Rituximab induced pulmonary fibrosis in a patient with lupus nephritis

We describe a 26-year-old woman who was diagnosed eleven years ago with systemic lupus erythematosus and who had suffered multiple relapses. She presented with class IV lupus nephritis with thrombotic microangiopathy, for which she received three doses of rituximab along with plasmapheresis, with no response, and soon became dialysis dependent. One month after the last dose of rituximab, she presented with dyspnoea and hypoxia. A transbronchial lung biopsy revealed pulmonary fibrosis. A diagnosis of rituximab induced pulmonary fibrosis was made after excluding other causes and she was treated with intravenous methyl prednisolone with which there was marked improvement in symptoms and hypoxemia. This is the first report of rituximab induced pulmonary fibrosis in a patient with lupus nephritis.     

Aurora Kinase B Expression,Its Regulation and Therapeutic Targeting in Human Retinoblastoma

PurposeAurora kinase B (AURKB) plays a pivotal role in the regulation of mitosis and is gaining prominence as a therapeutic target in cancers; however, the role of AURKB in retinoblastoma (RB) has not been studied. The purpose of this study was to determine if AURKB plays a role in RB, how its expression is regulated, and whether it could be specifically targeted.MethodsThe protein expression of AURKB was determined using immunohistochemistry in human RB patient specimens and immunoblotting in cell lines. Pharmacological inhibition and shRNA-mediated knockdown were used to understand the role of AURKB in cell viability, apoptosis, and cell cycle distribution. Cell viability in response to AURKB inhibition was also assessed in enucleated RB specimens. Immunoblotting was employed to determine the protein levels of phospho-histone H3, p53, p21, and MYCN. Chromatin immunoprecipitation–qPCR was performed to verify the binding of MYCN on the promoter region of AURKB.ResultsThe expression of AURKB was found to be markedly elevated in human RB tissues, and the overexpression significantly correlated with optic nerve and anterior chamber invasion. Targeting AURKB with small-molecule inhibitors and shRNAs resulted in reduced cell survival and increased apoptosis and cell cycle arrest at the G2/M phase. More importantly, primary RB specimens showed decreased cell viability in response to pharmacological AURKB inhibition. Additional studies have demonstrated that the MYCN oncogene regulates the expression of AURKB in RB.ConclusionsAURKB is overexpressed in RB, and targeting it could serve as a novel therapeutic strategy to restrict tumor cell growth.     

Ultrasonication assisted fabrication of a tungsten sulfide/tungstite heterostructure for ppb-level ammonia detection at room temperature

A heterostructure of WS₂/WO₃·H₂O has been prepared by partial oxidation of WS₂ nanosheets by exposing bulk WS₂ micron powder to ultrasonic waves in a bath sonicator. The as-prepared nanomaterial was used as a sensing film in an interdigitated electrode-based gas detecting device. The device was found to be specific towards ammonia gas among a group oxidizing and reducing gases. In particular, a response of as high as 11.36–254.66% was recorded for ammonia concentrations of 50 ppb to 2 ppm with excellent repeatability and reproducibility at room temperature. The response time and recovery time of the device was found to be a few tens of seconds suggesting its practicability. A plausible mechanism based on different active sites present in the receptor film is proposed and a logical reason behind its specificity towards ammonia gas is also inferred based on the Lewis acidic centers on the nano-surfaces. Overall, this proposed nanomaterial has very high potential for practical use as a room temperature ammonia sensor.

A tungsten sulfide/tungstite heterostructure is prepared via a modified liquid exfoliation technique. A chemiresistive sensor based on this nanomaterial demonstrates excellent sensitivity and selectivity towards ammonia gas even at room temperature.     

Apolipoprotein E s4 Allele and Outcomes of Traumatic Spinal Cord Injury

Abstract

Background/Objective: To test the hypothesis that apolipoprotein E (APOE) polymorphisms are associated with outcomes after spinal cord injury (SCI).

Methods: Retrospective cohort study, from rehabilitation admission to discharge.

Participants: Convenience sample of 89 persons with cervical SCI (C3-C8) treated from 1995 through 2003. Median age was 30 years (range 14-70); 67 were male (75%) and 83 were white (93%).

Main Outcome Measures: American Spinal Injury Association (ASIA) motor and sensory scores, ASIA Impairment Scale (AIS), time from injury to rehabilitation admission, and length of stay (LOS) in rehabilitation.

Results: Subjects with an APOE s4 allele (n = 15; 17%) had significantly less motor recovery during rehabilitation than did individuals without an s4 allele (median 3.0 vs 5.5; P < 0.05) and a longer rehabilitation LOS (median 106 vs 89 days; P = 0.04), but better sensory-pinprick recovery (median 5.0 vs 2.0; P = 0.03). There were no significant differences by APOE s4 allele status in sensory-light touch recovery, likelihood of improving AIS Grade, or time from injury to rehabilitation admission.

Conclusions: APOE ε4 allele was associated with differences in neurological recovery and longer rehabilitation LOS. Genetic factors may be among the determinants of outcome after SCI and warrant further study.     

