Associations of childhood overweight and obesity with upper-extremity fracture characteristics

Childhood obesity is a growing epidemic in the United States, and is associated with an increased risk of lower-extremity physeal fractures, and fractures requiring operative intervention. However, no study has assessed the risk upper extremity physeal fractures among overweight children. Our purpose was to compare the following upper-extremity fracture characteristics in overweight and obese children with those of normal-weight/underweight children (herein, “normal weight”): mechanism of injury, anatomical location, fracture pattern, physeal involvement, and treatment types. We hypothesized that overweight and obese children would be higher risk for physeal and complete fractures with low-energy mechanisms and would therefore more frequently require operative intervention compared with normal-weight children.We performed a cross-sectional review of our database of 608 patients aged 2 to 16 years, and included patients who sustained isolated upper-extremity fractures at our level-1 pediatric tertiary care center from January 2014 to August 2017. Excluded were patients who sustained pathologic fractures and those without basic demographic or radiologic information. Using body mass index percentile for age and sex, we categorized patients as obese (≥95th percentile), overweight (85th to <95th percentile), normal weight (5th to <85th percentile), or underweight (<5th percentile). The obese and overweight groups were analyzed both separately and as a combined overweight/obese group. Demographic data included age, sex, height, and weight. Fractures were classified based on fracture location, fracture pattern (transverse, comminuted, buckle, greenstick, avulsion, or oblique), physeal involvement, and treatment type. Of the 608 patients, 58% were normal weight, 23% were overweight, and 19% were obese. There were no differences in the mean ages or sex distributions among the 3 groups.Among patients with low-energy mechanisms of injury, overweight/obese patients had significantly greater proportions of complete fractures compared with normal-weight children (complete: 65% vs 55%, P = .001; transverse: 43% vs 27%, P = .006). In addition, the overweight/obese group sustained significantly more upper-extremity physeal fractures (37%) than did the normal-weight group (23%) (P = .007).Compared with those in normal-weight children, upper-extremity fracture patterns differ in overweight and obese children, who have higher risk of physeal injuries and complete fractures caused by low-energy mechanisms.Level of Evidence: Level III, retrospective comparative study.     

Elevation in serum thyroglobulin during prolonged Antarctic residence: effect of thyroxine supplement in the polar 3,5,3'-triiodothyronine syndrome

Extended Antarctic residence (AR) is associated with an increase in serum TSH, a decrease in free T(4), and an increase in T(3) production and clearance. It is not clear whether these adaptations reflect changes in clearance alone or whether intrinsic thyroidal synthetic activity also changes. Thyroglobulin (Tg) secretion is an independent marker of intrinsic thyroid activity whose kinetics are independent of those of T(3) and T(4). In this study we examined changes in Tg levels in healthy subjects before and during AR and their responses to thyroid supplementation to help determine whether alterations in thyroid activity, and not just kinetics of clearance, underlie the changes seen with the polar T(3) syndrome. In cohort 1, we compared measurements of TSH and Tg in 12 subjects before deployment and monthly for 11 months during AR. In cohort 2, we compared the same measurements in 12 subjects monthly for 11 months of AR. Subjects were randomized to receive either placebo or levothyroxine in cohort 1 for 7 months and in cohort 2 for 11 months. Tg increased over baseline during the first 4 months of AR by 17.0 +/- 4.6% and after 7 more months by 31.7 +/- 4.3% over baseline in the placebo group of both cohorts (P < 0.0002). When L-T(4) was taken, Tg returned to a value not different from baseline (4.5 +/- 3.9%). The percent changes from baseline in serum TSH and Tg during AR were highly correlated (P < 0.00003) in the placebo group for both cohorts. The rise in Tg with TSH and the reduction in Tg with L-T(4) provide evidence of target tissue response to TSH and further confirm the TSH rise as physiologically significant. The results also suggest that the adaptive changes in thyroid hormone economy with AR reflect TSH-dependent changes in thyroid synthetic activity, which may help explain a portion of the increases in T(3) production found with AR.     

