Refractory fungal infection: Three case reports highlighting good practice.

Refractory invasive fungal disease is a significant clinical problem, with high morbidity, mortality and costs. The complex causes of refractory infection include breakthrough infection due to antifungal resistance (both innate and acquired), suboptimal therapy and impaired immune responses in critically ill or immunocompromised patients. This case series details three reports on the identification and management of refractory fungal infections, two cases of azole resistance and one case of resistant candidiasis, highlighting the importance of accurate diagnosis, monitoring, implementation of biomarkers (serological markers, PCR), antifungal susceptibility testing and antifungal stewardship to optimise management and minimise risks of emergence of drug resistance.

Preschool and Me: Educational-clinical linkage to improve health equity for children with developmental delays and disabilities from historically marginalized communities.

Societal and structural inequities have resulted in longstanding health care disparities among Black, Latino/a/e, and low-income preschool children with developmental delays and disabilities (PCw/DD), depriving them of educational and therapeutic services that improve future academic, economic, and health outcomes. To address this issue, we developed Preschool and Me (PreM), a community-clinical linkage (CCL) implemented within healthcare settings serving historically marginalized communities. This novel CCL, an educational-medical linkage model, aims to increase access to school-based services for PCw/DD.

Investigation of potential anti-metastatic effect of metformin and caffeic acid combination therapy in breast cancer cell line in in-vitro culture model.

The invasion and metastasis of cancer cells transform localized cancers into systemic and life-threatening diseases, posing one of the most significant challenges in cancer treatment. This study tested the hypothesis that combined treatment with Caffeic acid (CA) and metformin (MTF) could inhibit or reduce effective signaling pathways involved in the proliferation, survival, and metastasis of MCF-7 breast cancer cells. Anti-proliferation analysis determined the IC50 values for MTF (4.

Structurally diverse sesquiterpenoids from Sarcandra glabra and their anti-inflammatory activities.

Fifteen sesquiterpenoids, including five previously undescribed monomers with oxidative rearranged skeletons (sarglabenoids A-E, 1-5) and three previously unreported lindenane [2 + 2] dimers (sarglabenoids F-H, 6-8), alongside seven related precursors (9-15), were isolated from the root of Sarcandra glabra. The structures of these compounds were elucidated using a combination of high-resolution electrospray ionization mass spectrometry, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, the circular dichroism exciton chirality method, electronic circular dichroism, and nuclear magnetic resonance calculations integrated with DP4+ analysis. Compounds 1 and 2 feature an unique 5/5 spiro ring system, which is likely derived from a pinacol rearrangement of precursor 14.

Perspectives on Implementing a Communication Facilitator Intervention From a Critical Care Setting.

Context: Critically-ill patients and their families often experience communication challenges during their ICU stay and across care transitions. An intervention using communication facilitators may help address these challenges.

Objectives: Using clinicians' perspectives, we identified facilitators and barriers to implementing a communication intervention.

Racial, Socioeconomic, and Geographic Disparities in Preamputation Vascular Care for Patients With Chronic Limb-Threatening Ischemia.

Background: Black patients, those with low socioeconomic status (SES), and those living in rural areas have elevated rates of major lower extremity amputation, which may be related to a lack of subspecialty chronic limb-threatening ischemia care. We evaluated the association between race, rurality, SES, and preamputation vascular care.

Methods: Among patients aged 66 to 86 years with fee-for-service Medicare who underwent major lower extremity amputation for chronic limb-threatening ischemia from July 2010 to December 2019, we compared the proportion who received vascular care in the 12 months before amputation by race (Black versus White), rurality, and SES (dual eligibility for Medicaid versus no dual eligibility) using multivariable logistic regression adjusting for clinical and demographic covariates.

Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy.

Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Two serious adverse event cases of immune-mediated myositis (IMM) were reported in the phase Ib ENDEAVOR trial (NCT04626674).

Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A α for targeted cancer therapy.

Eicosanoids are key players in inflammatory diseases and cancer. Targeting their production by inhibiting Group IVA cytosolic phospholipase A (cPLAα) offers a promising approach for cancer therapy. In this study, we synthesize a second generation of thiazolyl ketone inhibitors of cPLAα starting with compound GK470 (AVX235) and test their in vitro and cellular activities.

[Meningitis Due to Haemophilus influenzae Serotype A and Adenovirus: A Rare Case of Co-Infection in a Six-Month-Old Infant].

Haemophilus influenzae serotype A is a rare cause of meningitis and invasive disease in pediatric patients. A six-month-old infant presented to the emergency room with fever, cough and nasal drip. On admission, the infant was alert and hemodynamically stable but progressively became more lethargic with bulging of the fontanelle.

Experimental and Computational NMR Studies of Large Alkaloids Exemplified With Vindoline Trimer: Advantages and Limitations.

The complete H and C NMR assignments of a trimeric vindoline together with its individual components, dimeric vindolicine and monomeric vindoline, are performed based on a thorough analysis of the ROESY, COSY, HSQC, and HMBC spectra in combination with the state-of-the-art quantum-chemical calculations. A spatial structure of vindoline trimer is determined by means of computational conformational analysis in combination with the probability distribution map of its basic conformers. On the example of monoterpene indole alkaloid, the trimer vindoline, the present study reveals the power of modern computational NMR to perform identification and stereochemical studies of large natural compounds with some limitations, which may arise in the quantum chemical computing workflow.

Diminished attention network activity and heightened salience-default mode transitions in generalized anxiety disorder: Evidence from resting-state EEG microstate analysis.

