Multimodal mapping of human skin Heuke, S.; Vogler, N.; Meyer, T. ...
British journal of dermatology (1951),
October 2013, Letnik:
169, Številka:
4
Journal Article
Recenzirano
Summary
Background
The combination of coherent anti‐Stokes Raman scattering (CARS), second harmonic generation (SHG) and two‐photon excited fluorescence (TPEF) imaging – referred to as multimodal ...imaging – provides complementary contrast based on molecular vibrations, the structure of various tissue components and endogenous fluorophores, respectively.
Objectives
To present a comprehensive overview of the appearance of human skin in multimodal imaging.
Methods
Multimodal imaging of unstained skin cross‐sections of 32 individuals was performed using a laser scanning microscope and picosecond laser pulse for excitation.
Results
The epidermis, dermis and subcutis are distinguishable in all three applied modalities, but are unveiled best in multimodal images. While the subcutis is dominated by the CARS signal, predominately SHG and the secondary TPEF signal detect the dermis. In contrast, no SHG signal is detected in the epidermis, whereas CARS and TPEF show equal contributions. Additionally, the appearance of the major skin appendages is described, i.e. the hair follicle, sebaceous and sweat glands, and blood vessels belonging to the vascular system. All four investigated functional units show a characteristic morphochemistry in TPEF and CARS, allowing identification of further subunits, e.g. the major components of the hair follicle, while the SHG signal delineates the localization of the functional units.
Conclusions
Multimodal imaging is a powerful tool to investigate human skin by providing high contrast based on the molecular constitution. It is therefore suggested that multimodal imaging has a high potential in application to dermatological research and clinical diagnostics of various skin alterations.
What's already known about this topic?
Multimodal nonlinear optical techniques are known to be applicable for diagnostic purposes by providing morphochemical information about biomedical samples.
What does this study add?
This is the first comprehensive study to provide a map of well‐known normal structures in human skin in order to facilitate further in vivo and ex vivo experiments.
IntroductionAcute mental health presentations such as suicidality or psychosis are frequently accompanied by intoxication, substance use disorder, deliberate self-poisoning and social crises. There ...is a need to break down silos and provide integrated multi-disciplinary acute care for such individuals.ObjectivesHere we describe outcomes of the Psychiatry And Drug ANd Alcohol (PANDA) Unit, a unique physical space collocated with the emergency department (ED) along with a unique model of care, providing multidisciplinary care to individuals presenting with acute mental health concerns plus complex comorbidity.MethodsA description of the PANDA model of care and Service characteristics along with process and outcome measures across the first 12 months that the PANDA Unit was operational. These include number of patients admitted, patient demographics and characteristics, length of stay, referral destinations and impact on the occurrence of behavioural disturbance across the ED.ResultsPANDA opened in November 2020 and since then has admitted an average of 122 patients per month (15% Aboriginal) with an average bed occupancy of 79% and average length of stay of 1.3 days. An average of 12% of patients were scheduled under the mental health act and an average of two patients were stepped down from ICU each month, with the remainder being admitted via the ED. An average of 80.7% of these were discharged home directly while 7.2% were transferred for inpatient withdrawal management and 8.9% to inpatient mental health services. The top three substances of concern were alcohol methamphetamine and heroin and an average of 16.5% of people reported injecting drugs in the prior 3 months. An average of 37.8% patients had been seen by an emergency physician and admitted to the PANDA Unit within 4 hours, one of the best performing units hospital-wide. In the 6 months prior to PANDA becoming operational there was a median of 20 episodes of behavioural disturbance requiring restraint per month across the ED. This dropped to 12 episodes in the six months following the PANDA Unit opening.ConclusionsThe PANDA Unit model of care has proven feasible to implement and has made a positive impact on a previously underserved patient population. It has also contributed to improving the integration of care for mental health patients with comorbidity as well as reducing behavioural disturbance and improving patient flow across the emergency department.Disclosure of InterestNone Declared
Objective
Phenotypical comparisons between individuals with obesity without binge eating disorder (OB) and individuals with obesity and comorbid binge eating disorder (OB + BED) are subject to ...ongoing investigations. At the same time, gender‐related differences have rarely been explored, raising the question whether men and women with OB and OB + BED may require differently tailored treatments.
Method
We retrospectively compared pre‐ versus post‐treatment data in a matched sample of n = 180 men and n = 180 women with OB or OB + BED who received inpatient treatment.
Results
We found that men displayed higher weight loss than women independent of diagnostic group. In addition, men with OB + BED showed higher weight loss than men with OB after 7 weeks of treatment.
