Expression of matrix metalloproteinases and their inhibitors in corneal stromal fibroblasts and keratocytes from healthy and keratoconus corneas.

PURPOSE: To examine the in-vitro expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in corneal stromal cells by distinguishing between fibroblasts and keratocytes of healthy and keratoconus (KC) corneas. METHODS: Stromal cells were isolated from healthy and KC corneas (n = 8). A normal-glucose, serum-containing cell culture medium (NGSC-medium) was used for cultivation of healthy human corneal fibroblasts (HCFs) and KC human corneal fibroblasts (KC-HCFs). In order to obtain a keratocyte phenotype, the initial cultivation with NGSC-medium was changed to a low-glucose, serum-free cell culture medium for healthy (Keratocytes) and KC cells (KC-Keratocytes). Gene and protein expression of MMP-1, -2, -3, -7, -9 and TIMP-1, -2, -3 were measured by quantitative PCR and Enzyme-Linked Immunosorbent Assay (ELISA) from the cell culture supernatant. RESULTS: KC-HCFs demonstrated a lower mRNA gene expression for MMP-2 compared to HCFs. In contrast to their respective fibroblast groups (either HCFs or KC-HCFs), Keratocytes showed a higher mRNA gene expression of TIMP-3, whereas TIMP-1 mRNA gene expression was lower in Keratocytes and KC-Keratocytes. Protein analysis of the cell culture supernatant revealed lower concentrations of MMP-1 in KC-HCFs compared to HCFs. Compared to Keratocytes, TIMP-1 concentrations was lower in the cell culture supernatant of KC-Keratocytes. In HCFs and KC-HCFs, protein levels of MMP-1 and TIMP-1 were higher and MMP-2 was lower compared to Keratocytes and KC-Keratocytes, respectively. CONCLUSION: This study indicates an imbalance in MMP and TIMP expression between healthy and diseased cells. Furthermore, differences in the expression of MMPs and TIMPs exist between corneal fibroblasts and keratocytes, which could influence the specific proteolytic metabolism in-vivo and contribute to the progression of KC.

Dynamic optical coherence tomography for imaging acute wound healing.

The aim of this study was to investigate acute wound healing with dynamic optical coherence tomography (D-OCT). From 22 patients with 23 split skin graft donor sites, vessels at four wound edges, the wound bed, and adjacent and unaffected skin of the contralateral leg were measured by D-OCT at six time points from surgery to 4 weeks of healing. Changes in vessel orientation, density, diameter, morphology and pattern in horizontal, vertical and 3D images were analysed for wound healing and re-epithelialization. At 300 µm depth, there were significant differences of blobs and serpiginous vessels between normal and wounded skin. The wound had significantly more vertically oriented vessels, a higher degree of branching, vessel density and diameter compared with healthy skin. 3D images showed increased angiogenesis from healthy skin towards the wound centre, significantly higher vessel density at the wound than at normal skin and the highest at the interface. During wound healing blobs, coils and serpiginous vessels occurred significantly more frequently in lesional than healthy skin. Vessel density was greatest at the beginning, decreased and then increased by 4 weeks post-surgery. D-OCT helps to evaluate acute wound healing by visualizing and quantifying blood vessel growth in addition to re-epithelialization.

Depressive symptoms among individuals identifying as asexual: a cross-sectional study.

Although asexuality became a growing research subject over the last decade, data on the mental health of individuals identifying as asexual is still rare. The key objective of the present study was to examine depressive symptoms among individuals identifying as asexual. Data of LGBTQIA+ (Lesbian, Gay, Bi-sexual, Trans*, Queer, Inter*, Asexual and/or + indicating others within the community) and cisgender heterosexual individuals was collected through an online survey during the COVID-19 lockdowns in Germany. The survey included questions about sexual and gender identity, depressive symptoms, and asexual identity. An analysis of N = 6601 participants was conducted. A total of n = 445 individuals identified as asexual. Regression results indicated identifying as asexual being significantly associated with higher depressive symptoms. Results suggest that individuals identifying as asexual represent a vulnerable group within the group of sexual minorities, one that fundamentally requires special psychosocial support, especially in times of pandemics.

Dynamic optical coherence tomography of chronic venous ulcers.

