Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

A randomised control crossover trial of a theory based intervention to improve sun-safe and healthy behaviours in construction workers:Study protocol

Abstract Background Exposure to sunlight can have both positive and negative health impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause skin cancer, however insufficient exposure to sunlight has a detrimental effect on production of Vitamin D. In the construction industry there are onsite proactive behaviours for safety, but sun-safety remains a low priority. There is limited research on understanding the barriers to adopting sun-safe behaviours and the association this may have with Vitamin D production. This paper reports a protocol for an intervention study, using text messaging in combination with a supportive smartphone App. The intervention aims to both reduce UV exposure during months with higher UV levels and promote appropriate dietary changes to boost Vitamin D levels during months with low UV levels. Method/design Approximately 60 construction workers will be recruited across the United Kingdom. A randomised control crossover trial (RCCT) will be used to test the intervention, with randomisation at site level – i.e. participants will receive both the control (no text messages or supportive App support) and intervention (daily text messages and supportive App). Using the Theory of Planned Behaviour (TPB) the intervention focuses on supporting sun-safety and healthy dietary decisions in relation to Vitamin D intake. The intervention emphasises cultivating the perception of normative support in the workplace, increasing awareness of control and self-efficacy in taking sun-protective behaviours, making healthier eating choices to boost Vitamin D, and tackling stigmas attached to image and group norms. Each study epoch will last 21 days with intervention text messages delivered on workdays only. The supportive App will provide supplementary information about sun protective behaviours and healthy dietary choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level (obtained using blood spot sampling), which will be taken pre and post control and intervention periods. Secondary outcome measures are two-fold, (1) using the TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK peak radiation season (April–September) using body-mounted UV sensors. Discussion This study will provide important information about the effectiveness of a technology-based intervention to promote sun-safety and healthy behaviours in outdoor construction workers. Trial registration ISRCTN15888934 retrospectively registered 15.01.2018

A nationwide retrospective observational study of population newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in the Netherlands

To evaluate the Dutch newborn screening (NBS) for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency since 2007, a nationwide retrospective, observational study was performed of clinical, laboratory and epidemiological parameters of patients with MCAD deficiency born between 2007 and 2015. Severe MCAD deficiency was defined by ACADM genotypes associated with clinical ascertainment, or variant ACADM genotypes with a residual MCAD enzyme activity <10%. Mild MCAD deficiency was defined by variant ACADM genotypes with a residual MCAD enzyme activity ≥10%. The prevalence of MCAD deficiency was 1/8300 (95% CI: 1/7300-1/9600). Sensitivity of the Dutch NBS was 99% and specificity ~100%, with a positive predictive value of 86%. Thirteen newborns with MCAD deficiency suffered from neonatal symptoms, three of them died. Of the 189 identified neonates, 24% had mild MCAD deficiency. The acylcarnitine ratio octanoylcarnitine (C8)/decanoylcarnitine (C10) was superior to C8 in discriminating between mild and severe cases and more stable in the first days of life. NBS for MCAD deficiency has a high sensitivity, specificity, and positive predictive value. In the absence of a golden standard to confirm the diagnosis, the combination of acylcarnitine (ratios), molecular and enzymatic studies allows risk stratification. To improve evaluation of NBS protocols and clinical guidelines, additional use of acylcarnitine ratios and multivariate pattern-recognition software may be reappraised in the Dutch situation. Prospective recording of NBS and follow-up data is warranted covering the entire health care chain of preventive and curative medicine

A Nutrition and Conditioning Intervention for Natural Bodybuilding Contest Preparation: Case Study.

Bodybuilding competitions are becoming increasingly popular. Competitors are judged on their aesthetic appearance and usually exhibit a high level of muscularity and symmetry and low levels of body fat. Commonly used techniques to improve physique during the preparation phase before competitions include dehydration, periods of prolonged fasting, severe caloric restriction, excessive cardiovascular exercise and inappropriate use of diuretics and anabolic steroids. In contrast, this case study documents a structured nutrition and conditioning intervention followed by a 21 year-old amateur bodybuilding competitor to improve body composition, resting and exercise fat oxidation, and muscular strength that does not involve use of any of the above mentioned methods. Over a 14-week period, the Athlete was provided with a scientifically designed nutrition and conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not neglect any macronutrient groups; (iii) exercise regularly but not excessively and; (iv) incorporate rest days into his conditioning regime. This strategy resulted in a body mass loss of 11.7 kg’s, corresponding to a 6.7 kg reduction in fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there was a near 3-fold increase in the corresponding exercise intensity that elicited the maximal rate of fat oxidation; 21% V̇ O2max to 60% V̇ O2max. Hamstring concentric peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood-state (BRUMS scale) was not negatively influenced by the intervention and all values relating to the Athlete’s mood-state remained below average over the course of study. This intervention shows that a structured and scientifically supported nutrition strategy can be implemented to improve parameters relevant to bodybuilding competition and importantly the health of competitors, therefore questioning the conventional practices of bodybuilding preparation