Generalized anxiety disorder (GAD) is a common anxiety disorder characterized by excessive, uncontrollable worry and physical symptoms such as difficulty concentrating and sleep disturbances. Although functional magnetic resonance imaging (fMRI) studies have reported aberrant network-level activity related to cognition and emotion in GAD, its low temporal resolution restricts its ability to capture the rapid neural activity in mental processes. EEG microstate analysis offers millisecond-resolution for tracking the dynamic changes in brain electrical activity, thereby illuminating the neurophysiological mechanisms underlying the cognitive and emotional dysfunctions in GAD.

The Cryo-EM structure of human CD163 bound to haptoglobin-hemoglobin reveals molecular mechanisms of hemoglobin scavenging.

CD163, a macrophage-specific receptor, plays a critical role in scavenging hemoglobin released during hemolysis, protecting against oxidative effects of heme iron. In the bloodstream, hemoglobin is bound by haptoglobin, leading to its immediate endocytosis by CD163. While haptoglobin's structure and function are well understood, CD163's structure and its interaction with the haptoglobin-hemoglobin complex have remained elusive.

Clinical characteristics and serological profiles of Lyme disease in children: a 15-year retrospective cohort study in Switzerland.

Background: Lyme disease (LD) is caused by and is the most common tickborne disease in the northern hemisphere. Although classical characteristics of LD are well-known, the diagnosis and treatment are often delayed. Laboratory diagnosis by serological testing is recommended for most LD manifestations.

Cembranoid Diterpenes from South China Sea Soft Coral .

Cembranoid diterpenes are characteristic compounds of soft corals with diverse structures and significant activities, making them an important source of drug lead compounds. In this paper, five new cembranoid diterpenes, meijicrassolins A-E (-), were isolated from the soft coral , along with five previously reported compounds (-). The structures and absolute configuration for new compounds - were assigned by extensive spectroscopic analysis, single-crystal X-ray crystallography, quantum mechanical nuclear magnetic resonance (QM-NMR), and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations.

The Use of AgNP-Containing Nanocomposites Based on Galactomannan and κ-Carrageenan for the Creation of Hydrogels with Antiradical Activity.

Series of composites containing 2.5-17.0% Ag and consisting of spherical silver nanoparticles with sizes ranging from 5.

Phenylpropanoid dimers from Chrysanthemum indicum with antioxidant effects via activating the Nrf2 signaling pathway.

Five phenylpropanoid dimers chrysanthephenyls A-E, with the 1-O-1'-type (1) and 1-O-2'-type (2-5) ether bond linking modes, were isolated from the aerial parts of Chrysanthemum indicum. Among them, chrysanthephenyls D and E were two pairs of enantiomers, and chrysanthephenyl E was further resolved into its enantiomers (+)-chrysanthephenyl E and (-)-chrysanthephenyl E via chiral-phase HPLC. Their structures were characterized on the basic analysis of the spectroscopic techniques (IR, HRESIMS, 1D and 2D NMR), and their absolute configurations were determined by DP4+ NMR analysis and ECD calculation method.

Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs.

Background: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors.

Reduced ATR Signaling Contributes to Endothelial Dysfunction After Preeclampsia.

Background: Women who had preeclampsia (a history of preeclampsia) have a >4-fold risk of developing cardiovascular disease compared with women who had an uncomplicated pregnancy (history of healthy pregnancy). Despite the remission of clinical symptoms after pregnancy, vascular endothelial dysfunction persists postpartum, mediated in part by exaggerated Ang II (angiotensin II)-mediated constriction. However, the role of vasodilatory ATRs (Ang II type 2 receptors) in this dysfunction is unknown.

Duration, course and caregiver burden of croup in children: two observational cohorts.

Objectives: Although croup is a common respiratory illness, there is little published regarding symptom course. We aimed to assess symptom progression and caregiver burden, and whether age, sex or season and initial severity of disease are associated with symptom duration.

Design, Setting And Participants: We conducted a secondary analysis of two Canadian prospective cohorts of children 0-16 years old diagnosed with croup; one recruited from a paediatric emergency department (ED) (307 children) between November 1999 and March 2000, and the other from 26 general EDs (1214 children) between September 2002 and April 2006.

Response to clozapine in treatment resistant schizophrenia is related to alterations in regional cerebral blood flow.

PET and SPECT studies in treatment-resistant schizophrenia (TRS) have revealed significant alterations in regional cerebral blood flow (CBF) during clozapine treatment, which may vary according to the clinical response. Here, we used the more recent MRI approach of arterial spin labelling (ASL) to evaluate regional CBF in participants with TRS (N = 36) before starting treatment with clozapine compared to in healthy volunteers (N = 16). We then compared CBF in the TRS group, before and after 12 weeks of treatment with clozapine (N = 24); and examined the relationship of those differences against changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores over the treatment period.

Understanding Healthcare Barriers for Latino/a/e/x Families with Alzheimer's Disease: Insights from Primary Care Provider interviews.

Background: Alzheimer's Disease and Related dementias (ADRD) are disproportionately underdiagnosed, misdiagnosed, and undertreated in Latino/a/e/x populations living in the U.S. Latino/a/e/x families also experience low access to ADRD caregiver support services and high levels of depression.

Absorption study of fat-soluble vitamins into dipalmitoylphosphatidylcholine (DPPC) bilayer by MD simulations.

Retinol, α-tocopherol and phylloquinone (vitamins A, E, and K) are presented in high concentrations within the chloroplast and leaves of most plants. They are fat-soluble vitamins and absorb similarly to other dietary lipids. Because the molecular mechanism of retinol, α-tocopherol, and phylloquinone absorption is still unknown, this work aims to investigate the distribution of these vitamins at the water/membrane interface using molecular dynamics (MD) simulations.