Assessing the impact of obesity interventions in the early years: a systematic review of UK-based studies.

OBJECTIVES: Childhood obesity rates in the UK are high. The early years of childhood are critical for establishing healthy behaviours and offer interventional opportunities. We aimed to identify studies evaluating the impact of UK-based obesity interventions in early childhood. DESIGN: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Nine databases were searched in March 2023. ELIGIBILITY CRITERIA: We included UK-based obesity intervention studies delivered to children aged 6 months to 5 years that had diet and/or physical activity components and reported anthropometric outcomes. The primary outcome of interest was z-score Body Mass Index (zBMI) change (within and between subjects). Studies evaluating the effects of breastfeeding interventions were not included as obesity prevention interventions, given that best-practice formula feeding is also likely to encourage healthy growth. The publication date for studies was limited to the previous 12 years (2011-23), as earlier reviews found few evaluations of interventions in the UK. DATA EXTRACTION AND SYNTHESIS: The reviewers worked independently using standardised approach to search, screen and code the included studies. Risk of bias was assessed using Cochrane tools (ROB 2 or ROBINS-I). RESULTS: Six trials (five studies) were identified, including two randomised controlled trials (RCT), one cluster randomised trial (CRT), two feasibility CRTs and one impact assessment. The total number of participants was 566. Three trials focused on disadvantaged families and two included high-risk children categorised as having overweight or obesity. Compared with baseline, five interventions reported reductions in zBMI, three of which were statistically significant (p<0.05). Compared with control, five interventions showed zBMI reductions, one of which was significant. Only two trials were followed up beyond 12 months. All studies were found to have a high risk of bias. Meta-analysis was not possible due to the heterogeneity of studies. CONCLUSION: UK evidence was limited but some interventions showed promising results in promoting healthy growth. As part of a programme of policies, interventions in the early years may have an important role in reducing the risk of childhood obesity. PROSPERO REGISTRATION NUMBER: CRD42021290676.

Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy.

Psoriasis is a common inflammatory disease that affects mainly the skin. However, the moderate to severe forms have been associated with several comorbidities, such as psoriatic arthritis, Crohn's disease, metabolic syndrome and cardiovascular disease. Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells, peripheral immune cells and immune cells residing in the skin. Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis, offering novel specific targets to diagnose and treat psoriasis early. The present article discusses the metabolic reprogramming of activated T cells, tissue-resident memory T cells and keratinocytes in psoriatic skin, presenting associated metabolic biomarkers and therapeutic targets. In psoriatic phenotype, keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle, the amino acid metabolism and the fatty acid metabolism. Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes. Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects.

Reciprocal relationships between paternal psychological distress and child internalising and externalising difficulties from 3 to 14 years: a cross-lagged analysis.

Research shows that paternal psychological distress is associated with child emotional and behavioural difficulties. However, little is known about the direction of this association including whether it is bidirectional. The aim of this study was to explore the reciprocal relationships between paternal psychological distress and child emotional and behavioural problems longitudinally (at ages 3, 5, 7, 11 and 14 years) in a sample of 13,105 children (49% girls) who participated in the UK's Millennium Cohort Study (MCS), a large-scale, nationally representative, longitudinal survey. Four domains of child problems (emotional symptoms, peer relations, conduct problems and hyperactivity/inattention) were measured with the Strengths and Difficulties Questionnaire and paternal psychological distress was measured with the Kessler K-6 scale. Data were analysed using cross-lagged path models. At all ages, paternal psychological distress predicted both subsequent child emotional symptoms as well as peer problems. Paternal psychological distress at child's age 3 was related to more hyperactivity at age 5 and, at age 5, paternal psychological distress was associated with more conduct problems at age 7. At age 11, paternal distress was also related to age 14 conduct problems and hyperactivity. Child effects were fewer and were found mainly for behavioural problems. Notably, we found bidirectional links between paternal psychological distress and child peer difficulties, from 11 to 14 years. Paternal psychological distress appears to influence child behaviour more consistently than the converse. However, in early adolescence, there appears to be a reciprocal relationship between fathers' mental health problems and children's peer problems.

