Presence of Hypertension Is Reduced by Mediterranean Diet Adherence in All Individuals with a More Pronounced Effect in the Obese: The Hellenic National Nutrition and Health Survey (HNNHS)

Hypertension is a major risk of cardiovascular diseases. This study's aim was to examine associations between hypertension and a priori known lifestyle risk factors, including weight status and Mediterranean diet adherence. The study included a representative sample of the adult population (N = 3775 (40.8% males)), from the Hellenic National Nutrition and Health Survey (HNNHS), which took place from September 2013 to May 2015. Demographic and anthropometric data were collected using validated questionnaires, and blood pressure (BP) measurements were performed for the two main metropolitan areas (N = 1040; 41.1%). Hypertension diagnosis was according to the International Classification of Diseases (ICD-10) guidelines. Weighted proportions, extended Mantel-Haenszel (M-H) analyses, and multiple logistic regressions (for the survey data) were performed. Mean systolic BP (SBP) and diastolic BP (DBP) were 118.6 mmHg and 72.2 mmHg respectively, with both values being higher in males compared to females in all age groups (p < 0.001). Study participants with hyperlipidemia or diabetes, and those overweight, were almost twice as likely to be hypertensives, with the odds increasing to 4 for those obese (p for all, < 0.05). Stricter Mediterranean diet adherence significantly decreased the likelihood of hypertension by 36% (OR: 0.64; 95% CI: 0.439, 0.943), and a significant interaction was found between Mediterranean diet adherence and weight status on hypertension. The presence of hypertension is clustered with comorbidities, but is significantly associated with modifiable risk factors, including Mediterranean diet and weight status, underlining the need for personalized medical nutritional treatment

When Limb Surgery Has Become the Only Life-Saving Therapy in FOP: A Case Report and Systematic Review of the Literature

Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [18F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described

IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans

Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs. In contrast, disruption of motile cilia function causes subfertility, disruption of the left-right body axis, and recurrent airway infections with progressive lung damage. In this work, we characterize allele specific phenotypes resulting from IFT74 dysfunction in human and mice. We identified two families carrying a deletion encompassing IFT74 exon 2, the first coding exon, resulting in a protein lacking the first 40 amino acids and two individuals carrying biallelic splice site mutations. Homozygous exon 2 deletion cases presented a ciliary chondrodysplasia with narrow thorax and progressive growth retardation along with a mucociliary clearance disorder phenotype with severely shorted cilia. Splice site variants resulted in a lethal skeletal chondrodysplasia phenotype. In mice, removal of the first 40 amino acids likewise results in a motile cilia phenotype but with little effect on primary cilia structure. Mice carrying this allele are born alive but are growth restricted and developed hydrocephaly in the first month of life. In contrast, a strong, likely null, allele of Ift74 in mouse completely blocks ciliary assembly and causes severe heart defects and midgestational lethality. In vitro studies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia resulting from increased mechanical stress and repair needs could account for the motile cilia phenotype observed in human and mice

IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans

Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs. In contrast, disruption of motile cilia function causes subfertility, disruption of the left-right body axis, and recurrent airway infections with progressive lung damage. In this work, we characterize allele specific phenotypes resulting from IFT74 dysfunction in human and mice. We identified two families carrying a deletion encompassing IFT74 exon 2, the first coding exon, resulting in a protein lacking the first 40 amino acids and two individuals carrying biallelic splice site mutations. Homozygous exon 2 deletion cases presented a ciliary chondrodysplasia with narrow thorax and progressive growth retardation along with a mucociliary clearance disorder phenotype with severely shorted cilia. Splice site variants resulted in a lethal skeletal chondrodysplasia phenotype. In mice, removal of the first 40 amino acids likewise results in a motile cilia phenotype but with little effect on primary cilia structure. Mice carrying this allele are born alive but are growth restricted and developed hydrocephaly in the first month of life. In contrast, a strong, likely null, allele of Ift74 in mouse completely blocks ciliary assembly and causes severe heart defects and midgestational lethality. In vitro studies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia resulting from increased mechanical stress and repair needs could account for the motile cilia phenotype observed in human and mice

X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.</p

Fibrodysplasia Ossificans Progressiva: what have we achieved and where are we now? follow-up to the 2015 Lorentz Workshop

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics

Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system\u27s role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application

Effectiveness of school food environment policies on children's dietary behaviors: A systematic review and meta-analysis.

BACKGROUND: School food environment policies may be a critical tool to promote healthy diets in children, yet their effectiveness remains unclear. OBJECTIVE: To systematically review and quantify the impact of school food environment policies on dietary habits, adiposity, and metabolic risk in children. METHODS: We systematically searched online databases for randomized or quasi-experimental interventions assessing effects of school food environment policies on children's dietary habits, adiposity, or metabolic risk factors. Data were extracted independently and in duplicate, and pooled using inverse-variance random-effects meta-analysis. Habitual (within+outside school) dietary intakes were the primary outcome. Heterogeneity was explored using meta-regression and subgroup analysis. Funnel plots, Begg's and Egger's test evaluated potential publication bias. RESULTS: From 6,636 abstracts, 91 interventions (55 in US/Canada, 36 in Europe/New Zealand) were included, on direct provision of healthful foods/beverages (N = 39 studies), competitive food/beverage standards (N = 29), and school meal standards (N = 39) (some interventions assessed multiple policies). Direct provision policies, which largely targeted fruits and vegetables, increased consumption of fruits by 0.27 servings/d (n = 15 estimates (95%CI: 0.17, 0.36)) and combined fruits and vegetables by 0.28 servings/d (n = 16 (0.17, 0.40)); with a slight impact on vegetables (n = 11; 0.04 (0.01, 0.08)), and no effects on total calories (n = 6; -56 kcal/d (-174, 62)). In interventions targeting water, habitual intake was unchanged (n = 3; 0.33 glasses/d (-0.27, 0.93)). Competitive food/beverage standards reduced sugar-sweetened beverage intake by 0.18 servings/d (n = 3 (-0.31, -0.05)); and unhealthy snacks by 0.17 servings/d (n = 2 (-0.22, -0.13)), without effects on total calories (n = 5; -79 kcal/d (-179, 21)). School meal standards (mainly lunch) increased fruit intake (n = 2; 0.76 servings/d (0.37, 1.16)) and reduced total fat (-1.49%energy; n = 6 (-2.42, -0.57)), saturated fat (n = 4; -0.93%energy (-1.15, -0.70)) and sodium (n = 4; -170 mg/d (-242, -98)); but not total calories (n = 8; -38 kcal/d (-137, 62)). In 17 studies evaluating adiposity, significant decreases were generally not identified; few studies assessed metabolic factors (blood lipids/glucose/pressure), with mixed findings. Significant sources of heterogeneity or publication bias were not identified. CONCLUSIONS: Specific school food environment policies can improve targeted dietary behaviors; effects on adiposity and metabolic risk require further investigation. These findings inform ongoing policy discussions and debates on best practices to improve childhood dietary habits and health

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries