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Nanocrystals of apatitic calcium phosphate impart the organic-inorganic nanocomposite in bone with favorable mechanical properties. So far, the factors preventing crystal growth beyond the favorable thickness of ca. 3 nm have not been identified. Here we show that the apatite surfaces are studded with strongly bound citrate molecules, whose signals have been identified unambiguously by multinuclear magnetic resonance (NMR) analysis. NMR reveals that bound citrate accounts for 5.5 wt% of the organic matter in bone and covers apatite at a density of about 1 molecule per (2 nm)², with its three carboxylate groups at distances of 0.3 to 0.45 nm from the apatite surface. Bound citrate is highly conserved, being found in fish, avian, and mammalian bone, which indicates its critical role in interfering with crystal thickening and stabilizing the apatite nanocrystals in bone.

Alterations in reward processing may represent an early vulnerability factor for the development of depressive disorder. Depression in adults is associated with reward hyposensitivity and diminished reward seeking may also be a feature of depression in children and adolescents. We examined the role of reward responding in predicting depressive symptoms, functional impairment and new-onset depressive disorder over time in the adolescent offspring of depressed parents. In addition, we examined group differences in reward responding between currently depressed adolescents, psychiatric and healthy controls, and also cross-sectional associations between reward responding and measures of positive social/environmental functioning. Method We conducted a 1-year longitudinal study of adolescents at familial risk for depression (n = 197; age range 10-18 years). Reward responding and self-reported social/environmental functioning were assessed at baseline. Clinical interviews determined diagnostic status at baseline and at follow-up. Reports of depressive symptoms and functional impairment were also obtained. Low reward seeking predicted depressive symptoms and new-onset depressive disorder at the 1-year follow-up in individuals free from depressive disorder at baseline, independently of baseline depressive symptoms. Reduced reward seeking also predicted functional impairment. Adolescents with current depressive disorder were less reward seeking (i.e. bet less at favourable odds) than adolescents free from psychopathology and those with externalizing disorders. Reward seeking showed positive associations with social and environmental functioning (extra-curricular activities, humour, friendships) and was negatively associated with anhedonia. There were no group differences in impulsivity, decision making or psychomotor slowing. Reward seeking predicts depression severity and onset in adolescents at elevated risk of depression. Adaptive reward responses may be amenable to change through modification of existing preventive psychological interventions.

Sacubitril/valsartan is a combination drug described as a new class of dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) for heart failure. We present a case of a patient with NYHA class IV systolic heart failure who was refractory to all other classes of heart failure medications and was started on this new medication. On sacubitril/valsartan, he developed cardiogenic shock. This led us to reevaluate the use and risks of this medication in the class IV heart failure population.

The mid-IR spectrum of the interstellar medium contains both aromatic and aliphatic hydrocarbon features. These are generally attributed to carbonaceous dust. The aliphatic component is of particular interest because it produces a significant 3.4 μm absorption feature. The optical depth of this feature is related to the number and type of aliphatic carbon C–H bonds in the line of sight. It is possible to estimate the column density of aliphatic carbon from quantitative analysis of the 3.4 μm interstellar feature, providing that the absorption coefficient of interstellar aliphatic hydrocarbon is known. We produced interstellar dust analogues with spectra closely matching astronomical observations. Using a combination of FTIR and 13C NMR spectroscopy, we determined an integrated absorption coefficient of the aliphatic component. The results thus obtained permit direct calibration of astronomical observations, providing rigorous estimates of the amount of aliphatic carbon in the ISM.

Electrified aerosols have been observed in the lower troposphere and in the mesosphere, but have never been detected in the stratosphere and upper troposphere. We present measurements of aerosols obtained during a balloon flight to an altitude of ~ 24 km. The measurements were performed with an improved version of the Stratospheric and Tropospheric Aerosol Counter (STAC) aerosol counter dedicated to the search for charged aerosols. It is found that most of the aerosols are charged in the upper troposphere for altitudes below 10 km and in the stratosphere for altitudes above 20 km. Conversely, the aerosols seem to be uncharged between 10 km and 20 km. Model calculations are used to quantify the electrification of the aerosols with a stratospheric aerosol-ion model. The percentages of charged aerosols obtained with model calculations are in excellent agreement with the observations below 10 km and above 20 km. However, the model cannot reproduce the absence of electrification found in the lower stratosphere, as the processes leading to neutralisation in this altitude range are unknown. The presence of sporadic transient layers of electrified aerosol in the upper troposphere and in the stratosphere could have significant implications for sprite formation.

