COTiR: Molecular Communication Model for Synthetic Exosome-Based Tissue Regeneration.

Mesenchymal stem cell (MSC)-derived exosomes are recognized as an unparalleled therapy for tissue damage rendered by COVID-19 infection and subsequent hyper-inflammatory immune response. However, the natural targeting mechanism of exosomes is challenging to detect the damaged tissue over long diffusion distances efficiently. The coordinated movement of exosomes is desired for successful identification of target sites. In this work, we propose a molecular communication model, CoTiR, with a bio-inspired directional migration strategy (DMS) for guided propagation of exosomes to target the damaged tissues. The model includes directional propagation, reception, and regeneration of tissue. The proposed model has the potential to be used in designing efficient communication systems in the nanodomain. We compare the proposed model to the basic random propagation model and show the efficacy of our model regarding the detection of multiple targets and the detection time required. Simulation results indicate that the proposed model requires a shorter period of time for a similar number of exosomes to detect the targets compared to the basic random propagation model. Furthermore, the results reveal a 99.96% decrease in the collagen concentration in the absence of inflammatory cytokine molecules compared to the collagen concentration in the presence of inflammatory cytokine molecules.

Estimating Time Window to Administer Anti-Cytokine Therapeutic Drugs to COVID-19 Patients.

The severe COVID-19 infection often leads to "Cytokine Release Syndrome (CRS)", which is a serious adverse medical condition causing multiple organ failures. Anti-cytokine therapy has shown promising results for the treatment of the CRS. As part of the anti-cytokine therapy, the immuno-suppressants or anti-inflammatory drugs are infused to block the release of cytokine molecules. However, determining the time window to infuse the required dose of drugs is challenging due to the complex processes involving the release of inflammatory markers, such as IL-6 and C-reactive protein (CRP) molecules. In this work, we develop a molecular communication channel to model the transmission, propagation, and reception of cytokine molecules. The proposed analytical model can be used as a framework to estimate the time window to administer anti-cytokine drugs to get successful outcomes. Simulation results show that at a 50 s-1 release rate of IL-6 molecules, the cytokine storm is triggered at ~ 10 hours, and consequently, the CRP molecules reach the severe level of 97 mg/L at ~ 20 hours. Further, the results reveal that with one-half of the release rate of IL-6 molecules, the time to observe the severe level of 97 mg/L CRP molecules increases by 50%.

VIVID: In Vivo End-to-End Molecular Communication Model for COVID-19.

As an alternative to ongoing efforts for vaccine development, scientists are exploring novel approaches to provide innovative therapeutics, such as nanoparticle- and stem cell-based treatments. Thus, understanding the transmission and propagation dynamics of coronavirus inside the respiratory system has attracted researchers' attention. In this work, we model the transmission and propagation of coronavirus inside the respiratory tract, starting from the nasal area to alveoli using molecular communication theory. We performed experiments using COMSOL, a finite-element multiphysics simulation software, and Python-based simulations to analyze the end-to-end communication model in terms of path loss, delay, and gain. The analytical results show the correlation between the channel characteristics and pathophysiological properties of coronavirus. For the initial 50% of the maximum production rate of virus particles, the path loss increases more than 16 times than the remaining 50%. The delayed response of the immune system and increase in the absorption of virus particles inside the respiratory tract delay the arrival of virus particles at the alveoli. Furthermore, the results reveal that the virus load is more in case of asthmatic patients as compared to the normal subjects.

Clinico-Pathological Study of Cutaneous Granulomatous Lesions- a 5 yr Experience in a Tertiary Care Hospital in India.

BACKGROUND: Granulomatous dermatoses are common skin pathology, often need histopathological confirmation for diagnosis. Histologically six sub-types of granulomas found in granulomatous skin diseases- tuberculoid, sarcoidal, necrobiotic, suppurative, foreign body & histoid type. The aims of the present study were clinico-pathological evaluation of granulomatous skin lesions and their etiological classification based on histopathological examination. METHODS: It was a five years (Jan 2009- Dec 2013) retrospective study involving all the skin biopsies. Detailed clinical and histopathological features were analyzed and granulomatous skin lesions were categorized according to type of granuloma & etiology. Special stains were used in few cases for diagnostic purpose. RESULTS: Among 1280 skin biopsies, 186 cases (14.53%) were granulomatous skin lesions with a ratio 1:24. In histopathological sub-typing, tuberculoid granuloma was most common type (126 cases, 67.74%). Most common etiology of granuloma in the study was leprosy (107 cases, 57.52%). Other etiologies were cutaneous tuberculosis, foreign body granulomas, fungal lesions, cutaneous leishmaniasis, sarcoidosis and granuloma annulare. CONCLUSION: Histopathology is established as gold standard investigation for diagnosis, categorization and clinico-pathological correlation of granulomatous skin lesions.

Comparison between general anesthesia and spinal anesthesia in attenuation of stress response in laparoscopic cholecystectomy: A randomized prospective trial.

BACKGROUND: Laparoscopy though minimally invasive produces significant hemodynamic surge and neuroendocrine stress response. Though general anesthesia (GA) is the conventional technique, now-a-days, regional anesthesia has been accepted for laparoscopic diagnostic procedures, and its use is also being extended to laparoscopic surgeries. OBJECTIVE: The aim was to compare the hemodynamic surge and neuroendocrine stress response during laparoscopic cholecystectomy (LC) under GA and spinal anesthesia (SA) in American Society of Anesthesiologists (ASA) PS 1 patients. MATERIALS AND METHODS: Thirty ASA physical status I patients, aged 18-65 years were randomly allocated into two equal groups of 15 each. Group A received GA with controlled ventilation. Patients were preoxygenated for 5 min with 100/5 oxygen, premedicated with midazolam 0.03 mg/kg intravenous (i.v), fentanyl 2 mcg/kg i.v; induction was done with thiopentone 3-5 mg/kg i.v; intubation was achieved after muscle relaxation with 0.5 mg/kg atracurium besylate i.v. Anesthesia was maintained with 1-2% sevoflurane and N2O:O2 (60:40) and intermittent i.v injection of atracurium besylate. Group B SA with 0.5% hyperbaric bupivacaine and 25 µg fentanyl along with local anesthetic instillation in the subdiaphragmatic space. Mean arterial pressure, heart rate (HR), oxygen saturation, end tidal carbon-dioxide were recorded. Venous blood was collected for cortisol assay before induction and 30 min after pneumoperitoneum. All data were collected in Microsoft excel sheet and statistically analyzed using SPSS software version 16 (SPSS Inc., Chicago, IL, USA). All numerical data were analyzed using Student's t-test and paired t-test. Any value <0.05 was taken as significant. RESULTS: Mean arterial pressure and mean HR and postpneumoperitoneum cortisol level were lower in group B than group A though the difference was not statistically significant in hemodynamic parameters but significant in case of cortisol. CONCLUSION: Spinal anesthesia administered for LC maintained comparable hemodynamics compared to GA and did not produce any ventilatory depression. It also produced less neuroendocrine stress response as seen by reduction in the level of serum cortisol in ASA PS 1 patients put for LC.

Effect of dexmedetomidine as adjuvant in ropivacaine-induced supraclavicular brachial plexus block: A prospective, double-blinded and randomized controlled study.

BACKGROUND AND AIMS: Different additives have been used to prolong brachial plexus block. We evaluated the effect of adding dexmedetomidine to ropivacaine for supraclavicular brachial plexus blockade. The primary endpoints were the onset and duration of sensory and motor block and duration of analgesia. MATERIALS AND METHODS: A total of 84 patients (20-50 years) posted for elective forearm and hand surgery under supraclavicular brachial plexus block were divided into two equal groups (Group R and RD) in a randomized, double-blind fashion. In group RD (n = 42) 30 ml 0.5% ropivacaine +1 ml (100 µg) of dexmedetomidine and group R (n = 42) 30 ml 0.5% ropivacaine +1 ml normal saline were administered in supraclavicular block. Sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, postoperative visual analog scale (VAS), hemodynamics and side-effects were recorded for each patient. RESULTS: Though with similar demographic profile in both groups, sensory and motor block in group RD (P < 0.05) was earlier than group R. Sensory and motor block duration and time to first analgesic use were significantly longer and the total need for rescue analgesics was lower in group RD (P < 0.05) than group R. Post-operative VAS value at 12 h were significantly lower in group RD (P < 0.05). Intra-operative hemodynamics were significantly lower in group RD (P < 0.05) without any appreciable side-effects. CONCLUSION: It can be concluded that adding dexmedetomidine to supraclavicular brachial plexus block increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side-effects.