Impact of vitamin D receptor gene polymorphisms on vitiligo susceptibility and clinical features in a Southeastern European Caucasian population.

An association of vitamin D receptor (VDR) polymorphisms and vitiligo has been suggested. However, previous studies have reported contradictory results while including limited data among Caucasians. The aim of this single­center study was to evaluate the effect of three common VDR gene polymorphisms (FokI, TaqI and BsmI) on susceptibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. A total of 110 unrelated vitiligo cases and 509 general population controls were enrolled from October 2018 to November 2019. Genomic DNA was extracted from whole blood after de­identification and anonymization of the samples and genotyped for the selected VDR polymorphisms by the qPCR (melting curve analysis). Subgroup analysis by clinical features among subsets of patients indicated that, compared to subjects with the FokI TT genotype or T allele, carriers of the FokI CC genotype or C allele exhibited significantly decreased risk of developing vitiligo before the age of 30 [TT vs. CC: odds ratio (OR)=0.286, 95% confidence interval (CI): 0.083­0.984, P=0.041; T vs. C: OR=0.545, 95% CI: 0.313­0.948, P=0.031]. Intra­patient analysis also revealed that, compared to T allele, the presence of TaqI C allele was adversely associated with the incidence of concurrent leukotrichia (T vs. C: OR=1.874, 95% CI: 1.018­3.451, P=0.042). Comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and the VDR BsmI, TaqI, and FokI polymorphisms in this cohort. Thus, the studied VDR polymorphisms might indirectly impact the clinical course and treatment decision­making despite their lack of association with vitiligo per se. Further research with larger sample sizes, especially across Caucasian individuals, should be performed to confirm these findings.

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.

Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities.

A novel approach regarding the anti-aging of facial skin through collagen reorganization.

The needle shaping technique can be used to perform subcutaneous microtransplants, enabling the 'lifting' of the skin. This prospective cohort study aimed to examine the effects of needle shaping on facial skin tone, volume and histological structure. A total of 54 women underwent the needle shaping procedure performed by inserting a tiny acupuncture needle combined with mixed electrical currents. The overall treatment was completed within 4 sessions of 2 months apart, once every 15 days. Maintenance was ensured by 2 sessions (no longer than 15 days apart) every 6 months. Macroscopic skin appearance was evaluated by a specialized dermatologist and the satisfaction of the patients was assessed. The microscopic structure of the skin dermis was evaluated by optic and scanning electron microscopy. I-chrome staining demonstrated more compact dermis-collagen fibers which were larger and thicker as compared to the controls. Scanning electron microscopy demonstrated an increased dermis thickness as compared to pre-treatment. All patients that answered to the follow up reported satisfaction during assessment. The satisfaction of the patients was very good and excellent in 45% of cases. The results of the needle-shaping procedure are natural with no scaring or down time. Moreover, the result is lasting even for 1 year, depending always on the subject's lifestyle and general health condition.

The incidence of skin lesions in contrast media-induced chemical hypersensitivity.

Contrast agents are used in radiology to increase the sensibility and specificity of radiological techniques. Some of these compounds have side effects that include organ toxicity (with kidney being the most affected organ) and hypersensitivity reactions. We performed multiple PubMed searches from January, 2008 to January, 2018 for studies regarding adverse reactions to compounds used as contrast agents in imagistic techniques. The initial research identified 929 records written in English. After further excluding 223 non-human studies, 292 articles that had irrelevant designs as reviews, meta-analysis, commentaries, editorials and case reports, 414 studies were selected for retrieval. After reading the abstracts, we excluded 363 studies as they had little relevance to the study. In total, 51 full-articles were assessed for eligible studies to be included. Finally, 20 articles were included in the analysis. In our systematic literature search the incidence of overall skin immediate reactions to iodinated contrast media (ICM) had an incidence between 1.15 and 0.12%, depending on the cohort analyzed in the studies. The percentage of cutaneous manifestations in the cohort that experienced immediate hypersensitivity reactions was between 33.33 and 87.7%. The most frequent skin manifestations were urticaria, rashes, pruritus and limited facial edema. Non-iodinated contrast agents have a safer profile compared with ICM, the incidence of immediate adverse reactions being very low in gadolinium-based contrast agents and other agents used for contrast-enhanced ultrasound. The incidence of delayed reactions was between 10.1 and 0.03%. In the studies analyzed by us the main adverse reactions due to delayed hypersensitivity phenomena were cutaneous manifestations that were present between 70.27 and 100% of the cases. Regarding the risk factors for developing immediate adverse reactions, being female was a predisposing factor accompanied by history of allergy and history of reactions to contrast media. An accurate anamnesis of the patients and a correctly conducted pretreatment can limit the incidence and the severity of the adverse reactions and also can avoid the life occurrence of life-threatening reactions.

