Combined measures of oxygenation, haemodynamics and metabolism to understand neural responses in infants

fNIRS is an established research tool used to investigate typical and atypical brain development.Primarily, it provides measures of haemodynamic changes that are used to indirectly infer neural activity. Broadband NIRS provides a more direct marker of neuronal activation through measurement of changes in cytochrome-c-oxidase (CCO). As a cellular measure, CCO can be used as a bridge to improve our understanding of the link between neural and haemodynamic activity or “neurovascular coupling”. Study 1 demonstrated that changes in mitochondrial activity could be measured alongside haemodynamics during functional activation, over the temporal cortex, using a miniature system in four-to-six-month-old infants. In order to investigate the spatial specificity of CCO, its relation to haemodynamics and to build upon our understanding of neurovascular coupling mechanisms, multi-channel broadband NIRS was used alongside EEG in Study 2 where responses were measured over the visual cortex. Study 2 was performed in adults as the development of a concurrent NIRS and EEG protocol was methodologically challenging. Following this, Study 3 extended on experimental paradigms from Studies 1 and 2 to measure changes in metabolic activity and haemodynamics over the temporal and visual cortices, in four-to-seven-month-old infants. This study demonstrated simultaneous broadband NIRS and EEG use in infants for the first time. The results provided evidence of underdeveloped coupling of cerebral blood flow changes and mitochondrial activity in early infancy. Finally, Study 4 extended the protocol to investigate underlying biological mechanisms that may be altered in neurovascular coupling in autism, by studying infants at high familial risk for the disorder. The findings demonstrated that the combined protocol was not only feasible for use to study atypical brain development but also provided preliminary evidence of altered coupling between cerebral energy metabolism and haemodynamics.Taken together, this work illuminates hitherto undocumented evidence of neurovascular coupling during brain development and highlights the potential of using broadband NIRS with EEG for future neurodevelopmental research in typical and atypical populations

Combined measures of oxygenation, haemodynamics and metabolism to understand neural responses in infants

fNIRS is an established research tool used to investigate typical and atypical brain development.Primarily, it provides measures of haemodynamic changes that are used to indirectly infer neural activity. Broadband NIRS provides a more direct marker of neuronal activation through measurement of changes in cytochrome-c-oxidase (CCO). As a cellular measure, CCO can be used as a bridge to improve our understanding of the link between neural and haemodynamic activity or “neurovascular coupling”. Study 1 demonstrated that changes in mitochondrial activity could be measured alongside haemodynamics during functional activation, over the temporal cortex, using a miniature system in four-to-six-month-old infants. In order to investigate the spatial specificity of CCO, its relation to haemodynamics and to build upon our understanding of neurovascular coupling mechanisms, multi-channel broadband NIRS was used alongside EEG in Study 2 where responses were measured over the visual cortex. Study 2 was performed in adults as the development of a concurrent NIRS and EEG protocol was methodologically challenging. Following this, Study 3 extended on experimental paradigms from Studies 1 and 2 to measure changes in metabolic activity and haemodynamics over the temporal and visual cortices, in four-to-seven-month-old infants. This study demonstrated simultaneous broadband NIRS and EEG use in infants for the first time. The results provided evidence of underdeveloped coupling of cerebral blood flow changes and mitochondrial activity in early infancy. Finally, Study 4 extended the protocol to investigate underlying biological mechanisms that may be altered in neurovascular coupling in autism, by studying infants at high familial risk for the disorder. The findings demonstrated that the combined protocol was not only feasible for use to study atypical brain development but also provided preliminary evidence of altered coupling between cerebral energy metabolism and haemodynamics.Taken together, this work illuminates hitherto undocumented evidence of neurovascular coupling during brain development and highlights the potential of using broadband NIRS with EEG for future neurodevelopmental research in typical and atypical populations

Ischaemic pituitary tumour apoplexy and concurrent meningitis: a diagnostic dilemma

Pituitary tumour apoplexy is a rare but potentially life threatening clinical syndrome that mostly results from haemorrhage in the pre-existent tumour. Pure ischaemic subtype of apoplexy is even rarer. The presentation can be hard to differentiate clinically from bacterial meningitis. Moreover, the presence of one does not necessarily exclude the other and early diagnosis of both conditions is imperative for timely management. We report a case of ischaemic pituitary tumour apoplexy that may have precipitated in the setting of bacterial meningitis

Evaluation of serum ferritin for prediction of severity and mortality in COVID-19- A cross sectional study

Background: Ferritin even though widely recognized as a representative of total body iron stores, its prognostic utility is linked with COVID-19. This study was aimed at evaluation of the association of ferritin with severity in Coronavirus disease 2019 (COVID-19), hospitalized patients and to test the hypothesis that it is an independent predictor of mortality.Material and methods: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University (AKU), Karachi. Medical records of all in-patients including both genders, and all age groups with documented COVID-19 from 1st March to 10th August 2020 were reviewed. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. The details were recorded on a pre-structured performa. Between-group differences were tested using the Mann-Whitney\u27s U-test. The receiver operating characteristic curve was plotted for ferritin with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analyzed using Statistical Package for the Social Sciences (SPSS).Results: A total of 336 in patients were reviewed as declared COVID-19 positive during the study duration, and 157 were included in the final analysis including 108 males and 49 females. Statistically significant difference in ferritin was found in the two categories based on severity and mortality. Binary logistic regression showed ferritin to be an independent predictor of all-cause mortality supplemented with an AUC of 0.69 on ROC analysis.Conclusions: Serum ferritin concentration is a promising predictor of mortality in COVID-19 cases

