A simple intervention for disorders of consciousness- is there a light at the end of the tunnel?

Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30-71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low (M: 31%, Range: 13-66.4%, SD: 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant (p = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant (p = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level (p = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC.

Nephrotic syndrome with minimal change disease after the Pfizer-BioNTech COVID-19 vaccine: two cases.

We present two cases of nephrotic syndrome with minimal change disease after the Pfizer-BioNTech COVID-19 vaccine. We discuss the initial presentation, investigation and management of these patients along with a discussion around the current evidence base for vaccine-induced nephrotic syndrome.

Synthesis of Sodium Alginate-Silver Nanocomposites Using Plasma Activated Water and Cold Atmospheric Plasma Treatment.

In this study, sodium alginate (SA)-based, eco-friendly nanocomposites films were synthesized for potential food packaging applications using silver nitrate (AgNO3) as the metal precursor, reactive nitrogen and oxygen species (RNOS) created within plasma activated water (PAW), or through cold plasma treatment (CP) as reducing agent and SA as stabilizing agent. The formation of silver nanoparticles (AgNPs) was confirmed via the absorption peaks observed between 440 and 450 nm in UV-vis spectroscopy. The tensile strength (TS) and tensile modulus (TM) of the nanocomposite films were significantly higher than those of the SA films. An increase in the TS was also observed as the AgNP concentration was increased from 1 to 5 mM. The storage modulus (G') of the nanocomposite solution was higher than that of the SA solution. The synthesis of AgNPs resulted both in a higher solution viscosity and a more marked shear-thinning effect. The synthesized AgNPs showed antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The AgNPs were spherical in shape with an average size of 22 nm.

Nitrogen and metal pollution in the southern Caspian Sea: a multiple approach to bioassessment.

The Caspian Sea hosts areas of high ecological value as well as industrial, leisure, and agricultural activities that dump into the water body different kinds of pollutants. In this complex context, a proper description of the origin and potential sources of pollution is necessary to address management and mitigation actions aimed at preserving the quality of the water resource and the integrity of the ecosystems. Here, we aimed at detecting sources of both nitrogen inputs, by N stable isotope analysis of macroalgae, and metals in macroalgae and sediments in two highly anthropized coastal stretches at the Iranian side of the Caspian Sea. Sampling was done near the mouth of rivers and canals draining agricultural and urbanized areas. In the westernmost waters, facing a port city, low macroalgal δ15N signatures indicated industrial fertilizers as the principal source of pollution. By contrast, in the central coastal waters, facing touristic areas, the high macroalgal δ15N indicated N inputs from wastewaters. Here the lowest dissolved oxygen concentrations in waters were associated with excess dissolved inorganic nitrogen. Metal concentrations varied largely in the study areas and were lower in macroalgae than in sediments. Localized peaks of Pb and Zn in sediments were observed in the central coastal sites as probable byproducts of mining activity transported downstream. By contrast, Cr and Ni concentrations were high in all sampling sites, thus potentially representing hazardous elements for marine biota. Overall, macroalgal δ15N coupled with metal analysis in macroalgae and sediments was useful for identifying the main sources of pollution in these highly anthropized coastal areas. This double approach in comprehensive monitoring programs could thus effectively inform stakeholders on major environmental threats, allowing targeted management measures.

High-output cardiac failure secondary to high-output arteriovenous fistula: investigations, management and definitive treatment.

A 32 year-old woman was admitted to our institution with progressive dyspnoea. Her medical history was notable for end-stage renal failure secondary to chronic pyelonephritis, and she had undergone a cadaveric renal transplant in 2010. This had been preceded by haemodialysis treatment via a radiocephalic arteriovenous fistula. Her diagnostic evaluation was remarkable for pulmonary hypertension. A subsequent doppler ultrasound of her arteriovenous fistula revealed a blood flow of 3 L/min. This is consistent with a high output fistula. Echocardiography demonstrated an improvement in pulmonary artery pressure with occlusion of the fistula. After multidisciplinary discussion, a decision was made to surgically tie off her fistula. The patient experienced immediate improvement in her shortness of breath along with resolution of pulmonary hypertension on echocardiography. This case highlights the rare complication of high output cardiac failure from a dialysis fistula and its successful surgical management.