BACKGROUND: Chronic ulcers, especially venous leg ulcers, are a major burden on the healthcare system. To date there are only few non-invasive established procedures for evaluation of blood perfusion in wounds. Dynamic optical coherence tomography (D-OCT) provides images of the skin's superficial vascularisation. OBJECTIVES: This study aims to investigate if and how the D-OCT measurement of chronic wounds can provide new information about the vascularisation during the healing process. METHODS: We examined 16 venous ulcers over 16 weeks and evaluated the vessel morphology and density using D-OCT at the wound bed, borders, two centimetres adjacent to the wound und at non-ulcerated skin on the contralateral leg. RESULTS: In D-OCT scans clumps were unique and the most common vessel type in the wound area of venous ulcers, whereas lines and serpiginous vessels were the most common in non-ulcerated skin. At the wound border mottle and cluster patterns occurred more frequently. Healthy skin showed a significant increase of mesh pattern. Vessel density significantly increased at the wound area compared to non-ulcerated skin. During the healing process the wound border showed the most vascular changes while only an increase in curves was observed in the wound centre. Non-healing wounds had fewer dots and blobs at the borders, fewer dots, coils, clumps, lines and serpiginous vessels at the centre and fewer dots in adjacent skin. Temperature analysis showed higher temperatures in non-ulcerated skin, followed by the wound margin and centre. Non-healing wounds showed the lowest temperatures in the wound centre. CONCLUSIONS: These results highlight the non-invasive use of D-OCT for the examination and monitoring of wound healing in chronic venous ulcers. D-OCT imaging of blood vessels may offer the potential to detect disorders of wound healing at an early stage, differentiate ulcers of different genesis and to tailor more individualized, patient-oriented therapy.

Surgical management of complicated Descemet's membrane detachment in corneas without prior endothelial keratoplasty.

PURPOSE: To provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention. METHODS: Retrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD. RESULTS: Fourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months - 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet's membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes. CONCLUSION: PKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly.

[Modern corneal diagnostics as the key for the correct classification of the disease and optimal treatment decisions]. / Moderne Hornhautdiagnostik als Schlüssel für die korrekte Einordnung der Erkrankung und optimale Therapieentscheidung.

Corneal diseases include a wide spectrum of different manifestations (inflammatory/noninflammatory) that need to be accurately classified for precise diagnosis and targeted treatment. In addition to the anamnesis and slit lamp biomicroscopy, further device-based examinations can be performed to narrow down the diagnosis. Nowadays, modern corneal imaging provides a variety of technologies, such as topography, tomography, in vivo confocal microscopy and analysis of biomechanics, which are able to reliably classify different pathologies. Knowledge of the available examination modalities helps to guide differential diagnostic considerations, facilitating the indication for stage-appropriate microsurgical intervention.

[Changes in the provision of primary care and psychotherapy in Germany during the first two lockdowns in 2020 and 2021: A two-wave survey giving consideration to gender identity and sexual orientation]. / Veränderung hausärztlicher und psychotherapeutischer Versorgung in Deutschland während der ersten beiden COVID-19-Lockdowns 2020 und 2021: Zwei Befragungswellen unter Berücksichtigung von Geschlechtsidentität und sexueller Orientierung.

INTRODUCTION: Measures against the COVID-19 pandemic led to restrictions in ambulatory health care in Germany. While the restrictions have been described from claims data, the patients' perspective has been missing. Lesbian, gay, bisexual, trans-, inter- and asexual persons (LGBTIA) might have been particularly affected by these restrictions because of their vulnerability. Thus, our research questions were: 1) How did the restrictions during the pandemic influence primary care and psychotherapy in Germany from the patients' perspective? 2) Are there differences between LGBTIA and cis-heterosexual persons regarding these restrictions? METHODS: We conducted an online survey with two survey waves in March/April 2020 and January/February 2021. Sampling was conducted via multiplicators and via snowball sampling. Amongst others, the survey contained open-ended questions regarding primary care and psychotherapy. From the answers of the first survey wave we constructed quantitative items for the second survey wave. Descriptive and inferential statistical analysis was conducted, including linear regression with R. RESULTS: 6,784 participants took part in the survey (2,641 in the first survey wave), 5,442 of whom identified as LGBTIA. Categories of changes in primary care were: no health care utilization, no changes in primary care, insecurity regarding primary care, and changes in primary care which could be less frequent utilization, differing procedures or changes in ways of communication. In the second wave, LGBTIA participants rated the worsening of primary care during the pandemic as being more pronounced. Regarding psychotherapy, the change can be described as no change in care, changes in the form of therapy, treatment in emergencies only and a longer break from psychotherapy. There was no different rating by LGBTIA persons compared to cis-heterosexual persons in the second survey wave. Telephone and video consultations were more common in psychotherapy than in primary care. DISCUSSION: LGBTIA persons were oversampled, so the sample included more people from urban areas than the German population. Due to the online survey form, older people were underrepresented relative to their numbers in the general German population. CONCLUSION: With respect to future pandemics general practitioners in primary care must be prepared that psychotherapy might be paused and delayed for some time. Video and telephone consultations should be offered to overcome pandemic-related restrictions in the future. General practitioners should know the gender identity and sexual orientation of their patients in order to proactively address health care barriers.

