Tracking water dimers in ambient nanocapsules by vibrational spectroscopy.

Nanoconfined few-molecule water clusters are invaluable systems to study fundamental aspects of hydrogen bonding. Unfortunately, most experiments on water clusters must be performed at cryogenic temperatures. Probing water clusters in noncryogenic systems is however crucial to understand the behavior of confined water in atmospheric or biological settings, but such systems usually require either complex synthesis and/or introduce many confounding external bonds to the clusters. Here, we show that combining Raman spectroscopy with the molecular nanocapsule cucurbituril is a powerful technique to sequester and analyze water clusters in ambient conditions. We observe sharp peaks in vibrational spectra arising from a single rigid confined water dimer. The high resolution and rich information in these vibrational spectra allow us to track specific isotopic exchanges inside the water dimer, verified with density-functional theory and kinetic population modeling. We showcase the versatility of such molecular nanocapsules by tracking water cluster vibrations through systematic changes in confinement size, in temperatures up to 120° C, and in their chemical environment.

Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes.

RATIONALE: Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported. OBJECTIVES: We investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes. METHODS: Hierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters. MEASUREMENTS AND MAIN RESULTS: We identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes. CONCLUSIONS: These findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes. TRIAL REGISTRATION NUMBER: ISRCTN20769191, ISRCTN12776039.

Identifying the molecular drivers of ALS-implicated missense mutations.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressively fatal, neurodegenerative disease associated with both motor and non-motor symptoms, including frontotemporal dementia. Approximately 10% of cases are genetically inherited (familial ALS), while the majority are sporadic. Mutations across a wide range of genes have been associated; however, the underlying molecular effects of these mutations and their relation to phenotypes remain poorly explored. METHODS: We initially curated an extensive list (n=1343) of missense mutations identified in the clinical literature, which spanned across 111 unique genes. Of these, mutations in genes SOD1, FUS and TDP43 were analysed using in silico biophysical tools, which characterised changes in protein stability, interactions, localisation and function. The effects of pathogenic and non-pathogenic mutations within these genes were statistically compared to highlight underlying molecular drivers. RESULTS: Compared with previous ALS-dedicated databases, we have curated the most extensive missense mutation database to date and observed a twofold increase in unique implicated genes, and almost a threefold increase in the number of mutations. Our gene-specific analysis identified distinct molecular drivers across the different proteins, where SOD1 mutations primarily reduced protein stability and dimer formation, and those in FUS and TDP-43 were present within disordered regions, suggesting different mechanisms of aggregate formation. CONCLUSION: Using our three genes as case studies, we identified distinct insights which can drive further research to better understand ALS. The information curated in our database can serve as a resource for similar gene-specific analyses, further improving the current understanding of disease, crucial for the development of treatment strategies.

SERS Sensing of Dopamine with Fe(III)-Sensitized Nanogaps in Recleanable AuNP Monolayer Films.

Sensing of neurotransmitters (NTs) down to nm concentrations is demonstrated by utilizing self-assembled monolayers of plasmonic 60 nm Au nanoparticles in close-packed arrays immobilized onto glass substrates. Multiplicative surface-enhanced Raman spectroscopy enhancements are achieved by integrating Fe(III) sensitizers into the precisely-defined <1 nm nanogaps, to target dopamine (DA) sensing. The transparent glass substrates allow for efficient access from both sides of the monolayer aggregate films by fluid and light, allowing repeated sensing in different analytes. Repeated reusability after analyte sensing is shown through oxygen plasma cleaning protocols, which restore pristine conditions for the nanogaps. Examining binding competition in multiplexed sensing of two catecholamine NTs, DA and epinephrine, reveals their bidentate binding and their interactions. These systems are promising for widespread microfluidic integration enabling a wide range of continuous biofluid monitoring for applications in precision health.

A reinforcement learning framework for pooled oligonucleotide design.

MOTIVATION: The goal of oligonucleotide (oligo) design is to select oligos that optimize a set of design criteria. Oligo design problems are combinatorial in nature and require computationally intensive models to evaluate design criteria. Even relatively small problems can be intractable for brute-force approaches that test every possible combination of oligos, so heuristic approaches must be used to find near-optimal solutions. RESULTS: We present a general reinforcement learning (RL) framework, called OligoRL, to solve oligo design problems with complex constraints. OligoRL allows 'black-box' design criteria and can be adapted to solve many oligo design problems. We highlight the flexibility of OligoRL by building tools to solve three distinct design problems: (i) finding pools of random DNA barcodes that lack restriction enzyme recognition sequences (CutFreeRL); (ii) compressing large, non-degenerate oligo pools into smaller degenerate ones (OligoCompressor) and (iii) finding Not-So-Random hexamer primer pools that avoid rRNA and other unwanted transcripts during RNA-seq library preparation (NSR-RL). OligoRL demonstrates how RL offers a general solution for complex oligo design problems. AVAILABILITY AND IMPLEMENTATION: OligoRL and all simulation codes are available as a Julia package at http://jensenlab.net/tools and archived at https://archive.softwareheritage.org/browse/origin/directory/?origin_url=https://github.com/bmdavid2/OligoRL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Platelet-Rich Plasma in Plastic Surgery: A Systematic Review.

Introduction: Platelet-rich plasma (PRP) is gaining popularity and is applied in a variety of clinical settings. This review aims to present and evaluate available evidence regarding the use of PRP in various applications in plastic surgery. Methods: PubMed, Web of Science, Medline, and Embase were searched using predefined MeSH terms to identify studies concerning the application of PRP alone or in combination with fat grafting for plastic surgery. The search was limited to articles in English or German. Animal studies, in vitro studies, case reports, and case series were excluded. Results: Of 50 studies included in this review, eleven studies used PRP for reconstruction or wound treatment, eleven for cosmetic procedures, four for hand surgery, two for burn injuries, five for craniofacial disorders, and 17 as an adjuvant to fat grafting. Individual study characteristics were summarized. Considerable variation in preparation protocols and treatment strategies were observed. Even though several beneficial effects of PRP therapy were described, significance was not always demonstrated, and some studies yielded conflicting results. Efficacy of PRP was not universally proven in every field of application. Conclusion: This study presents an overview of current PRP treatment options and outcomes in plastic surgery. PRP may be beneficial for some indications explored in this review; however, currently available data are insufficient and systematic evaluation is limited due to high heterogeneity in PRP preparation and treatment regimens. Further randomized controlled trials employing standardized protocols are warranted.

Evaluation of a Wearable in-Ear Sensor for Temperature and Heart Rate Monitoring: A Pilot Study.

In the context of the COVID-19 pandemic, wearable sensors are important for early detection of critical illness especially in COVID-19 outpatients. We sought to determine in this pilot study whether a wearable in-ear sensor for continuous body temperature and heart rate monitoring (Cosinuss company, Munich) is sufficiently accurate for body temperature and heart rate monitoring. Comparing with several anesthesiologic standard of care monitoring devices (urinary bladder and zero-heat flux thermometer and ECG), we evaluated the in-ear sensor during non-cardiac surgery (German Clinical Trials Register Reg.-No: DRKS00012848). Limits of Agreement (LoA) based on Bland-Altman analysis were used to study the agreement between the in-ear sensor and the reference methods. The estimated LoA of the Cosinuss One and bladder temperature monitoring were [-0.79, 0.49] °C (95% confidence intervals [-1.03, -0.65] (lower LoA) and [0.35, 0.73] (upper LoA)), and [-0.78, 0.34] °C (95% confidence intervals [-1.18, -0.59] (lower LoA) and [0.16, 0.74] (upper LoA)) of the Cosinuss One and zero-heat flux temperature monitoring. 89% and 79% of Cosinuss One temperature monitoring were within ± 0.5 °C limit of bladder and zero-heat flux monitoring, respectively. The estimated LoA of Cosinuss One and ECG heart rate monitoring were [-4.81, 4.27] BPM (95% confidence intervals [-5.09, -4.56] (lower LoA) and [4.01, 4.54] (upper LoA)). The proportion of detection differences within ± 2BPM was 84%. Body temperature and heart rate were reliably measured by the wearable in-ear sensor.

Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait.

The heterogeneity of chronic obstructive pulmonary disease (COPD) creates many diagnostic, prognostic, treatment and management challenges, as the pathogenesis of COPD is highly complex and the underlying cellular and molecular mechanisms remain poorly understood. A reliable, easy-to-measure, clinically relevant biomarker would be invaluable for improving outcomes for patients. International and national guidance for COPD suggests using blood eosinophil counts as a biomarker to help estimate likely responsiveness to inhaled corticosteroids (ICS) and, potentially, to aid effective management strategies. However, with the mechanism underlying the association between higher eosinophil levels and ICS effect unknown, use of the blood eosinophil count in COPD continues to be widely debated by the respiratory community.Two international meetings involving respiratory medicine specialists, immunologists and primary and secondary care clinicians were held in November 2018 and March 2019, facilitated and funded by GlaxoSmithKline plc. The aims of these meetings were to explore the role of eosinophils in the disease processes of COPD and as prognostic and diagnostic markers, and to identify areas of deficient knowledge that warrant further research. The consensus views of the attendees on key topics, contextualised with current literature, are summarised in this review article, with the aim of aiding ongoing research into the disease processes of COPD and the development of biomarkers to aid clinical management.Under certain conditions, eosinophils can be recruited to the lung, and increasing evidence supports a role for eosinophilic inflammation in some patients with COPD. Infiltration of eosinophils across the bronchial vascular epithelium into the airways is promoted by the actions of immunoregulatory cells, cytokines and chemokines, where eosinophil-mediated inflammation is driven by the release of proinflammatory mediators.Multiple studies and two meta-analyses suggest peripheral blood eosinophils may correlate positively with an increased likelihood of exacerbation reduction benefits of ICS in COPD. The studies, however, vary in design and duration and by which eosinophil levels are viewed as predictive of an ICS response. Generally, the response was seen when eosinophil levels were 100-300 cells/µL (or higher), levels which are traditionally viewed within the normal range. Some success with interleukin-5-targeted therapy suggests that the eosinophilic phenotype may be a treatable trait.The use of biomarkers could help to stratify treatment for COPD-the goal of which is to improve patient outcomes. Some evidence supports eosinophils as a potential biomarker of a treatable trait in COPD, though it is still lacking and research is ongoing. A unified consensus and a practical, accessible and affordable method of utilising any biomarker for COPD was thought to be of most importance. Challenges around its utilisation may include presenting a clear and pragmatic rationale for biomarker-driven therapy, guidance on ICS withdrawal between primary and secondary care and a lack of financial incentives supporting broad application in clinical practice. Future treatments should, perhaps, be more targeted rather than assuming the primary disease label (COPD or asthma) will define treatment response.

Mercapturate pathway metabolites of sotorasib, a covalent inhibitor of KRASG12C, are associated with renal toxicity in the Sprague Dawley rat.

Sotorasib is a first-in class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KRAS p.G12C mutation. In the nonclinical toxicology studies of sotorasib, the kidney was identified as a target organ of toxicity in the rat but not the dog. Renal toxicity was characterized by degeneration and necrosis of the proximal tubular epithelium localized to the outer stripe of the outer medulla (OSOM), which suggested that renal metabolism was involved. Here, we describe an in vivo mechanistic rat study designed to investigate the time course of the renal toxicity and sotorasib metabolites. Renal toxicity was dose- and time-dependent, restricted to the OSOM, and the morphologic features progressed from vacuolation and necrosis to regeneration of tubular epithelium. The renal toxicity correlated with increases in renal biomarkers of tubular injury. Using mass spectrometry and matrix-assisted laser desorption/ionization, a strong temporal and spatial association between renal toxicity and mercapturate pathway metabolites was observed. The rat is reported to be particularly susceptible to the formation of nephrotoxic metabolites via this pathway. Taken together, the data presented here and the literature support the hypothesis that sotorasib-related renal toxicity is mediated by a toxic metabolite derived from the mercapturate and ß-lyase pathway. Our understanding of the etiology of the rat specific renal toxicity informs the translational risk assessment for patients.

