Prolonged Dyspnea after Interscalene Block: Attributed to Undiagnosed Addison's Disease and Myasthenia Gravis

This report describes a patient who had a series of daily interscalene nerve blocks to treat pain following a shoulder manipulation for postsurgical stiffness. She experienced acute respiratory compromise that persisted for many weeks. All typical and unusual causes of these symptoms were ruled out. Her treating pulmonologist theorized that the ipsilateral carotid body had been injured. However, it was subsequently determined that the constellation of symptoms and their prolonged duration were best explained by a poor stress response from Addison's disease coupled with exacerbation of early onset myasthenia gravis. This patient's case is not a typical reaction to interscalene nerve blocks, and thus preoperative testing would not be recommended for myasthenia gravis or Addison's disease without underlying suspicion. We describe this report to inform physicians to consider a workup for these diagnoses if a typical workup rules out all usual causes of complications from an interscalene block

Transformation of PVP coated silver nanoparticles in a simulated wastewater treatment process and the effect on microbial communities

Extent: 18p.Background: Manufactured silver nanoparticles (AgNPs) are one of the most commonly used nanomaterials in consumer goods and consequently their concentrations in wastewater and hence wastewater treatment plants are predicted to increase. We investigated the fate of AgNPs in sludge that was subjected to aerobic and anaerobic treatment and the impact of AgNPs on microbial processes and communities. The initial identification of AgNPs in sludge was carried out using transmission electron microscopy (TEM) with energy dispersive X-ray (EDX) analysis. The solid phase speciation of silver in sludge and wastewater influent was then examined using X-ray absorption spectroscopy (XAS). The effects of transformed AgNPs (mainly Ag-S phases) on nitrification, wastewater microbial populations and, for the first time, methanogenesis was investigated. Results: Sequencing batch reactor experiments and anaerobic batch tests, both demonstrated that nitrification rate and methane production were not affected by the addition of AgNPs [at 2.5 mg Ag L-1 (4.9 g L-1 total suspended solids, TSS) and 183.6 mg Ag kg -1 (2.9 g kg-1 total solids, TS), respectively]. The low toxicity is most likely due to AgNP sulfidation. XAS analysis showed that sulfur bonded Ag was the dominant Ag species in both aerobic (activated sludge) and anaerobic sludge. In AgNP and AgNO3 spiked aerobic sludge, metallic Ag was detected (~15%). However, after anaerobic digestion, Ag(0) was not detected by XAS analysis. Dominant wastewater microbial populations were not affected by AgNPs as determined by DNA extraction and pyrotag sequencing. However, there was a shift in niche populations in both aerobic and anaerobic sludge, with a shift in AgNP treated sludge compared with controls. This is the first time that the impact of transformed AgNPs (mainly Ag-S phases) on anaerobic digestion has been reported. Conclusions: Silver NPs were transformed to Ag-S phases during activated sludge treatment (prior to anaerobic digestion). Transformed AgNPs, at predicted future Ag wastewater concentrations, did not affect nitrification or methanogenesis. Consequently, AgNPs are very unlikely to affect the efficient functioning of wastewater treatment plants. However, AgNPs may negatively affect sub-dominant wastewater microbial communities.Casey L Doolette, Mike J McLaughlin, Jason K Kirby, Damien J Batstone, Hugh H Harris, Huoqing Ge and Geert Corneli

Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract

<div><p>Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.</p></div

Comparison of Target Cell Density in Various Tissue Types of Rhesus and Pigtail Macaques.

<p>Menstrual cycle phases were designated as follicular (day 1 of menstruation until day 14), midcycle (days 14–16), or luteal (days 17 to day prior to menstruation). DMPA refers to those animals that were pre-treated with intramuscular injections of 30 mg Depo-provera 4–5 weeks (28–33 days) prior to sacrifice. TCNumber/EpiArea refers to the number of target cells divided by the area of the epithelium analyzed. Each data point represents the mean cell density from a 40x panel image. Each animal had 10 panel images, 1 panel per random section, taken per tissue type from multiple blocks when available. Error bars represent SEM. (a). Analysis of CD4+ T-cell density in untreated (n = 4) and DMPA-treated rhesus macaques (n = 6), comparing vaginal tissue biopsies and terminal tissue collections (Ectocervix and Vagina). (b). Analysis of CD68+ macrophage density in untreated (n = 4) and DMPA-treated rhesus macaques (n = 6), comparing vaginal tissue biopsies and terminal tissue collections (Ectocervix and Vagina). (c). Analysis of CD4+ T-cell and CD68+ macrophage density in the squamous epithelium of infected pigtail macaques by phase of the menstrual cycle, with comparison to 28–33 day post-DMPA treatment in vaginal biopsies of SHIV infected and non-infected animals: (Top left) CD4+ T-cell density in the ectocervix, (top right) CD4+ T-cell density in the vagina, (bottom left) CD68+ macrophage density in the ectocervix, (bottom right) CD68+ macrophage density in the vagina.</p

HIV-1 and 200nm bead diffusion in pigtail macaque mucus before, during and after administration of DMPA.