Loneliness and depressive symptoms differ by sexual orientation and gender identity during physical distancing measures in response to COVID-19 pandemic in Germany.

During the COVID-19 pandemic, physical distancing measures to prevent transmission of the virus have been implemented. The effect of physical distancing measures on loneliness especially for vulnerable groups remained unclear. Thus, we aimed to investigate loneliness in relation with depressive symptoms among lesbian, gay, bisexual, trans, inter, asexual, and queer (LGBT) persons compared with cis-heterosexual persons during the pandemic. We conducted an online survey during the first two waves of the COVID-19 pandemic in Germany. The survey contained self-categorizations regarding sexual orientation and gender identity, questions on loneliness, social contacts, depressive symptoms, and healthcare. Descriptive and regression analysis and propensity score matching across cohorts was conducted using R; 2641 participants took part in first wave of the survey and 4143 participants in the second wave. The proportion of lonely people was higher in the second wave compared with the first wave. LGBT persons were more lonely than cis-heterosexual persons. In both waves, being LGBT was associated with depressive symptoms, but loneliness mediated the effect, even when adjusting for social contacts. Psychologists and other practitioners should be aware that LGBT clients might have an increased risk for loneliness and depressive symptoms and of the potential burden of the pandemic measures.

Electrocardiographic Changes During Initiation of Lithium Augmentation of Antidepressant Pharmacotherapy.

PURPOSE/BACKGROUND: Lithium augmentation of antidepressants represents a common strategy to overcome treatment resistance in patients with major depressive disorder. The use of lithium has been associated with cardiovascular adverse effects such as QTc prolongation and tachyarrhythmia. Although the previous studies investigated monotherapy with lithium, the aim of this study was to investigate electrocardiographic changes in LA. METHODS/PROCEDURES: A 12-lead surface electrocardiogram (ECG) was obtained from 38 patients with major depressive disorder before and during LA. Changes in heart rate, PQ, QRS and QTc interval, QT dispersion, ST segment, and T- and U-wave alterations were analyzed using a linear mixed model. FINDINGS/RESULTS: The ECG readings of 33 patients were evaluated. Lithium augmentation was not significantly associated with changes in heart rate, QTc, PQ, or QRS interval. We found a significant decrease in QT dispersion. These results were independent of sex, age, stable comedication, and comorbidities. During LA, we observed 9 cases of T-wave alterations and 2 cases of new U waves. CONCLUSIONS: Our data provide no evidence for serious ECG abnormalities at therapeutic serum lithium levels in patients treated with LA. In particular, we did not find evidence for QTc time lengthening or tachyarrhythmia, such as torsades des pointes. The recommended intervals for ECG checks should be considered to detect long-term effects of LA.

Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression.

INTRODUCTION: Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. METHOD: Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. RESULTS: We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. CONCLUSIONS: Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

Well-being during COVID-19 pandemic: A comparison of individuals with minoritized sexual and gender identities and cis-heterosexual individuals.

BACKGROUND: Preliminary empirical data indicates a substantial impact of the COVID-19 pandemic on well-being and mental health. Individuals with minoritized sexual and gender identities are at a higher risk of experiencing such negative changes in their well-being. The objective of this study was to compare levels of well-being among cis-heterosexual individuals and individuals with minoritized sexual and gender identities during the COVID-19 pandemic. METHODS: Using data obtained in a cross-sectional online survey between April 20 to July 20, 2020 (N = 2332), we compared levels of well-being (WHO-5) across subgroups (cis-individuals with minoritized sexual identities, individuals with minoritized gender identities and cis-heterosexual individuals) applying univariate (two-sample t-test) and multivariate analysis (multivariate linear regression). RESULTS: Results indicate overall lower levels of well-being as well as lower levels of well-being in minoritized sexual or gender identities compared to cis-heterosexual individuals. Further, multivariate analyses revealed that living in urban communities as well as being in a relationship were positively associated with higher levels of well-being. Furthermore, a moderation analysis showed that being in a relationship reduces the difference between groups in terms of well-being. CONCLUSION: Access to mental healthcare for individuals with minoritized sexual and gender identities as well as access to gender-affirming resources should be strengthened during COVID-19 pandemic. Healthcare services with low barriers of access such as telehealth and online peer support groups should be made available, especially for vulnerable groups.

Defining pathways to healthy sustainable urban development.

