Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature.</p> <p>Case presentation</p> <p>A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease.</p> <p>Conclusions</p> <p>Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.</p

Surgical aortic valve replacement in the era of transcatheter aortic valve implantation: a review of the UK national database

Objectives To date the reported outcomes of surgical aortic valve replacement (SAVR) are mainly in the settings of trials comparing it with evolving transcatheter aortic valve implantation. We set out to examine characteristics and outcomes in people who underwent SAVR reflecting a national cohort and therefore ‘real-world’ practice. Design Retrospective analysis of prospectively collected data of consecutive people who underwent SAVR with or without coronary artery bypass graft (CABG) surgery between April 2013 and March 2018 in the UK. This included elective, urgent and emergency operations. Participants’ demographics, preoperative risk factors, operative data, in-hospital mortality, postoperative complications and effect of the addition of CABG to SAVR were analysed. Setting 27 (90%) tertiary cardiac surgical centres in the UK submitted their data for analysis. Participants 31 277 people with AVR were identified. 19 670 (62.9%) had only SAVR and 11 607 (37.1%) had AVR+CABG. Results In-hospital mortality for isolated SAVR was 1.9% (95% CI 1.6% to 2.1%) and was 2.4% for AVR+CABG. Mortality by age category for SAVR only were: 75 years=2.2%. For SAVR+CABG these were; 2.2%, 1.8% and 3.1%. For different categories of EuroSCORE, mortality for SAVR in low risk people was 1.3%, in intermediate risk 1% and for high risk 3.9%. 74.3% of the operations were elective, 24% urgent and 1.7% emergency/salvage. The incidences of resternotomy for bleeding and stroke were 3.9% and 1.1%, respectively. Multivariable analyses provided no evidence that concomitant CABG influenced outcome. However, urgency of the operation, poor ventricular function, higher EuroSCORE and longer cross clamp and cardiopulmonary bypass times adversely affected outcomes. Conclusions Surgical SAVR±CABG has low mortality risk and a low level of complications in the UK in people of all ages and risk factors. These results should inform consideration of treatment options in people with aortic valve disease

Swordfish bill injury involving abdomen and vertebral column: case report and review

<p>Abstract</p> <p>Background</p> <p>Penetrating injuries of the abdomen and spinal canal that involve organic material of animal origin are extremely rare and derive from domestic and wild animal attacks or fish attacks.</p> <p>Case presentation</p> <p>In this case report we present the unique, as far as the literature is concerned, unprovoked woman's injury to the abdomen by a swordfish. There are only four cases of swordfish attacks on humans in the literature - one resulted to thoracic trauma, two to head trauma and one to knee trauma, one of which was fatal - none of which were unprovoked. Three victims were professional or amateur fishermen whereas in the last reported case the victim was a bather as in our case. Our case is the only case where organic debris of animal's origin remained in the spinal canal after penetrating trauma.</p> <p>Conclusions</p> <p>Although much has been written about the management of penetrating abdominal and spinal cord trauma, controversy remains about the optimal management. Moreover, there is little experience in the management of patients with such spinal injuries, due to the fact that such cases are extremely rare. In this report we focus on the patient's treatment with regard to abdominal and spinal trauma and present a review of the literature.</p

Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages

Ala-Ala-Pro-Val (AAPV) is a bioactive tetrapeptide that inhibits human neutrophil elastase (HNE), an enzyme involved in skin chronic inflammatory diseases like psoriasis. Caged derivatives of this peptide were prepared by proper N- and C-terminal derivatisation through a carbamate or ester linkage, respectively, with two photoactive moieties, namely 7-methoxycoumarin-2-ylmethyl and pyren-2-ylmethyl groups. These groups were chosen to assess the influence of the photosensitive group and the type of linkage in the controlled photorelease of the active molecule. The caged peptides were irradiated at selected wavelengths of irradiation (254, 300, and 350 nm), and the photolytic process was monitored by HPLC-UV. The results established the applicability of the tested photoactive groups for the release of AAPV, especially for the derivative bearing the carbamate-linked pyrenylmethyl group, which displayed the shortest irradiation times for the release at the various wavelengths of irradiation (ca. 4 min at 254 nm, 8 min at 300 nm and 46 min at 350 nm).Thanks are due to the Fundação para a Ciência e Tecnologia (FCT, Portugal) for financial support to the portuguese NMR network (PTNMR, Bruker Avance III 400- Univ. Minho), FCT and FEDER (European Fund for Regional Development)- COMPETE-QREN-EU for financial support through the Chemistry Research Centre of the University of Minho (Ref. UID/QUI/00686/2013 and UID/QUI/0686/2016). A PhD grant to A.M.S. (SFRH/BD/80813/2011) is also acknowledged.info:eu-repo/semantics/publishedVersio

