A problem at any age: a case report of congenital malrotation with bowel ischemia in an 84-year-old

Background: Malrotation with bowel ischemia is classically thought of as a disease of infants. However, the true prevalence of malrotation in both the pediatric and adult population is unknown due to the unclear number of asymptomatic patients. Case presentation: A previously healthy 84-year-old man with no prior abdominal surgeries presented with an acute abdomen and was found on CT to have small bowel located in the right hemiabdomen and an abnormal SMA-SMV relationship suggestive of intestinal malrotation, as well as pneumatosis intestinalis. He underwent an exploratory laparotomy, where he was found to have a paraduodenal space which did not contain any bowel but was the likely source of an internal hernia. His duodenojejunal flexure was located to the right of the spinal column, the cecum in the left lower quadrant, a thick congenital band at the proximal jejunum, and multiple Ladd’s bands at the level of the duodenum. The bowel appeared viable and a Ladd’s procedure was performed. The patient had an uneventful post-operative course. Conclusions: There is a lack of guidelines regarding screening for and management of asymptomatic malrotation in older children and adults. However, the traditional thinking is that asymptomatic malrotation diagnosed after two years of age poses minimal risk. This case illustrates the potential risk of an internal hernia in the setting of malrotation at any time during one’s lifetime

Structural abnormalities in the non-dilated ascending aortic wall of bicuspid aortic valve patients

Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients. Methods: BAV (n=41) and tricuspid aortic valve (TAV) (n=18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompassing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracellular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells. Results: The non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis (P<.001). The medial layer is significantly thicker (P<.001) with more mucoid extracellular matrix accumulation (P<.001). All other medial pathologic features were more prominent in the TAV (P<.001). The media has significantly less differentiated vascular smooth muscle cells (P<.001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV (P<.0001). Conclusions: The BAV ascending aorta without dilatation is characterized by a differentiation defect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt pathologic features

A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway

Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum

4D printing and annealing of PETG composites reinforced with short carbon fibers

In this study, for the first time, post-heat treatment was applied to improve the stress recovery of short carbon fiber reinforced PETG (SCFRPETG). PETG and SCFRPETG composite were printed under optimal conditions, and constrained and free shape memory cycles were applied under compression and three-point bending loadings to assess shape and stress recovery. The results of the free shape memory test for both vertical and horizontal patterns showed that PETG composite also has a higher shape memory effect (SME) compared to PETG. The SME was significantly improved by performing heat treatment. The stress recovery values for pure PETG, reinforced PETG before and after annealing are 2.48 MPa, 3.04 MPa and 3.18 MPa, respectively. It showed that the addition of 1.5% carbon fiber increases the stress recovery by 22%. The increasing trend reaches 28% by performing post-heat treatment. Additionally, altering the printing pattern affects the programming and stress recovery values. For the SCFRPETG composite samples before and after annealing, changing the printing pattern from horizontal to vertical, resulted in a 16% and 7% increase in recovery stress, respectively. SEM results confirm that the annealing process removes the layered structure, micro-holes caused by shrinkage and 4D printing mechanism. Using the controlled heat treatment method can be a practical solution to solve the problem of adhesion and reduce the anisotropy of FDM 3D printed layers

Infection efficiency of Phaeoisariopsis personata and the influence of different wetness patterns on germ-tube growth of the pathogen

Controlled environment studies with P. personata [Mycosphaerella berkeleyi], the causal agent of late leaf spot disease of groundnut, showed that infection is enhanced if leaves are exposed to alternate wet and dry periods (intermittent wetness) compared with continuous wetness. Detailed investigations to elucidate this phenomenon revealed more germ tubes per conidium and more branching of germ tubes with intermittent wetness than with continuous wetness. With intermittent wetness there was clear evidence of tropic growth of germ tubes and branches towards stomata and subsequent penetration. With continuous wetness, germ tube growth did not appear to be directional and germ tubes commonly passed over the stomatal guard cells, therefore leading to relatively few stomatal penetrations. For both wetness regimes, stomatal penetrations continued to increase with increased leaf wetness for at least 6 d after inoculation and there was a linear relationship between the number of stomatal penetrations and the number of resultant lesions. Infection efficiency was markedly increased when the spore load was reduced to 0.1 conidia/cm² (c. 1 spore/leaflet)

Brugia malayi Antigen (BmA) inhibits HIV-1 trans-infection but neither BmA nor ES-62 alter HIV-1 infectivity of DC induced CD4+ Th-cells

One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs

Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected childre

Microbiological testing of adults hospitalised with community-acquired pneumonia: An international study

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p&lt;0.01), while ERS concordance was higher in North America than in Europe (33.5% versus 19.5%; p&lt;0.01). Testing practices of adults hospitalised with CAP varied significantly by geography and disease severity. There was a wide discordance between real-life testing practices and IDSA/ATS/ERS guideline recommendations

Prevalence and etiology of community-acquired pneumonia in immunocompromised patients

Background. The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. Methods. We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. Results. At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non\u2013community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). Conclusions. Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses