Ultra‐short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

We conducted an adaptive design single‐center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra‐short‐term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)‐nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R?). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12‐week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first‐line DAA therapy; and two after retreatment with second‐line DAA). At a median follow‐up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4‐day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%‐20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R ? transplants.     

Effect of Silicon Nitride and Graphene Nanoplatelets on the Properties of Aluminum Metal Matrix Composites

This research work aims at investigating the influence of a fixed content of silicon nitride (Si₃N₄) and varied contents of graphene nanoplatelets (GNPs) on the physical (density, structural, morphological) and mechanical properties (microhardness, nanoindentation) of Al-Si₃N₄-GNPs composites. The composites were fabricated by a microwave-assisted powder metallurgy route. The Si₃N₄ concentration was fixed at (5 wt.%) in Al-Si₃N₄-GNPs composites while the GNPs concentration was varied between (0 wt.%) to (1.5 wt.%) with an increment of (0.5 wt.%). The structural analysis indicates the formation of phase pure materials with high crystallinity. The microstructural analysis confirmed the presence of the Si₃N₄ and GNPs showing enhanced agglomeration with the increasing amount of GNPs. Moreover, the surface roughness of the synthesized composites increases with an increasing amount of GNPs reaching its maximum value (RMS = 65.32 nm) at 1.5 wt.% of GNPs. The Al-Si₃N₄-GNPs composites exhibit improved microhardness and promising load-indentation behavior during nanoindentation when compared to pure aluminum (Al). Moreover, Al-Si₃N₄-GNPs composites demonstrate higher values of compressive yield strength (CYS) and ultimate compressive strength (UCS) when compared to pure Al despite showing a declining trend with an increasing amount of GNPs in the matrix. Finally, a shear mode of fracture is prevalent in Al-Si₃N₄-GNPs composites under compression loading.     

Serial spot hydroxyproline/creatinine ratios in metastatic prostatic cancer

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.     

Immunoblastic lymphosarcoma: a light, immunofluorescence, and electron microscopic study.

Immunoblastic lymphosarcoma (ILS) is a newly recognized malignant lymphoreticular neoplasm and is included in the recent W.H.O. classification of lymphomas. This report concerns six cases of ILS studied by light, immunofluorescence (IF), and electron microscopy (EM). Four patients were female and all except one were over 50 years of age. Four patients had some immunological abnormality. Light microscopy showed a monomorphic population of immunoblasts with pyroninophilic cytoplasm and variable plasmacytoid differentiation. Intracytoplasmic IgG was demonstrated by IF in four cases, and IgA in one. Large lymphoid cells with varying proportions of polysomes, rough endoplasmic reticulum, and Golgi apparatus were seen by EM in four cases. Mean survival was 4.8 months in five cases; death in four was due to disseminated ILS. We concluded that our cases of ILS are of B cell origin, are often associated with immunological abnormalities, and carry a poor prognosis. Immunofluorescence and EM are helpful in its diagnosis.     

Memory strategy training in children with cerebral infarcts related to sickle cell disease

Cerebral infarcts occur in approximately 30% of children with sickle cell disease (SCD), but little information exists regarding remediation of associated cognitive deficits. The authors examined the benefits of training children with infarcts to use memory strategies. Six children with SCD-related infarcts received academic tutoring; three of these children received additional training in memory strategies (silent rehearsal to facilitate short-term memory and semantic organization to facilitate long-term memory). The performance of children receiving strategy training appeared to improve more than that of children receiving only tutoring. Memory in children with SCD-related infarcts may be enhanced through strategy training.     

Intracranial hemorrhage progressing to porencephaly as a result of congenitally acquired cytomegalovirus infection--an illustrative report

OBJECTIVE: To report ultrasound and magnetic resonance imaging (MRI) findings in a fetus with intracranial hemorrhage and porencephaly, presumed secondary to intrauterine cytomegalovirus (CMV) infection. METHODS: A 20-year-old, G2, P1 woman presented at 28.6 weeks' gestation after ultrasound examination demonstrated apparently isolated fetal ascites. Evaluation included maternal serology, amniocentesis, and repeated ultrasound examinations. Fetal MRI evaluation was also performed. The infant was born at 35 weeks' gestational age. RESULTS: Maternal serology was positive for CMV IgG. Intrauterine CMV infection was confirmed using polymerase chain reaction (PCR). At 31.6 weeks' gestation, ultrasound demonstrated borderline lateral cerebral ventriculomegaly. MRI of the fetal brain on the same day demonstrated parenchymal hemorrhage in the right posterior temporal and parietal regions along with mild ventricular enlargement. Sonography one day before delivery revealed brain parenchymal cystic change consistent with porencephaly of the right posterior temporal and parietal region. Postnatal ultrasound, computed tomography (CT), and MRI confirmed the diagnosis of a porencephalic cyst communicating with the posterior body of the right lateral ventricle. Placental pathology was consistent with CMV infection. CONCLUSION: This case report illustrates that fetal MRI is a useful adjunct in the evaluation of intrauterine infection with CMV.     

Scintigraphic manifestation of iliotibial band injury in an endurance athlete.

The scintigraphic appearance of an overuse injury at the insertion of the iliotibial band is described. This injury was depicted on three-phase bone scintigraphy as focally increased radionuclide concentration in the anterolateral tibial condyle (lateral tibial tubercle) where the iliotibial band inserts. Overuse injuries involving the insertion of the iliotibial band are uncommon and are not to be confused with a stress fracture or other bony lesion involving the lateral tibial condyle.     

Peroxynitrite-induced modification of H2A histone presents epitopes which are strongly bound by human anti-DNA autoantibodies: role of peroxynitrite-modified-H2A in SLE induction and progression

Peroxynitrite is a potent oxidant and nitrating agent and has in vivo existence. It is a powerful proinflammatory substance and may increase vascular permeability in inflamed tissues. Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease of unknown etiology. Since its discovery, numerous self- and non-self, nuclear, and cytoplasmic antigens have been suggested as stimuli for SLE initiation, but the exact trigger is yet to be identified. In this study, an attempt has been made to investigate the binding characteristics of SLE anti-DNA autoantibodies to native DNA and native and peroxynitrite-modified H2A histone to explore the possible role of modified protein antigen(s) in SLE initiation and progression. The nuclear protein (H2A histone) was modified by peroxynitrite synthesized in our laboratory. The peroxynitrite-modified H2A revealed generation of nitrotyrosine, dityrosine, and carbonyls when subjected to investigation by physicochemical methods. Binding characteristics and specificity of SLE anti-DNA antibodies were analyzed by direct binding and inhibition enzyme-linked immunosorbent assay. The data show preferential binding of SLE autoantibodies to peroxynitrite-modified H2A histone in comparison with native H2A histone or native DNA. A band shift assay further substantiated the enhanced recognition of peroxynitirite-modified H2A histone by anti-DNA autoantibodies. The results suggest that peroxynitrite modification of self-antigen(s) can generate neoepitopes capable of inducing SLE characteristic autoantibodies. The preferential binding of peroxynitrite-modified H2A histone by SLE anti-DNA antibodies points out the likely role of oxidatively modified and nitrated H2A histone in the initiation/progression of SLE. Moreover, oxidatively modified and nitrated nuclear protein antigen, rather than nucleic acid antigens, appear to be more suitable as a trigger for SLE.