Towards the Next-Generation Disinfectant: Composition, Storability and Preservation Potential of Plasma Activated Water on Baby Spinach Leaves.

Plasma activated water (PAW) has rapidly emerged as a promising alternative to traditional sanitizers applied in the fresh produce industry. In the present study, PAW chemistry and storage stability were assessed as a function of plasma operating conditions. Increasing plasma exposure time (5, 12.5, 20 min) and power (16, 26, 36 W) led to a significant drop in pH (2.4) and higher nitrates and nitrites levels (320 and 7.2 mg/L, respectively) in the PAW. Non-detectable hydrogen peroxide concentration, irrespective of the treatment conditions, was attributed to its instability in acidic environments and the remote PAW generation mode. pH, nitrates and nitrites levels in the PAW remained unaffected after two weeks at 4 °C. The potential of PAW for microbial inactivation and quality retention was demonstrated on baby spinach leaves. Rinsing steps influenced colour development during chilled storage to a greater extent than PAW treatment itself. About 1 log reduction in total bacterial counts (5 log CFU/g) was achieved through PAW rinsing, with no variability after eight days at 4 °C (typical shelf-life at retailers). Moreover, microbial levels on PAW-treated samples after storage were significantly lower than those on control samples, thus contributing to extended product shelf-life and reduced food waste generation.

Patients with a severe prolonged Disorder of Consciousness can show classical EEG responses to their own name compared with others' names.

Patients in Vegetative State (VS), also known as Unresponsive Wakefulness State (UWS) are deemed to be unaware of themselves or their environment. This is different from patients diagnosed with Minimally Conscious state (MCS), who can have intermittent awareness. In both states, there is a severe impairment of consciousness; these disorders are referred to as disorders of consciousness (DOC) and if the state is prolonged, pDOC. There is growing evidence that some patients who are behaviourally in VS/UWS can show neural activation to environmental stimuli and that this response can be detected using functional brain imaging (fMRI/PET) and electroencephalography (EEG). Recently, it has also been suggested that a more reliable detection of brain responsiveness and hence a more reliable differentiation between VS/UWS and MCS requires person-centred and person-specific stimuli, such as the subject's own name stimulus. In this study we obtained event related potential data (ERP) from 12 healthy subjects and 16 patients in pDOC, five of whom were in the VS/UWS and 11 in the Minimally Conscious State (MCS). We used as the ERP stimuli the subjects' own name, others' names and reversed other names. We performed a sensor level analysis using Statistical Parametric Mapping (SPM) software. Using this paradigm in 4 DOC patients (3 in MCS, and 1 in VS/UWS) we detected a statistically significant difference in EEG response to their own name versus other peoples' names with ERP latencies (~300 ms and ~700 ms post stimuli). Some of these differences were similar to those found in a control group of healthy subjects. This study shows the feasibility of using self-relevant stimuli such as a subject's own name for assessment of brain function in pDOC patients. This neurophysiological test is suitable for bed-side/hospital based assessment of pDOC patients. As it does not require sophisticated scanning equipment it can feasibly be used within a hospital or care setting to help professionals tailor medical and psycho-social management for patients.

Late recovery of awareness in prolonged disorders of consciousness -a cross-sectional cohort study.

PURPOSE: To detect any improvement of awareness in prolonged disorders of consciousness in the long term. METHODS: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21-73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2-16 years later using Coma Recovery Scale-Revised. RESULTS: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76). CONCLUSIONS: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered. Implications for rehabilitation Long-term regular follow-up of people with prolonged disorders of consciousness is important. Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases. Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness.

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task.

Recurrent life-threatening haemoptysis from a bleeding vertebral artery pseudoaneurysm: A diagnostic dilemma.