Goals and pathways to achieve sustainable urban development have multiple interlinkages with human health and wellbeing. However, these interlinkages have not been examined in depth in recent discussions on urban sustainability and global urban science. This paper fills that gap by elaborating in detail the multiple links between urban sustainability and human health and by mapping research gaps at the interface of health and urban sustainability sciences. As researchers from a broad range of disciplines, we aimed to: 1) define the process of urbanization, highlighting distinctions from related concepts to support improved conceptual rigour in health research; 2) review the evidence linking health with urbanization, urbanicity, and cities and identify cross-cutting issues; and 3) highlight new research approaches needed to study complex urban systems and their links with health. This novel, comprehensive knowledge synthesis addresses issue of interest across multiple disciplines. Our review of concepts of urban development should be of particular value to researchers and practitioners in the health sciences, while our review of the links between urban environments and health should be of particular interest to those outside of public health. We identify specific actions to promote health through sustainable urban development that leaves no one behind, including: integrated planning; evidence-informed policy-making; and monitoring the implementation of policies. We also highlight the critical role of effective governance and equity-driven planning in progress towards sustainable, healthy, and just urban development.

Chronotype is associated with psychological well-being depending on the composition of the study sample.

Past studies examining the effect of chronotype and social jetlag on psychological well-being have been inconsistent so far. Here, we recruited participants from the general population and enquired about their natural sleeping behavior, sleep quality, depressive symptoms, and perceived stress. Partial correlations were computed between sleep variables and indicators of psychological well-being, controlling for age and sex. Less sleep during work days was found a good indicator for impairments in psychological well-being. In exploratory follow-up analyses, the same correlations were calculated within groups of early, intermediate, and late chronotype. We observed that the composition of the sample in terms of chronotype influenced whether associations between sleep variables and psychological well-being could be observed, a finding that is advised to be taken into account in future studies.

Treatment response of lithium augmentation in geriatric compared to non-geriatric patients with treatment-resistant depression.

BACKGROUND: Lithium augmentation (LA) of antidepressants is an effective strategy for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients. The purpose of this study was to investigate treatment response of LA in geriatric compared to non-geriatric patients. METHOD: In a prospective multicenter cohort study, severity of depression was measured weekly in 167 patients with unipolar depression (nage≥65years = 22; nage<65years = 145) at baseline and over at least four weeks of LA. RESULTS: Geriatric patients showed a significantly better response to LA compared to non-geriatric patients (Hazard Ratio = 1.91; p = 0.04). LIMITATIONS: An important limitation of our study is the lack of a control group of LA and the missing evaluation of side effects in both groups. CONCLUSIONS: This is the first study investigating the efficacy of LA for TRD in geriatric compared to non-geriatric patients. Our data suggest that LA is an effective treatment option in geriatric patients that clinicians might consider more frequently and earlier on in the course of treatment.

How Effective Is Algorithm-Guided Treatment for Depressed Inpatients? Results from the Randomized Controlled Multicenter German Algorithm Project 3 Trial.

Background: Treatment algorithms are considered as key to improve outcomes by enhancing the quality of care. This is the first randomized controlled study to evaluate the clinical effect of algorithm-guided treatment in inpatients with major depressive disorder. Methods: Inpatients, aged 18 to 70 years with major depressive disorder from 10 German psychiatric departments were randomized to 5 different treatment arms (from 2000 to 2005), 3 of which were standardized stepwise drug treatment algorithms (ALGO). The fourth arm proposed medications and provided less specific recommendations based on a computerized documentation and expert system (CDES), the fifth arm received treatment as usual (TAU). ALGO included 3 different second-step strategies: lithium augmentation (ALGO LA), antidepressant dose-escalation (ALGO DE), and switch to a different antidepressant (ALGO SW). Time to remission (21-item Hamilton Depression Rating Scale ≤9) was the primary outcome. Results: Time to remission was significantly shorter for ALGO DE (n=91) compared with both TAU (n=84) (HR=1.67; P=.014) and CDES (n=79) (HR=1.59; P=.031) and ALGO SW (n=89) compared with both TAU (HR=1.64; P=.018) and CDES (HR=1.56; P=.038). For both ALGO LA (n=86) and ALGO DE, fewer antidepressant medications were needed to achieve remission than for CDES or TAU (P<.001). Remission rates at discharge differed across groups; ALGO DE had the highest (89.2%) and TAU the lowest rates (66.2%). Conclusions: A highly structured algorithm-guided treatment is associated with shorter times and fewer medication changes to achieve remission with depressed inpatients than treatment as usual or computerized medication choice guidance.