Conclusions
The present findings add to an emerging yet overall still sparse body of studies comparing phenotypical features and treatment outcomes in men and women with OB and OB + BED; implications for further research are discussed.
Clinical Trial Registration
The study was prospectively registered with the German Clinical Trial Register as part of application DRKS00028441.
Highlights
Pre‐ versus post‐treatment data were analysed regarding eating disorder‐specific and general psychopathology, and treatment outcomes (e.g., body mass index trajectories) in men versus women with obesity without binge eating disorder (OB) versus obesity and binge eating disorder (OB + BED).
Men displayed higher weight loss than women independent of diagnostic group. In addition, men with OB + BED showed higher weight loss than men with OB after 7 weeks of treatment.
This study contributes to the currently limited body of evidence on gender‐related aspects of obesity and eating disorders; gender‐related investigations are needed to amplify knowledge and help design and implement future individualised treatments.
Summary
The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and ...non‐immediate allergic reactions to penicillins and other beta‐lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web‐based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta‐lactams, molecular structure, formulations available in the UK and a description of known beta‐lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross‐reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta‐lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.
Calcium dysregulation ("Calcium Hypothesis") is an early and critical event in Alzheimer's and other neurodegenerative diseases. Calcium binds to and regulates the small regulatory protein calmodulin ...that in turn binds to and regulates several hundred calmodulin binding proteins. Initial and continued research has shown that many calmodulin binding proteins mediate multiple events during the onset and progression of Alzheimer's disease, thus establishing the "Calmodulin Hypothesis". To gain insight into the general applicability of this hypothesis, the involvement of calmodulin in neuroinflammation in Alzheimer's, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, frontotemporal dementia, and other dementias was explored. After a literature search for calmodulin binding, 11 different neuroinflammatory proteins (TREM2, CD33, PILRA, CR1, MS4A, CLU, ABCA7, EPHA1, ABCA1, CH3L1/YKL-40 and NLRP3) were scanned for calmodulin binding domains using the Calmodulin Target Database. This analysis revealed the presence of at least one binding domain within which visual scanning demonstrated the presence of valid binding motifs. Coupled with previous research that identified 13 other neuroinflammation linked proteins (BACE1, BIN1, CaMKII, PP2B, PMCA, NOS, NMDAR, AchR, Ado A2AR, Aβ, APOE, SNCA, TMEM175), this work shows that at least 24 critical proteins involved in neuroinflammation are putative or proven calmodulin binding proteins. Many of these proteins are linked to multiple neurodegenerative diseases indicating that calmodulin binding proteins lie at the heart of neuroinflammatory events associated with multiple neurodegenerative diseases. Since many calmodulin-based pharmaceuticals have been successfully used to treat Huntington's and other neurodegenerative diseases, these findings argue for their immediate therapeutic implementation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sawn-timber drying is the wood industry's most time- and energy-consuming process. This process can be more efficient than the conventional method by elevating the dry-bulb temperature to above 100 ...°C in a high-temperature drying (HTD) process, which for some species shortens the drying process by up to 50% without deteriorating the quality. Comprehending the complex correlation between the wood drying physics at high temperatures and the anatomical features of the specific species, along with its mechanical and physical properties, is crucial, as it limited its application from being broadly implemented in industry and the necessity of generalizing this method for wood species. The present study has been conducted to comprehensively review and tackle the challenges of applying this method on various species and the consequences, such as high moisture content gradients resulting in stress residual, unevenness, and color changes. Energy, environment, and economic (3E) assessments of HTD were evaluated. The accelerated drying process in HTD reduces heat losses and air leaks, resulting in higher energy efficiency than the conventional methods. Furthermore, it was proved to be 20% economically in the long term. Confliction in reported studies, such as HTD's effect on permeability and volatile organic compound (VOC) emissions, was raised, highlighting the importance of further studies for generalizing this method to adapt appropriate drying schedules, focusing on Scandinavian species by referring to previous industrial trials.
Major facilitator superfamily domain-containing protein 8 (MFSD8) is a transmembrane protein that has been reported to function as a lysosomal chloride channel. In humans, homozygous mutations in ...MFSD8 cause a late-infantile form of neuronal ceroid lipofuscinosis (NCL) called CLN7 disease. In the social amoeba Dictyostelium discoideum, Mfsd8 localizes to cytoplasmic puncta and vesicles, and regulates conserved processes during the organism’s life cycle. Here, we used D. discoideum to examine the effect of mfsd8-deficiency on the secretome during the early stages of multicellular development. Mass spectrometry revealed 61 proteins that were differentially released by cells after 4 and 8 h of starvation. Most proteins were present in increased amounts in mfsd8- conditioned buffer compared to WT indicating that loss of mfsd8 deregulates protein secretion and/or causes the release of proteins not normally secreted by WT cells. GO term enrichment analyses showed that many of the proteins aberrantly released by mfsd8- cells localize to compartments and regions of the cell associated with the endo-lysosomal and secretory pathways. Mass spectrometry also revealed proteins previously known to be impacted by the loss of mfsd8 (e.g., cathepsin D), as well as proteins that may underlie mfsd8-deficiency phenotypes during aggregation. Finally, we show that mfsd8-deficiency reduces intracellular proteasome 20S activity due to the abnormal release of at least one proteasomal subunit. Together, this study reveals the impact of mfsd8 loss on the secretome during D. discoideum aggregation and lays the foundation for follow up work that investigates the role of altered protein release in CLN7 disease.
•Aberrant protein release explains mfsd8-deficiency phenotypes in D. discoideum.•Loss of mfsd8 alters the release of cathepsins B, D, F, and Z.•Loss of mfsd8 alters the release of proteins that interact with Mfsd8 and Cln5.•Loss of mfsd8 or cln3 affects the release of common proteins.•Loss of mfsd8 reduces intracellular proteasome 20 S activity.
Mutations in
CLN5
cause a subtype of neuronal ceroid lipofuscinosis (NCL) called CLN5 disease. The NCLs, commonly referred to as Batten disease, are a family of neurodegenerative lysosomal storage ...diseases that affect all ages and ethnicities globally. Previous research showed that CLN5 participates in a variety of cellular processes. However, the precise function of CLN5 in the cell and the pathway(s) regulating its function are not well understood. In the model organism
Dictyostelium discoideum
, loss of the
CLN5
homolog,
cln5
, impacts various cellular and developmental processes including cell proliferation, cytokinesis, aggregation, cell adhesion, and terminal differentiation. In this study, we used comparative transcriptomics to identify differentially expressed genes underlying
cln5
-deficiency phenotypes during growth and the early stages of multicellular development. During growth, genes associated with protein ubiquitination/deubiquitination, cell cycle progression, and proteasomal degradation were affected, while genes linked to protein and carbohydrate catabolism were affected during early development. We followed up this analysis by showing that loss of
cln5
alters the intracellular and extracellular amounts of proliferation repressors during growth and increases the extracellular amount of conditioned medium factor, which regulates cAMP signalling during the early stages of development. Additionally,
cln5
-
cells displayed increased intracellular and extracellular amounts of discoidin, which is involved in cell-substrate adhesion and migration. Previous work in mammalian models reported altered lysosomal enzyme activity due to mutation or loss of
CLN5
. Here, we detected altered intracellular activities of various carbohydrate enzymes and cathepsins during
cln5
-
growth and starvation. Notably,
cln5
-
cells displayed reduced β-hexosaminidase activity, which aligns with previous work showing that
D. discoideum
Cln5 and human CLN5 can cleave the substrate acted upon by β-hexosaminidase. Finally, consistent with the differential expression of genes associated with proteasomal degradation in
cln5
-
cells, we also observed elevated amounts of a proteasome subunit and reduced proteasome 20S activity during
cln5
-
growth and starvation. Overall, this study reveals the impact of
cln5
-deficiency on gene expression in
D. discoideum
, provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease.
Peer-assisted learning (PAL) is a common teaching and learning method in medical education worldwide. In the setting of skills laboratories (skills labs), student tutors are often employed as an ...equivalent alternative to faculty teachers. However, to the best of our knowledge, there is a lack of qualitative studies which explore the reasons for the personal commitment of student tutors. The aim of our study was to examine how undergraduate students experienced and evaluated their roles as skills lab student tutors, what their motivation was, and whether social and cognitive congruence played a role in their teaching experiences.
We conducted in-depth, semi-structured interviews with student tutors who were currently teaching in a skills lab. After the interviews had been transcribed verbatim, two independent investigators performed a qualitative content analysis according to Mayring.
In total, we conducted nine interviews with student tutors. Our results revealed that all student tutors showed great enthusiasm and motivation for their jobs as peer teachers. One of the main motivating factors for student tutors to teach in a skills lab was the possibility to simultaneously share and improve their knowledge and expertise. In general, the participants of our study had high aspirations for their teaching. They found it particularly important to be empathetic with the student learners. At the same time, they thought they would personally benefit from their teaching activities and develop a certain expertise as student tutors.
With the present study we are able to gain some insight into what motivates student tutors to teach in a skills lab and what kind of experiences they have. Our results provide an important input for the future training of highly qualified student tutors.
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