Integrated Safety Update of Abrocitinib in 3802 Patients with Moderate-to-Severe Atopic Dermatitis: Data from More than 5200 Patient-Years with Up to 4 Years of Exposure.

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile.

Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program.

Methods: Analysis included 3802 patients (exposure: 5213.

Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

Background: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden.

Objectives: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD.

Methods: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]).

Americans' Awareness of Access Changes and Utilization of Telehealth During COVID-19: A Survey in the United States.

We examine how and why Americans have experienced interrupted health care during the COVID-19 pandemic and measure awareness and usage of expanded benefits offered by health insurers and employers. We use an expanded concept of health literacy to include knowledge of access conditions and consider if patients' knowledge of the health system may relate to utilization of care. We conducted an online survey of 451 U.

Understanding treatment patterns and patient-reported outcomes associated with the use of authorized generics and corresponding independent generics across multiple therapeutic areas.

Objectives: To assess patient characteristics, treatment patterns, and patient-reported outcomes (PROs) associated with authorized generics (AGs) and independent generics (IGs) use.

Methods: Prescription claims and National Health and Wellness Survey (NHWS) data were linked. Adults with billable national drug code (AG or IG), NHWS completion from June 2015 to July 2019, AG or IG on-hand at NHWS completion, and continuous insurance eligibility in 12 months pre- and post-NHWS completion were included.

Understanding authorized generics-A review of the published clinical data.

What Is Known And Objectives: Despite the large body of evidence demonstrating equivalent efficacy and safety for branded drugs and their generic counterparts, some patients and providers have the perception that generics may be less safe and effective than branded agents. Authorized generics (AGs) are a category of generic drugs defined by the United States Food and Drug Administration (FDA) as being the same as the brand-name drug without the brand's name on the label and which may have minor differences, such as tablet or capsule markings for identification. Studies in which AGs are considered along with other generics may increase our understanding of factors that may influence perceptions about generics and shed light on areas where education may be impactful.

Lessons from mass vaccination response to meningococcal B outbreaks at US universities.

College students in the United States are at an increased risk for meningococcal serogroup B disease or MenB, which causes the majority of invasive meningococcal disease in the country among adolescents and young adults (62%) and also across all age groups (36%) as of 2018. Approximately one-third of MenB cases among college students occur during campus outbreaks, which trigger substantial public health concern and costs associated with conducting rapid mass vaccination campaigns in an emergency setting. Eleven US college outbreaks of MenB disease have occurred since the initial licensure and recommendation of two MenB vaccines in 2014/2015; both vaccines have been used as part of outbreak responses on campuses, but vaccine coverage and multidose series completion among the general adolescent population are very low (approximately 17% of 17-year-olds in the United States received ≥1 dose in 2018).

A review of the immunogenicity, safety and current recommendations for the meningococcal serogroup B vaccine, MenB-FHbp.

What Is Known And Objective: This review describes invasive meningococcal disease (IMD) epidemiology in the United States, provides a brief overview of available meningococcal vaccines and discusses meningococcal serogroup B (MenB) vaccine development. Particular focus is given to the recombinant protein MenB vaccine, MenB-FHbp (Trumenba , bivalent rLP2086) in light of recent publication of phase 3 data; the other MenB vaccine (Bexsero , MenB-4C) has been recently reviewed. Current recommendations of the US Advisory Committee on Immunization Practices (ACIP) for MenB vaccination and potential barriers to immunization are also discussed.

Meningococcal vaccination: a discussion with all adolescents, whether college-bound or not.

: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-recommended MenACWY and MenB vaccines are available. We investigated invasive meningococcal disease (IMD) burden and vaccination among non-college adolescents.

Concomitant administration of meningococcal vaccines with other vaccines in adolescents and adults: a review of available evidence.

Invasive meningococcal disease (IMD), a rapidly progressing and potentially fatal illness, disproportionately affects adolescents and young adults. While IMD is best prevented by vaccination, vaccine uptake in these groups is low. An evidence-based understanding of the safety and effectiveness of concomitant vaccination of meningococcal vaccines, including the newer MenB protein vaccines and the more established MenACWY conjugate vaccines, with other vaccines recommended for adolescents and young adults may help maximize vaccination opportunities.

Understanding the Changing Health Care Needs of Individuals Aging With Spinal Cord Injury.

Individuals over age 65 are projected to account for over 20% of the general population by 2030. This trend is reflected in an increase in the age of individuals sustaining traumatic spinal cord injury (SCI). Based on current evidence, there is concern regarding the needs of older individuals aging with SCI and current health care services.

Posterior hyoid space as related to excision of the thyroglossal duct cyst.

Objectives/hypothesis: The anatomy of the anterior neck in the area of the hyoid, thyrohyoid membrane, and epiglottis is herein redescribed and compared to its classical depiction. The concept of the posterior hyoid space (PHS) is defined and substantiated through review of archived tissue and cadaver larynx dissection as well as by observation at many surgical dissections. The true anatomy of these relationships provides an insight into the effectiveness of the Sistrunk procedure.

Doxorubicin plus interleukin-2 chemoimmunotherapy against breast cancer in mice.

As recently characterized, following s.c. implantation into syngeneic C57BL/6 mice, E0771 tumor invades locally into dermal layers and peritoneum, metastasizes to the lung, and induces a nonspecific immunosuppression in the host.

Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics.

Currently available serum biomarkers are insufficiently reliable to distinguish patients with epithelial ovarian cancer (EOC) from healthy individuals. Metabonomics, the study of metabolic processes in biologic systems, is based on the use of (1)H-NMR spectroscopy and multivariate statistics for biochemical data generation and interpretation and may provide a characteristic fingerprint in disease. In an effort to examine the utility of the metabonomic approach for discriminating sera from women with EOC from healthy controls, we performed (1)H-NMR spectroscopic analysis on preoperative serum specimens obtained from 38 patients with EOC, 12 patients with benign ovarian cysts and 53 healthy women.

