Spiro derivatives are important scaffolding substances found in many natural products and pharmaceuticals. In the last decade, numerous new approaches based on multicomponent reactions have been ...explored for the selective and efficient development of new spiro derivatives using various organocatalytic and transition metal‐based catalytic systems. This Review discusses pioneering advances in the field of catalytic stereoselective multicomponent reactions for the preparation of various spiro derivatives. These include stereoselective Michael cascade cyclization reactions, cycloadditions, diastereoselective reactions, and miscellaneous reactions for the synthesis of spiro‐hetero/carbocycles. Advances in the last decade have made it possible to synthesize various spiro compounds with good to excellent stereoselectivity under appropriate reaction conditions. However, achieving high regioselectivity in several described multicomponent reactions remains a challenge. Organocatalysts and transition‐metal‐based catalysts play a crucial role in achieving this milestone. Proposed catalytic mechanisms and supporting evidence are highlighted in this Review. The progress described in catalytic stereoselective approaches for spiro derivatives is immense. However, it is expected that new stereoselective synthetic methods will soon be developed that can be widely used for the preparation of spiro‐heterocycles/carbocycles.
The catalytic stereoselective synthesis of spiro compounds is a challenging task for organic chemists. This Review discusses recent advances in catalytic stereoselective, multicomponent reaction‐based methods for the synthesis of spiro compounds. Advantages, limitations, and mechanistic aspects are also highlighted.
Objectives: Health status is associated with socioeconomic status (SES) of the individuals. The aim of this study was to identify any link between the SES and influenza-like illness (ILI). Materials ...and Methods: This observational case-control study was done on 18-70 years old patients presented with ILI (cases) at tertiary care hospital of western India. Controls were selected from demographically matched elective surgery patients except the SES. SES was evaluated as per the Modified B G Prasad 2017 scale and participants were further classified in lower SES (per capita income <2000 INR) and non-lower SES groups. Results: 810 cases and 830 controls were compared. Many cases were from lower SES, had poor hand hygiene, and were using soil, mud, ash (SMA) for hand cleaning as compared to the control. Among the cases significant numbers were from lower SES (543/81067%,P < 0.02), many were alcoholics, smokers, had poor hand hygiene, were using SMA for hand cleaning, and had preexisting chronic obstructive pulmonary disease (COPD), while few were having diabetes in the lower SES group as compared to the non-lower SES group. ILI was more common among lower SES class in unadjusted analysis (odds ratio OR 1.58, 95% CI 0.89-2.76) and the results were significant even after the adjustment of covariates (OR 1.62, 95% CI, 0.94-2.85). Conclusion: Lower SES people were 2.8 times more prone to ILI as compared to the age- and sex-matched control in western part of India.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We introduce a new large scale unconstrained crowd counting dataset (JHU-CROWD++) that contains "4,372" images with "1.51 million" annotations. In comparison to existing datasets, the proposed ...dataset is collected under a variety of diverse scenarios and environmental conditions. Specifically, the dataset includes several images with weather-based degradations and illumination variations, making it a very challenging dataset. Additionally, the dataset consists of a rich set of annotations at both image-level and head-level. Several recent methods are evaluated and compared on this dataset. The dataset can be downloaded from http://www.crowd-counting.com . Furthermore, we propose a novel crowd counting network that progressively generates crowd density maps via residual error estimation. The proposed method uses VGG16 as the backbone network and employs density map generated by the final layer as a coarse prediction to refine and generate finer density maps in a progressive fashion using residual learning. Additionally, the residual learning is guided by an uncertainty-based confidence weighting mechanism that permits the flow of only high-confidence residuals in the refinement path. The proposed Confidence Guided Deep Residual Counting Network (CG-DRCN) is evaluated on recent complex datasets, and it achieves significant improvements In errors.
Postlicensure data has identified a causal link between rotavirus vaccines and intussusception in some settings. As rotavirus vaccines are introduced globally, monitoring intussusception will be ...crucial for ensuring safety of the vaccine programs.
To obtain updated information on background rates and clinical management of intussusception, we reviewed studies of intussusception in children <18 years of age published since 2002. We assessed the incidence of intussusception by month of life among children <1 year of age, seasonality, method of diagnosis, treatment, and case-fatality.
We identified 82 studies from North America, Asia, Europe, Oceania, Africa, Eastern Mediterranean, and Central & South America that reported a total of 44,454 intussusception events. The mean incidence of intussusception was 74 per 100,000 (range: 9-328) among children <1 year of age, with peak incidence among infants 5-7 months of age. No seasonal patterns were observed. A radiographic modality was used to diagnose intussusception in over 95% of the cases in all regions except Africa where clinical findings or surgery were used in 65% of the cases. Surgical rates were substantially higher in Africa (77%) and Central and South America (86%) compared to other regions (13-29%). Case-fatality also was higher in Africa (9%) compared to other regions (<1%). The primary limitation of this review relates to the heterogeneity in intussusception surveillance across different regions.