A bleeding vertebral artery pseudoaneurysm is a rare cause of haemoptysis. Pseudoaneurysm can arise due to radionecrosis from previous radiotherapy in the base of skull and neck region and may present with haemoptysis many years later. It is important to be aware of this entity in the work-up of haemoptysis, particularly in patients with previous base of skull and neck radiotherapy. Our patient was successfully treated with endovascular occlusion.

Human EEG shows long-range temporal correlations of oscillation amplitude in Theta, Alpha and Beta bands across a wide age range.

OBJECTIVE: Long-range temporal correlations (LRTC) of EEG amplitude fluctuations in adults reveal power-law statistics and have been interpreted within the framework of self-organized criticality (SOC). In physical systems states of self-organized criticality showing power-law statistics take time to develop. In this paper we have sought evidence for the idea that brain development tends towards SOC through examining the hypothesis that during normal human development a power law behaviour of EEG oscillations is approached with increasing chronological age. METHODS: We examined EEGs from central and parietal electrodes in 36 subjects aged between 0 and 660months during performance of a steady wrist extension task with their dominant hand and applied spectral and detrended fluctuation analysis in 36 subjects to assess long-range temporal correlations of oscillation amplitude in the Theta, Alpha and Beta frequency bands. RESULTS: Our data indicate that at all subject ages power-law statistics dominate the records at Alpha, Beta and Theta frequencies. Small consistent effects of chronological age were detected for amplitude fluctuations at Theta and Beta frequencies. CONCLUSIONS: The data suggest that the scale-free nature of EEG LRTCs is a feature from early childhood through to maturity but that there are changes in the magnitude of these effects with age. SIGNIFICANCE: This study is the first to have explored long-range temporal correlations over a wide range of chronological age.

On the development of human corticospinal oscillations: age-related changes in EEG-EMG coherence and cumulant.

Changes in coherence and cumulant calculated between electroencephalograph (EEG) recorded from the scalp over primary motor cortex and rectified surface electromyograph (EMG) recorded from the contralateral wrist extensor muscles have been studied during development in humans (48 subjects, age 0-59 years). Using the techniques of EEG-EMG coherence and cumulant analysis and pooled coherence and cumulant analysis we demonstrate that between childhood, adolescence and adulthood there are increases in the prevalence and magnitude of coherence at frequencies between 15 and 35 Hz with corresponding development of a tri-phasic feature in the EEG-EMG cumulant. The results show for the first time that changes in the cortical approximately 20 Hz oscillatory drive to human motoneurone pools take place during motor development.

Changes in EMG coherence between long and short thumb abductor muscles during human development.

In adults, motoneurone pools of synergistic muscles that act around a common joint share a common presynaptic drive. Common drive can be revealed by both time domain and frequency domain analysis of EMG signals. Analysis in the frequency domain reveals significant coherence in the range 1-45 Hz, with maximal coherence in low (1-12 Hz) and high (16-32 Hz) ranges. The high-frequency range depends on cortical drive to motoneurones and is coherent with cortical oscillations at approximately 20 Hz frequencies. It is of interest to know whether oscillatory drive to human motoneurone pools changes with development. In the present study we examined age-related changes in coherence between rectified surface EMG signals recorded from the short and long thumb abductor muscles during steady isometric contraction obtained while subjects abducted the thumb against a manipulandum. We analysed EMG data from 36 subjects aged between 4 and 14 years, and 11 adult subjects aged between 22 and 59 years. Using the techniques of pooled coherence analysis and the chi(2) difference of coherence test we demonstrate that between the ages of 7 and 9 years, and 12 and 14 years, there are marked increases in the prevalence and magnitude of coherence at frequencies between 11 and 45 Hz. The data from subjects aged 12-14 years were similar to those obtained from adult controls. The most significant differences between younger children and the older age groups were detected at frequencies close to 20 Hz. We believe that these are the first reported results demonstrating significant late maturational changes in the approximately 20 Hz common oscillatory drive to human motoneurone pools.