No abstract

Background and Purpose: The primary cannabinoids, Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and Δ⁸-tetrahydrocannabinol (Δ⁸-THC) are known to disturb the mitochondrial function and possess antitumor activities. These observations prompted us to investigate their effects on the mitochondrial O₂ consumption in human oral cancer cells (Tu183). This epithelial cell line overexpresses bcl-2 and is highly resistant to anticancer drugs. Experimental Approach: A phosphorescence analyzer that measures the time-dependence of O₂ concentration in cellular or mitochondrial suspensions was used for this purpose. Key Results: A rapid decline in the rate of respiration was observed when Δ⁹-THC or Δ⁸-THC was added to the cells. The inhibition was concentration-dependent, and Δ⁹-THC was the more potent of the two compounds. Anandamide (an endocannabinoid) was ineffective; suggesting the effects of Δ⁹-THC and Δ⁸-THC were not mediated by the cannabinoidreceptors. Inhibition of O₂ consumption by cyanide confirmed the oxidations occurred in the mitochondrial respiratory chain. Δ⁹-THC inhibited the respiration of isolated mitochondria from beef heart. Conclusions and Implications: These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.

We report on the pneumatocyte structure and function of mouse lung specimens exposed in vitro to two calcined mesoporous silica particles, MCM41-cal (spheres, ∼300 to 1000 nm in diameter) and SBA15-cal (irregular rods averaging ∼500 nm in diameter and ∼1000 nm in length). These mesoporous silica particles are in consideration for potential medical application as delivery vehicles for genes, drugs, and bio-imagers. In the study, lung specimens (about 10 mg each) were excised from male Balb/c mice, immediately immersed in Krebs-Henseleit buffer, ice-cold, and continuously gassed with O(2):CO(2) (95:5). The samples were incubated at 37°C in the same buffer with and without 200 μg/mL MCM41-cal or SBA15-cal for 5-14 h. The tissues were then rinsed thoroughly and processed for light and electron microscopy. Normal alveolar morphology was evident in all the studied specimens. There was no significant difference in the number of apoptotic cells between the treated and untreated samples. Despite their relatively large sizes, the particles were abundantly present in pneumocytes, macrophages, endothelial cells, fibroblasts, and interstitium. They were seen in different areas of the cytoplasm, suggesting intracellular movements. Their presence did not appear to disturb cellular configuration or micro-organelles. Due to their rigidity and surface charges, some were firmly attached to (indenting) the nuclear membrane. The rate of respiration (cellular mitochondrial O(2) consumption, in μM O(2)/min/mg) in specimens exposed to 200 μg/mL particles for up to 12 h was the same as untreated specimens. These findings confirm "reasonable" bioavailability and biocompatibility of calcined mesoporous silicas with mouse lung within at least 5-14 h of exposure time.

BackgroundInterpreting the erythroid lineage in populations with high frequency of α+ thalassemia allele is challenging due to the high prevalence of α+ thalassemia homozygotes. For such populations, separate reference values for normal and α+ thalassemia homozygotes are needed.MethodsWe studied the erythroid lineage in 1,079 citizens of United Arab Emirates (UAE). Subjects with abnormal hemoglobin (39), iron deficiency (136) or erroneous entries (8) were excluded. MCV distribution in the remaining individuals (896) was visibly bimodal. Statistical mixture analysis with Normix program was used to separate subpopulations with normal and small red cells. Hardy-Weinberg equation was used to estimate genotype frequencies.ResultsMCV of 78.0 fl separated phenotype-derived normal homozygotes (715) from phenotype-derived α+ thalassemia homozygotes (181). The erythrocyte indices were significantly different between the two groups (p < 0.0001). The overall prevalence of phenotype-derived α+ thalassemia homozygotes (-α/-α) was 0.20 and markedly varied among tribes, 0 to 0.31 (Mean = 0.15). The frequency of phenotype-derived α+ thalassemia allele was 0.44; when accounting for tribal population structure and inbreeding, the calculated frequency was 0.34. These values were very similar to those found in the same population by genotyping and other phenotyping methods. The erythrocyte reference values for phenotype-derived normal homozygotes in Emiratis closely overlapped with those for Caucasians and normal homozygotes defined by genotyping. The reference values for phenotype-derived α+ thalassemia homozygotes in Emiratis also closely overlapped with those for α+ thalassemia homozygotes defined by genotyping.ConclusionIn populations with frequent α+ thalassemia mutations, two sets of erythrocyte reference values could be determined without genotyping.

Purpose First, to investigate the added diagnostic value of chest computed tomography (CT) for evaluating COVID‐19 in symptomatic children by comparing chest CT findings with chest radiographic findings, and second, to identify the imaging signs and patterns on CT associated with COVID‐19 pneumonia in children. Materials and Methods From March 2020 to December 2020, 56 consecutive children (33 males and 23 girls; mean age ± SD , 14.8 ± 5.0 years; range, 9 months–18 years) with mild to moderate symptom and laboratory confirmed COVID‐19 (based on Centers for Disease Control criteria) underwent both chest radiography and chest CT on the same day within the first 2 days of initial presentation to the hospital. Two experienced radiologists independently evaluated chest radiographs and chest CT studies for thoracic abnormalities. The findings from chest radiography and chest CT were compared to evaluate the added diagnostic value of chest CT for affecting patient management. Interobserver agreement was measured with Cohen's κ statistics. Results Eleven (19.6%) of 56 patients had abnormal chest radiographic findings, including ground‐glass opacity (GGO) in 5/11 (45.4%) and combined GGO and consolidation in 6/11 (54.5%). On chest CT, 26 (46.4%) of 56 patients had abnormal CT findings, including combined GGO and consolidation in 19/26 (73.1%), GGO in 6/26 (23.1%), and consolidation in 1/26 (3.8%). Chest CT detected all thoracic abnormalities seen on chest radiography in 11/26 (42.3%) cases. In 15/26 (57.7%), chest CT detected lung abnormalities that were not observed on chest radiography, which included GGO and consolidation in 9/15 (60%), GGO in 5/15 (33.3%), and consolidation in 1/15 (6.6%) cases. These additional CT findings did not affect patient management. In addition, chest CT detected radiological signs and patterns, including the halo sign, reversed halo sign, crazy paving pattern, and tree‐in‐bud pattern. There was almost perfect interobserver agreement between the two reviewers for detecting findings on both chest radiographs ( κ , 0.89, p = .001) and chest CT ( κ , 0.96, p = .001) studies. Conclusion Chest CT detected lung abnormalities, including GGO and/or consolidation, that were not observed on chest radiography in more than half of symptomatic pediatric patients with COVID‐19 pneumonia. However, these additional CT findings did not affect patient management. Therefore, CT is not clinically indicated for the initial evaluation of mild to moderately symptomatic pediatric patients with COVID‐19 pneumonia.

No abstract

In the United Arab Emirates, BCG (Bacillus Calmette-Guérin) is administered to all newborns. We present here a young infant with an inborn error of immunity (IEI) who developed fatal adverse events to this live-attenuated vaccine. This male infant received BCG (Serum Institute of India Pvt., Ltd., India) on Day 11 of life. On Day 25, he developed fever, followed by cervical lymphadenitis and bilateral otitis media with fluid drainage. On Day 118, he was admitted with severe hemophagocytic lymphohistiocytosis (HLH), and passed away on Day 145. The diagnostic exome sequencing test identified a hemizygous nonsense variant, NM_000397.3(CYBB):c.676C&gt;T, p.Arg226* (rs137854592). Pathogenic variants of CYBB [cytochrome b(-245), beta subunit; Mendelian Inheritance in Man [MIM] accession code, 300481] are known to cause “immunodeficiency 34, mycobacteriosis, X-linked” (IMD34, MIM#300645) and “chronic granulomatous disease, X-linked” (CGDX, MIM#306400). The natural history of his illness is consistent with “X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD).” This entity is responsible for his BCG disease and is a likely trigger of his HLH. This disastrous event underlines the importance of developing worldwide policies that target BCG disease prevention, especially in communities with high prevalence of IEI. Moreover, screening for genetic causes of MSMD in the community could pave the way, at least partially, for scale-up of tuberculosis (TB) prevention.

A 14-month-old girl presented with the recurring bouts of vomiting and diarrhoea and failure to thrive. At 7 months of age, the baby was found to be exclusively breast fed and her blood tests revealed low calcium, low phosphorous and markedly elevated alkaline phosphatase. She was started on vitamin D and calcium supplements. Five months later, she came in with lower-limb bowing, irritability, vomiting and loose stools. The laboratory studies revealed very low serum hydroxyvitamin D, and high serum dihydroxyvitamin D. Vitamin D dose was doubled. Ten weeks later, her growth velocity had fallen and she continued to have intermittent loose stools. The oesophagogastroduodenoscopy was done and the biopsies showed Helicobacter pylori gastritis and mild duodenitis. After eradication of H pylori, there was a dramatic improvement in her growth and activity and upon 6 months follow- up there was no clinical or radiologic evidence of rickets.