Dihydrothymine lesion in X-irradiated DNA: characterization at the molecular level and detection in cells.

Purpose: To study the formation of the dihydrothymine lesion produced in DNA by ionizing radiation in an anaerobic environment.

Materials And Methods: The dihydrothymine lesion, along with other lesions, was isolated from an X-irradiated aqueous solution of the dinucleoside monophosphate d(TpA) and analysed by correlated two-dimensional nuclear magnetic resonance spectroscopy. The dihydrothymine lesion was obtained by enzymatic digestion of irradiated DNA in the form of modified dinucleoside monophosphates, d(T(d)A), where T(d) stands for dihydrothymidine.

Complex oligosaccharide investigations: synthesis of an octasaccharide incorporating the dimeric Le(x) structure of PSGL-1.

The synthesis of an octasaccharide containing the dimeric Le(x) oligosaccharide structure found in PSGL-1 carbohydrate chains is reported. Several approaches were investigated employing regioselective and stereoselective glycosylation procedures, and a novel Lewis(x) trisaccharide donor, 7, was prepared and utilized as a key intermediate building block in the scheme developed for the construction of octasaccharide 3. Toward the preparation of 7, investigations into the influence of different protecting groups upon the relative reactivities of disaccharide acceptor moieties, 25 or 26, and the fucosyl donors, 10 and 11, were conducted using similar glycosylating conditions.

Synthesis, structure, and conformation of anti-tumor agents in the solid and solution states: hydroxyl derivatives of Ftorafur.

The pyrimidine antimetabolite Ftorafur [FT; 5-fluoro-1-(tetrahydro-2-furyl)uracil] has shown significant antitumor activity in several adenocarcinomas with a spectrum of activity similar to, but less toxic than, 5-fluorouracil (5-FU). It is considered as a prodrug that acts as a depot form of 5-FU, and hence the two drugs exhibit a similar spectrum of chemotherapeutic activity. Ftorafur is metabolized in animals and humans when hydroxyl groups are introduced into the tetrahydrofuran moiety.

A convergent synthesis of core 2 branched sialylated and sulfated oligosaccharides.

A convergent pathway for the syntheses of core 2 oligosaccharide analogues 1 and 2, and a natural form sialylated and sulfated hexasaccharide 3 was developed. Construction of pentasaccharides 24, 27 and hexasaccharide 28 was achieved by complete regioselective glycosylation of the 6-OH in the acceptors 5, 7 and 8, respectively, owing to the much higher reactivity of the primary hydroxyl group over the secondary axial hydroxyl group in these structures. Stereoselective sialylation was accomplished using donor 10 with defined configuration established through X-ray crystallographic analysis.

A novel synthetic route to fused propenochlorin and benzochlorin photodynamic therapy probes.

Reaction of meso-(2-formylvinyl)octaethylporphyrin with (CH3)3SiCN-Cu(OTf)2 produced unexpected 10(3)-trimethylsiloxyl and 10(3)-hydroxyl fused propenochlorins which, in H2SO4, underwent subsequent migration of the 8-ethyl group to the 10(3)-position of the exocyclic benzene ring to form a novel benzochlorin.

A theoretical study of the cis-syn pyrimidine dimers in the gas phase and water cluster and a tautomer-bypass mechanism for the origin of UV-induced mutations.

A quantum mechanical study of all cis-syn cyclobutane pyrimidine photodimers including the normal and rare tautomeric forms of bases has been performed using the ab initio method at HF/6-31G(d.p), MP2(fc)//HF/6-31G(d,p) and MP2(fc)/6-31G(d,p) levels. A puckering angle of the cyclobutyl ring and twist angle of pyrimidine rings with respect to each other is well described by these calculations.

Assembly of a polytopic membrane protein structure from the solution structures of overlapping peptide fragments of bacteriorhodopsin.

Three-dimensional structures of only a handful of membrane proteins have been solved, in contrast to the thousands of structures of water-soluble proteins. Difficulties in crystallization have inhibited the determination of the three-dimensional structure of membrane proteins by x-ray crystallography and have spotlighted the critical need for alternative approaches to membrane protein structure. A new approach to the three-dimensional structure of membrane proteins has been developed and tested on the integral membrane protein, bacteriorhodopsin, the crystal structure of which had previously been determined.

Structures of the transmembrane helices of the G-protein coupled receptor, rhodopsin.

An hypothesis is tested that individual peptides corresponding to the transmembrane helices of the membrane protein, rhodopsin, would form helices in solution similar to those in the native protein. Peptides containing the sequences of helices 1, 4 and 5 of rhodopsin were synthesized. Two peptides, with overlapping sequences at their termini, were synthesized to cover each of the helices.

Effect of meso-substituents on the osmium tetraoxide reaction and pinacol-pinacolone rearrangement of the corresponding vic-dihydroxyporphyrins.

To investigate the effects of electron-donating and electron-withdrawing substituents upon the reaction of porphyrins with osmium tetraoxide, and the pinacol-pinacolone rearrangement of the resulting diols, a series of meso-substituted porphyrins were prepared by total synthesis. Porphyrins with electron-donating substitutents at the meso-positions gave vic-dihydroxychlorins in which the adjacent pyrrole subunit was predominantly oxidized. No such selectivity was observed in a porphyrin containing a methoxycarbonyl as the electron-withdrawing group, whereas a formyl substituent again resulted in oxidation at the pyrrole unit adjacent to the meso-substituent.