Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT.

The seroprevalence of SARS-CoV-2-specific antibodies in Australian children: A cross-sectional study.

Background: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated.

Objective: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years.

A giant pelvic infiltrating schwannoma misdiagnosed as an ovarian neoplasm that was resected using a laparoscopic approach: A case report.

Introduction and importance: Large retroperitoneal schwannomas are rare and present significant challenges in surgical management, particularly when located in the pelvic region. Gynecologists can encounter rare problems when a pelvic schwannoma is mistaken for an adnexal pathology. Case Presentation: A 62-year-old woman presented with a giant retroperitoneal mass suspected of a potentially malignant ovarian tumor preoperatively.

Lifestyle Medicine for the Health Care Worker, Workplace, and Community Well-Being: A Butterfly Effect.

Description Burnout is a prevalent and expensive problem in the US, and the National Plan For Health Workforce Well-Being included a goal to institutionalize well-being as a long-term value. Lifestyle Medicine (LM), an evidence-based practice using behavioral interventions to treat, prevent, and reverse certain chronic conditions, can achieve this goal. Implementing small changes in the workplace that support lifestyle medicine has a butterfly effect on both workplace and community well-being.

Proton Pump Inhibitor Use and Adverse Effects in South Atlantic Hospitals.

Background: Proton pump inhibitors (PPI) have transformed the management of acid-related gastrointestinal disorders, becoming one of the top-selling medications in the United States. There is no doubt that PPIs have a significant therapeutic impact on patients with gastroesophageal reflux disease and gastrointestinal bleeding. However, evidence is mounting that PPIs are overprescribed, leading to more patients possibly experiencing adverse effects.

Pleasure before business: emotions and age effects on daily activity scheduling.

Activity scheduling represents a key process in daily life, involving the evaluation of the costs and benefits of the resources to be invested, but also a preference for when to engage in pleasant or unpleasant activities. Aging affects the evaluation processes and individual preferences due to changes in cognitive functioning and life perspectives. The present study investigated the differences between younger adults (age range 19-33) and older adults (age range 65-87) in a task assessing preferential scheduling of activities.

Resilience.

Description On one of the busiest parkways, in the midst of a spring drought, despite the lack of soil a sunflower blooms. This tiny beacon of hope represents the enduring spirit of humanity managing to struggle through this recent global pandemic. For me as a program director, it conjures to mind my graduating family medicine residents.

Unity.

Description Community health is vital to increase the lifespan and quality of life of the people on our planet. We must unite to fight disease through education and implementing quality healthcare. This piece was created prior to the pandemic, but its message is so incredibly pertinent in these troubling times.

Selection and Control of Process Conditions Enable the Preparation of Curcumin-Loaded Poly(lactic--glycolic acid) Nanoparticles of Superior Performance.

Curcumin (CUR) is one natural bioactive compound acknowledged for diverse therapeutic activities, but its use is hindered by its poor bioavailability, fast metabolism, and susceptibility to pH variations and light exposure. Thus, the encapsulation in poly(lactic--glycolic acid), or PLGA, has been successfully used to protect and enhance CUR absorption in the organism, making CUR-loaded PLGA nanoparticles (NPs) promising drug delivery systems. However, few studies have focused beyond CUR bioavailability, on the environmental variables involved in the encapsulation process, and whether they could help obtain NPs of superior performance.

Statistical Picking of Multivariate Waveforms.

In this paper, we propose a new approach based on the fitting of a generalized linear regression model in order to detect points of change in the variance of a multivariate-covariance Gaussian variable, where the variance function is piecewise constant. By applying this new approach to multivariate waveforms, our method provides simultaneous detection of change points in functional time series. The proposed approach can be used as a new picking algorithm in order to automatically identify the arrival times of P- and S-waves in different seismograms that are recording the same seismic event.

Doxorubicin nanoformulations on therapy against cancer: An overview from the last 10 years.

Doxorubicin (DOX) is a natural antibiotic with antineoplastic activity. It has been used for over 40 years and remains one of the most used drugs in chemotherapy for a variety of cancers. However, cardiotoxicity limits its use for long periods.

Curcumin encapsulation in nanostructures for cancer therapy: A 10-year overview.

Curcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent.

Exploring sources of poor reading comprehension in English language learners.

This study examined the sources of reading comprehension difficulties in English language learners (ELLs). The characteristics of ELL poor comprehenders were compared to their English as a first language (EL1) peers. Participants included 124 ELLs who spoke Chinese as an L1 and 79 EL1 students.

Polymeric micelles using cholinium-based ionic liquids for the encapsulation and release of hydrophobic drug molecules.

