Faculty Publications (CoM)

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1,2,3-Triazolyl ester of ketorolac (15K), a potent PAK1 blocker, inhibits both growth and metastasis of orthotopic human pancreatic cancer xenografts in mice
(2019) Adrian, Thomas E
More than 90% of human pancreatic cancers carry the oncogenic mutant of Ki-RAS and their growth depends on its downstream kinase PAK1, mainly because PAK1 blocks the apoptosis of cancer cells selectively. We developed a highly cell-permeable PAK1-blocker called 15K from an old pain-killer (ketorolac), that is shown here to inhibit the growth of three pancreatic cancer cell lines with IC50 values ranging 41-88 nM in vitro. The anti-cancer effect of 15K was further investigated in an orthotopic xenograft model with gemcitabine (GEM)-resistant human pancreatic cancer cell lines (AsPC-1 and BxPC-3) expressing luciferase in athymic mice. During 4 weeks, 15K blocks total burden (growth) of both AsPC-1 and BxPC-3 tumors (measured as radians/sec) with the IC50 below daily dose of 0.1 mg/kg, i.p. In a similar manner 15K reduced both their invasion and metastases as well, while it had no effect on either body weight or hematological parameters even at 5 mg/kg/day. To the best of our knowledge, 15K is so far the most potent among synthetic PAK1-blockers in vivo, and could be potentially useful for therapy of GEM-resistant cancers.
A 12‑month prospective real‑life study of opicapone efficacy and tolerability in Emirati and non‑White subjects with Parkinson’s disease based in United Arab Emirates
(2023) Benamer, Hani T S.
Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and the condition is complicated by the emergence of wearing of/motor fuctuations with levodopa treatment after a variable period. COMT inhibitors when used as adjunct therapy to levodopa tend to smoothen out these wearing of fuctuations by enhancing delivery of levodopa and increasing its bioavailability to the brain. The study was conducted to investigate the motor and nonmotor efect, safety and tolerability of the third generation once-daily COMT inhibitor (opicapone), as add-on, adjuvant therapy to levodopa and at 6 and 12 months follow-up in a real-life cohort of consecutive Emirati and non-White PD patients. A real-life observational analysis using tolerability parameters as used previously by Rizos et al. and Shulman et al. based on clinical database of cases rat Kings College Hospital Dubai Parkinson care database. This was a prospective, single-arm follow-up clinical evaluation study that evaluated the efectiveness of opicapone 50 mg once-daily regime in 50 patients diagnosed with idiopathic neurodegenerative disorder. All patients were assessed with scales used in clinical pathway and include motor Unifed Parkinson’s Disease Rating Scale (UPDRS), nonmotor symptom scale (NMSS), quality of life (PDQ8) Parkinson’s fatigue scale (PFS16) and King’s Parkinson’s Pain Scale (KIPS). Out of 50 patients treated with opicapone (72% male, mean age 66.9 years (SD 9.9, range 41–82 years) and mean duration of disease 5.7 years (SD 2.5 range (2–11), there was signifcant statistical improvements shown in motor function-UPDRS part 3: baseline 40.64±2.7, at 6 months 32.12±3.14 and after 12 months 33.72±3.76. Nonmotor burden NMSS: 107.00±21.86, at 6 months 100.78±17.28 and 12 months 96.88±16.11. Reduction in dyskinesias (UPDRS part 4): baseline 8.78±1.07, at 6 months 7.4±0.81 and 12 months 6.82±0.75. Opicapone provides benefcial motor and nonmotor efects in Emirati and other non-White Parkinson’s patients, resident in UAE, proving its efcacy across diferent racial groups as COMT activity may vary between races.
2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
(2020) Nowotny, Norbert
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
(2021) Nowotny, Norbert
Abstract: In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratifcation vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/ or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
2022 taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
(2022-11) Nowotny, Norbert
Abstract: In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratifcation vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study
(2024-02) Krieger, Derk W
Abstract: Background: The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. Methods and results: The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction>0.2500 for all). Similar findings were yielded when assessing the ABC-stroke score as a continuous variable. Conclusions: In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study. Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.