Soyasaponin Ag inhibits α­MSH­induced melanogenesis in B16F10 melanoma cells via the downregulation of TRP­2.

Saponins, which are glycosylated, represent a diverse group of biologically functional products in plants. In the present study, we investigated the effects of soyasaponin Ag, a secondary metabolite extracted from soybean, on α­melanocyte-stimulating hormone (α­MSH)­induced melanin synthesis in B16F10 mouse melanoma cells and the underlying molecular mechanisms. To elucidate the mechanisms through which soyasaponin Ag inhibits melanin synthesis, we performed cellular tyrosinase activity assays and analyzed the expression of the melanogenesis­related genes, tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2. We demonstrated that soyasaponin Ag inhibited α­MSH­induced melanin synthesis in melanoma cells. Of note, soyasaponin Ag had no inhibitory effect on intracellular tyrosinase activity. However, soyasaponin Ag inhibited TRP­2 expression in a dose­dependent manner. Therefore, the depigmenting effect of soyasaponin Ag may be due to the inhibition of tyrosinase expression or the enhancement of tyrosinase degradation. Moreover, soyasaponin Ag did not exert any toxic on B16F10 mouse melanoma cells, suggesting that soyasaponin is a safe component for use in skin care cosmetic formulations that are used for skin whitening.

Neuroendocrine factors: The missing link in non­melanoma skin cancer (Review).

Non­melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun­protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun­exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. Aside from the well­known etiopathogenic factors, studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with the exception of penile SCC, for which a paucity of specific data on their pathogenic role exists. The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene­related peptide and somatostatin, as well as neurohormones, such as proopiomelanocortin and its derived peptides, α­melanocyte­stimulating hormone and adrenocorticotropin. All these factors have been, at least at some point, a subject of debate regarding their precise role in the pathogenesis of NMSC. There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC. Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. Further studies are required in order to elucidate the exact mechanisms through which neuroactive molecules promote or inhibit cutaneous carcinogenesis, as this could lead to the development of more sophisticated and tailored treatment protocols, as well as open new perspectives in skin cancer research.

Age-dependent endocrine disorders involved in the pathogenesis of refractory acne in women.

Acne is a disorder of the pilosebaceous unit, common among adolescents, which may be extended to adulthood. The aim of this study was to assess the prevalence of hormonal disorders in women with acne resistance to conventional therapy. We included 72 women aged between 15 and 36 years (divided in two age groups) who presented to our clinic between May and October 2014, suffering from moderate and severe forms of papulopustular and nodulocystic acne. The subjects were non­responsive to classic dermatological treatment or had clinical manifestation of hyperandrogenism. Based on age, we divided the women into two groups, group I with 40 patients aged 15­22 years and group II with 32 patients aged 23-36 years. Using ELISA, a hormonal profile was performed for each patient in days 1­3 of the menstrual cycle including, total testosterone, dehydroepiandrosterone sulfate (DHEA­S), follicle­stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, and plasma cortisol. For statistical analysis we used Stata 13 software. We compared the hormonal profile of the two groups and identified significant differences for: testosterone levels (mean value, 0.64±0.35 vs. 0.97±0.50 ng/ml; p<0.0001), DHEA­S levels (mean value, 0.85±0.27 vs. 1.05±0.33 mg/24 h; p=0.001), prolactin levels (mean value, 281.85±91.113 vs. 353.969±102.841 mIU/ml; p=0.002) and LH levels (14.8±6.7 vs. 20.1±8.2 mIU/ml; p=0.002) were higher in group â…¡. No statistically significant differences were found for estradiol (p=0.588) and cortisol (p=0.182) levels. In conclusion, refractory acne can be the first sign of systemic illness including polycystic ovary syndrome. Thus, for a correct therapeutic approach it is necessary to interpret the clinical and biochemical elements in correlation with the medical history.