We generated stable amphiphilic copolymer-based polymeric micelles (PMs) with temperature-responsive properties utilizing Pluronic® L35 and a variety of ionic liquids (ILs) to generate different aqueous two-phase micellar systems (ATPMSs). The partitioning of the hydrophobic model compound curcumin (CCM) into the PM-rich phase and the drug delivery capabilities of the PMs were investigated. ATPMSs formed using more hydrophobic ILs (i.

Cutaneous Malignant Melanoma: A Synthesis on Updated Guidelines for the Primary Care Perspective.

Description Cutaneous malignant melanoma (CMM) is a condition wherein malignant cells form in the melanocytic cells. CMM is a potentially lethal form of skin cancer, commonly found in sun-exposed areas of the body. There are multiple risk factors for disease development, such as genetic mutation and UV radiation among others.

The Overlap of Poor Reading Comprehension in English and French.

This study examined overlap and correlates of poor reading comprehension in English and French for children in early French immersion. Poor comprehenders were identified in grade 3 in English and French using a regression method to predict reading comprehension scores from age, non-verbal reasoning, word reading accuracy, and word reading fluency. Three groups of poor comprehenders were identified: 10 poor comprehenders in English and French, 11 poor comprehenders in English, and 10 poor comprehenders in French, and compared to 10 controls with good reading comprehension in both English and French.

Predicting growth in English and French vocabulary: The facilitating effects of morphological and cognate awareness.

The present study investigated the contribution of morphological and cognate awareness to the development of English and French vocabulary knowledge among young minority and majority language children who were enrolled in a French immersion program. Participating children (n = 75) were assessed in English and French on measures of morphological awareness, cognate awareness, and vocabulary knowledge from Grades 1 to 3. Hierarchical linear modeling was used to investigate linear trends in English and French vocabulary growth for minority and majority language children and to identify metalinguistic contributions to Grade 1 and Grade 3 English and French vocabulary performance and rate of growth.

Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).

The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo.

Selective class I phosphoinositide 3-kinase inhibitors: optimization of a series of pyridyltriazines leading to the identification of a clinical candidate, AMG 511.

The phosphoinositide 3-kinase family catalyzes the phosphorylation of phosphatidylinositol-4,5-diphosphate to phosphatidylinositol-3,4,5-triphosphate, a secondary messenger which plays a critical role in important cellular functions such as metabolism, cell growth, and cell survival. Our efforts to identify potent, efficacious, and orally available phosphatidylinositol 3-kinase (PI3K) inhibitors as potential cancer therapeutics have resulted in the discovery of 4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (1). In this paper, we describe the optimization of compound 1, which led to the design and synthesis of pyridyltriazine 31, a potent pan inhibitor of class I PI3Ks with a superior pharmacokinetic profile.

Structure-based design of a novel series of potent, selective inhibitors of the class I phosphatidylinositol 3-kinases.

A highly selective series of inhibitors of the class I phosphatidylinositol 3-kinases (PI3Ks) has been designed and synthesized. Starting from the dual PI3K/mTOR inhibitor 5, a structure-based approach was used to improve potency and selectivity, resulting in the identification of 54 as a potent inhibitor of the class I PI3Ks with excellent selectivity over mTOR, related phosphatidylinositol kinases, and a broad panel of protein kinases. Compound 54 demonstrated a robust PD-PK relationship inhibiting the PI3K/Akt pathway in vivo in a mouse model, and it potently inhibited tumor growth in a U-87 MG xenograft model with an activated PI3K/Akt pathway.

Structure-based design of novel class II c-Met inhibitors: 1. Identification of pyrazolone-based derivatives.

Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles.

Structure-based design of novel class II c-Met inhibitors: 2. SAR and kinase selectivity profiles of the pyrazolone series.

As part of our effort toward developing an effective therapeutic agent for c-Met-dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1), was identified. Knowledge of the binding mode of this molecule in both c-Met and VEGFR-2 proteins led to a novel strategy for designing more selective analogues of 1. Along with detailed SAR information, we demonstrate that the low kinase selectivity associated with class II c-Met inhibitors can be improved significantly.

Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors.

Phosphoinositide 3-kinase α (PI3Kα) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3Kα has become a target of intense research for drug discovery.

Treatments for autism: parental choices and perceptions of change.

Empirically conducted studies of the efficacy of various treatments for autism are limited, which leaves parents with little evidence on which to base their treatment decisions (Kasari, Journal of Autism and Developmental Disorders, 32: 447-461, 2002). The purpose of this study was to examine the types of treatments in current use by families of children with ASD. In addition, parents' perceptions of improvement in their child's functioning were explored.

Design, synthesis, and biological evaluation of potent c-Met inhibitors.

c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor.