Spatial reorganization of putaminal dopamine D2-like receptors in cranial and hand dystonia

The putamen has a somatotopic organization of neurons identified by correspondence of firing rates with selected body part movements, as well as by complex, but organized, differential cortical projections onto putamen. In isolated focal dystonia, whole putaminal binding of dopamine D(2)-like receptor radioligands is quantitatively decreased, but it has not been known whether selected parts of the putamen are differentially affected depending upon the body part affected by dystonia. The radioligand [(18)F]spiperone binds predominantly to D(2)-like receptors in striatum. We hypothesized that the spatial location of [(18)F]spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To address statistical and methodological concerns, we chose a straightforward but robust image analysis method. An automated algorithm located the peak location of [(18)F]spiperone binding within the striatum, relative to a brain atlas, in each of 14 patients with cranial dystonia and 8 patients with hand dystonia. The mean (left and right) |x|, y, and z coordinates of peak striatal binding for each patient were compared between groups by t test. The location of peak [(18)F]spiperone binding within the putamen differed significantly between groups (cranial dystonia z<hand dystonia z, p = 0.016). We conclude that in isolated focal dystonia, dopamine D(2)-like receptors are distributed differently in the putamen depending on the body part manifesting dystonia

Neonatal Intensive Care Unit Resource Use for Infants at 22 Weeks\u27 Gestation in the US, 2008-2021

IMPORTANCE: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks\u27 gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown. OBJECTIVE: To characterize recent trends in NICU resource utilization for infants born at 22 weeks\u27 gestation compared with other extremely preterm infants (≤28 weeks\u27 gestation) and other NICU-admitted infants. DESIGN, SETTING, AND PARTICIPANTS: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. Data analysis was performed from October 2022 to August 2023. EXPOSURES: Year and gestational age at birth. MAIN OUTCOMES AND MEASURES: Measures of resource utilization included NICU admissions, NICU bed-days, and ventilator-days. RESULTS: Of 825 112 infants admitted from 2008 to 2021, 60 944 were extremely preterm and 872 (466 [53.4%] male; 18 [2.1%] Asian; 318 [36.5%] Black non-Hispanic; 218 [25.0%] Hispanic; 232 [26.6%] White non-Hispanic; 86 [9.8%] other or unknown) were born at 22 weeks\u27 gestation. NICU admissions at 22 weeks\u27 gestation increased by 388%, from 5.7 per 1000 extremely preterm admissions in 2008 to 2009 to 27.8 per 1000 extremely preterm admissions in 2020 to 2021. The number of NICU admissions remained stable before the publication of updated clinical guidance in 2014 to 2016 and substantially increased thereafter. During the study period, bed-days for infants born at 22 weeks increased by 732%, from 2.5 per 1000 to 20.8 per 1000 extremely preterm NICU bed-days; ventilator-days increased by 946%, from 5.0 per 1000 to 52.3 per 1000 extremely preterm ventilator-days. The proportion of NICUs admitting infants born at 22 weeks increased from 22.6% to 45.3%. Increases in NICU resource utilization during the period were also observed for infants born at less than 22 and at 23 weeks but not for other gestational ages. In 2020 to 2021, infants born at less than or equal to 23 weeks\u27 gestation comprised 1 in 117 NICU admissions, 1 in 34 of all NICU bed-days, and 1 in 6 of all ventilator-days. CONCLUSIONS AND RELEVANCE: In this serial cross-sectional study of 137 US NICUs from 2008 to 2021, an increasing share of resources in US NICUs was allocated to infants born at 22 weeks\u27 gestation, corresponding with changes in national clinical guidance

Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study

<p>Abstract</p> <p>Background</p> <p>Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.</p> <p>Methods</p> <p>Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.</p> <p>Results</p> <p>Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.</p> <p>Conclusions</p> <p>Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.</p> <p>Trial Registration</p> <p>D9614C00097; ClinicalTrials.gov identifier NCT00228527.</p

