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Photochemical reactivity and fate of the toxic transformation product of naproxen in water.

2-Acetyl-6-methoxynaphthalene (2A6MN) is an important environmental transformation product of the anti-inflammatory drug naproxen (NPX), and causes accumulating concerns because of its undesired toxicity. Understanding the persistence and environmental fate of 2A6MN in natural and engineered systems is crucial for the ecological risk assessment of NPX transformation products. In this study, we systematically investigated the photochemical reactivity and behavior of 2A6MN under 254 nm ultraviolet (UV254) and natural sunlight irradiation. Our results indicated that 2A6MN exhibited strong absorpt

Front-line treatment approaches in multiple myeloma: real-world data from a community-based oncology network.

BACKGROUND: The front-line (1L) treatment landscape for newly diagnosed multiple myeloma (NDMM) is rapidly evolving with guidelines endorsing triplet and quadruplet regimens as new standard-of-care. Despite this, real-world evidence on current treatment patterns for NDMM remain limited, especially in community settings, where most care is delivered. This study describes 1L treatment patterns for NDMM using recent data from a large US community oncology network. METHODS: This retrospective, observational study analyzed structured and unstructured medical records of patients treated at Texas On

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… The 1L treatment landscape for patients with newly diagnosed MM (NDMM) is rapidly evolving, with recent approvals of triplet and quadruplet regimens. These triplet and quadruplet regimens include drugs with different modes of action, which overcome drug resistance mechanisms ( 6 ). … Stacked bar chart showing percentages of patients receiving first-line treatment regimens by year from 2015 to 2022 with categories: monotherapy (red), doublets (black), triplets (gray), and quadruplets (blue). Triplets increased over time, becoming the dominant regimen by 2017. …

Variation in multiple classes of simple sequence repeats can alter drug susceptibility in Mycobacterium tuberculosis.

Insertions and deletions (INDELs) in simple sequence repeats (SSRs) generate relatively high-frequency reversible genetic changes that facilitate bacterial adaptation to changing environments. Analyses of global Mycobacterium tuberculosis (Mtb) isolates indicate that many SSRs are under diversifying selection, and several of the resulting INDELs in homopolymer tracts (HTs) can increase the pathogen's fitness during exposure to host and antibiotic stresses. However, the functional impact of most variable SSRs, particularly those within more complex repeat sequences than HT, remains unclear.  He

Spin-orbit coupling effects hidden behind the photophysics of phosphorescent chiral cyclometalated Pt(II) complexes.

The electronic and (chiro-) optical properties of [Pt(pCpy)(acac)] 1 and [Pt(pCpz)(acac)] 2 (pCpy = 2-[2,2]-paracyclophane-4-yl)pyridyl; pCpz = 1-[2,2]-paracyclophane-4-yl)pyrazolyl; acac = dimethyl-substituted acetylacetonato), representative of phosphorescent chiral cyclometalated Pt(II) complexes, are investigated by means of density functional theory (DFT) and its time-dependent extension so-called TD-DFT, including spin-orbit coupling (SOC) effects. The computed absorption, phosphorescence and circularly polarized luminescence (CPL) spectra are compared to the available experimental spect

Interplay between Through-Space and Through-Bond Electronic Coupling in Singlet Fission.

Singlet fission (SF) is a spin-allowed photophysical process that generates two triplet excited states for one absorbed photon. It therefore has the potential to boost solar cell efficiencies beyond the 33% detailed balance limit. A better understanding of through-space and through-bond electronic coupling in SF, and their interplay, is essential for practical applications of SF materials. We have therefore designed three structurally complex pentacene dimers, two of which contain additional subphthalocyanines (SubPcs). These dimers, on the one hand, provide a continuum of electronic coupling

Carfilzomib in relapsed/refractory multiple myeloma patients - real world evidence - experiences of the Croatian cooperative group for hematologic diseases (KROHEM).

BACKGROUND: Carfilzomib-based regimens brought a significant improvement in the treatment of relapsed/refractory multiple myeloma (RRMM). Ev … re cohort were 9.4 and 13.2 months, respectively. Median PFS was 12.8 months and 4.1 months for the triplets and doublets, respectively; the corresponding median OS was 18.6 and 7.9 months, respectively. The most common adverse events were anemia and thrombocytopenia; 19 patients (16 %) experienced cardiovascular events. CONCLUSION: This is the first stud …

ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study.