Botulinum toxin type A--treatment of a patient with multiple cutaneous piloleiomyomas.

BACKGROUND: Treatment of multiple cutaneous piloleiomyomas which are rare, frequently painful, benign tumors originating from the arrector pilorum muscle of hair follicles is difficult. OBJECTIVE: To determine the efficiency of botulinum toxin type A (BT-A) treatment for pain relief of cutaneous piloleiomyomas. METHODS: A patient with multiple painful piloleiomyomas was treated with local injections of 200 units of BT-A. RESULTS: There was a rapid and sustained decrease in pain. Treatment was repeated every 3 months for 2 years with the same efficacy. CONCLUSION: BT-A may be a promising new treatment option for multiple painful cutaneous piloleiomyomas.

Fibroblast growth factor-2 modulates melanoma adhesion and migration through a syndecan-4-dependent mechanism.

Fibroblast growth factor-2 (FGF-2), the most abundant growth factor produced by melanoma cells but not by normal melanocytes, is an important regulator of cell proliferation, migration and differentiation. In this study we show that M5 human metastatic melanoma cells' ability to migrate is significantly enhanced by exogenously added FGF-2 while, neutralization of endogenous FGF-2 stimulates their adhesion. Previously, we have demonstrated that FGF-2 distinctly modulates the synthesis of individual glycosaminoglycans/proteoglycans (GAGs/PGs) subclasses, changing both their amounts and distribution in M5 cells. Here, treatment with FGF-2 strongly reduces the expression levels of the heparan sulfate-containing proteoglycan, syndecan-4. Syndecan-4 is a focal adhesion component in a range of cell types, adherent to several different matrix molecules, including fibronectin (FN). The reduction in syndecan-4 expression by utilizing specific siRNA discriminately increased melanoma cell motility and decreased their attachment on FN, demonstrating a regulatory role of syndecan-4 on these cell functions. Syndecan-4 has previously been demonstrated to regulate focal adhesion kinase (FAK) phosphorylation. In this study FGF-2 was shown to downregulate FAK Y397-phosphorylation during FN-mediated M5 cell adhesion, promoting their migration. The observed decrease in FAK Y397 activation was correlated to syndecan-4 expression levels. Thus, a balance in syndecan-4 expression perpetrated by FGF-2 may be required for optimal M5 cell migration. These results suggest that essential in melanoma progression FGF-2, specifically regulates melanoma cell ability to migrate through a syndecan-4-dependent mechanism.

Clinical and prognostic value of elevated CA125 levels in patients with congestive heart failure.

BACKGROUND: Increased serum levels of carbohydrate antigen 125 (CA125), a tumor marker associated with ovarian cancer, have also been reported in other malignant and non-malignant diseases. We assessed the correlation of the CA125 serum levels with the severity of congestive heart failure (CHF) and investigated their potential prognostic value in relation to major cardiovascular events. METHODS: CA125 levels were measured in 95 male patients aged 70+/-10 years, admitted for decompensated CHF. The patients were divided into three groups, according to their New York Heart Association (NYHA) functional class. Group A contained 23 patients in NYHA IV, group B 34 patients in NYHA III, and group C 38 patients in NYHA I-II. The patients were also divided into two groups according to their CA125 value on admission. Group 1 included 45 patients with normal CA125 levels and group 2 50 patients with elevated CA125. All patients were followed for 15+/-8.5 months and the major cardiovascular events (death and re-hospitalizations due to CHF) were recorded. RESULTS: Serum levels of CA125 were higher in groups A and B than in group C (36.4 [19.8-82] U/ml and 34.6 [26-78] U/ml vs. 25.3 [9.1-29] U/ml, respectively, p<0.05). No correlation was detected between CA125 levels and left ventricular ejection fraction. However, patients with pulmonary congestion and peripheral edemas had higher levels of CA125 (p=0.002 and p<0.03, respectively). Nineteen patients died during the follow-up period, but the mortality rate was not significantly different between groups 1 and 2 (p=0.8). Nevertheless, the patients of group 1 reported fewer re-hospitalizations than patients of group 2 (p=0.003). The relative risk (RR) for re-hospitalization was calculated to be RR: 0.4, 95% CI: 0.215-0.76 (p<0.005), in patients with elevated levels of CA125. Cox regression analysis revealed that CA125 had independent prognostic value (OR: 1.007 [95% CI: 1.004-1.010], p<0.0001) for re-hospitalizations. CONCLUSION: Serum levels of CA125 are associated with the severity of CHF and are also independent predictive markers for re-hospitalizations. We therefore conclude that CA125 can be used as a prognostic marker of disease severity and increased morbidity in patients with decompensated CHF.