Evidence for sinistral strike-slip deformation in the Solomon Island arc

6 pages, 4 figuresDuring the SOPACMAPS 2 crusie carried out by IFREMER (Institut Français de Recherche pour l'Exploitation de la Mer) and ORSTOM (Institut Français de Recherche Scientifique pour le dévelopement en Coopération) on theR/V L'Atalante, in the Central Solomon Arc area, multibeam bathymetric and imagery data and single-channel seismic reflection profiles were collected from an area of about 3500 km2, to evaluate regional tectonics. Structural data geophysical profiles interpretation provide evidence for left-lateral transtensional tectonics on the southern edge of the Central Solomon Trough. This transtensional deformation is represented by faulting, block tilting, and rhombohedral deformation. The regional geology and the analysis of the sedimentary cover allow us to demonstrate that this tectonic occurred in two different phases during Oligocene to Miocene and Pliocene to Pleistocene timesPeer reviewe

Immunotherapy of Cancer: Developments and Reference Points, an Unorthodox Approach.

Oncology is currently a sector of medical science with accelerated progress due to rapid technological development, the advancement in molecular biology, and the invention of many innovative therapies. Immunotherapy partially accounts for this advance, since it is increasingly playing an important role in the treatment of cancer patients, bringing on a sense of hope and optimism through a series of clinical studies and cases with spectacular results. Immunotherapy, after the initial successes it experienced in the early 20th century, was forgotten after chemotherapy and radiotherapy prevailed and developed slowly in the background. Today, it is the new hope for cancer treatment, despite the unorthodox path it has followed. In this article, we study the course and key points of the discovery of immune-oncology from the oncologist's point of view. We also record the questions that have been posed about immunotherapy that sometimes lead to confusion or stalemate

Belonging to a different landscape: repurposing nationalist affects

This is an article about the embodied, sensual experience of rural landscape as a site where racialized feelings of national belonging get produced. Largely impervious to criticism and reformation by 'thin' legal-political versions of multicultural or cosmopolitan citizenship, it is my suggestion that this racialized belonging is best confronted through the recognition and appreciation of precisely what makes it so compelling. Through an engagement with the theorization of affect in the work of Divya Praful Tolia-Kelly, I consider the resources immanent to the perception of landscapes of national belonging that might be repurposed to unravel that belonging from within. I suggest that forms of environmental consciousness can unpick the mutually reinforcing relationships between nature and nation, opening up opportunities for thinking identity and belonging in different ways, and allowing rural landscapes to become more hospitable places

Pathologic complete response in patients with localized soft tissue sarcoma treated with neoadjuvant therapy and its correlation with clinical outcomes : a systematic review

Soft tissue sarcomas (STS), comprising approximately 1% of adult solid malignancies, are primarily treated with surgery, with the choice of perioperative treatment being a challenging and highly individualized decision. Clinical trials assessing neoadjuvant modalities in STS predominantly use clinical outcomes or radiologic response as endpoints, with pathologic complete response (pCR) not being employed as a designated study endpoint. Our systematic review aimed to assess the rates of pCR in clinical trials of different neoadjuvant modalities for STS and its correlation with patient clinical outcomes. 23 phase I, II and III studies were included, from which data regarding rates of pCR with each treatment, as well as correlation of pCR with clinical outcomes were retrieved. In 16 trials that assessed pCR, the percentage of patients who achieved a pCR ranged from 8 to 58%. Most of these trials did not aim to establish an association between pCR and clinical outcomes. However, among those that did investigate this correlation, a positive association was identified between pCR and both 5-year disease-specific survival (DSS) and 5-year overall survival (OS). While pCR serves as a crucial marker guiding treatment decisions in other neoplasms like triple negative breast cancer and urothelial cancer, it is not yet used in a similar setting for STS. Our findings indicate variability in patients achieving pCR across different neoadjuvant treatments for STS and a possible positive correlation with patient outcomes. Consequently, we propose considering pCR as a surrogate endpoint in future prospective trials for STS

The Guinea Pig as a model for sporadic Alzheimer's Disease (AD): the impact of cholesterol intake on expression of AD-related genes

Extent: 12p.We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes.Mathew J. Sharman, Seyyed H. Moussavi Nik, Mengqi M. Chen, Daniel Ong, Linda Wijaya, Simon M. Laws, Kevin Taddei, Morgan Newman, Michael Lardelli, Ralph N. Martins, Giuseppe Verdil