Melphalan flufenamide (melflufen), a first-in-class, alkylating peptide-drug conjugate, demonstrated clinical benefit in combination with dexamethasone in triple-class refractory multiple myeloma (MM). The phase I/IIa ANCHOR study evaluated melflufen (30 or 40 mg) and dexamethasone (40 mg with daratumumab; 20 mg followed by 40 mg with bortezomib; dose reduced if aged ≥75 years) in triplet combination with daratumumab (16 mg/kg; daratumumab arm) or bortezomib (1.3 mg/m2; bortezomib arm) in patients with relapsed/refractory MM refractory to an immunomodulatory agent and/or a proteasome inhibitor

Mechanistic Insight and Intersystem Crossing Dynamics of the C(3P) + H2CO/D2CO Reaction.

The reaction of atomic carbon, C(3P), with H2CO has been investigated using the direct dynamics trajectory surface hopping (DDTSH) method with Tully's fewest switches algorithm. The lowest lying ground triplet and single states are considered for the dynamics study at a reagent collision energy of 8.0 kcal/mol. From the trajectory calculations, we observed that CH2 + CO and H + HCCO are the two major product channels for the title reaction. The insertion mechanism of the C(3P) + H2CO reaction is rather complex and is followed by three distinct intermediates with no entrance channel barrier to

Theoretical study of C6F5-corrole molecules functionalized with aromatic groups for Photodynamic Therapy.

The singlet oxygen generation by electronically excited molecules in photodynamic therapy (PDT) requires light absorption within a specific wavelength window, and a subsequent intersystem crossing transition to a triplet excited state that is, at least, 0.98 eV higher in energy than the singlet ground state. Tetrapyrrolic macrocycles, such as porphyrin and corrole, have been widely used in oxygen singlet generation for PDT. Suitable functionalization can potentialize these macrocycles as photosensitizers. In this contribution, we use Density Functional Theory (DFT) calculations to determine th

Naphthalimide-Carbazole Compact Electron Donor-Acceptor Dyads: Effect of Molecular Geometry and Electron-Donating Capacity on the Spin-Orbit Charge Transfer Intersystem Crossing.

We prepared a series of naphthalimide (NI)-carbazole (Cz) compact electron donor-acceptor dyads showing different substitution positions, C-N/C-C linkers, and conformation restriction magnitudes to study the spin-orbit charge transfer intersystem crossing (SOCT-ISC). The varied conformation restrictions lead to different dihedral angles between the donor and acceptor (37°-81°) and electronic coupling magnitude (matrix elements V: 1290-3070 cm-1). Based on the comparison between the dyads containing C-N and C-C linkers, we found that a large dihedral angle between the donor and acceptor is favo

Singlet oxygen and radical-mediated mechanisms in the oxidative cellular damage photosensitized by the protease inhibitor simeprevir.

Hepatitis C, a liver inflammation caused by the hepatitis C virus (HCV), is treated with antiviral drugs. In this context, simeprevir (SIM) is an NS3/4A protease inhibitor used in HCV genotypes 1 and 4. It is orally administered and achieves high virological cure rates. Among adverse reactions associated with SIM treatment, photosensitivity reactions have been reported. In the present work, it is clearly shown that SIM is markedly phototoxic, according to the in vitro NRU assay using BALB/c 3T3 mouse fibroblast. This result sheds light on the nature of the photosensitivity reactions induced by

[Perinatal Management for Monochorionic Twin Reversed Arterial Perfusion Sequence].

OBJECTIVE: To evaluate the perinatal managementof monochorionic twin pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. METHODS: A retrospectively study was performed on the management and perinatal outcome of monochorionic multiple pregnanciescomplicated by TRAP sequence at West China Second University Hospital from May 2010 to May 2014. RESULTS: Thirteen cases of TRAP sequence were identified during the study period, included 4 monochorionicmonoamniotic (MCMA) twins, 7 monochorionic diamniotic(MCDA) twins,1 monochorionic-triamniotic (MCTA) triplet pregnancy and 1

Atypical presentation of preeclampsia in high-order multifetal gestations.

OBJECTIVE: To describe our experience with preeclampsia in high-order multifetal gestations. METHODS: Records for all triplet and quadruplet pregnancies delivered after 24 weeks' gestation from January 1988 through June 1994 were reviewed. All patients were treated with bed rest from 20 weeks' gestation onward and received corticosteroids weekly beginning at 24 weeks. Tocolytics were used as needed. RESULTS: Twenty-one triplet and eight quadruplet pregnancies were studied. The mean gestational age at delivery was 32.3 and 27.9 weeks, and mean birth weights were 1547 and 1028 g, respectively.