A Computational Study of Liquid Shock Absorption for Prevention of Traumatic Brain Injury.

Mild traumatic brain injury (mTBI), more colloquially known as concussion, is common in contact sports such as American football, leading to increased scrutiny of head protective gear. Standardized laboratory impact testing, such as the yearly National Football League (NFL) helmet test, is used to rank the protective performance of football helmets, motivating new technologies to improve the safety of helmets relative to existing equipment. In this work, we hypothesized that a helmet which transmits a nearly constant minimum force will result in a reduced risk of mTBI. To evaluate the plausibility of this hypothesis, we first show that the optimal force transmitted to the head, in a reduced order model of the brain, is in fact a constant force profile. To simulate the effects of a constant force within a helmet, we conceptualize a fluid-based shock absorber system for use within a football helmet. We integrate this system within a computational helmet model and simulate its performance on the standard NFL helmet test impact conditions. The simulated helmet is compared with other helmet designs with different technologies. Computer simulations of head impacts with liquid shock absorption predict that, at the highest impact speed (9.3 m/s), the average brain tissue strain is reduced by 27.6% ± 9.3 compared to existing helmet padding when tested on the NFL helmet protocol. This simulation-based study puts forth a target benchmark for the future design of physical manifestations of this technology.

The Mangled Extremity Severity Score Fails to be a Good Predictor for Secondary Limb Amputation After Trauma with Vascular Injury in Central Europe.

BACKGROUND: The Mangled Extremity Severity Score (MESS) was constructed as an objective quantification criterion for limb trauma. A MESS of or greater than 7 was proposed as a cut-off point for primary limb amputation. Opinions concerning the predictive value of the MESS vary broadly in the literature. The aim of this study was to evaluate the applicability of the MESS in a contemporary civilian Central European cohort. METHODS: All patients treated for extremity injuries with arterial reconstruction at two centres between January 2005 and December 2014 were assessed. The MESS and the amputation rate were determined. RESULTS: Seventy-one patients met the inclusion criteria and could be evaluated for trauma mechanism and injury patterns. The mean MESS was 4.97 (CI 4.4-5.6). Seventy-three per cent of all patients (52/71) had a MESS < 7 and 27% (19/71) of ≥7. Eight patients (11%) underwent secondary amputation. Patients with a MESS ≥ 7 showed a higher, but statistically not significant secondary amputation rate (21.1%; 4/19) than those with a MESS < 7 (7.7%; 4/52; p = 0.20). The area under the ROC curve was 0.57 (95% CI 0.41; 0.73). CONCLUSIONS: Based on these results, the MESS appears to be an inappropriate predictor for amputation in civilian settings in Central Europe possibly due to therapeutic advances in the treatment of orthopaedic, vascular, neurologic and soft-tissue traumas.

CYP2C9-mediated warfarin and milk thistle interaction.

WHAT IS KNOWN AND OBJECTIVE: In vitro studies suggest a CYP2C9-mediated interaction between milk thistle and warfarin, but there has been no in vivo case report on this interaction. CASE DESCRIPTION: A White Hispanic man in his 30s was well controlled on warfarin therapy for mitral valve replacement. His INR increased from 2.64 to 4.12, and he denied changes to his medications and diet but noted starting a 'liver cleanse' supplement which contained milk thistle (200 mg). After stopping the supplement his INR normalized, and he remains on the same warfarin dose. WHAT IS NEW AND CONCLUSION: This is the first in vivo report of an interaction between milk thistle and warfarin.

