy in segmenting ESM images with an acceptable decrease in computational efficiency; (3) and the proposed method is applicable for segmenting practical EMS images. (Matlab code of the proposed method can be obtained by contacting with the corresponding author.).

Evolution of High-Temperature Superconductivity from a Low-T_{c} Phase Tuned by Carrier Concentration in FeSe Thin Flakes.

We report the evolution of superconductivity in an FeSe thin flake with systematically regulated carrier concentrations by the liquid-gating technique. With electron doping tuned by the gate voltage, high-temperature superconductivity with an onset at 48 K can be achieved in an FeSe thin flake with T_{c} less than 10 K. This is the first time such high temperature superconductivity in FeSe is achieved without either an epitaxial interface or external pressure, and it definitely proves that the simple electron-doping process is able to induce high-temperature superconductivity with T_{c}^{onset} as high as 48 K in bulk FeSe. Intriguingly, our data also indicate that the superconductivity is suddenly changed from a low-T_{c} phase to a high-T_{c} phase with a Lifshitz transition at a certain carrier concentration. These results help to build a unified picture to understand the high-temperature superconductivity among all FeSe-derived superconductors and shed light on the further pursuit of a higher T_{c} in these materials.

Modulating of ocular inflammation with macrophage migration inhibitory factor is associated with notch signalling in experimental autoimmune uveitis.

The aim of this study was to examine whether macrophage migration inhibitory factor (MIF) could exaggerate inflammatory response in a mouse model of experimental autoimmune uveitis (EAU) and to explore the underlying mechanism. Mutant serotype 8 adeno-associated virus (AAV8) (Y733F)-chicken ß-actin (CBA)-MIF or AAV8 (Y733F)-CBA-enhanced green fluorescent protein (eGFP) vector was delivered subretinally into B10.RIII mice, respectively. Three weeks after vector delivery, EAU was induced with a subcutaneous injection of a mixture of interphotoreceptor retinoid binding protein (IRBP) peptide with CFA. The levels of proinflammatory cytokines were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Retinal function was evaluated with electroretinography (ERG). We found that the expression of MIF and its two receptors CD74 and CD44 was increased in the EAU mouse retina. Compared to AAV8.CBA.eGFP-injected and untreated EAU mice, the level of proinflammatory cytokines, the expression of Notch1, Notch4, delta-like ligand 4 (Dll4), Notch receptor intracellular domain (NICD) and hairy enhancer of split-1 (Hes-1) increased, but the ERG a- and b-wave amplitudes decreased in AAV8.CBA.MIF-injected EAU mice. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) reduced the expression of NICD, Hes-1 and proinflammatory cytokines. Further, a MIF antagonist ISO-1 attenuated intraocular inflammation, and inhibited the differentiation of T helper type 1 (Th1) and Th17 in EAU mice. We demonstrated that over-expression of MIF exaggerated ocular inflammation, which was associated with the activation of the Notch signalling. The expression of both MIF and its receptors are elevated in EAU mice. Over-expression of MIF exaggerates ocular inflammation, and this exaggerated inflammation is associated with the activation of the Notch signalling and Notch pathway. Our data suggest that the MIF-Notch axis may play an important role in the pathogenesis of EAU. Both the MIF signalling pathways may be promising targets for developing novel therapeutic interventions for uveitis.

Neutral alpha-1,4-glucosidase and fructose levels contribute to discriminating obstructive and nonobstructive azoospermia in Chinese men with azoospermia.

Nowadays, whether neutral alpha-1,4-glucosidase (NAG) and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese azoospermic patients remains unclear. In this study, we retrospectively analysed the levels of NAG and fructose in 229 patients with obstructive azoospermia and 415 patients with nonobstructive azoospermia from three different medical central. Results indicated that NAG and fructose levels in patients with nonobstructive azoospermia were significantly higher compared with those with obstructive azoospermia (P < 0.05). According to the reference value of NAG and fructose defined by the World Health Organization (WHO, 2010), decreased level of NAG was observed in 77.3% of patients with obstructive azoospermia, which was significantly higher than those with nonobstructive azoospermia (55.2%, P < 0.0001). Low level of fructose was observed in 48.0% of patients with obstructive azoospermia, which is also obviously higher than those with nonobstructive azoospermia (31.8%, P < 0.0001). Moreover, the decrease of both NAG and fructose was only recorded in 3.7% of patients with SCO syndrome, 5.0% of patients with severe hypospermatogenesis and 18.2% of patients with maturation arrest. Therefore, our results indicated that NAG and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese patients based on the histological types of testes.

Angular-Dependent Phase Factor of Shubnikov-de Haas Oscillations in the Dirac Semimetal Cd_{3}As_{2}.

We measure the magnetotransport properties of the three-dimensional Dirac semimetal Cd_{3}As_{2} single crystal under magnetic fields up to 36 T. Shubnikov-de Haas (SdH) oscillations are clearly resolved and the n=1 Landau level is reached. A detailed analysis on the intercept of the Landau index plot reveals a significant dependence of the SdH phase factor on the orientation of the applied magnetic field. When the magnetic field is applied in the [001] direction, i.e., along the fourfold screw axis of the tetragonal crystal structure, a nontrivial π Berry phase, as predicted for the Dirac fermions, is observed. However, in a magnetic field tilted away from the [001] direction, the π Berry phase is evidently reduced, and a considerable enhancement of the effective mass is also revealed. Our observations demonstrate that the Dirac dispersion in Cd_{3}As_{2} is effectively modified in a tilted magnetic field, whereas the preserved π Berry phase in a magnetic field along the [001] direction can be related to the realization of the Weyl fermions. The sudden change of the SdH phase also indicates a possible topological phase transition induced by the symmetry-breaking effect.