This review of the intussusception literature from the past decade provides pertinent information that should facilitate implementation of intussusception surveillance for monitoring the postlicensure safety of rotavirus vaccines.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A versatile and substrate oriented multicomponent reaction for the syntheses of novel highly diastereoselective tetrahydro-1'
-spiropyrazolo4,3-
quinoline-8,5'-pyrimidine-2',4',6'(3'
)-triones (d.r. ...up to 20 : 1 (
:
)) and tetrahydro-8
-pyrazolo4,3-
pyrimido4,5-
quinoline-8,10(9
)-diones
formation of selective multiple C-C bonds under identical reaction conditions (
ethanol as a reaction medium and deep eutectic mixture as a catalyst) is demonstrated. Both approaches involve mild reaction conditions, use of non-hazardous solvents, and facilitate good to excellent reaction yields of the target compounds.
The SARS‐CoV‐2 virus, which causes coronavirus disease 2019 (COVID‐19), has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the ...close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID‐19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. Laryngoscope, 130:2537–2543, 2020
Propofol exposure to neurons during synaptogenesis results in apoptosis, leading to cognitive dysfunction in adulthood. Previous work from our laboratory showed that isoflurane neurotoxicity occurs ...through p75 neurotrophin receptor (p75(NTR)) and subsequent cytoskeleton depolymerization. Given that isoflurane and propofol both suppress neuronal activity, we hypothesized that propofol also induces apoptosis in developing neurons through p75(NTR).
Days in vitro 5-7 neurons were exposed to propofol (3 μM) for 6 h and apoptosis was assessed by cleaved caspase-3 (Cl-Csp3) immunoblot and immunofluorescence microscopy. Primary neurons from p75(NTR-/-) mice or wild-type neurons were treated with propofol, with or without pretreatment with TAT-Pep5 (10 μM, 15 min), a specific p75(NTR) inhibitor. P75(NTR-/-) neurons were transfected for 72 h with a lentiviral vector containing the synapsin-driven p75(NTR) gene (Syn-p75(NTR)) or control vector (Syn-green fluorescent protein) before propofol. To confirm our in vitro findings, wild-type mice and p75(NTR-/-) mice (PND5) were pretreated with either TAT-Pep5 or TAT-ctrl followed by propofol for 6 h.
Neurons exposed to propofol showed a significant increase in Cl-Csp3, an effect attenuated by TAT-Pep5 and hydroxyfasudil. Apoptosis was significantly attenuated in p75(NTR-/-) neurons. In p75(NTR-/-) neurons transfected with Syn-p75(NTR), propofol significantly increased Cl-Csp3 in comparison with Syn-green fluorescent protein-transfected p75(NTR-/-) neurons. Wild-type mice exposed to propofol exhibited increased Cl-Csp3 in the hippocampus, an effect attenuated by TAT-Pep5. By contrast, propofol did not induce apoptosis in p75(NTR-/-) mice.
These results demonstrate that propofol induces apoptosis in developing neurons in vivo and in vitro and implicate a role for p75(NTR) and the downstream effector RhoA kinase.
The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (B
CSF
) are two of the most complex and sophisticated concierges that defend the central nervous system (CNS) by numerous ...mechanisms. While they maintain the neuro-ecological homeostasis through the regulated entry of essential biomolecules, their conservative nature challenges the entry of most of the drugs intended for CNS delivery. Targeted delivery challenges for a diverse spectrum of therapeutic agents/drugs (non-small molecules, small molecules, gene-based therapeutics, protein and peptides, antibodies) are diverse and demand specialized delivery and disease-targeting strategies. This review aims to capture the trends that have shaped the current brain targeting research scenario. This review discusses the physiological, neuropharmacological, and etiological factors that participate in the transportation of various drug delivery cargoes across the BBB/B
CSF
and influence their therapeutic intracranial concentrations. Recent research works spanning various invasive, minimally invasive, and non-invasive brain- targeting approaches are discussed. While the pre-clinical outcomes from many of these approaches seem promising, further research is warranted to overcome the translational glitches that prevent their clinical use. Non-invasive approaches like intranasal administration, P-glycoprotein (P-gp) inhibition, pro-drugs, and carrier/targeted nanocarrier-aided delivery systems (alone or often in combination) hold positive clinical prospects for brain targeting if explored further in the right direction.
A
bstract
A non-supersymmetric renormalizable SO(10) model is investigated for its viability in explaining the observed fermion masses and mixing parameters along with the baryon asymmetry produced ...via thermal leptogenesis. The Yukawa sector of the model consists of complex 10
H
and
126
¯
H
scalars with a Peccei-Quinn like symmetry and it leads to strong correlations among the Yukawa couplings of all the standard model fermions including the couplings and masses of the right-handed (RH) neutrinos. The latter implies the necessity to include the second lightest RH neutrino and flavor effects for the precision computation of leptogenesis. We use the most general density matrix equations to calculate the temperature evolution of flavoured leptonic asymmetry. A simplified analytical solution of these equations, applicable to the RH neutrino spectrum predicted in the model, is also obtained which allows one to fit the observed baryon to photon ratio along with the other fermion mass observables in a numerically efficient way. The analytical and numerical solutions are found to be in agreement within a factor of
O
1
. We find that the successful leptogenesis in this model does not prefer any particular value for leptonic Dirac and Majorana CP phases and the entire range of values of these observables is found to be consistent. The model specifically predicts (a) the lightest neutrino mass
m
v
1
between 2–8 meV, (b) the effective mass of neutrinoless double beta decay
m
ββ
between 4–10 meV, and (c) a particular correlation between the Dirac and one of the Majorana CP phases.
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