Interventions to Prevent Relapse or Recurrence of Preconception Anxiety and/or Depression in Perinatal Women: A Systematic Review.

Objectives: Women with preconception anxiety and/or depression experience high rates of relapse or recurrence of the disorders in the perinatal period. This review aimed to identify perinatal interventions that were designed to prevent relapse or recurrence in women with a history of anxiety and/or depression.

Methods: The review was conducted based on the PRISMA guidelines.

toxicological evaluation of pouched portioned oral nicotine products.

Introduction: Modern oral nicotine pouch products (ONPs) are a category of oral nicotine products which contain pharmaceutical-grade nicotine, flavors, and other food-grade ingredients but no tobacco leaf. Recent reports indicate that ONPs in general do not contain (or only at minimal levels) the harmful and potentially harmful constituents (HPHCs) identified in cigarette smoke, suggesting their potential as alternative products for reducing harm from cigarette smoking.

Methods: We assessed toxicological effects of eight ONPs, designated as modern oral (MO) 1 to 8 along with an ONP, an oral tobacco (snus), and a combustible cigarette market comparator using established regulatory toxicological assays including Ames, micronucleus (ivMN), and neutral red uptake (NRU) assays.

Hominin fossil inventory: Quantification and comparison of discrete regional and element representation among early African fossil hominins prior to the emergence of Homo erectus.

For all but the past few hundred thousand years, skeletal and dental morphology is the only evidence we have of our extinct ancestors and close hominin relatives. With a few exceptions, most lists of early hominin fossils have been assembled for single sites, formations, or taxa, with little attention paid to how different regions of the skeleton contribute to taxon hypodigms. We recognize there are different ways to divide up the hominin fossil record into taxa, but here, we present an inventory of the fossil evidence for the hypodigms of 14 early African hominin taxa that predate the emergence of Homo erectus.

Evaluation of Cytotoxicity and Oxidative Stress of Whole Aerosol from Vuse Alto ENDS Products.

Assessment of in vitro cytotoxicity is an important component of tobacco product toxicological evaluations. However, current methods of regulatory testing involve exposing monolayer cell cultures to various preparations of aerosols from cigarettes or other emerging products such as electronic nicotine delivery systems (ENDS), which are not representative of human exposure. In the present study, a whole aerosol (WA) system was used to expose lung epithelial cultures (2D and 3D) to determine the potential of six Vuse Alto ENDS products that varied in nicotine content (1.

Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study.

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options.

The Effect of Patient- and Treatment-Related Factors on Circuit Lifespan During Continuous Renal Replacement Therapy in Critically Ill Children.

Objectives: To examine the effects of patient and treatment variables on circuit lifespan in critically ill children requiring continuous renal replacement therapy.

Design: Retrospective observational study based on a prospective registry.

Setting: Tertiary referral 30-bed PICU.

Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens.

Functional genomics approaches can overcome limitations-such as the lack of identification of robust targets and poor clinical efficacy-that hamper cancer drug development. Here we performed genome-scale CRISPR-Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritize new targets in defined tissues and genotypes.

Mortality of Critically Ill Children Requiring Continuous Renal Replacement Therapy: Effect of Fluid Overload, Underlying Disease, and Timing of Initiation.

Objective: To identify risk factors associated with mortality in critically ill children requiring continuous renal replacement therapy.

Design: Retrospective observational study based on a prospective registry.

Setting: Tertiary and quaternary referral 30-bed PICU.

Dichotomous parvalbumin interneuron populations in dorsolateral and dorsomedial striatum.

Key Points: There are two electrophysiological dichotomous populations of parvalbumin (PV) interneurons located in the dorsal striatum. Striatal PV interneurons in medial and lateral regions differ significantly in their intrinsic excitability. Parvalbumin interneurons in the dorsomedial striatum, but not in the dorsolateral striatum, receive afferent glutamatergic input from cingulate cortex.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

Background: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery.

Methods: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients.

Chromis-1, a Ratiometric Fluorescent Probe Optimized for Two-Photon Microscopy Reveals Dynamic Changes in Labile Zn(II) in Differentiating Oligodendrocytes.

Despite the significant advantages of two-photon excitation microscopy (TPEM) over traditional confocal fluorescence microscopy in live-cell imaging applications, including reduced phototoxicity and photobleaching, increased depth penetration, and minimized autofluorescence, only a few metal ion-selective fluorescent probes have been designed and optimized specifically for this technique. Building upon a donor-acceptor fluorophore architecture, we developed a membrane-permeant, Zn(II)-selective fluorescent probe, chromis-1, that exhibits a balanced two-photon cross section between its free and Zn(II)-bound form and responds with a large spectral shift suitable for emission-ratiometric imaging. With a K of 1.

Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

Objective: To characterize the clinical indications, procedural safety, and outcome of critically ill children requiring therapeutic plasma exchange.

Design: Retrospective observational study based on a prospective registry.

Setting: Tertiary and quaternary referral 30-bed PICU.

Rhabdomyolysis in a Tertiary PICU: A 10-Year Study.

Objectives: Rhabdomyolysis is a disorder of muscle breakdown. The aim of this study was to describe the epidemiology of rhabdomyolysis in children admitted to a PICU and to assess the relationship between peak creatinine kinase and mortality.

Design: Retrospective cohort study in children admitted to the PICU with rhabdomyolysis between January 1, 2005, and December 31, 2014.