<p>Estimated means and standard errors were calculated for (a). Mean-squared displacement (MSD) values for all particle types in each mucus sample collected before (n = 29), during (n = 16) and after (n = 34) DMPA administration. (b). Alpha (α) values for all particle types in each mucus sample collected before (n = 29), during (n = 16) and after (n = 34) DMPA administration. For each treatment condition, generalized linear mixed models were run to compare estimated means for particle MSD and α.</p

Mechanistic Model of How HIV-1 Interacts with the Female Reproductive Tract during Various Phases of the Menstrual Cycle and/or with the use of DMPA.

<p>(a). The simple columnar epithelium of the endocervix: (Left) as mid-cycle progresses into luteal phase, a small number of virions are able to enter the cervical canal to associate with the simple columnar epithelium of the endocervix. (Middle) During the luteal phase and/or with the use of progesterone contraceptives (e.g., DMPA), virions are more readily able to enter the cervical canal to interact with the simple columnar epithelium of the endocervix. (Right) During the follicular phase, virions rarely enter the cervical canal to interact with the endocervical simple columnar. Tissue layers are labeled as follows: C = simple columnar, LP = lamina propria. (b). The stratified squamous epithelium of the ectocervix and vagina: (Left) At the midcycle phase, the squamous epithelium is thickest and virions may penetrate the non-viable stratum corneum. However, target cells are primarily located below the epidermis, in the lamina propria; therefore, the likelihood of virus interacting with a target cell is minimal. (Middle) Although few virions are visualized penetrating the stratified squamous epithelium due to the lack of stratum corneum during the luteal phase (or with exogenous progesterone treatments; e.g., DMPA), there is a greater propensity for virus to interact with an infiltrating intraepithelial target cell near the luminal surface. (Right) Like the mid-cycle phase, the squamous epithelium during the follicular phase is thick, and virions are associated with the non-viable stratum corneum. However, target cells are primarily located below the epidermis, in the lamina propria; therefore, the likelihood of virus interacting with a target cell is minimal. Tissue layers are labeled as follows: SC = stratum corneum, G = granulosum, S = spinosum, and B = basal layer, LP = lamina propria.</p

Average Stratum Corneum (SC) Thickness of the Ectocervix and Vagina of Rhesus and Pigtail Macaques.

<p>Menstrual cycle phases were designated as follicular (day 1 of menstruation until day 14), midcycle (days 14–16), or luteal (days 17 to day prior to menstruation). DMPA refers to those animals that were pre-treated with intramuscular injections of 30 mg Depo-provera 4–5 weeks (28–33 days) prior to sacrifice. Error bars represent SEM. (a). SC thickness of the ectocervix of progesterone-treated and untreated rhesus macaques. Arrows represent those animals whose SC was absent. (b). SC thickness of the vagina of progesterone-treated and untreated rhesus macaques. Arrows represent those animals whose SC was absent. (c). SC thickness of the ectocervix of infected pigtail macaques by phase of the menstrual cycle and post-DMPA treatment. (d). SC thickness of the vagina of infected pigtail macaques by phase of the menstrual cycle and post-DMPA treatment (30mg). (e). Fluorescent deconvolution image (40x) of the SC thickness in a representative infected pigtail macaque at mid-cycle menstrual cycle phase. Adherens junctions (red), DAPI (blue), tissue background (green). Size bar is 40μm. (f). Fluorescent deconvolution image (40x) of the SC thickness in a representative infected pigtail macaque at luteal menstrual cycle phase pigtail macaque. Adherens junctions (red), DAPI (blue), tissue background (green). Size bar is 40μm. (g). Fluorescent deconvolution image (40x) of the SC thickness in a representative infected pigtail macaque after DMPA treatment. Adherens junctions (red), DAPI (blue), tissue background (green). Size bar is 40μm. Tissue layers are described to the right of image.</p

<i>In Vivo</i> PA-HIV-1 Penetration of Rhesus and Pigtail Macaque Genital Tracts.

<p>Each data point displayed represents an individual penetrating virion. Each animal had ~20 100x images for each available block of each tissue type. Error bars represent SEM. (a). (Left) Virus penetration in the female reproductive tract of untreated rhesus macaques. (Right) Virus penetration in the female reproductive tract of progesterone-treated rhesus macaques. (b). Virus penetration of the ectocervix of infected pigtail macaques (n = 8) by day of the menstrual cycle. (c). Virus penetration of the vagina of infected pigtail macaques by day of the menstrual cycle. (d). Virus penetration of the endocervix of infected pigtail macaques by day of the menstrual cycle. (e). Virus penetration of the ectocervix (b) and endocervix (d) combined. n = number of animals.</p