Effects of antidepressant treatment on mice lacking brain‐derived neurotrophic factor expression through promoter IV

Brain‐derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depression; mice lacking BDNF expression through promoter IV (BDNF‐KIV) exhibit a depression‐like phenotype. We tested our hypothesis that deficits caused by promoter IV deficiency (depression‐like behavior, decreased levels of BDNF, and neurogenesis in the hippocampus) could be rescued by a 3‐week treatment with different types of antidepressants: fluoxetine, phenelzine, duloxetine, or imipramine. Each antidepressant reduced immobility time in the tail suspension test without affecting locomotor activity in the open field test in both BDNF‐KIV and control wild type mice, except that phenelzine increased locomotor activity in wild type mice and anxiety‐like behavior in BDNF‐KIV mice. The antidepressant treatments were insufficient to reverse decreased BDNF levels caused by promoter IV deficiency. No antidepressant treatment increased the hippocampal progenitors of either genotype, whereas phenelzine decreased the surviving progenitors in both genotypes. The antidepressant treatments differently affected the dendritic extension of hippocampal immature neurons: fluoxetine and imipramine increased extension in both genotypes, duloxetine increased it only in BDNF‐KIV mice, and phenelzine decreased it only in wild type mice. Interestingly, a saline‐only injection increased neurogenesis and dendrite extensions in both genotypes. Our results indicate that the behavioral effects in the tail suspension test by antidepressants do not require promoter IV‐driven BDNF expression and occur without a detectable increase in hippocampal BDNF levels and neurogenesis but may involve increased dendritic reorganisation of immature neurons. In conclusion, the antidepressant treatment demonstrated limited efficacy; it partially reversed the defective phenotypes caused by promoter IV deficiency but not hippocampal BDNF levels.     

Prolapse or incontinence: what affects sexual function the most?

Introduction and hypothesis

Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) adversely affect sexual function in women. Comparative studies of the two subgroups are few and results are conflicting. The aim of this study was to compare the effect of POP and SUI on the sexual function of women undergoing surgery for these conditions.

Methods

The study population comprised women with POP or SUI in a tertiary referral hospital in the UK. Women who underwent SUI surgery had no symptoms of POP and had urodynamically proven stress incontinence. Patients with POP had ≥ stage 2 prolapse, without bothersome urinary symptoms. Pre-operative data on sexual function were collected and compared using an electronic pelvic floor assessment questionnaire (ePAQ). The incidence of sexual dysfunction and comparison of symptoms in both groups were calculated using the Mann–Whitney U test.

Results

Three hundred and forty-three women undergoing surgery for either SUI or POP were included. Patients were age-matched, with 184 undergoing SUI surgery (age range 33–77 years) and 159 POP surgery (age range 27–78 years; p?=?0.869). The overall impact of POP and SUI was not significantly different in the two subgroups (p?=?0.703). However, both patients (73 % vs 36 %; p?=?0.00) and partners (50 % vs 24 %; p?=?0.00) avoid intercourse significantly more frequently in cases with POP compared with SUI. This did not have a significant impact on quality of life.

Conclusions

The impact of bothersome SUI or POP on sexual function was found to be similar, but patient and partner avoidance in women with POP was greater than those with SUI.

     

Risk factors for recurrent obstetric anal sphincter injury (rOASI): a systematic review and meta-analysis

Objectives

The objective of this study was to estimate the risk of recurrent obstetric anal sphincter injury (rOASI) in women who have suffered anal sphincter injury in their previous pregnancy and analyse risk factors for recurrence through a systematic review and meta-analysis.

Data sources

A review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were made in Ovid MEDLINE (1996 to May 2015), PubMed, EMBASE and Google Scholar, including bibliographies and conference proceedings.

Methods of study selection

Observational studies (cohort/case–control) evaluating rOASI and risk factors were selected by two reviewers who also analysed methodological quality of those studies. Pooled odds ratios (OR) for rOASI and individual risk factors were calculated using RevMan 5.3.

Tabulation, integration and results

From the eight studies assessed, overall risk of rOASI was 6.3 % compared with a 5.7 % risk of OASI in the first pregnancy. The risk in parous women with no previous OASI was 1.5 %. Factors that increased the risk in a future pregnancy were instrumental delivery with forceps [OR 3.12, 95 % confidence interval (CI) 2.42–4.01) or ventouse (OR 2.44, 95 % CI 1.83–3.25), previous fourth-degree tear (OR 1.7, 95 % CI 1.24–2.36) and birth weight ≥4 kg (OR 2.29, 95 % CI 2.06–2.54). Maternal age ≥35 years marginally increased the risk (OR 1.16, 95 % CI 1–1.35).

Conclusion

The overall rate of rOASI and associated risk factors for recurrence are similar to the rate and risk factors of primary OASI. Antenatal decisions could be based on assessment of foetal weight and intrapartum decisions based upon the requirement for an instrumental delivery.

     

Changes in matrix phosphorylation during bovine dentin development

Phosphorylation of the organic matrix proteins of dentin is important for the initiation of mineralization, but its relevance in later mineralization stages is controversial. The objective of this study was to analyze changes in the total matrix phosphate content during dentin development and to identify their origin. Amino acid and total matrix phosphate analyses of microdissected developing mantle and circumpulpal fetal bovine dentin specimens were performed. The amino acid composition showed few changes during mantle and circumpulpal dentin maturation. However, the total matrix phosphate content showed a significant, positive correlation with tissue maturation in both mantle and circumpulpal dentin, with a two- and a three-fold increase, respectively, being observed. The data indicate that changes occur in the pattern of phosphorylation of matrix proteins during dentin maturation, which we suggest may play a functional role in later stages of tooth mineralization.