Bilateral pneumothorax as possible atypical presentation of coronavirus disease 2019 (COVID-19)

© 2020 The Authors Coronavirus disease 2019 (COVID-19) is most frequently associated with a mild presentation of fever, cough, and shortness of breath. Typical radiographic findings of COVID-19 are bilateral ground-glass opacities on computed tomography (CT) scans. However, there have been instances of pneumothorax, giant bulla, and pneumomediastinum, mainly in elderly COVID-19 patients and predominately occurring at least one week after symptom onset. Here, we report a case where a healthy, young Hispanic man presented with three days of fever, cough, and dyspnea. On admission to the emergency department, he was found to have bilateral pneumothoraces, pneumomediastinum, and pneumopericardium requiring bilateral chest tubes. The patient had no predisposing risk factors for pneumothorax, such as a history of trauma, smoking, past intubations, asthma, high pressure oxygen delivery, or a history of prior pneumothorax. The only positive diagnostic test was a SARS-CoV-2 test by real-time reverse transcriptase–polymerase chain reaction assay. This case highlights the potential atypical presentation of a COVID-19 infection and is the first reported case, to our knowledge, that features bilateral spontaneous pneumothoraces, pneumomediastinum, and pneumopericardium as a probable rare presentation of COVID-19

Placental transmogrification of the lung associated with unilateral pleural effusion: A case report with a comprehensive review of the literature

© 2018 The Authors Placental transmogrification of the lung (PTL) is a rare benign pulmonary lesion resembling chorionic villi. With fewer than 40 cases reported in literature, associations have thus far been made with bullous emphysema, pulmonary fibrochondromatous hamartomas and adenocarcinoma of the lung. Typically presenting as unilateral solitary cystic or bullous lesion, we report the first case of PTL presenting with unilateral pleural effusion. A 70-year-old male presented with recurrent unilateral pleural effusion that failed to resolve with multiple thoracenteses. He underwent thoracoscopic excision and biopsy of a cystic mass identified on computed tomography (CT) scan which revealed characteristic villous and papillary changes. We describe the case and review the literature on this benign but rare pulmonary disease entity

Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

Laparoscopy is widely utilised to diagnose and treat acute and chronic, gynaecological and general surgical conditions. It has only been in recent years that laparoscopy has become an acceptable surgical alternative to open surgery in pregnancy. To date there is little clinical guidance pertaining to laparoscopic surgery in pregnancy. This is why the BSGE commissioned this guideline. MEDLINE, EMBASE, CINAHL and the Cochrane library were searched up to February 2017 and evidence was collated and graded following the NICE-approved process. The conditions included in this guideline are laparoscopic management of acute appendicitis, acute gall bladder disease and symptomatic benign adnexal tumours in pregnancy. The intended audience for this guideline is obstetricians and gynaecologists in secondary and tertiary care, general surgeons and anaesthetists. However, only laparoscopists who have adequate laparoscopic skills and who perform complex laparoscopic surgery regularly should undertake laparoscopy in pregnant women, since much of the evidence stems from specialised centres

Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation

The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85α mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85α mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85α towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85α BH domain mutants (E137K, E217K, R262T E297K) for bovine p85α BH and found that the mutations did not alter the overall domain structure. Thus, several p85α mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85α BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activit

Thymoma calcification: Is it clinically meaningful?

