Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95)

Morphological studies have shown that macrophages and microglia undergo apoptosis in the central nervous system (CNS) in acute experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative levels of macrophage and microglial apoptosis, and the molecular mechanisms involved in this process, we used three-colour flow cytometry to identify CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the inflammatory cells isolated from the spinal cords of Lewis rats 13 days after immunization with myelin basic protein (MBP) and complete Freund's adjuvant. Simultaneously, we analyzed the DNA content of these cell populations to assess the proportions of cells undergoing apoptosis and in different stages of the cell cycle or examined their expression of three apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and Bcl-2. Microglia were highly vulnerable to apoptosis and were over-represented in the apoptotic population. Macrophages were less susceptible to apoptosis than microglia and underwent mitosis more frequently than microglia. The different susceptibilities of microglia and macrophages to apoptosis did not appear to be due to variations in Fas, FasL or Bcl- 2 expression, as the proportions of microglia and macrophages expressing these proteins were similar, and were relatively high. Furthermore, in contrast to T cell apoptosis, apoptosis of microglia/macrophages did not occur more frequently in cells expressing Fas or FasL, or less frequently in cells expressing Bcl-2. These results indicate that the apoptosis of microglia and CNS macrophages in EAE is not mediated through the Fas pathway, and that Bcl-2 expression does not protect them from apoptosis. Expression of FasL by macrophages and microglia may contribute to the pathogenesis and immunoregulation of EAE through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high level of microglial apoptosis in EAE indicates that microglial apoptosis may be an important homeostatic mechanism for controlling the number of microglia in the CNS following microglial activation and proliferation.      

The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Evidence for the involvement of more than one metal cation in the Schiff base deprotonation process during the photocycle of bacteriorhodopsin

The removal of metal cations inhibits the deprotonation process of the protonated Schiff base during the photocycle of bacteriorhodopsin. To understand the nature of the involvement of these cations, a spectroscopic and kinetic study was carried out on bacteriorhodopsin samples in which the native Ca²⁺ and Mg²⁺ were replaced by Eu³⁺, a luminescent cation. The decay of Eu³⁺ emission in bacteriorhodopsin can be fitted to a minimum of three decay components, which are assigned to Eu³⁺ emission from three different sites. This is supported by the response of the decay components to the presence of ²H₂O and to the changes in the Eu³⁺/bR molar ratio. The number of water molecules coordinated to Eu³⁺ in each site is determined from the change in its emission lifetime when ²H₂O replaces H₂O. Most of the emission originates from two “wet” sites of low crystal-field symmetry—e.g., surface sites. Protonated Schiff base deprotonation has no discernable effect on the emission decay of protein-bound Eu³⁺, suggesting an indirect involvement of metal cations in the deprotonation process. Adding Eu³⁺ to deionized bacteriorhodopsin increases the emission intensity of each Eu³⁺ site linearly, but the extent of the deprotonation (and color) changes sigmoidally. This suggests that if only the emitting Eu³⁺ ions cause the deprotonation and bacteriorhodopsin color change, ions in more than one site must be involved—e.g., by inducing protein conformation changes. The latter could allow deprotonation by the interaction between the protonated Schiff base and a positive field of cations either on the surface or within the protein.     

Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature

We have reported 7 new cases of Bipolaris infection and 2 of Exserohilum infection, which demonstrate the capability of these 2 genera to cause invasive as well as "allergic" disease. As noted previously, it is likely that all of the cases of "Helminthosporium" and Drechslera infections reported in the literature were caused by Bipolaris or Exserohilum. Infections due to these 2 genera are probably more common than previously recognized. They should be included in the differential diagnosis of central nervous system and disseminated fungal disease, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, and allergic bronchopulmonary disease. These various entities have distinct histopathologic characteristics. With disseminated disease in the immunocompromised patient, the most frequent findings are acute inflammation with prominent vascular invasion, thrombosis, and infarction. In contrast, granulomatous inflammation and leukocytoclastic vasculitis are seen in meningoencephalitis caused by these fungi. The histologic features of allergic bronchopulmonary disease and sinusitis are similar. A chronic inflammatory infiltrate of lymphocytes, plasma cells and eosinophils within edematous granulation tissue is found in addition to squamous metaplasia and thickening of the basement membrane. Infections caused by Bipolaris/Exserohilum and Aspergillus show many clinical and pathologic similarities despite the lack of taxonomic relationship between these fungi. Both cause disseminated disease in immunocompromised patients that is characterized by tissue necrosis and vascular invasion. Both cause central nervous system disease, osteomyelitis, and sinusitis and are associated with allergic bronchopulmonary disease. Sinusitis, the most common form of disease caused by Bipolaris and Exserohilum, occurs in otherwise healthy patients with nasal polyposis and allergic rhinitis. Although pathologic evidence of bone invasion may not be found, there frequently is radiographic evidence of invasive disease. Most patients who are treated initially with surgical debridement and amphotericin B have apparently been cured. However, longer follow-up will be necessary in these patients. Amphotericin B appears to be the treatment of choice for invasive infections caused by Bipolaris/Exserohilum species. Ketoconazole and other imidazole derivatives may also be effective in certain of the disease entities caused by these black moulds; however, their role has yet to be defined.(ABSTRACT TRUNCATED AT 400 WORDS)     

Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study

We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry. Linear models were used to compare metabolite levels between the groups. In urine, 19 identifiable untargeted metabolites differed between groups at p < 0.05. These included a variety of phenolic acids and their microbial metabolites that were higher during the DASH diet, with many at false discovery rate (FDR) adjusted p < 0.2. In plasma, eight identifiable untargeted metabolites were different at p < 0.05, but only gamma-tocopherol was significantly lower on DASH at FDR adjusted p < 0.2. The results provide insights into the mechanisms of benefit of the DASH diet.     

