The usability of daytime and night-time heart rate dynamics as digital biomarkers of depression severity.

BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

Colloidal polymer composites: Are nano-fillers always better for improving mechanical properties?

HYPOTHESIS: Colloidal polymer composites, in which polymer particles are blended with a filler, are widely used in applications including pharmaceuticals, crop protection, inks, and protective coatings. It is generally found that the presence of hard particulate fillers will increase the elastic modulus of a polymer colloid composite. However, the influence of the size of the filler particle on the large-strain deformation and fracture and on the viscoelastic characteristics, including creep, is not well explored. We hypothesize that the size ratio of the filler to the colloidal polymer will play a critical role in determining the properties of the composite. EXPERIMENTS: Colloidal composites were prepared by blending soft polymer colloids (as a binder) with calcium carbonate fillers having four different sizes, spanning from 70 nm to 4.5 µm. There is no bonding between the filler and matrix in the composites. The large-strain deformation, linear viscoelasticity, and creep were determined for each filler size for increasing the filler volume fractions (ϕCC). Weibull statistics were used to analyze the distributions of strains at failure. FINDINGS: We find that the inclusion of nano-fillers leads to brittle fracture at a lower ϕCC than when µm-size fillers are used. The data interpretation is supported by Weibull analysis. However, for a given ϕCC, the storage modulus is higher in the rubbery regime, and the creep resistance is higher when nanoparticles are used. Using scanning electron microscopy to support our arguments, we show that the properties of colloidal composites are correlated with their microstructure, which can be altered through control of the filler:polymer particle size ratio. Hard nanoparticles pack efficiently around larger particles to provide reinforcement (manifested as a higher storage modulus and greater creep resistance), but they also introduce weak points that lead to brittleness.

Stratification in binary colloidal polymer films: experiment and simulations.

When films are deposited from mixtures of colloidal particles of two different sizes, a diverse range of functional structures can result. One structure of particular interest is a stratified film in which the top surface layer has a composition different than in the interior. Here, we explore the conditions under which a stratified layer of small particles develops spontaneously in a colloidal film that is cast from a binary mixture of small and large polymer particles that are suspended in water. A recent model, which considers the cross-interaction between the large and small particles (Zhou et al., Phys. Rev. Lett., 2017, 118, 108002), predicts that stratification will develop from dilute binary mixtures when the particle size ratio (α), initial volume fraction of small particles (ϕS), and Péclet number are high. In experiments and Langevin dynamics simulations, we systematically vary α and ϕS in both dilute and concentrated suspensions. We find that stratified films develop when ϕS is increased, which is in agreement with the model. In dilute suspensions, there is reasonable agreement between the experiments and the Zhou et al. MODEL: In concentrated suspensions, stratification occurs in experiments only for the higher size ratio α = 7. Simulations using a high Péclet number, additionally find stratification with α = 2, when ϕS is high enough. Our results provide a quantitative understanding of the conditions under which stratified colloidal films assemble. Our research has relevance for the design of coatings with targeted optical and mechanical properties at their surface.

A new technique for the radiolabelling of mixed leukocytes with zirconium-89 for inflammation imaging with positron emission tomography.

Mixed leukocyte (white blood cells [WBCs]) trafficking using positron emission tomography (PET) is receiving growing interest to diagnose and monitor inflammatory conditions. PET, a high sensitivity molecular imaging technique, allows precise quantification of the signal produced from radiolabelled moieties. We have evaluated a new method for radiolabelling WBCs with either zirconium-89 ((89) Zr) or copper-64 ((64) Cu) for PET imaging. Chitosan nanoparticles (CNs) were produced by a process of ionotropic gelation and used to deliver radiometals into WBCs. Experiments were carried out using mixed WBCs freshly isolated from whole human blood. WBCs radiolabelling efficiency was higher with [(89) Zr]-loaded CN (76.8 ± 9.6% (n = 12)) than with [(64) Cu]-loaded CN (26.3 ± 7.0 % (n = 7)). [(89) Zr]-WBCs showed an initial loss of 28.4 ± 5.8% (n = 2) of the radioactivity after 2 h. This loss was then followed by a plateau as (89) Zr remains stable in the cells. [(64) Cu]-WBCs showed a loss of 85 ± 6% (n = 3) of the radioactivity after 1 h, which increased to 96 ± 6% (n = 3) loss after 3 h. WBC labelling with [(89) Zr]-loaded CN showed a fast kinetic of leukocyte association, high labelling efficiency and a relatively good retention of the radioactivity. This method using (89) Zr has a potential application for PET imaging of inflammation.

Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction.

Mesenchymal stromal cells (MSCs) are cardioprotective in acute myocardial infarction (AMI). Besides, we have shown that intramyocardial injection of plasmid-VEGF(165) (pVEGF) in ovine AMI reduces infarct size and improves left ventricular (LV) function. We thus hypothesized that MSCs overexpressing VEGF(165) (MSCs-pVEGF) would afford greater cardioprotection than non-modified MSCs or pVEGF alone. Sheep underwent an anteroapical AMI and, 1 week later, received intramyocardial MSCs-pVEGF in the infarct border. One month post treatment, infarct size (magnetic resonance) decreased by 31% vs pre-treatment. Of note, myocardial salvage occurred predominantly at the subendocardium, the myocardial region displaying the largest contribution to systolic performance. Consistently, LV ejection fraction recovered to almost its baseline value because of marked decrease in end-systolic volume. None of these effects were observed in sheep receiving non-transfected MSCs or pVEGF. Although myocardial retention of MSCs decreased steeply over time, the treatment induced significant capillary and arteriolar proliferation, which reduced subendocardial fibrosis. We conclude that in ovine AMI, allogeneic VEGF-overexpressing MSCs induce subendocardial myocardium salvage through microvascular proliferation, reducing infarct size and improving LV function more than non-transfected MSCs or the naked plasmid. Importantly, the use of a plasmid rather than a virus allows for repeated treatments, likely needed in ischemic heart disease.

An integrated approach to safety-driven and ICT-enabled process reengineering: methodological advice and a case study.

Patient safety is a central concern inside any healthcare environment. With the progress of Information and Communication Technologies (ICTs), new solutions have become available to support care and management processes. Analyzing process risks helps identifying areas of improvement and provides ICT-solutions design with indications on what portions of the process need primary interventions. Understanding the link between process reengineering, technology assessment of enabling technologies and risk management allows user acceptance and patient safety improvements. Fondazione IRCCS Istituto Nazionale dei Tumori (INT), offers a good example of process reengineering driven by the purpose of increasing patient safety, enabled by new technologies. A pillar of the evolution of ICT process support at INT is based on Radio Frequency Identification technologies, implemented to identify and trace items and people across processes. This paper will present an integrated approach, based on process reengineering methodologies and risk assessment studies, and methodological advice applied to a case of surgical kits management procedures.

A complicated case of intracranial hypotension: diagnostic and management strategies.

We report a case of a patient aged 66 years, with spontaneous intracranial hypotension presenting initially with postural headache, complicated by subdural haematomas and followed by progressive decline of his clinical condition evolving in obtundation state, cranial nerve involvement and gaze paralysis. The patient underwent a long course of different therapeutical approaches: medical and surgical treatment, intrathecal saline infusion and epidural blood patching (EBP). Rapid and dramatic relief of the patient's symptoms was obtained after a third lumbar EBP and he was discharged asymptomatic two weeks later.

Hemifacial spasm: endoscopic vascular decompression.

Sixty patients with primitive hemifacial spasm were treated by means of a minimally invasive retrosigmoid approach in which endoscopic and microsurgical procedures were combined. Intraoperative endoscopic examination of the cerebellopontine angle showed that for 56 of the patients vessel-nerve conflict was the cause of hemifacial spasm. The most common offending vessel was the posterior inferior cerebellar artery (39 patients), next was the vertebral artery (23 patients), and last was the anterior inferior cerebellar artery (16 patients). Nineteen of the patients had multiple offending vascular loops. In one patient, another cause of hemifacial spasm was an epidermoid tumor of the cerebellopontine angle. For three patients, it was not possible to determine the exact cause of the facial disorder. Follow-up information was reviewed for 54 of 60 patients; the mean follow-up period was 14 months. Fifty of the patients were in the vessel-nerve conflict group. Forty of the 50 were free of symptoms, and four had marked improvement. The overall success rate was 88%, and there was minimal morbidity (no facial palsy, two cases of severe hearing loss).