Correlations among Brain Gray Matter Volumes, Age, Gender, and Hemisphere in Healthy Individuals

To determine the relationship between age and gray matter structure and how interactions between gender and hemisphere impact this relationship, we examined correlations between global or regional gray matter volume and age, including interactions of gender and hemisphere, using a general linear model with voxel-based and region-of-interest analyses. Brain magnetic resonance images were collected from 1460 healthy individuals aged 20–69 years; the images were linearly normalized and segmented and restored to native space for analysis of global gray matter volume. Linearly normalized images were then non-linearly normalized and smoothed for analysis of regional gray matter volume. Analysis of global gray matter volume revealed a significant negative correlation between gray matter ratio (gray matter volume divided by intracranial volume) and age in both genders, and a significant interaction effect of age × gender on the gray matter ratio. In analyzing regional gray matter volume, the gray matter volume of all regions showed significant main effects of age, and most regions, with the exception of several including the inferior parietal lobule, showed a significant age × gender interaction. Additionally, the inferior temporal gyrus showed a significant age × gender × hemisphere interaction. No regional volumes showed significant age × hemisphere interactions. Our study may contribute to clarifying the mechanism(s) of normal brain aging in each brain region

Cysteamine Attenuates the Decreases in TrkB Protein Levels and the Anxiety/Depression-Like Behaviors in Mice Induced by Corticosterone Treatment

OBJECTIVE: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders. MATERIALS AND METHODS: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure. RESULTS: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine. CONCLUSIONS: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders

Risk factors for methamphetamine use in youth: a systematic review

<p>Abstract</p> <p>Background</p> <p>Methamphetamine (MA) is a potent stimulant that is readily available. Its effects are similar to cocaine, but the drug has a profile associated with increased acute and chronic toxicities. The objective of this systematic review was to identify and synthesize literature on risk factors that are associated with MA use among youth.</p> <p>More than 40 electronic databases, websites, and key journals/meeting abstracts were searched. We included studies that compared children and adolescents (≤ 18 years) who used MA to those who did not. One reviewer extracted the data and a second checked for completeness and accuracy. For discrete risk factors, odds ratios (OR) were calculated and when appropriate, a pooled OR with 95% confidence intervals (95% CI) was calculated. For continuous risk factors, mean difference and 95% CI were calculated and when appropriate, a weighted mean difference (WMD) and 95% CI was calculated. Results were presented separately by comparison group: low-risk (no previous drug abuse) and high-risk children (reported previous drug abuse or were recruited from a juvenile detention center).</p> <p>Results</p> <p>Twelve studies were included. Among low-risk youth, factors associated with MA use were: history of heroin/opiate use (OR = 29.3; 95% CI: 9.8–87.8), family history of drug use (OR = 4.7; 95% CI: 2.8–7.9), risky sexual behavior (OR = 2.79; 95% CI: 2.25, 3.46) and some psychiatric disorders. History of alcohol use and smoking were also significantly associated with MA use. Among high-risk youth, factors associated with MA use were: family history of crime (OR = 2.0; 95% CI: 1.2–3.3), family history of drug use (OR = 4.7; 95% CI: 2.8–7.9), family history of alcohol abuse (OR = 3.2; 95% CI: 1.8–5.6), and psychiatric treatment (OR = 6.8; 95% CI: 3.6–12.9). Female sex was also significantly associated with MA use.</p> <p>Conclusion</p> <p>Among low-risk youth, a history of engaging in a variety of risky behaviors was significantly associated with MA use. A history of a psychiatric disorder was a risk factor for MA for both low- and high-risk youth. Family environment was also associated with MA use. Many of the included studies were cross-sectional making it difficult to assess causation. Future research should utilize prospective study designs so that temporal relationships between risk factors and MA use can be established.</p

Gene Transcription Changes in Asthmatic Chronic Rhinosinusitis with Nasal Polyps and Comparison to Those in Atopic Dermatitis

Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma.Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD.Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases