HIV pre-exposure prophylaxis (PrEP) has likely contributed to large decreases in HIV incidence among men who have sex with men (MSM) in several major cities. Berlin has seen a smaller decline, and ...affordable PrEP has been accessible through formal channels in Germany only since autumn 2017. We aimed to investigate knowledge and use of PrEP among MSM in Berlin, and factors predictive of a desire to use PrEP and history of PrEP use.
Multicentre, paper-based, self-administered survey of adult MSM whose HIV status was negative or unknown at time of participation. Data were collected from 1 October 2017 to 2 April 2018.
473 of 875 questionnaires were returned (response rate 54.1%; mean age 37.4 years, range 18-79). 90.0% of participants were aware of PrEP and, of these, 48.2% felt well informed about it. Among the 17.2% of participants reporting PrEP use, 59.3% indicated obtaining some or all of it from informal sources. 23.7% of those with no history of PrEP use reported having condomless anal intercourse (CAI) with two or more partners over the past six months. Worries about side effects, cost, not having a doctor who prescribes it, and a lack of information were the most frequently reported barriers to PrEP use. A desire to use PrEP and history of PrEP use were associated in our multivariable model with having multiple CAI partners. A history of PrEP use was associated with having a university degree, one or two parents born outside Germany, or friends living with HIV.
We found high awareness of PrEP among MSM in Berlin, but also a strong need for more education on its pros, cons and proper use. The frequency of informal PrEP use was also high, raising urgent individual and public health concerns. Policy makers need to consider recent calls to improve access to PrEP and PrEP education through regular health services.
Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of ...cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen
MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.
We quantify the impact of atmospheric transport and limited marine boundary layer sampling on changes in global and regional methane burdens estimate using tracer transport model simulations with ...annually repeating methane emissions and sinks but varying atmospheric transport patterns. We find the 1σ error due to this transport and sampling effect on annual global methane increases to be 1.11 ppb/year and on zonal growth rates to be 3.8 ppb/year, indicating that it becomes more critical at smaller spatiotemporal scales. We also find that the trends in inter‐hemispheric and inter‐polar difference of methane are significantly influenced by the effect. Contrary to a negligible trend in the inter‐hemispheric difference of measurements, we find, after adjusting for the transport and sampling, a trend of 0.37 ± 0.06 ppb/year. This is consistent with the emission trend from a 3‐D inversion of the measurements, suggesting a faster increase in emissions in the Northern Hemisphere than in the Southern Hemisphere.
Plain Language Summary
Changes in global and regional atmospheric burdens of methane are determined by the net effect of sources and sinks and atmospheric transport. Many studies approximate the burdens based on measurements from a network of globally distributed surface air sampling sites. Here we quantify the impact of atmospheric transport and limited marine boundary layer sampling (transport and sampling) on changes in global and regional methane burden estimates using tracer transport model simulation with annually repeating methane emissions and sinks but varying atmospheric transport patterns. We find that for assessing the annual global methane increases, a measurement‐only approach is fairly accurate. However, extending the measurement‐only analysis to hemispheric or latitudinal variations is more problematic as transport influences quickly become significant or even dominant. We find a large impact of transport and sampling effect on the inter‐hemispheric and inter‐polar difference.
Key Points
Transport gives rise to CH4 variations in the spatiotemporal gradients, which are not caused by source or sink changes
We find the transport and sampling error on annual global CH4 increases to be 1.11 ppb/year and on zonal growth rates to be 3.8 ppb/year
The transport‐adjusted inter‐hemispheric difference has a trend of 0.37 ppb/year, consistent with the emission trend from a 3‐D inversion
Older adults are more likely than younger adults to falsely recall past episodes that occurred differently or not at all. We examined whether older adults' propensity for false associative memory is ...related to declines in postretrieval monitoring processes and their modulation with varying memory representations. Younger (N = 20) and older adults (N = 32) studied and relearned unrelated scene-word pairs, followed by a final cued recall that was used to distribute the pairs for an associative recognition test 24 hours later. This procedure allowed individualized formation of rearranged pairs that were made up of elements of pairs that were correctly recalled in the final cued recall ("high-quality" pairs), and of pairs that were not correctly recalled ("low-quality" pairs). Both age groups falsely recognized more low-quality than high-quality rearranged pairs, with a less pronounced reduction in false alarms to high-quality pairs in older adults. In younger adults, cingulo-opercular activity was enhanced for false alarms and for low-quality correct rejections, consistent with its role in postretrieval monitoring. Older adults did not show such modulated recruitment, suggesting deficits in their selective engagement of monitoring processes given variability in the fidelity of memory representations. There were no age differences in hippocampal activity, which was higher for high-quality than low-quality correct rejections in both age groups. These results demonstrate that the engagement of cingulo-opercular monitoring mechanisms varies with memory representation quality and contributes to age-related deficits in false associative memory.
Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal ...organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.
Stereophotogrammetry can be used to study facial morphology in both healthy individuals as well as subjects with orofacial clefts because it shows good reliability, ability to capture images rapidly, ...archival capabilities, and high resolution, and does not require ionizing radiation. This study aimed to compare the three-dimensional (3D) facial morphology of infants born with unilateral cleft lip and palate (UCLP) with an age-matched normative 3D average face before and after primary closure of the lip and soft palate.