[Quantitative Intraoperative Measurement of Tissue Perfusion of Transplanted Kidneys by Indocyanine Green Angiography]. / Quantitative intraoperative Messung der Gewebeperfusion von Nierentransplantaten mittels Indocyaningrün-Angiografie.

Postoperative delayed graft function (DGF) after kidney transplantation is a risk factor for kidney failure and reduced kidney allograft survival after transplantation. The aim of this study was to measure the quantitative perfusion of kidney transplants during kidney transplantation and to investigate whether differences in perfusion predict the development of DGF. Over a period of one year, intraoperative quantitative ICG perfusion measurements were performed with the IC-View camera (Pulsion®) in 36 patients for whom informed consent for ICG perfusion measurement had been obtained. The groups were divided into donation after brain death and living donors and into the occurrence or absence of a DGF. An area with sufficient and low ICG perfusion was determined intraoperatively. The maximum perfusion was significantly decreased in the DGF group compared to living donors in areas with sufficient ICG perfusion and the slope of perfusion in these areas was documented. In addition, the maximum perfusion ratio was investigated. Evaluation was carried out by IC-Calc software (Pulsion). A total of 36 patients were included in this study. DGF occurred in 10 of the patients. No DGF was found in the group of living donors. The maximum perfusion and the slope of perfusion in the defined areas were fewer, but not significant in the group with BDB donor. The less perfused areas showed significant differences between DGF and living donors in maximum perfusion, absolute slope of perfusion and ratio to the standard area. A difference between BDB donor without DGF and the DGF group could not be predicted. This study shows that quantitative perfusion of kidney transplants can be evaluated safely during kidney transplantation. DGF being defined as one or more dialyses after kidney transplantation can only be detected postoperatively, however, it may be predicted intraoperatively.

Plasmon-induced optical control over dithionite-mediated chemical redox reactions.

External-stimuli controlled reversible formation of radical species is of great interest for synthetic and supramolecular chemistry, molecular machinery, as well as emerging technologies ranging from (photo)catalysis and photovoltaics to nanomedicine. Here we show a novel hybrid colloidal system for light-driven reversible reduction of chemical species that, on their own, do not respond to light. This is achieved by the unique combination of photo-sensitive plasmonic aggregates and temperature-responsive inorganic species generating radicals that can be finally accepted and stabilised by non-photo-responsive organic molecules. In this system Au nanoparticles (NPs) self-assembled via sub-nm precise molecular spacers (cucurbit[n]urils) interact strongly with visible light to locally accelerate the decomposition of dithionite species (S2O42-) close to the NP interfaces. This light-driven process leads to the generation of inorganic radicals whose electrons can then be reversibly picked up by small organic acceptors, such as the methyl viologen molecules (MV2+) used here. During light-triggered plasmon- and heat-assisted generation of radicals, the S2O42- species work as a chemical 'fuel' linking photo-induced processes at the NP interfaces with redox chemistry in the surrounding water environment. By incorporating MV2+ as a Raman-active reporter molecule, the resulting optically-controlled redox processes can be followed in real-time.

Confocal laser microscopy as novel approach for real-time and in-vivo tissue examination during minimal-invasive surgery in colon cancer.

BACKGROUND: Histological analysis of surgical specimen is the gold standard for cancer classification. In particular, frozen histological diagnosis of vague peritoneal spots or uncertain excision of tumors plays a crucial role in the decision to proceed with or abandon an operation. Confocal laser microscopy (CLM) enables in-vivo and real-time high-resolution tissue analysis. This method has already been used during endoscopic assessments analyzing transformation of esophageal or colon mucosa. We examined whether a CLM device enables to distinguish between non-malignant and malignant tissue in vivo and real time and enables to assign peritoneal carcinomatosis spots to their primary tumor. In addition, we investigated whether the newly developed CLM camera device causes any tissue damage. METHODS: CC531 colon carcinoma cells were implanted on the serosa side of the colon and intraperitoneally in Wag/Rija rats via laparotomy. After 7 days of tumor growth, confocal laser microscopy in vivo was performed by re-laparotomy. Images of non-malignant and malignant tissue were characterized in terms of specific signal pattern. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Potential tissue damage was examined by conventional histology. RESULTS: All animals survived the operative procedure and could be evaluated 7 days following surgery. No unexpected death occurred after surgery. Non-malignant colon is defined by small cycles of the microvilli of the colon. There is repetitive deregulated structure in colon carcinoma. Peritoneal carcinomatosis showed the same structural pattern as in primary colon carcinoma. In all examined cases, it was possible to differentiate between peritoneal carcinomatosis spots and non-malignant peritoneum. The CLM device did not cause any tissue damage. CONCLUSIONS: The CLM camera device reported here is feasible to identify peritoneal carcinomatosis spots, assign these spots to the primary tumor, as well as distinguish between non-malignant and malignant tissue in without using any fluorescent dye.

[Laparoscopic Treatment of Splenic Artery Aneurysm]. / Laparoskopisches Ausschalten eines Aneurysmas der A. lienalis.

OBJECTIVE: Visceral artery aneurysms are a rare but dangerous vascular pathology. The branches of the coeliac trunc are most frequently affected, especially the splenic artery. A visceral aneurysm is usually diagnosed only when a bleeding complication occurs due to rupture. It is therefore recommended to treat this pathology at an early stage after diagnosis. Endovascular elimination is the preferred procedure. However, if endovascular elimination is not suitable, the visceral aneurysm can be successfully treated by minimally invasive surgery. INDICATIONS: Splenic artery aneurysms are located at the splenic hilum, and are therefore considered to be at high risk of splenic ischemia and secondary complications following endovascular coiling. PROCEDURE: Laparoscopic treatment of splenic artery aneurysm. CONCLUSION: In the case of complex vascular pathologies unsuitable for an endovascular approach, laparoscopic treatment of splenic artery aneurysm is a safe and effective minimally invasive option and alternative.

Analysis of laparoscopic laser liver resection in standardized porcine model.

BACKGROUND: Hepatocellular carcinoma is a highly prevalent and lethal primary neoplasia of the liver and metastases of other malignancies affect most frequently the liver. Minimally invasive surgical approach for liver resections is advancing. Dissection of liver parenchyma by laparoscopic technique remains challenging and new technologies are in need. Therefore, we asked whether it is feasible to dissect liver tissue comparably in terms of speed and hemostasis with a non-contact 1.9-µm cw-laser device and whether there are differences in the postoperative healing process compared to a gold standard device (ultrasound aspirator) in an experimental model. METHODS: Laparoscopic laser and ultrasound aspirator standardized partial liver resections were performed in seven pigs. Resection time, hemostasis time, and blood loss were evaluated. After at least 10 days, representative specimen of the resection areas was collected via re-laparoscopy and biopsy and side effects like hematoma, abscess, or bilioma were noted. Histologically, coagulation necrosis margin, granulation tissue zone, tissue fibrosis, and giant cell count were analyzed. RESULTS: Laparoscopic laser liver resection was three times faster compared to the laparoscopic ultrasound aspirator. Blood loss was equal in both groups. No side effects like hematoma or bilioma occurred. Histologically, specimen showed the same expansion of coagulation necrosis zone and granulation tissue. Fibrotic scar could be determined in three cases in both groups, respectively. However, giant cell count was significant higher in the laser resection group. CONCLUSIONS: The 1.9-µm cw-laser device enables a safe and fast liver resection in an experimental pig model compared to a gold standard (ultrasound aspirator) laparoscopic liver resection method. Wound healing is not interfered by laser liver resection.

Chinese non-psychiatric hospital doctors' attitudes toward management of psychological/psychiatric problems.