Rab11-FIP1 phosphorylation by MARK2 regulates polarity in MDCK cells.

MARK2/Par1b/EMK1, a serine/threonine kinase, is required for correct apical/basolateral membrane polarization in epithelial cells. However, the specific substrates mediating MARK2 action are less well understood. We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.

Oncology Education in Medical Schools: Towards an Approach that Reflects Australia's Health Care Needs.

Cancer has recently overtaken heart disease to become the number 1 cause of mortality both globally and in Australia. As such, adequate oncology education must be an integral component of medical school if students are to achieve learning outcomes that meet the needs of the population. The aim of this review is to evaluate the current state of undergraduate oncology education and identify how Australian medical schools can improve oncology learning outcomes for students and, by derivative, improve healthcare outcomes for Australians with cancer.

Rab11-FIP1A regulates early trafficking into the recycling endosomes.

The Rab11 family of small GTPases, along with the Rab11-family interacting proteins (Rab11-FIPs), are critical regulators of intracellular vesicle trafficking and recycling. We have identified a point mutation of Threonine-197 site to an Alanine in Rab11-FIP1A, which causes a dramatic dominant negative phenotype when expressed in HeLa cells. The normally perinuclear distribution of GFP-Rab11-FIP1A was condensed into a membranous cisternum with almost no GFP-Rab11-FIP1A(T197A) remaining outside of this central locus.

Modification of Hepatic Venous Conduit to Manage Pulmonary Arteriovenous Malformations.

While the Fontan operation is a reliable treatment option for many complex congenital heart defects, the development of pulmonary arteriovenous malformations (PAVMs) remains a problematic outcome for some Fontan patients. Pulmonary arteriovenous malformations stem from an imbalance of hepatic blood flow in the pulmonary system. Balancing this hepatic flow has shown promising results in the treatment of PAVMs.

Rab11-FIP2 interaction with MYO5B regulates movement of Rab11a-containing recycling vesicles.

A tripartite association of Rab11a with both Rab11-FIP2 and MYO5B regulates recycling endosome trafficking. We sought to define the intermolecular interactions required between Rab11-FIP2 and MYO5B. Using a random mutagenesis strategy, we identified point mutations at S229P or G233E in Rab11-FIP2 that caused loss of interaction with MYO5B in yeast two-hybrid assays as well as loss of interaction of Rab11-FIP2(129-356) with MYO5B tail when expressed in HeLa cells.

Subcellular redistribution and mitotic inheritance of transition metals in proliferating mouse fibroblast cells.

Synchrotron X-ray fluorescence microscopy of non-synchronized NIH 3T3 fibroblasts revealed an intriguing redistribution dynamics that defines the inheritance of trace metals during mitosis. At metaphase, the highest density areas of Zn and Cu are localized in two distinct regions adjacent to the metaphase plate. As the sister chromatids are pulled towards the spindle poles during anaphase, Zn and Cu gradually move to the center and partition into the daughter cells to yield a pair of twin pools during cytokinesis.

Selective organ preservation in operable locally advanced head and neck squamous cell carcinomas guided by primary site restaging biopsy: long-term results of two sequential brown university oncology group chemoradiotherapy studies.

Objectives: The long-term outcomes of selective organ preservation in operable, locally advanced head and neck cancers in two sequential chemoradiotherapy (CRT) protocols (HN-53, HN-67) are reported.

Methods: A total of 65 patients were treated with CRT consisting of carboplatin (AUC=1/week) and paclitaxel (60 or 40 mg/m2/week) with radiation (1.8 Gy/day).

Copper redistribution in Atox1-deficient mouse fibroblast cells.

Quantitative synchrotron X-ray fluorescence (SXRF) imaging of adherent mouse fibroblast cells deficient in antioxidant-1 (Atox1), a metallochaperone protein responsible for delivering Cu to cuproenzymes in the trans-Golgi network, revealed striking differences in the subcellular Cu distribution compared with wild-type cells. Whereas the latter showed a pronounced perinuclear localization of Cu, the Atox1-deficient cells displayed a mostly unstructured and diffuse distribution throughout the entire cell body. Comparison of the SXRF elemental maps for Zn and Fe of the same samples showed no marked differences between the two cell lines.

Molecular recognition based on low-affinity polyvalent interactions: selective binding of a carboxylated polymer to fibronectin fibrils of live fibroblast cells.

To explore molecular recognition of biomolecules in the complex environment of the extracellular matrix, we utilized two fluorescent poly(p-phenyleneethynylene)s bearing either cationic alkylammonium or negatively charged carboyxlate side chains. While incubation of live NIH 3T3 fibroblast cells with the cationic polymer yielded perinuclear punctate staining reminiscent of endocytotic vesicles, the carboxylated polymer revealed a characteristic filamentous staining pattern. Histochemical and immunofluorescence studies demonstrated that the anionic PPE selectively binds to fibronectin fibrils of the extracellular matrix.

Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53).

Background: A phase II study was conducted using concurrent paclitaxel, carboplatin, and external beam radiotherapy (RT) in patients with advanced head and neck cancer.

Methods: Forty-three patients (stage III, n = 12; stage IV, n = 31) were treated with 8 cycles of weekly paclitaxel (60 mg/m(2)), carboplatin (area under the curve [AUC] = 1), and RT (1.8 Gy daily; total dose, 66-72 Gy).