Among anterior mediastinal lesions, thymoma is the most common. Thymomas are tumors of thymic epithelial cell origin that are distinguished by inconsistent histological and biologic behavior. Chest imaging studies typically show a round or lobulated tumor in the anterior mediastinum. Calcifications in thymomas are classically punctuate or amorphous, positioned within the lesion. Chest computed tomography (CT) features suggesting higher risk thymoma consist of tumor heterogeneity, vascular involvement, lobulation, pulmonary nodules, lymphadenopathy, and pleural manifestations. Imaging findings have an imperfect ability to predict stage and prognosis for thymoma patients. Our objective is to highlight the clinical implications of thymoma calcifications on the diagnosis, clinical manifestation and prognosis. A pubmed and google search was performed using the following words: thymoma calcification, calcified thymus, mediastinal calcification, anterior mediastinal calcification, and calcified thymoma. After reviewing 370 articles, 32 eligible articles describing thymoma calcifications were found and included in this review. Although the presence of thymus calcifications was more common in patients with invasive thymomas, they were present in significant portion of non-invasive thymomas. The presence of calcifications was not a significant factor in differentiating between benign and malignant thymoma. As a result, the type, location, size or other characteristics of thymus gland calcifications were not relevant features in clinical and radiologic diagnosis of thymoma. The histopathological diagnosis is still the only possible way to confirm the neoplastic nature of thymoma. All types of thymomas should be evaluated and managed independently of the presence of calcifications

Specific Roles of Akt iso Forms in Apoptosis and Axon Growth Regulation in Neurons

Akt is a member of the AGC kinase family and consists of three isoforms. As one of the major regulators of the class I PI3 kinase pathway, it has a key role in the control of cell metabolism, growth, and survival. Although it has been extensively studied in the nervous system, we have only a faint knowledge of the specific role of each isoform in differentiated neurons. Here, we have used both cortical and hippocampal neuronal cultures to analyse their function. We characterized the expression and function of Akt isoforms, and some of their substrates along different stages of neuronal development using a specific shRNA approach to elucidate the involvement of each isoform in neuron viability, axon development, and cell signalling. Our results suggest that three Akt isoforms show substantial compensation in many processes. However, the disruption of Akt2 and Akt3 significantly reduced neuron viability and axon length. These changes correlated with a tendency to increase in active caspase 3 and a decrease in the phosphorylation of some elements of the mTORC1 pathway. Indeed, the decrease of Akt2 and more evident the inhibition of Akt3 reduced the expression and phosphorylation of S6. All these data indicate that Akt2 and Akt3 specifically regulate some aspects of apoptosis and cell growth in cultured neurons and may contribute to the understanding of mechanisms of neuron death and pathologies that show deregulated growth

Breeding histories and selection criteria for oilseed rape in Europe and China identified by genome wide pedigree dissection

Selection breeding has played a key role in the improvement of seed yield and quality in oilseed rape (Brassica napus L.). We genotyped Tapidor (European), Ningyou7 (Chinese) and their progenitors with the Brassica 60 K Illumina Infinium SNP array and mapped a total of 29,347 SNP markers onto the reference genome of Darmor-bzh. Identity by descent (IBD) refers to a haplotype segment of a chromosome inherited from a shared common ancestor. IBDs identified on the C subgenome were larger than those on the A subgenome within both the Tapidor and Ningyou7 pedigrees. IBD number and length were greater in the Ningyou7 pedigree than in the Tapidor pedigree. Seventy nine QTLs for flowering time, seed quality and root morphology traits were identified in the IBDs of Tapidor and Ningyou7. Many more candidate genes had been selected within the Ningyou7 pedigree than within the Tapidor pedigree. These results highlight differences in the transfer of favorable gene clusters controlling key traits during selection breeding in Europe and China

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response

Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance

Tuberous sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR). To understand the function of this pathway in neural development, we have examined the contributions of multiple components of this pathway in both neuromuscular junction assembly and photoreceptor axon guidance in Drosophila. Expression of Rheb in the motoneuron, but not the muscle of the larval neuromuscular junction produced synaptic overgrowth and enhanced synaptic function, while reductions in Rheb function compromised synapse development. Synapse growth produced by Rheb is insensitive to rapamycin, an inhibitor of Tor complex 1, and requires wishful thinking, a bone morphogenetic protein receptor critical for functional synapse expansion. In the visual system, loss of Tsc1 in the developing retina disrupted axon guidance independently of cellular growth. Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1 effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1 mosaics, while reductions in Tor function suppressed those phenotypes. These findings show that Tsc-mediated control of axon guidance and synapse assembly occurs via growth-independent signaling mechanisms, and suggest that Tor complex 2, a regulator of actin organization, is critical in these aspects of neuronal development