Citrate in synovial fluid and its relation to inflammation and crystal presence.

OBJECTIVE: To investigate the role of citrate in the pathophysiology of arthritides with calcium pyrophosphate dihydrate (CPPD) crystals and/or apatite-like material. METHODS: We measured citrate concentrations in the plasma and synovial fluid (SF) of 23 joints whose SF contained these crystals and 33 joints without crystals. The SF originated from 25 joints each of patients with rheumatoid arthritis (RA) and primary osteoarthritis (OA) and 10 patients with various other inflammatory joint diseases. RESULTS: There was significant correlation between citrate concentrations in the SF and plasma with values globally twice as high in the SF as in the plasma. Citrate concentrations in the SF of patients whose SF contained CPPD crystals and/or apatite-like material were not significantly lower than those without crystals. On the other hand, citrate concentrations were significantly lower in the SF of patients with RA and other inflammatory joint diseases versus those with OA. CONCLUSION: We have no evidence that lower amounts of citrate in SF favor the presence of CPPD crystals or apatite-like material. Our results, however, do suggest a complex regulation of the citrate concentration in SF where cellular metabolic processes and citrates arising from the plasma and neighboring tissues probably interact to produce the levels recorded.

[Neurinomas of the cochlear nerve]. / Neurinomes du nerf cochléaire.

Usually, schwannomas of the eight nerve arise from the vestibular nerve. Yet, the authors have operated from September 1993 to September 1995 three neuromas whose origin is certainly the cochlear nerve. Surgery was performed by retro-sigmoid approach magnified by endoscopic procedure of the cerebello-pontine angle before and after removing the tumor. We report here the cases and the literature is documented. Similar cases of observing cochlear neuromas at the moment of the procedure are exceptional. Because of more and more early diagnosis of these tumors, advances of microsurgery in ponto-cerebellar angle and endoscopic improvements in this area, observation of this kind of pathology could be more and more frequent.

[Neuro-vascular decompression in hemifacial spasm: anatomical, electrophysiological and therapeutic results apropos of 100 cases]. / Décompression neuro-vasculaire dans le spasme de l'hémiface: résultats anatomiques, électrophysiologiques et thérapeutiques à propos de 100 cas.

Hemifacial spasm is a neurological disorder due to abnormal hyperactivity of the facial nerve. The most common cause of hemifacial spasm is a neuro-vascular conflict in the cerebellopontine angle between a vascular loop and the root of the facial nerve (96% of cases). Tumors are the cause of hemifacial spasm in only 1% of cases). The authors present their results in 100 patients who underwent microvascular decompression for essential hemifacial spasm between 1990 and 1995. They used microsurgical and endoscopic procedures by a minimal retrosigmoid approach in all cases. The most common offending vessels were the posterior inferior cerebellar artery (70%), the vertebral artery (41%) and the anterior inferior cerebellar artery (28%). An aberrant vein was found in 2 cases. There were 38% of multiple artery-nerve conflicts. Physiopathology of hemifacial spasm is explained by two principal theories: in the ephaptic theory, hyperactivity and an abnormal nervous impulse pathway are due to a short demyelinated area on the nerve trunk caused by the offending vessel, inducing short circuiting between adjacent nerve fibers. In the nuclear theory, hyperactivity of the facial nerve is due to an abnormal and automatic activity of the facial nerve nucleus itself, induced by the vessel. The authors used pre and postoperative electromyographic tests and intraoperative electromyographic tests. Their results tend to prove the nuclear theory. Ninety per cent of the patients had a good result, with a mean follow-up time of 30 months in 60 cases. In 82% of the cases, there was a total recovery after a single procedure. There was no mortality and no facial palsy. Hearing loss occurred in less than 5%.