A systematic review of early intrauterine intervention at 12 + 0 to 16 + 6 weeks in twin reversed arterial perfusion sequence.

UNLABELLED: There is some evidence that in twin reversed arterial perfusion sequence, intervention at early gestational age could prevent a spontaneous death of the pump twin, achieving a better global survival. OBJECTIVE: To review the perinatal outcomes of early intervention in pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. STUDY DESIGN: A comprehensive search from inception to December 2022 was conducted on databases including MEDLINE, EMBASE, Cochrane Library and LILACS. All studies that reported intervention in twin or triplet pregnancy complicated with TRA

[Chorionic villus sampling in multiple pregnancies].

Prenatal genetic diagnosis is recommended in multiple pregnancies because of the increased prevalence of genetic abnormalities in such fetuses. It can be done early by chorionic villus sampling or later by amniocentesis. Several studies have demonstrated the efficacy and safety of chorionic villus sampling in multiple pregnancies. Our study describes the results of this method in a twin pregnancy and in 3 triplet pregnancies, which represent 3% of the chorionic villus samplings performed in our ultrasound unit during 1989-95. All genetically deformed fetuses in these pregnancies were identifie

Ontogenetic Variation in Plant-to-Plant Signaling Effects on Direct and Indirect Defenses in Wild Cotton (Gossypium hirsutum).

Various plant-related factors have been shown to influence volatile organic compound (VOC)-mediated plant-to-plant interactions, but effects of plant ontogeny have been rarely considered. Here, we tested if these interactions differ between two ontogenetic stages in wild cotton, Gossypium hirsutum. We used 2.5- and 4.5-month-old plants (seedlings and juveniles, respectively), arranged in triplets where one plant acted as an emitter and two as receivers (all plants within a cage were of the same developmental stage). Half of the emitters were subjected to herbivory by Alabama argillacea caterpi…

Pyrrolo[1,2-a]quinoxaline: A Combined Experimental and Computational Study on the Photophysical Properties of a New Photofunctional Building Block.

We report a detailed photophysical exploration of medicinally important pyrrolo[1,2-a]quinoxalines. Pyrrolo[1,2-a]quinoxaline (QHH), 2,4-dip … PQN moieties were absent. The S1 states of these latter nonrigid molecules undergo ISC with higher triplets (T2/T3) through further twisting along the C-C bonds, accompanied by high charge transfer with a 1.5- to 3.0-fold increase in the dipole moments. These triplets were identified as the phosphorescent states, while triplet T1 seems to be responsible f …

Endless possibilities and how to exploit them? What is the optimal treatment sequence?

The therapeutic landscape of multiple myeloma has undergone a profound transformation with the incorporation of anti-CD38 monoclonal antibod … duct currently, albeit with some unique toxicities such as parkinsomism. Belantamab mafadotin-based triplets have shown impressive efficacy in lenalidomide and anti-CD38 mAb-refractory patients, although ocular toxicity remains a concern. Anti-CD38 mAb and carfilzomib-based triplets remain an essential therapeutic option in patients not refractory to anti- …

Delayed interval delivery of preterm multiples: experience from a large specialized twin center.

OBJECTIVE: Preterm delivery is a recognized complication of twins and higher order multiple pregnancies. Delayed interval delivery is a rare … poor, with 5 out of 7 (71%) dying from extreme prematurity. However, out of the remaining twins or triplets, 5/8 (62%) survived. The mean gestation of delivery of the remaining infant (or infants in the triplets) was 25 + 0 weeks (range 23 + 0 to 30 + 2 weeks). Only one mother (16%) developed clinical chorioamnionitis requiring iatrogenic delivery of the …

Characteristics of Rest and Postural Tremors in Parkinson's Disease: An Analysis of Motor Unit Firing Synchrony and Patterns.

The neural mechanisms responsible for resting and postural tremor in Parkinson's disease (PD) have been the object of considerable study, mu … e characterized by the presence of 4-8 Hz overt tremor, enhanced MU synchrony and spike-doublets or triplets bearing a one-to-one relation to each tremor cycle. Epoch-I resembled physiological tremor in that it was characterized by 6-10 Hz non-overt tremor, lower MU synchrony and rhythmical MU firing at the intrinsic rate of the unit. The frequency of over …