A new fluorinated chalcone (
E
)-3-(2,6-difluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one was synthesized in 90% yield and crystallized by a slow evaporation technique. Its full structural ...characterization and purity were determined by scanning electron microscopy, infrared spectroscopy, gas chromatography-mass spectrometry,
1
H,
13
C and
19
F nuclear magnetic resonance, thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman microspectroscopy, UV-Vis absorption spectroscopy, single crystal X-ray diffraction (XRD) and Hirshfeld surface (HS) analysis. The fluorinated chalcone crystallized in centrosymmetric space group
P
2
1
/
c
stabilized by the C-H O and C-H F interactions and the π π contact. The crystalline environment was simulated through the supermolecule approach where a bulk with 378 000 atoms was built. The electric parameters were calculated at the DFT/CAM-B3LYP/6-311++G(d,p) level as function of the electric field frequency. The macroscopic parameters such as linear refractive index and third-order nonlinear susceptibility (
χ
(3)
) were calculated, and the results were compared with experimental data obtained from the literature. The
χ
(3)
-value for the chalcone crystal is 369.294 × 10
−22
m
2
V
−2
, higher than those obtained from a few similar types of molecule, showing that the chalcone crystal can be considered as a nonlinear optical material. Also, molecular theoretical calculations such as infrared spectrum assignments, frontier molecular orbital analysis and MEP were implemented, revealing that the most positive region is around the hydrogen atoms of the aromatic rings, and electrophilic attack occurs on the carbonyl group.
A new fluorinated chalcone (
E
)-3-(2,6-difluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one was synthesized in 90% yield and crystallized by a slow evaporation technique.
Objective
To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at ...diagnosis.
Methods
This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm3) and AIHA.
Results
The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2–10) vs 9.5 (6.6–10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE (p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161).
Conclusions
We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence/severity in children and concomitant constitutional symptoms in the majority of them.
•The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were significantly lower than those of healthy controls during the COVID-19 pandemic.•The frequencies of ...abnormal hyperactivity and inattention SDQ scores from adolescents with chronic diseases were significantly lower than those of healthy controls.•Abnormal emotional scores from adolescents with chronic diseases were as independently associated with female sex, poor sleep quality, and intrafamilial violence during the pandemic.•Abnormal hyperactivity and inattention SDQ scores from patients were inversely associated with total PedsQL score, changes in medical appointments during the pandemic, and reliable COVID-19 information remained.
To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases.
A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0).
The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 32% vs. 38/108 35%, p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 23% vs. 29/108 27%, p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio OR = 3.76; 95% Confidence Interval (95% CI) 2.00‒7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08‒3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12‒4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93‒0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95‒0.99; p = 0.010, changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16‒0.77; p = 0.026) remained inversely associated with abnormal HI scores.
The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.
Yellow fever virus (YFV) was isolated from Haemagogus leucocelaenus mosquitoes during an epizootic in 2001 in the Rio Grande do Sul State in southern Brazil. In October 2008, a yellow fever outbreak ...was reported there, with nonhuman primate deaths and human cases. This latter outbreak led to intensification of surveillance measures for early detection of YFV and support for vaccination programs. We report entomologic surveillance in 2 municipalities that recorded nonhuman primate deaths. Mosquitoes were collected at ground level, identified, and processed for virus isolation and molecular analyses. Eight YFV strains were isolated (7 from pools of Hg. leucocelaenus mosquitoes and another from Aedes serratus mosquitoes); 6 were sequenced, and they grouped in the YFV South American genotype I. The results confirmed the role of Hg. leucocelaenus mosquitoes as the main YFV vector in southern Brazil and suggest that Ae. serratus mosquitoes may have a potential role as a secondary vector.
Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein ...6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness.
Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling motifs provides an opportunity to ...regulate specific receptor initiated signaling cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of antagonist therapies for individuals with pulmonary arterial hypertension (PAH). These therapies have had success but have been accompanied by adverse reactions. Also, unlike the CPP which target specific signaling cascades, the antagonists target the entire function of the receptor. Using the CPP strategy of biased antagonism of the ETB receptor's intracellular loop 2 (ICB2), we demonstrate blunting of hypoxic pulmonary hypertension (HPH) in the rat, including indices of pulmonary arterial pressure, right ventricular hypertrophy and pulmonary vascular remodeling. Further, ex vivo analysis of the pulmonary artery treated with the IC2B peptide upon injection manifests marked reductions in Akt and ERK activation. Both kinases have been intimately related to cell proliferation and vascular contraction, the hallmarks of PAH. These observations in sum illustrate an involvement of the ETB receptor in HPH and furthermore provide a basis for a novel, CPP-based, strategy in the treatment of PAH, ultimately able to target not only ET-1, but also other factors involved in the development of PAH.