Endoscopy of the cerebellopontine angle.

The authors present their experience of 191 patients from June 1990 to December 1993 with endoscopy of the cerbellopontine angle using a limited retrosigmoid approach. The advantages of endoscopy of the cerebellopontine angle are the simplicity and efficiency of the procedure, and less invasive surgery. The authors emphasize the importance of the endoscopic procedure: first in acoustic neuroma surgery to get more accurate information about the relationship between the tumour and the adjacent structures, and to control the lateral end of the internal auditory canal; second in hemifacial spasm or facial neuralgia surgery, intraoperative endoscopy is the key point giving a sure and safe way to recognize the offending vessels.

Canal wall prosthesis--new devices.

In our experience, management of the troublesome mastoid cavity a "rehabilitation" of the middle ear, usually involves post canal wall reconstruction. The purpose of the long canal wall reconstruction is to restore the anatomy as perfectly as possible in order to induce satisfactory wound healing of both epidermal a mucosal layers. The numerous materials and different surgical procedures to date, demonstrate the difficulty of reconstruction of the ear canal. Over twenty years we have performed 386 cases using various materials: cortical bone, ear canal allograft, ceravital, porous and dense hydroxylapatite. More recently to improve the anatomical results we have used a new titanium prosthesis. The pros and cons of each device are discussed.

Surgical perspectives of endoscopy of the cerebellopontine angle.

Owing to distal light and panoramic view, the endoscope expands the view inside the cerebellopontine angle without touching the cerebellum or the brain stem and allows clear identification of the vascular and nervous components crossing the cerebellopontine angle. Using a retrosigmoid approach with a combined surgical and endoscopic procedure, the surgeon gets more accurate information to visualize the adjacent structures to a small acoustic neuroma, to check the lateral part of the internal auditory canal, and to locate a vasculonervous cross-conflict. In the future, an endoscopic vestibular neurotomy or an endoscopic microvascular decompression seems to be a possible approach.

Different patterns of CSF neurotransmitter metabolism in patients with left or right hemispheric stroke.

In 30 ischemic stroke patients, divided into 2 groups depending on the side of their hemispheric cerebral lesion, the authors evaluated the levels of CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The changes of these metabolites in CSF samples collected 3, 14 and 25 days after stroke have been correlated to the clinical course. In both groups, which were similar in respect to the localization of the infarcted area and to the volume of the lesion, the levels of HVA and 5-HIAA increased in the first 2-3 days and gradually declined to normal values in the following 3 weeks, in parallel with the regression of neurological deficits. The increase of HVA and 5-HIAA was statistically significant only in left hemisphere-injured patients. A linear regression analysis between the clinical score values and the CSF levels of the two metabolites at different time-points of observation revealed a significant correlation only for the HVA in the left-lesioned patients.

Caerulein peripheral injection: a study on the correlation with dopaminergic metabolism.

Immunocytochemical and electrophysiological studies indicate the existence of a functional relationship between Cholecystokinin (CCK) and dopaminergic transmission. In order to gain more information on this relationship, the effect of Caerulein, a CCK stable analogue, on rat spontaneous locomotor activity and on biochemical markers of dopaminergic transmission were measured simultaneously. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and the spontaneous or K+ evoked release of dopamine were studied in rat striatum and nucleus accumbens immediately after testing for motor activity. An almost complete reduction in locomotor activity but not significant changes in DOPAC content and dopamine release were observed in rats injected with the peptide (0.25/microgram/Kg, intraperitoneally). DOPAC concentrations were slightly (30%) decreased by increasing 200 folds caerulein dose. In addition, a very minute dose of haloperidol (25 /microgram/Kg) potentiated the caerulein (0.25/microgram/Kg) induced hypomotility, while the parameters of dopaminergic metabolism were unaffected. Our results indicate the existence of a relevant pharmacological interaction between caerulein and dopamine antagonists, although it is not clear whether this interaction takes place at the dopamine terminals level.