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An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE): A Phase Ib/IIa Randomised Controlled Trial.

High circulating galectin-3 is associated with poor outcomes in patients with COVID-19. We hypothesised that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with anti-inflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis.

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Fetal Growth and Neonatal Outcomes in Pregestational Diabetes Mellitus in a Population with a High Prevalence of Diabetes.

The aim of this retrospective study, conducted in an Italian tertiary care hospital, was to evaluate maternal-fetal and neonatal clinical outcomes in a group of patients with pregestational diabetes mellitus (PGDM), such as diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), and maturity onset diabetes of the young (MODY). Overall, 174 pregnant women, nulliparous and multiparous, with a single pregnancy were enrolled. Data on pregnancy, childbirth, and newborns were collected from medical records. The selected patients were divided into two groups: the PGDM group (42 with DM1, 14 with DM2, and 2 with MODY), and the control group (116 patients with a negative pathological history of diabetes mellitus). We reported an incidence of preterm delivery of 55.2% in the PGDM group, including 59.5% of those with DM1 and 42.9% of those with DM2, vs. 6% in the controls. Fetal growth disorders, such as intrauterine growth retardation, small for gestational age, and fetal macrosomia were found in 19% and 3.6% in the case and control groups, respectively. A relationship between DM2 and gestational hypertension was found.

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Structural scoliosis secondary to thoracic osteoid osteoma: a case report of delayed diagnosis.

The aim of this case report is to show that late diagnosis of vertebral osteoid osteoma gives rise to structural scoliosis which sometimes requires long-term management.

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Baculovirus Display of Varicella-Zoster Virus Glycoprotein E Induces Robust Humoral and Cellular Immune Responses in Mice.

Varicella-zoster virus (VZV) is the causative agent of varicella and herpes zoster (HZ) and can pose a significant challenge to human health globally. The initial VZV infection-more common in children-causes a self-limiting chicken pox. However, in later life, the latent VZV can become reactivated in these patients, causing HZ and postherpetic neuralgia (PHN), a serious and painful complication. VZV glycoprotein E (gE) has been developed into a licensed subunit vaccine against HZ (Shingrix). However, its efficacy relies on the concomitant delivery of a robust adjuvant (AS01B). Here, we sought to create a new immunogen for vaccine design by displaying the VZV-gE on the baculovirus surface (Bac-gE). Correct localization and display of gE on the engineered baculovirus was verified by flow cytometry and immune electron microscopy. We show that Bac-gE provides excellent antigenicity against VZV and induces not only stronger gE-specific CD4 and CD8 T cell responses but also higher levels of VZV-specific neutralizing antibodies as compared with other vaccine strategies in mice. Collectively, we show that the baculovirus display of VZV-gE confers ideal humoral and cellular immune responses required for HZ vaccine development, paving the way for a baculovirus-based vaccine design.

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Stages of lipoedema: experiences of physical and mental health and health care.

Lipoedema is a progressive adipose (fat) disorder, and little is known about its psychological effect. This study aimed to determine the experiences of physical and mental health and health care across stages of lipoedema.

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Neuropathic Pain Symptom Inventory (NPSI) Questionnaire-Persian Version Can Differentiate Neuropathic from Non-Neuropathic Pain.

Neuropathic pain (NP) is a common condition that impacts life negatively. This type of pain responds poorly to treatment. Neuropathic Pain Symptom Inventory (NPSI) is a common instrument used for the assessment of NP response to the treatment.

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The use of OCT to detect signs of intracranial hypertension in patients with sagittal suture synostosis: Reference values and correlations.

To obtain pediatric normative reference values and determine whether optical coherence tomography (OCT) corresponds better with clinical signs of intracranial hypertension (ICH) compared to the traditional screening method fundoscopy in a large cohort of one type of single suture craniosynostosis.

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Absence of NC14A domain of collagen XVII/BP180 in mice results in IL-17-associated skin inflammation.

The deletion of exon 18 from Col17a1 in transgenic ΔNC14A mice results in the absence of the NC14A, which corresponds to the human NC16A domain, the immunodominant epitope in bullous pemphigoid. Before the age of one year 84% of ΔNC14A mice have developed severe itch and skin erosion. Further characterization of mice with mutated collagen XVII (ColXVII/BP180) revealed acanthosis, subepidermal blistering and inflammatory cell infiltrate, especially neutrophils, eosinophils and mast cells in the lesional skin. Direct immunofluorescence analysis detected linear C3, IgG and/or IgA deposition in the dermo-epidermal junction of symptomatic ΔNC14A mice. Elevated gene expression of IL-17-associated cytokines was detected in the lesional skin. An increased proportion of dendritic cells, myeloid-derived suppressor cells and NK cells and the decrease of T cells were found in both the spleen and lymph nodes of symptomatic ΔNC14A mice. The proportions of B cells and Tregs were increased in lymph nodes. An 8-week treatment with an anti-IL-17A decreased the expression of Il6, Il23a and Cxcl1 in the nonlesional skin. Our results suggest that the absence of the NC14A domain of ColXVII in mice causes an autoimmune response against the cutaneous basement membrane and manifests as an IL-17-associated inflammation in the skin.

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Patient-Reported Outcomes Correlate With Microbial Community Composition Independent of Mucosal Inflammation in Pediatric Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) involve an aberrant host response to intestinal microbiota causing mucosal inflammation and gastrointestinal symptoms. Patient-reported outcomes (PROs) are increasingly important in clinical care and research. Our aim was to examine associations between PROs and fecal microbiota in patients 0 to 22 years of age with IBD.

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Cardiac Enhanced Recovery Program Implementation and Its Effect on Opioid Administration in Adult Cardiac Surgery.

In light of the worsening opioid epidemic and nationwide parenteral opioid shortage, our institution created an enhanced recovery after surgery (ERAS) protocol. Our objective was to evaluate our initial experience transitioning to ERAS in cardiac surgery. An institutional cardiac ERAS protocol was implemented in April 2018, consisting of opioid-sparing analgesia, liberalization of fasting and activity restrictions, and goal-directed standardization of perioperative care. Clinical outcomes, opioid administration, and pain scores of patients undergoing nonemergent cardiac surgery were reviewed from March 2017 to July 2018. Patients were propensity score matched into pre-ERAS and transition-to-ERAS (t-ERAS) cohorts and compared by univariate analysis. Of 467 patients, 236 patients were well-matched (118 per cohort). The transition to ERAS resulted in a 79% reduction in morphine equivalents through postoperative day one (359.3 mg pre-ERAS vs 75.4 mg ERAS, p<0.0001). Despite less opioid utilization, t-ERAS patients reported lower pain scores (median 4.88 vs 4.14, p=0.011). There was no difference in mortality (2% vs 0%, p=0.498) or postoperative complications including initial hours ventilated (5.3 vs 5.2 hours, p=0.380), prolonged ventilation (9.3% vs 6.8%, p=0.473), renal failure (3.4% vs 2.5%, p=0.701), and ICU length of stay (58.3 vs 70.4 hours, p=0.272). The transition to cardiac ERAS resulted in significantly reduced opioid administration and improved patient pain scores while maintaining excellent outcomes. Well-supported, multidisciplinary teams of cardiac surgeons, anesthesiologists, and intensivists can dramatically reduce opioid use without sacrificing pain control or excellent clinical outcomes.

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