Context.
Accreting planetary-mass objects have been detected at H
α
, but targeted searches have mainly resulted in non-detections. Accretion tracers in the planetary-mass regime could originate from ...the shock itself, making them particularly susceptible to extinction by the accreting material. High-resolution (
R
> 50 000) spectrographs operating at H
α
should soon enable one to study how the incoming material shapes the line profile.
Aims.
We calculate how much the gas and dust accreting onto a planet reduce the H
α
flux from the shock at the planetary surface and how they affect the line shape. We also study the absorption-modified relationship between the H
α
luminosity and accretion rate.
Methods.
We computed the high-resolution radiative transfer of the H
α
line using a one-dimensional velocity–density–temperature structure for the inflowing matter in three representative accretion geometries: spherical symmetry, polar inflow, and magnetospheric accretion. For each, we explored the wide relevant ranges of the accretion rate and planet mass. We used detailed gas opacities and carefully estimated possible dust opacities.
Results.
At accretion rates of
Ṁ
≲ 3 × 10
−6
M
J
yr
−1
, gas extinction is negligible for spherical or polar inflow and at most
A
H
α
≲ 0.5 mag for magnetospheric accretion. Up to
Ṁ
≈ 3 × 10
−4
M
J
yr
−1
, the gas contributes
A
H
α
≲ 4 mag. This contribution decreases with mass. We estimate realistic dust opacities at H
α
to be
κ
~ 0.01–10 cm
2
g
−1
, which is 10–10
4
times lower than in the interstellar medium. Extinction flattens the
L
H
α
–
Ṁ
relationship, which becomes non-monotonic with a maximum luminosity
L
H
α
~ 10
−4
L
⊙
towards
Ṁ
≈ 10
−4
M
J
yr
−1
for a planet mass ~10
M
J
. In magnetospheric accretion, the gas can introduce features in the line profile, while the velocity gradient smears them out in other geometries.
Conclusions.
For a wide part of parameter space, extinction by the accreting matter should be negligible, simplifying the interpretation of observations, especially for planets in gaps. At high
Ṁ
, strong absorption reduces the H
α
flux, and some measurements can be interpreted as two
Ṁ
values. Highly resolved line profiles (
R
~ 10
5
) can provide (complex) constraints on the thermal and dynamical structure of the accretion flow.
Summary Background Leber congenital amaurosis, caused by mutations in RPE65 and LRAT , is a severe form of inherited retinal degeneration leading to blindness. We aimed to assess replacement of the ...missing chromophore 11-cis retinal with oral QLT091001 (synthetic 9-cis-retinyl acetate) in these patients. Methods In our open-label, prospective, phase 1b trial, we enrolled patients (aged ≥6 years) with Leber congenital amaurosis and RPE65 or LRAT mutations at McGill University's Montreal Children's Hospital. Patients received 7 days of oral QLT091001 (10–40 mg/m2 per day). We assessed patients at baseline and days 7, 9, 14, and 30, and then 2 months and every 2 months thereafter for up to 2·2 years for safety outcomes and visual function endpoints including Goldmann visual fields (GVF), visual acuity, and functional MRI assessment. We regarded patients as having an improvement in vision if we noted at least a 20% improvement in retinal area on GVF compared with baseline or a visual acuity improvement of five or more letters compared with baseline in two consecutive study visits (or any improvement from no vision at baseline). This study is registered with ClinicalTrials.gov , number NCT01014052. Findings Between December, 2009, and June, 2011, we enrolled and treated 14 patients aged 6–38 years who were followed up until March, 2012. Ten (71%) of 14 patients had an improvement in GVF areas (mean increase in retinal area of 28–683%). Six (43%) patients had an improvement in visual acuity (mean increase of 2–30 letters). Self-reported or parent-reported improvements in activities of daily living supported these findings. After 2 years, 11 (79%) patients had returned to their baseline GVF retinal area and ten (71%) had returned to baseline visual acuity letter values. Thus, three (21%) patients had a sustained GVF response and four (30%) had a sustained visual acuity response. Four patients had functional MRI scans, which correlated with visual response or absence of response to treatment. No serious adverse events occurred, although we noted transient headaches (11 patients), photophobia (11 patients), reduction in serum HDL concentrations (four patients), and increases in serum triglycerides (eight patients) and aspartate aminotransferase concentrations (two patients). Interpretation Non-invasive oral QLT091001 therapy is well tolerated, and can rapidly improve visual function in some patients with Leber congenital amaurosis and RPE65 and LRAT mutations. Funding QLT, Foundation Fighting Blindness Canada, CIHR, FRSQ, Reseau Vision.
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