ACE2 polymorphisms impact COVID-19 severity in obese patients
(2022-12) Jalaleddine, Nour; Hachim, Mahmood Yaseen; Senok, Abiola; Al Heialy, Saba
Abstract: A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. Accordingly, we hypothesize that obesity-associated ACE2 polymorphisms increase the severity of COVID-19. In this study, we profiled eight frequently reported ACE2 SNPs in a cohort of lean and obese COVID-19 patients (n = 82). We highlight the significant association of rs2285666, rs2048683, rs879922, and rs4240157 with increased severity in obese COVID-19 patients as compared to lean counterparts. These co-morbid-associated SNPs tend to positively correlate, hence proposing possible functional cooperation to ACE2 regulation. In obese COVID-19 patients, rs2285666, rs879922, and rs4240157 are significantly associated with increased blood nitrogen urea and creatinine levels. In conclusion, we highlight the contribution of ACE2 SNPs in enhancing COVID-19 severity in obese individuals. The results from this study provide a basis for further investigations required to shed light on the underlying mechanisms of COVID-19 associated SNPs in COVID-19 obese patients.
Action of 1,25(OH)2D3 on Human Asthmatic Bronchial Fibroblasts: Implications for Airway Remodeling in Asthma
(2020) Al Heialy, Saba
Background: Airway fibroblasts are major contributors to the histopathological feature of airway remodeling in asthma by their implication in the cell invasiveness and profibrogenic secretory phenotype observed in subepithelial fibrosis. 1,25 Dihydroxy vitamin D3 (1,25(OH)2D3) is an important therapeutic agent that blocks many features of airway remodeling induced by profibrogenic mediators, such as transforming growth factor beta 1 (TGF-β1) or T helper type 1 inflammatory cytokines. Objective: We hypothesized that 1,25(OH)2D3 opposes the TGF-β1 or tumor necrosis factor alpha (TNF-α)-Interleukin 1 beta (IL-1β) stimulation on airway fibroblast profibrogenic secretory phenotype observed in severe asthmatic patients. Our aim was to investigate the anti-fibrogenic effect of 1,25(OH)2D3 in TGF-β1 or TNF-α-IL-1β-stimulated human bronchial fibroblast cells (HBFCs) from severe asthmatic compared with non-asthmatic subjects. Patients and Methods: All experiments were performed on primary HBFCs from asthmatic (DHBFCs, n=4) and non-asthmatic subjects (NHBFCs, n=4). mRNA expression and protein quantification of key fibrogenic markers were analyzed by RT-qPCR and ELISA, comparing HBFCs from asthmatic and non-asthmatic subjects. Vitamin D receptor (VDR) mRNA expression and its functionality in HBFCs were assessed by RT-qPCR. HBFCs proliferation was assessed by flow cytometry using BrdU-FITC/7AAD bivariate staining, while HBFCs apoptosis by Annexin V-FITC/7AAD. Results: VDR is constitutively expressed in HBFCs and the addition of 1,25(OH)2D3 significantly increased mRNA expression of CYP24A1 (a direct VDRs’ target gene) in both HBFCs groups. DHBFCs cultured in the presence of TGF-β1 or TNF-α-IL-1β showed increased mRNA expression and protein secretion of fibrogenic markers when compared to NHBFCs. Additionally, we observed decreased mRNA expression of FN 1, LUM, BGN, MMP2, COL5A1, TIMP1 and CC-chemokines (CCL2, CCL5, CCL11) in response to 1,25(OH)2D3 addition to the TGF-β1 or TNF-α-IL-1β-stimulated HBFCs. Cell culture media obtained from TGF-β1 or TNF-α-IL-1β-stimulated DHBFCs showed decreased protein secretion (fibronectin 1, lumican, MCP1, RANTES and eotaxin-1) in response to 1,25(OH)2D3 when compared to NHBFCs. 1,25(OH)2D3 inhibited proliferation in TGF- β1-stimulated HBFCs through G0/G1 cell cycle arrest and these effects were not correlated with the induction of apoptosis. Conclusion: DHBFCs under TGF-β1 or TNF-α-IL-1β stimulation showed higher fibrogenic capacity when compared to NHBFCs. 1,25(OH)2D3 significantly blocked these effects and highlight 1,25(OH)2D3 as a possible therapeutic target for severe asthma.
Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain
(2023) Lipovich, Leonard
Abstract: The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy.
Acute cardiac injury is associated with adverse outcomes, including mortality in COVID-19 patients
(2020) Hachim, Mahmood Yaseen
Abstract: Objectives: To evaluate acute cardiac injury in COVID-19 patients and its association with adverse outcomes including mortality in the United Arab Emirates (UAE) population. Methods: A retrospective study conducted between February and June 2020 in Dubai, UAE, for all laboratory-confirmed Coronavirus disease-19 patients. Demographic, clinical, laboratory, radiological, and clinical outcomes were compared between patients with and without acute cardiac injury. Results: During the study period, 203 patients were included, of which, 44 (21.7%) had evidence of acute cardiac injury. Compared with patients without acute cardiac injury, patients with acute cardiac injury were: older, had more shortness of breath, diabetes, hypertension, and more bilateral airspace shadowing on admission chest radiography. These patients also had a higher neutrophil count, C-reactive protein, procalcitonin, ferritin, D-dimers and lactate dehydrogenase but lower lymphocyte count. Regarding outcomes, these patients had higher intensive care admissions; a higher rate of complications including acute kidney and liver injury, acidosis, septic shock, acute respiratory distress syndrome, needed more mechanical ventilation, and had a significantly higher risk of death. Conclusion: Acute cardiac injury is common among Coronavirus disease-19 patients. These patients present with higher comorbidities, have high inflammatory markers and have greater risk for in-hospital multiorgan damage, need for mechanical ventilation, and death. Prompt full assessment and intervention are recommended.
Acute heart failure presentations and outcomes during the fasting month of Ramadan: an observational report from seven Middle Eastern countries
(2018) Alsheikh-Ali, Alawi
Background: Fasting during the month of Ramadan is practiced by over 1.5 billion Muslims worldwide. It remains unclear, however, how this change in lifestyle affects heart failure, a condition that has reached epidemic dimensions. This study examined the effects of fasting in patients with acute heart failure (AHF) using data from a large multi-center heart failure registry. Methods and results: Data were derived from Gulf CARE (Gulf aCute heArt failuRe rEgistry), a prospective multi-center study of consecutive patients hospitalized with AHF during February–November 2012. The study included 4,157 patients, of which 306 (7.4%) were hospitalized with AHF in the fasting month of Ramadan, while 3,851 patients (92.6%) were hospitalized in other days. Clinical characteristics, precipitating factors, management, and outcome were compared among the two groups. Patients admitted during Ramadan had significantly lower prevalence of symptoms and signs of volume overload compared to patients hospitalized in other months. Atrial arrhythmias were significantly less frequent and cholesterol levels were significantly lower in Ramadan. Hospitalization in Ramadan was not independently associated with increased immediate or 1-year mortality. Conclusions: The current study represents the largest evaluation of the effects of fasting on AHF. It reports an improved volume status in fasting patients. There were also favorable effects on atrial arrhythmia and total cholesterol and no effects on immediate or long-term outcomes.
Adolescent-Acquired Flatfeet: The Tip of the Iceberg
(2022-11) Alshryda, Sattar
Abstract: There has been a substantive change in our lifestyle over the last two decades. The widespread availability of entertaining digital devices created an unhealthy culture of a sedentary lifestyle, with our children hooked to their digital devices for countless hours. The mental and social consequences have been well explored in several studies. Leading a sedentary lifestyle has been shown to be associated with obesity, diabetes, cardiovascular diseases, and even early death. The adolescent-acquired flatfeet is another addition to the ever-growing list. The lack of physical activities among children nowadays has led to a pandemic of long muscles tightness in children, particularly during the growth spurt. The mismatch between the long bones and adjacent muscles growth caused relative muscles shortening, particularly the muscles that cross more than one growth center, such as the hamstring muscles and gastrocnemius muscles. As a result, it has become common to see children who cannot touch the floor on forward bending because of hamstring muscles tightness or inability to walk on their heels because of gastrocnemius muscles tightness. While muscles tightness is relatively benign, its consequences, such as adolescent-acquired flatfeet, are not. In this review, we have explored the condition, its prevention, and treatment to raise awareness among the public and professionals.