Potential Sexual Transmission of Zika Virus

In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.Zika virus (ZIKV) is a mosquitoborne arbovirus in the family Flaviviridae, genus Flavivirus. It was first isolated in 1947 from a rhesus monkey in the Zika forest of Uganda (1). Sporadic human cases were reported from the 1960s in Asia and Africa. The first reported large outbreak occurred in 2007 on Yap Island, Federated States of Micronesia (2). The largest known ZIKV outbreak reported started in October 2013 in French Polynesia, South Pacific (3), a territory of France comprising 67 inhabited islands; an estimated 28,000 persons (11% of the population) sought medical care for the illness (4). The most common symptoms of Zika fever are rash, fever, arthralgia, and conjunctivitis. Most of the patients had mild disease, but severe neurologic complications have been described in other patients in French Polynesia (5).     

A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE_Ph–AgCl and (NHE_Ph–AgCl)₂ with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver–tetrylene complexes (NHE–Ag) and bis-silver–tetrylene complexes (NHE–Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC–Ag and NHC–Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl)₂, whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE–Ag bond in the complex families follows the order of NHC–Ag > NHSi–Ag > NHGe–Ag and NHSi–Ag-bis > NHGe–Ag-bis > NHC–Ag-bis. The natural bond orbital analysis implies that the [NHE_Ph→AgCl] and [(NHE_Ph)₂→(AgCl)₂] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver–carbene NHC–Ag, bis-silver–carbene NHC–Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from −17.5 to −16.5 kcal mol⁻¹ and −16.9 to −16.6 kcal mol⁻¹, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver–carbene NHC–Ag and bis-silver–carbene NHC–Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.

Simultaneous inhibition of silver–carbene complexes to ACE2 and PDB6LU7 is conducive for the prevention of SARS-CoV-2 infection: a virtual prediction.     

Three new C-14 oxygenated taxanes from the wood of Taxus yunnanensis

Three new C-14 oxygenated taxane-type diterpenes, hongdoushans A-C (1-3), were isolated from the wood of Taxus yunnanensis together with four known diterpenes and two lignans. The absolute stereochemistry of the 2-methylbutyryloxy group attached at C-14 of the taxane skeleton was determined to be S by GC analysis of the methyl ester of 2-methylbutyric acid obtained after alkaline hydrolysis of 1 and 4 followed by treatment with CH(2)N(2). The complete stereostructure of the known compound 2alpha,5alpha,10beta-triacetoxy-14beta-[(S)-2-methylbutyryloxy]-4(20),11-taxadiene (4) was established for the first time. The isolates obtained were evaluated for their antiproliferative activity toward murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cell lines.     

Regulation of glioma cell migration by serine-phosphorylated P311

P311, an 8-kDa polypeptide, was previously shown to be highly expressed in invasive glioma cells. Here, we report the functional characteristics of P311 with regard to influencing glioma cell migration. P311 is constitutively serine-phosphorylated; decreased phosphorylation is observed in migration-activated glioma cells. The primary amino acid sequence of P311 indicates a putative serine phosphorylation site (S59) near the PEST domain. Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration. Coimmunoprecipitation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis identified Filamin A as a binding partner of P311, and immunofluorescence studies showed that both proteins colocalized at the cell periphery. Moreover, P311-induced cell migration was abrogated by inhibition of beta1 integrin function using TACbeta1A, a dominant-negative inhibitor of beta1 integrin signaling, suggesting that P311 acts downstream of beta1 signaling. Finally, overexpression of P311 or P311 S59A mutant protein activates Rac1 GTPase; small interfering RNA-mediated depletion of Rac1 suppresses P311-induced motility. Collectively, these results suggest a role for levels of P311 in regulating glioma motility and invasion through the reorganization of actin cytoskeleton at the cell periphery.