Non-Covid causes of acute undifferentiated febrile illness during the Covid pandemic: an etiological analysis from Uttar Pradesh, India

Background and Aims: febrile illnesses are one of the leading causes of morbidity and mortality in India, which are very common in the monsoon and post-monsoon season in tropical countries. Acute Undifferentiated Febrile Illness (AUFI) is a term usually used to refer to such conditions until diagnosed. This study was conducted to understand the prevalence of mixed infections, and the etiology and seasonal distribution of AUFI cases during the Corona Virus Disease (COVID) pandemic. Materials and Methods: this study was a hospital-based crosssectional study of six months (August 2021 to January 2022). Samples were collected by random sampling method from SN Medical College, Agra, and Mathura District. The diagnosis was made by Rapid Diagnostic Test for Malaria, and ELISA for Dengue, Chikungunya, Leptospira, and Scrub typhus. Results: a total of 9016 non-repetitive serum samples were collected, from males (4657) and females (4359), with a mean age of 42 years. The most common infections were: dengue (26.5%), malaria (0.85%), leptospira (0.54%), scrub typhus (0.32%), and Chikungunya (0.14%). The commonest co-infection was dengue with scrub typhus. Triple infections were also observed. Conclusions: the diversity of clinical presentations and etiological agents with limited diagnostic facilities demonstrates the complexity of AUFI. The knowledge of the local and seasonal distribution of acute febrile illnesses is thus very useful to formulate clinical, diagnostic, and management algorithms for positive outcomes, reducing hospital costs, and burden on healthcare facilities. Further upliftment of health services at the root level is still a long way to go

High Frequency Migraine Is Associated with Lower Acute Pain Sensitivity and Abnormal Insula Activity Related to Migraine Pain Intensity, Attack Frequency, and Pain Catastrophizing

Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful), we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds and pre-scan pain ratings to mildly painful thermal stimuli, patients had aberrant suprathreshold nociceptive processing. Compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain versus mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS); bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA) and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula cortex, associated with indices of disease severity in migraine

Biosensor Development: Optimizing Immunomagnetic Separation of Bacteria

For years, there have been several millions of deaths around the world from diseases such as Tuberculosis, Meningitis, Pneumonia, Cholera, etc. which are caused by different types of bacteria. In addition, a large number of food industries face a challenge of bacterial contamination that further results in human death and wastage of food resources. With the recent advancements in nanotechnology, many methods have been demonstrated to separate and detect bacteria from a given sample using magnetic nanoparticles (ex- Fe3O4) of small size (1-100 nm). However, there is still no optimization reported for use of Fe3O4 nanoparticles for immuno-magnetic separation of bacteria. To construct a suitable biosensor technology and a small microfluidic device, we have optimized the immuno-magnetic separation of bacteria using very small ~7 nm iron oxide nanoparticles (NPs). In this work, we have synthesized ~7 nm Fe3O4 nanoparticles using organic phase synthesis and further tuned their surface chemistry to disperse them in water. Polyclonal antibodies targeting E. coli K-12 were then immobilized over Fe3O4 nanoparticles dispersed in water. We then tested different ratio of NPs : E. coli cells to – (a) evaluate toxicity of NPs towards E. coli cells, (b) find the optimal number of nanoparticles required for efficient capture, and (c) derive capture efficiency for different concentrations of E. coli K-12. The optimization for the use of ~7nm Fe3O4 NPs for capture of bacteria has provided us with results that led to a conclusion for using 106:1 ratio of NP: E. coli cells, meanwhile minimally affecting cell viability. The same ratio provided us with maximum capture efficiency of more than 60% with average capture of more than 50% for all different concentrations of E. coli cells. In addition, we have successfully demonstrated the proof of concept and specificity of our assay using transmission electron and fluorescence microscopy imaging. Our results have successfully optimized bacterial capture using ~7nm Fe3O4 NPs (the smallest to be reported in literature) which will be further used for the construction of a suitable biosensor and hand-held microfluidic device for detection of pathogenic bacteria at very low concentrations (<100 cfu/ml)

Altered cognition-related brain activity and interactions with acute pain in migraine

Little is known about the effect of migraine on neural cognitive networks. However, cognitive dysfunction is increasingly being recognized as a comorbidity of chronic pain. Pain appears to affect cognitive ability and the function of cognitive networks over time, and decrements in cognitive function can exacerbate affective and sensory components of pain. We investigated differences in cognitive processing and pain–cognition interactions between 14 migraine patients and 14 matched healthy controls using an fMRI block-design with two levels of task difficulty and concurrent heat (painful and not painful) stimuli. Across groups, cognitive networks were recruited in response to a difficult cognitive task, and a pain–task interaction was found in the right (contralateral to pain stimulus) posterior insula (pINS), such that activity was modulated by decreasing the thermal pain stimulus or by engaging the difficult cognitive task. Migraine patients had less task-related deactivation within the left dorsolateral prefrontal cortex (DLPFC) and left dorsal anterior midcingulate cortex (aMCC) compared to controls. These regions have been reported to have decreased cortical thickness and cognitive-related deactivation within other pain populations, and are also associated with pain regulation, suggesting that the current findings may reflect altered cognitive function and top-down regulation of pain. During pain conditions, patients had decreased task-related activity, but more widespread task-related reductions in pain-related activity, compared to controls, suggesting cognitive resources may be diverted from task-related to pain-reduction-related processes in migraine. Overall, these findings suggest that migraine is associated with altered cognitive-related neural activity, which may reflect altered pain regulatory processes as well as broader functional restructuring