Selective Uncoupling of Individual Mitochondria within a Cell Using a Mitochondria-Targeted Photoactivated Protonophore

Depolarization of an individual mitochondrion or small clusters of mitochondria within cells has been achieved using a photoactivatable probe. The probe is targeted to the matrix of the mitochondrion by an alkyltriphenylphosphonium lipophilic cation and releases the protonophore 2,4-dinitrophenol locally in predetermined regions in response to directed irradiation with UV light via a local photolysis system. This also provides a proof of principle for the general temporally and spatially controlled release of bioactive molecules, pharmacophores, or toxins to mitochondria with tissue, cell, or mitochondrion specificity

Neurosteroid Dehydroepiandrosterone Interacts with Nerve Growth Factor (NGF) Receptors, Preventing Neuronal Apoptosis

The neurosteroid dehydroepiandrosterone (DHEA), produced by neurons and glia, affects multiple processes in the brain, including neuronal survival and neurogenesis during development and in aging. We provide evidence that DHEA interacts with pro-survival TrkA and pro-death p75NTR membrane receptors of neurotrophin nerve growth factor (NGF), acting as a neurotrophic factor: (1) the anti-apoptotic effects of DHEA were reversed by siRNA against TrkA or by a specific TrkA inhibitor; (2) [3H]-DHEA binding assays showed that it bound to membranes isolated from HEK293 cells transfected with the cDNAs of TrkA and p75NTR receptors (KD: 7.4±1.75 nM and 5.6±0.55 nM, respectively); (3) immobilized DHEA pulled down recombinant and naturally expressed TrkA and p75NTR receptors; (4) DHEA induced TrkA phosphorylation and NGF receptor-mediated signaling; Shc, Akt, and ERK1/2 kinases down-stream to TrkA receptors and TRAF6, RIP2, and RhoGDI interactors of p75NTR receptors; and (5) DHEA rescued from apoptosis TrkA receptor positive sensory neurons of dorsal root ganglia in NGF null embryos and compensated NGF in rescuing from apoptosis NGF receptor positive sympathetic neurons of embryonic superior cervical ganglia. Phylogenetic findings on the evolution of neurotrophins, their receptors, and CYP17, the enzyme responsible for DHEA biosynthesis, combined with our data support the hypothesis that DHEA served as a phylogenetically ancient neurotrophic factor

Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures

DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling we used biotinylated-trimethylpsoralen as a DNA structure probe to show the genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF binding sites. Under-wound domains are transcriptionally active, enriched in topoisomerase I, “open” chromatin fibers and DNaseI sites, but are depleted of topoisomerase II. Furthermore DNA supercoiling impacts on additional levels of chromatin compaction as under-wound domains are cytologically decondensed, topologically constrained, and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation providing an evolutionary purpose for clustering genes along chromosomes

Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs

Abstract PURPOSE: To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms. METHODS: Twenty-eight mechanically ventilated pigs were randomized to four groups of seven each: control; acute intracranial hypertension (AICH); acute respiratory distress syndrome (ARDS); acute respiratory distress syndrome in combination with acute intracranial hypertension (ARDS + AICH). AICH was induced with an intracranial balloon catheter and the inflation volume was adjusted to keep intracranial pressure (ICP) at 30-40 cmH2O. ARDS was induced by oleic acid infusion. Respiratory function, hemodynamics, extravascular lung water index (ELWI), lung and brain computed tomography (CT) scans, as well as inflammatory mediators, S100B, and neuronal serum enolase (NSE) were measured over a 4-h period. Lung and brain tissue were collected and examined at the end of the experiment. RESULTS: In both healthy and injured lungs, AICH caused increases in NSE and TNF-alpha plasma concentrations, extravascular lung water, and lung density in CT, the extent of poorly aerated (dystelectatic) and atelectatic lung regions, and an increase in the brain tissue water content. ARDS and AICH in combination induced damage in the hippocampus and decreased density in brain CT. CONCLUSIONS: AICH induces lung injury and also exacerbates pre-existing damage. Increased extravascular lung water is an early marker. ARDS has a detrimental effect on the brain and acts synergistically with intracranial hypertension to cause histological hippocampal damage