An analysis framework for the integration of broadband NIRS and EEG to assess neurovascular and neurometabolic coupling

With the rapid growth of optical-based neuroimaging to explore human brain functioning, our research group has been developing broadband Near Infrared Spectroscopy (bNIRS) instruments, a technological extension to functional Near Infrared Spectroscopy (fNIRS). bNIRS has the unique capacity of monitoring brain haemodynamics/oxygenation (measuring oxygenated and deoxygenated haemoglobin), and metabolism (measuring the changes in the redox state of cytochrome-c-oxidase). When combined with electroencephalography (EEG), bNIRS provides a unique neuromonitoring platform to explore neurovascular coupling mechanisms. In this paper, we present a novel pipeline for the integrated analysis of bNIRS and EEG signals, and demonstrate its use on multi-channel bNIRS data recorded with concurrent EEG on healthy adults during a visual stimulation task. We introduce the use of the Finite Impulse Response functions within the General Linear Model for bNIRS and show its feasibility to statistically localize the haemodynamic and metabolic activity in the occipital cortex. Moreover, our results suggest that the fusion of haemodynamic and metabolic measures unveils additional information on brain functioning over haemodynamic imaging alone. The cross-correlation-based analysis of interrelationships between electrical (EEG) and haemodynamic/metabolic (bNIRS) activity revealed that the bNIRS metabolic signal offers a unique marker of brain activity, being more closely coupled to the neuronal EEG response

Using multi-modal neuroimaging to characterise social brain specialisation in infants

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain

Using multi-modal neuroimaging to characterise social brain specialisation in infants

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4-to-7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high frequency brain activity. The development of simultaneous multi-modal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain

Immune Modulatory Effects of Vitamin D on Viral Infections.

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections

Procalcitonin as a predictor of severity and mortality in a cohort of patients hospitalised with COVID-19

Introduction: To evaluate the association of Procalcitonin (PCT) with severity in Coronavirus disease 2019 (COVID-19), hospitalised patients and to test the hypothesis that it is an independent predictor of mortality.Materials and methods: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University (AKU), Karachi Pakistan. Electronic medical records of all in-patients including both genders and all age groups with documented COVID-19 from March to August 2020 were reviewed and recorded on a pre-structured performa. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. Between-group differences were tested using the Chi-square and Mann-Whitney\u27s U-test. The receiver operating characteristic curve was plotted for serum PCT with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analysed using SPSS.Results: 336 patients were reviewed as declared COVID-19 positive during the study duration, and 136 were included in the final analysis including 101 males and 35 females. A statistically significant difference in PCT was found between severe and non-severe COVID-19 (p value=0.01); and survivors and nonsurvivors (p valueConclusion: Baseline serum PCT concentration is a promising predictor of mortality and severity in COVID-19 cases when considered in combination with clinical details and other laboratory tests

Does Short Term Atorvastatin Treatment Improve Symptomatic Control in Patients with Mild to Moderate & Uncontrolled Asthma?

Introduction: Asthma is a chronic disease characterized by recurrent episodes of breathlessness and wheezing. Keeping in view the problems in asthma control and side effects of available medication, there is a need for alternative treatments with better efficacies and fewer side effects. Atorvastatin is a statin that blocks HMG CoA reductase enzyme found in the liver, inhibiting the synthesis of cholesterol. Blockade of this pathway also inhibits production of GTPases which are involved in airway inflammation, airway remodeling and contraction of smooth muscles of the bronchi. Aims & Objectives: To evaluate the symptomatic control in mild to moderate and uncontrolled asthma patients using standard treatment versus its combination with atorvastatin. Place and duration of study: This study was conducted in Pulmonology Department of Lahore General Hospital; Lahore over a 4-week duration from October 2018 till February 2019. Material & Methods: Patients of mild to moderate and uncontrolled asthma were enrolled in this study based on inclusion and exclusion criteria. Patients were divided into two groups by lottery method, Group 1 and Group 2, with 34 patients in each group. Group 1 was continued with standard therapy of asthma and the Group 2 was administered atorvastatin 40 mg, once daily in addition to standard therapy for 4 weeks. The control of asthma before and after treatment was assessed based on Global Initiative for asthma (GINA) guideline questionnaire score. SPSS (Statistical Package for Social Sciences) version 22 was used for analysis of data. P-Value < 0.05 was taken as significant. Results: Nonsignificant results were obtained when comparison between the groups was made based on GINA guidelines questionnaire score by Mann Whitney Utest Conclusion: It was concluded that atorvastatin has no role in symptomatic control in patients of mild to moderate and uncontrolled asthma