The significance of CA125 levels in patients with chronic congestive heart failure. Correlation with clinical and echocardiographic parameters.

OBJECTIVE: To assess serum levels of carbohydrate antigen 125 (CA125) in patients with chronic congestive heart failure (CHF) and to assess any correlation with clinical symptoms and echocardiographic indices. PATIENTS AND METHODS: We enrolled 77 male patients (mean age: 73+/-10 years) admitted to the Cardiology Emergency Department (ED) with cardiac symptoms requiring hospitalization. Diagnosis of CHF was based upon medical history or initial echocardiographic evaluation on current admission. Serum CA125 was measured by an enzyme immunoradiometric assay, on admission and before discharge. RESULTS: The median overall CA125 value was 22.4 (11.5-48.9) U/ml. Serum CA125 levels were related to the severity of CHF [New York Heart Association (NYHA) class I: 19.2 (7.2-31) U/ml, NYHA class II: 17.6 (10-23) U/ml, NYHA class III: 32 (25-77) U/ml and NYHA class IV: 34.3 (18.6-77) U/ml (p<0.04)]. Patients in NYHA classes III and IV had significantly higher mean values of CA125, than patients in class II (p<0.005 and p<0.05, respectively). Moreover, patients with fluid congestion (pulmonary congestion, ankle edema) had higher levels of serum CA125 than patients without congestion (p=0.002 and p<0.03, respectively). Finally, levels of serum CA125 correlated weakly with right ventricular systolic pressure (RVSP) and renal function, while no significant correlation was found between CA125 and E wave deceleration time on Doppler echocardiography, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), liver function and the medical treatment prescribed. CONCLUSION: Serum CA125 is associated with the clinical severity of CHF and the symptoms and signs of fluid congestion and therefore may be a useful additional tool for the evaluation and clinical staging of these patients.

The epidemiology of peripheral vein complications: evaluation of the efficiency of differing methods for the maintenance of catheter patency and thrombophlebitis prevention.

BACKGROUND AND AIMS: Peripheral vein catheter patency and infusion thrombophlebitis remains a significant problem in everyday clinical practice. The aim of the study was to investigate the epidemiology of peripheral vein complications and to evaluate three different methods for the maintenance of peripheral vein catheter patency and the prevention of vein thrombophlebitis. METHODS: A total of 300 post-operative patients undergoing elective orthopaedic surgery were prospectively studied. Patients were divided into three groups: controls--catheters not flushed following drug administration; saline group--the catheters flushed with 3 mL of normal saline 0.9% after each catheter use; heparin group--the catheters flushed with 3 mL of 100-U/mL heparin in normal saline 0.9% after each catheter use. RESULTS: Complications occurred in 36% of the patients and the incidence of thrombophlebitis was 8% and only 4% in the control group. In the normal saline group there was a significant increase in total complications and obstruction together with thrombophlebitis as compared with the control group. Kaplan-Meier curves demonstrate that the control group had a significantly higher proportion of catheters without complications. CONCLUSIONS: The use of normal saline solutions in post-operative patients thus should be avoided for catheter maintenance. In patients receiving low molecular weight heparin, no intravenous flushing should be used for preventing catheter obstruction or thrombophlebitis in order to reduce costs and nursing workload.