BACKGROUND: Psychiatric comorbidities are common among patients treated for physical disorders. Attitudes of non-psychiatric doctors toward psychological/psychiatric problems have significant implications for care provision in the general hospital setting. Our objective was to investigate non-psychiatric doctors' attitudes in China. METHOD: An anonymous online questionnaire pertaining to relevant attitudes was distributed to Chinese hospital-based non-psychiatric doctors using a mobile App. RESULTS: A total of 306 non-psychiatric doctors in China voluntarily completed the questionnaire. All but two (99.3%) respondents agreed with the importance of psychological factors underlying physical illness and 85.6% agreed they had a high degree of responsibility for management of patients' emotional problems. Most respondents endorsed routine assessment of patients' psychological factors and were willing to consider psychiatric referrals for patients in need; despite 52.0% believing that mental health care by general hospital doctors was impractical. Almost all respondents welcomed more contact with psychiatric services and indicated a need for more time and professional help to manage psychological issues. Respondents' demographic characteristics and vocational status had some influence on attitudes; female doctors were more likely and surgeons less likely to consider psychological assessment and emotional care for patients with physical illness. More doctors working in hospitals with established consultation-liaison psychiatric services did not feel responsible for their patients' emotional care (17.7% vs. 6.6%, P = 0.012). CONCLUSIONS: Our pilot survey demonstrates a potential generally positive attitude toward management of patients' psychological problems and an urgent need for more time and specialist support for non-psychiatric doctors in China.

Middle age has a significant impact on gene expression during skin wound healing in male mice.

The vast majority of research on the impact of age on skin wound healing (WH) compares old animals to young ones. The middle age is often ignored in biogerontological research despite the fact that many functions that decline in an age-dependent manner have starting points in mid-life. With this in mind, we examined gene expression patterns during skin WH in late middle-aged versus young adult male mice, using the head and back punch models. The rationale behind this study was that the impact of age would first be detectable at the transcriptional level. We pinpointed several pathways which were over-activated in the middle-aged mice, both in the intact skin and during WH. Among them were various metabolic, immune-inflammatory and growth-promoting pathways. These transcriptional changes were much more pronounced in the head than in the back. In summary, the middle age has a significant impact on gene expression in intact and healing skin. It seems that the head punch model is more sensitive to the effect of age than the back model, and we suggest that it should be more widely applied in aging research on wound healing.

The Angelina effect revisited: Exploring a media-related impact on public awareness.

BACKGROUND: In 2013, Angelina Jolie's double mastectomy and publication of her personal treatment choice for BRCA1 positivity generated considerable media attention. To the authors' knowledge, the current study is the first prospective survey conducted among the general public to measure a quantifiable media-related effect on public awareness. METHODS: The authors analyzed the changes in the general public's awareness of reconstructive options in breast cancer among 2 female population-matched cohorts aged 18 to 65 years (1000 participants in each cohort) before (March 2013; poll 1) and after (June 2013; poll 2) the announcement of Ms. Jolie's mastectomy in May 2013. RESULTS: There was an observed increase in public awareness: significantly more women from poll 2 were aware of reconstructive breast surgery being possible after breast cancer-related mastectomy, notably with regard to autologous tissue and single-stage reconstructions. Approximately 20% of the women in poll 2 (205 women) indicated that media coverage regarding Ms. Jolie affected their interest in breast cancer. A question that was exclusive to poll 2 revealed a preference for autologous (66.2%) versus implant-based (8.2%) reconstructions, with the remainder indicating no preference (25.6%). None of the stratification variables were found to be associated with the above findings. CONCLUSIONS: To the best of the authors' knowledge, this is the first prospective study to demonstrate a statistically significant impact of a celebrity announcement on public awareness regarding breast cancer treatment. The results underscore the importance of a media-related impact for professionals in the health care sector, which can serve as a tipping point for raising awareness and improving knowledge concerning a specific disease among the general public.