Adoption of the ADA/EASD guidelines in 10 Eastern and Southern European countries: Physician survey and good clinical practice recommendations from an international expert panel
(2020) Mikhailidis, Dimitri P
Abstract: The aim of the present study was to assess the adoption of the ADA/EASD guidelines in a convenience sample of physicians from Eastern and Southern Europe, the barriers to the implementation of these guidelines and the measures needed to facilitate their implementation. Methods: Attendees at two international diabetes conferences could volunteer to respond to a fully anonymous survey. Responses were analysed descriptively and a panel of experts from around the region was consulted to interpret the survey results. Results: Responses (n = 96) from 10 countries were analysed. Most participants (63.4%) considered the ADA/EASD guidelines fundamental to their practice. All respondents saw the value of the CVOT-based ADA/EASD recommendations and 77–80% generally implemented them. Measures suggested to improve adherence to the ADA/EASD guidelines included aligning reimbursement policy with the guidelines (54.4%), publishing guidelines in a simple and concise form (42.4%) and translating guidelines into local languages (33.3%). Conclusions: Aligning reimbursement with recent evidence and providing short summaries of the ADA/EASD guidelines in local languages could facilitate physician adherence.
Afghanistan's humanitarian crisis and its impacts on the mental health of healthcare workers during COVID-19
(2022-12) Nawaz, Faisal A
Abstract: Afghanistan’s humanitarian crisis has severely impacted the mental health of frontline workers. With the introduction of the Taliban government, ongoing civil unrest, and other forms of violent attacks, healthcare workers (HCWs) continue to provide patient care despite minimal resources. A severe contraction in the economy, poor supply of medications, political turmoil, and insufficient humanitarian aid have added to pre-existing problems. High levels of insecurity and instability as well as decades of traumatic experiences have contributed to increasing mental health challenges amongst frontline workers. Despite the scarcity of mental health services, HCWs continue to persevere with their service to the community. However, inadequate interventions may have serious implications for HCWs bearing the brunt of multiple traumas. Thus, governmental and international involvement is needed to address both the economic and psychological needs of HCWs in Afghanistan
AFM-compatible microfluidic platform for affinity-based capture and nanomechanical characterization of circulating tumor cells
(2020) Janahi, Farhad
Abstract: Circulating tumor cells (CTCs) carried by the patient’s bloodstream are known to lead to the metastatic spread of cancer. It is becoming increasingly clear that an understanding of the nanomechanical characteristics of CTCs, such as elasticity and adhesiveness, represents advancements in tracking and monitoring cancer progression and metastasis. In the present work, we describe a combined microfluidic–atomic force microscopy (AFM) platform that uses antibody–antigen capture to routinely isolate and nanomechanically characterize CTCs present in blood samples from prostate cancer patients. We introduce the reversible assembly of a microfluidic device and apply refined and robust chemistry to covalently bond antibodies onto its glass substrate with high density and the desired orientation. As a result, we show that the device can efficiently capture CTCs from patients with localized and metastatic prostate cancer through anti-EpCAM, anti-PSA, and anti-PSMA antibodies, and it is suitable for AFM measurements of captured intact CTCs. When nanomechanically characterized, CTCs originating from metastatic cancer demonstrate decreased elasticity and increased deformability compared to those originating from localized cancer. While the average adhesion of CTCs to the AFM tip surface remained the same in both the groups, there were fewer multiple adhesion events in metastatic CTCs than there were in their counterparts. The developed platform is simple, robust, and reliable and can be useful in the diagnosis and prognosis of prostate cancer as well as other forms of cancer.
African Swine Fever, the forgotten pandemic
(2021) Nowotny, Norbert
Summary: African Swine Fever (ASF) is one of the most important diseases prevalent in swine populations. In recent times, it has devasted the pork industry—both commercial and backyard—throughout much of the world. ASF virus (ASFV) is highly contagious, and its persistence in pig meat, feed, fomites and the environment has facilitated its transboundary spread. Despite the global spread and impact of ASF, this pandemic has not garnered the widespread attention or alarm that has human diseases. Outside of the animal health community, in many respects it is the forgotten pandemic.