Thirty infants with a non-syndromic complete unilateral cleft lip, alveolus, and palate participated in the study. Three-dimensional images were acquired at 3, 6, 9, and 12 months of age. All subjects were treated according to the primary surgical protocol consisting of surgical closure of the lip and the soft palate at 6 months of age. Three-dimensional images of UCLP patients at 3, 6 (pre-treatment), 9, and 12 months of age were superimposed on normative datasets of average facial morphology using the children's reference frame. Distance maps of the complete 3D facial surface and the nose, upper lip, chin, forehead, and cheek regions were developed.
Assessments of the facial morphology of UCLP and control subjects by using color-distance maps showed large differences in the upper lip region at the location of the cleft defect and an asymmetry at the nostrils at 3 and 6 months of age. At 9 months of age, the labial symmetry was completely restored although the tip of the nose towards the unaffected side showed some remnant asymmetry. At 12 months of age, the symmetry of the nose improved, with only some remnant asymmetry noted on both sides of the nasal tip. At all ages, the mandibular and chin regions of the UCLP patients were 2.5-5 mm posterior to those in the average controls.
In patients with UCLP deviations from the normative average 3D facial morphology of age-matched control subjects existed for the upper lip, nose, and even the forehead before lip and soft palate closure was performed. Compared to the controls symmetry in the upper lip was restored, and the shape of the upper lip showed less variation after primary lip and soft palate closure. At this early age, retrusion of the soft-tissue mandible and chin, however, seems to be developing already.
With increasing urbanization and related loss of biodiversity, it has become increasingly important to understand the determinants of biodiversity in cities, and to learn how we can maintain existing ...habitats and improve their quality for both wildlife and humans. Detrimental effects of urbanization on animals such as noise and light pollution, have frequently been reported, but comparatively little is known about the connection between different types of traffic infrastructure and their impacts on urban birds. Here, we provide an overview of the existing knowledge about bird responses to traffic-related stressors, and most importantly, we highlight that this aspect has not been satisfactorily investigated in urban environments. Therefore, we suggest suitable study systems and designs with which the effects of traffic infrastructure on bird communities in cities could be studied, and how biodiversity, in tandem with human wellbeing, in cities would benefit from improvements to the existing infrastructures. In doing so, we aim to strengthen the connection between human wellbeing and birds through research that will ultimately facilitate the development of sustainable cities.
Background
Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with ...esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC.
Methods
Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group.
Results
Overall, 129 (19%) of 689 patients included had SRCs (nCT:
n
= 64; nCRT:
n
= 65). The SRC group had a more advanced ypT stage (
p
= 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range IQR) 2 0–5 vs. 1 0–3;
p
= 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%;
p
= 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median IQR 12 5–50 vs. 23 8–164;
p
= 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT.
Conclusions
SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.
Objective
The objective of this study was to assess the effectiveness of a low‐dose intravenous S‐ketamine treatment on refractory pain in patients with Complex Regional Pain Syndrome (CRPS).
Methods
...In this retrospective study, patients with CRPS who received intravenous S‐ketamine from March 2010 to April 2019 were included. According to our inpatient protocol, S‐ketamine dose was increased until pain reduction was achieved or side effects were observed. Maximum dose was 14 mg/h and treatment duration was 7 days. Primary outcome parameters were pain scores (Numeric Rating Scale) at baseline (T0), end of infusion (T1), and approximately 4 weeks postinfusion (T2). Patients were categorized as responder/nonresponder at T1 and T2. Patients were considered a responder in case there was pain score reduction of greater than or equal to 2 points or if treatment was reported as successful.
Results
Forty‐eight patients were included. Mean disease duration was 5 years (interquartile range IQR = 6 years). Median pain score significantly decreased from 8 (IQR = 2) at T0 to 6 (IQR = 4) at T1 (p < 0.001). At T1, 62% of the patients were responders. At T2, 48% of the patients remained a responder. A significant proportion of the responders at T1 turned into nonresponders at T2 (p = 0.03).
Conclusion
In a group of patients with CRPS with refractory pain, low‐dose intravenous S‐ketamine treatment resulted in effective pain relief during infusion. Although a significant proportion of initial responders became nonresponders at follow‐up, half of the patients were still a responder at ~ 4 weeks postinfusion. Further research is needed to investigate mechanisms responsible for pain relief by S‐ketamine infusions and to ascertain possible predictors of response to the treatment.
Abstract To clarify findings of elevated cytokine levels in major depression (MD), this study aimed to investigate the relationship between serum levels of cytokines, symptoms of MD and ...antidepressant treatment outcome. At baseline (T0) and 4 weeks following initiation of antidepressant treatment (T1), levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)−2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), CRP and depression ratings HAMD-17 and BDI-II were assessed in 30 patients with MD and 30 age-and sex-matched controls. At T0, in the patient group, cytokines, but not CRP, negatively correlated with individual BDI-II-items, factors and severities and showed both negative and positive correlations with HAMD-17 items. At T1 and within the controls, no such relationships were observed. At T0 and T1, levels of both pro- and anti-inflammatory cytokines were significantly higher in treatment responders (ΔHAMD-17 T0-T1≥50%,n=15) compared to non-responders. When controlled for baseline BDI, differences between groups were only found significant for IL-2 at T0. The results suggest cytokines are not generally pro-depressive but rather relate to more specific regulation of symptoms and severities in MD. Together with the association between cytokines and treatment responder status, these data support cytokines as a promising but still controversial biomarker of depression.
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