Background Alcohol consumption is associated with apolipoproteins (Apos), key biomarkers for cardiovascular health. This meta-analysis assesses the effect of moderate alcohol intake (up to 40 g/day) on Apos concentration and evaluates the risk of bias in the available studies. Methods Twenty-five human intervention studies were analysed. Randomised studies (n = 15) were evaluated using the Cochrane Risk of Bias 2 (ROB 2) tool across five domains: the randomisation process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. Non-randomised studies (n = 10) were evaluated using the Risk of Bias Assessment tool for non-randomised studies (ROBINS-I), across seven domains: bias due to confounding, participant selection, intervention classification, deviations, missing data, outcome measurement, and result selection. Each study was rated as low, moderate, high or critical risk of bias for each domain. Results Moderate alcohol intake increased ApoA-I (MD: 7.77 mg/dl; 95% CI: 4.95-10.59) and ApoA-II (MD: 1.61 mg/dl; 95% CI: 0.33-2.90) levels compared to controls. However, in randomised studies, only one was rated low risk across all domains. Most studies showed inadequate randomisation or allocation concealment. Nine crossover trials failed to address carry-over effects due to an absent or insufficient washout period. All non-randomised studies (n = 10) were at critical risk of bias, mainly from unaddressed confounding. Six studies showed critical bias due to unclear adherence, affecting the domain of deviation from the intervention. Conclusions Significant risk of bias is present in the current literature assessing the effect of moderate alcohol intake on Apos. Future research must prioritise rigorous study design, better reporting, and control for confounders to improve the quality of evidence. Key messages • Moderate alcohol intake increases ApoA-I and ApoA-II levels, but study quality compromises the validity of the evidence. • Bias-controlled studies are needed for accurate assessment.

HUMAN-TO-HUMAN TRANSMISSION OF LANGYA VIRUS NEEDS EXTENSIVE RESEARCH Most disease outbreaks during the past two decades have been of zoonotic origin [3]. Rapid climate changes and increased human activity has increased the risk of viral exchange across different species of animals, which occasionally results in the transmission of zoonotic diseases to human beings [5]. GLOBAL PERSPECTIVES ON LANGYA VIRAL PREVENTION AND MANAGEMENT Farmers and manufacturing workers are the populations most vulnerable to LayV [7,11], as research has shown that proximity to animals and working in agricultural settings are linked to LayV virus infection.

Aortoesophageal fistula (AEF) is a rare cause of massive upper gastrointestinal hemorrhage. Thoracic aortic aneurysm, esophageal foreign body, esophageal cancer and post-surgical complications are common causes of AEF; however, AEF induced by radiation therapy is a rare phenomenon and seldom described in the literature. It is a catastrophic condition which requires rapid implementation of resuscitative measures, broad-spectrum antibiotics and surgical or endovascular intervention. Transthoracic endovascular aortic repair (TEVAR) is a newer and less invasive technique, which helps to achieve rapid hemostasis in patients with severe hemodynamic instability and offers advantages over conventional repair of the aorta in emergency situations. However initial TEVAR should be followed up with a more definitive surgical repair of the aorta and the esophagus, to lower the mortality rate and achieve better outcomes. We describe here a case of a seventy-year-old male who presented with massive upper gastrointestinal bleeding due to AEF induced by radiation therapy, and his subsequent successful initial management with TEVAR.

A female patient presented with progressive weakness, asthenia and generalized hyperpigmentation. The characteristic hyperpimentation pointed towards possibility of Addison’s disease which was proved by markedly decreased plasma cortisol levels, hyponatremia and hyperkalemia. This could be one of the very few cases of Addison’s Disease reported.