Age-related alterations and senescence of mesenchymal stromal cells: Implications for regenerative treatments of bones and joints
(2021) Nau, Thomas
Abstract: The most common clinical manifestations of age-related musculoskeletal degeneration are osteoarthritis and osteoporosis, and these represent an enormous burden on modern society. Mesenchymal stromal cells (MSCs) have pivotal roles in musculoskeletal tissue development. In adult organisms, MSCs retain their ability to regenerate tissues following bone fractures, articular cartilage injuries, and other traumatic injuries of connective tissue. However, their remarkable regenerative ability appears to be impaired through aging, and in particular in age-related diseases of bones and joints. Here, we review age-related alterations of MSCs in musculoskeletal tissues, and address the underlying mechanisms of aging and senescence of MSCs. Furthermore, we focus on the properties of MSCs in osteoarthritis and osteoporosis, and how their changes contribute to onset and progression of these disorders. Finally, we consider current treatments that exploit the enormous potential of MSCs for tissue regeneration, as well as for innovative cell-free extracellular-vesicle-based and anti-aging treatment approaches.
AI-enhanced solutions during COVID-19: Current trends and future innovations
(2022-08) Nawaz, Faisal A; Boillat, Thomas; Khan, Abdul Rahman
Abstract: Artificial Intelligence (AI) is defined as a branch of Computer Science that is capable of simulating intelligent behavior through machine automation systems. There has been a significant rise in research and application of AI in addressing various aspects of Engineering and Medicine. This mutual overlap between the two fields has led to a new discipline, so-called “Artificial Intelligence in Medicine”, or AIM in short [1]. Not only is AIM being applied for image processing and analysis, but also for prognose [2–4], treatment [5–7], and patient monitoring [1,8] among others. In this matter, AIM has been instrumental during the Corona Virus Disease 2019 (COVID-19) pandemic. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been brought to global attention and was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 [9]. The exponential increase in the number of cases worldwide has prompted for emergent innovations and collaborations in the fields of Medicine and Engineering. While there have been contrasting opinions on the scope of AI during this period, we are observing a continuum of interdisciplinary growth across this field [10]. The early impact of AI during COVID-19 has been observed in 1) Early warning system and predictive modeling 2) Contact Tracing 3) Diagnostics 4) Drug discovery and development and 5) Social Control. As depicted in Fig. 1, this article aims to explore these domains [10] in the context of AI-assisted applications and their impact on addressing COVID-19. This article describes the contributions of AI during COVID-19, along with trends and innovations related to these technologies in harnessing sustainable healthcare solutions.
Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD
(2020) Al Heialy, Saba
Abstract: It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). To investigate the expression level of these SARS-CoV-2 host cell entry genes in the lung airway, we used public gene expression datasets. We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. Children were found to have significantly lower expression of COVID-19 receptors in the upper and lower airways (nasal and bronchial). Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.
Analgesia and sedation modalities used with botulinum toxin injections in children with cerebral palsy: a literature review
(2021) Alhoot, Shahad
Abstract: Cerebral palsy (CP) is a non-progressive motor dysfunction leading to multiple morbidities, including spasticity, which can be managed with botulinum toxin injection (BTI). This literature review aims to examine published studies on the efficacy and safety of different interventions used to reduce pain and anxiety associated with BTI in children with CP. A literature review of all published evidence in English language, or with an English translation between 1999 and 2019, using PubMed, EBSCO host, and Medline databases was carried out. All identified papers were screened for inclusion criteria. Data from included papers were entered and analyzed on an Excel database. Twenty-one studies conducted in multiple clinical settings identified 10 different analgesia and sedation modalities including intravenous ketamine, midazolam, inhaled nitrous oxide, general anesthesia, and Eutectic Mixture of Local Anesthetics (EMLA®) cream. Most of the studies were descriptive with the exception of two clinical trials and one qualitative study. All interventions had some adverse effects, but they were generally mild and no long-term sequelae were reported. The combination of inhaled nitrous oxide with EMLA® cream showed promising primary results. However, ketamine and midazolam combination could be a safe alternative. Currently, there is no sufficient data to draw on the superiority of any modality. Further high-quality studies are warranted.

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