Lipoma of the temporal region: a rare case series

Lipomas are common benign tumours that can occur in most parts of the body. Lipomas arising from the deep temporal fat pad, found between the two layers of the deep temporal fascia, are rare, however; there has been only one documented case report to our knowledge. We describe a second case arising from the temporal fat pad in a patient treated at our unit, having previously reported the first one, and discuss the relevant anatomy and management.     

Evaluating and Strengthening the Evidence for Nutritional Bone Research: Ready to Break New Ground?

A healthy diet is essential to attain genetically determined peak bone mass and maintain optimal skeletal health across the adult lifespan. Despite the importance of nutrition for bone health, many of the nutritional requirements of the skeleton across the lifespan remain underexplored, poorly understood, or controversial. With increasingly aging populations, combined with rapidly changing diets and lifestyles globally, one anticipates large increases in the prevalence of osteoporosis and incidence of osteoporotic fractures. Robust, transparent, and reproducible nutrition research is a cornerstone for developing reliable public health recommendations to prevent osteoporosis and osteoporotic fractures. However, nutrition research is often criticized or ignored by healthcare professionals due to the overemphasis of weak science, conflicting, confusing or implausible findings, industry interests, common misconceptions, and strong opinions. Conversely, spurious research findings are often overemphasized or misconstrued by the media or prominent figures especially via social media, potentially leading to confusion and a lack of trust by the general public. Recently, reforms of the broader discipline of nutrition science have been suggested and promoted, leading to new tools and recommendations to attempt to address these issues. In this perspective, we provide a brief overview of what has been achieved in the field on nutrition and bone health, focusing on osteoporosis and osteoporotic fractures. We discuss what we view as some of the challenges, including inherent difficulties in assessing diet and its change, disentangling complex interactions between dietary components and between diet and other factors, selection of bone-related outcomes for nutrition studies, obtaining evidence with more unbiased designs, and perhaps most importantly, ensuring the trust of the public and healthcare professionals. This perspective also provides specific recommendations and highlights new developments and future opportunities for scientists studying nutrition and bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Contemporary techniques and outcomes of robotic assisted radical cystectomy with intracorporeal urinary diversion

The open approach to radical cystectomy continues to be accompanied by significant morbidity despite enhanced recovery protocols (ERP). Robotic assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) has become an increasingly popular technique for removal of aggressive bladder cancer and subsequent urinary diversion. Randomized clinical trials comparing the robotic and open techniques address the uncertainty surrounding oncological efficacy of the RARC and show that RARC is at least comparable to open radical cystectomy (ORC) in terms of oncologic adequacy and survival. Although RARC with ICUD is a technically challenging procedure, surgeons have noted ergonomic advantages while patients experience less blood loss and quicker time to recovery and to adjuvant chemotherapy (AC), if necessary. Even with these benefits, there is a paucity of data describing outcomes of ICUD. For those surgeons who have switched to ICUD, priority remains standardization of a protocol for the reconstructive component and for a safe transition from extracorporeal urinary diversion (ECUD) to ICUD. Additionally, there is a need for evidence of reduced financial toxicity for the patient, as well as more comprehensive cost-effectiveness analyses. The literature from this review represents 10 years of accumulating data on techniques and outcomes of RARC with ICUD.     

A host-cell-selected variant of influenza B virus with a single nucleotide substitution in HA affecting a potential glycosylation site was attentuated in virulence for volunteers

Summary An influenza B virus was passaged in man (virus A) and then in human embryo trachea (C) and into embryonated eggs (D) or directly into eggs (B). Virus A, B, and C had the same (cell-like) haemagglutinin phenotype on reaction with selected monoclonal antibodies while D had an egg-like phenotype. The viruses were administered at a dose of 1,000 TCD₅₀ (for MDCK cells) by intranasal inoculation to groups of 27 or 28 volunteers. Viruses A, B, and C all produced disease in six to eight volunteers, whereas D produced no illness and only four volunteers were infected. The viruses shed by the volunteers were indistinguishable from those with which they were inoculated. The haemagglutinin genes of the viruses were sequenced and changes were detected indicating amino acid substitutions at position 196–198 in the attenuated egg-grown virus D whereby a potential glycosylation site present in the other viruses was lost.     

The influence of the victim's consumption of alcohol on perceptions of stranger and acquaintance rape

This study examines the influence of the victim's consumption of alcohol on perceptions in stranger and acquaintance rape. Participants were composed of 218 male and 227 female undergraduates. They participated in group discussions and were given information materials containing demographic background questions, a hypothetical scenario involving rape or attempted rape, and questions relating to their impressions of the story and the characters. Likert-type scales were used to rate the degree to which the participants thought the woman was responsible for the incident, and to rate the cautiousness/carelessness of the female character. Results revealed that the victim was rated significantly more responsible for the attack when the perpetrator was a stranger, when the victim drank alcohol, and when the outcome was a completed rape. Although both males and females rated the victim as more careless when she had been drinking, only female participants rated the drinking victim as more responsible than the nondrinking victim. The study therefore concluded that alcohol consumption by a victim of sexual assault might lead to more negative perceptions about the victim; wherein they are viewed as more careless and culpable for the assault.