The Relationship between Insomnia and the Pathophysiology of Major Depressive Disorder: An Evaluation of a Broad Selection of Serum and Urine Biomarkers.

Insomnia exhibits a clinically relevant relationship with major depressive disorder (MDD). Increasing evidence suggests that insomnia is associated with neurobiological alterations that resemble the pathophysiology of MDD. However, research in a clinical population is limited. The present study, therefore, aimed to investigate the relationship between insomnia and the main pathophysiological mechanisms of MDD in a clinical sample of individuals with MDD. Data were extracted from three cohorts (N = 227) and included an evaluation of depression severity (Quick Inventory of Depressive Symptomatology, QIDS-SR16) and insomnia severity (QIDS-SR16 insomnia items) as well as serum and urine assessments of 24 immunologic (e.g., tumour necrosis factor α receptor 2 and calprotectin), neurotrophic (e.g., brain-derived neurotrophic factor and epidermal growth factor), neuroendocrine (e.g., cortisol and aldosterone), neuropeptide (i.e., substance P), and metabolic (e.g., leptin and acetyl-L-carnitine) biomarkers. Linear regression analyses evaluating the association between insomnia severity and biomarker levels were conducted with and without controlling for depression severity (M = 17.32), antidepressant use (18.9%), gender (59.0% female; 40.5% male), age (M = 42.04), and the cohort of origin. The results demonstrated no significant associations between insomnia severity and biomarker levels. In conclusion, for the included biomarkers, current findings reveal no contribution of insomnia to the clinical pathophysiology of MDD.

The chimeric medial sural artery perforator flap as the ideal for partial tongue reconstruction: A case series and technical refinements.

BACKGROUND: The medial sural artery perforator free flap (MSAP) has gained increasing popularity in head and neck reconstruction. Its slightly bulkier nature than the radial forearm flap, combined with negligible donor site morbidity, makes it an ideal candidate for the reconstruction of partial glossectomy defects. The ability to harvest the MSAP as a chimeric flap with a portion of the medial gastrocnemius muscle gives it greater flexibility in soft tissue reconstruction. METHODS: A retrospective study of patients with partial glossectomy defects reconstructed using the MSAP by a single surgeon was performed. Perioperative data, donor and recipient site characteristics, complications, and outcomes were analyzed. A video is included to show technical points for the harvest of the flap. RESULTS: A total of 10 patients were included. The average age was 59.1 years, with a mean of 43.5% of the tongue resected. All flaps survived, with no major complications. At follow-up, the patients had regained an average of 86.5% of original speech, with none requiring NG feeding. The average MSAP skin flap thickness was 7.8 mm, with 6 flaps being harvested as chimeric fasciocutaneous muscle flaps. Five flaps incorporated 2 perforators. Two case examples are presented. CONCLUSION: The chimeric MSAP perforator allows for more robust partial glossectomy reconstruction with improved postoperative functional outcomes. It should be considered as the workhorse flap for partial tongue reconstruction.

A Head-to-Head Comparison of the Medial Sural Artery Perforator versus Radial Forearm Flap for Tongue Reconstruction.

BACKGROUND: For tongue reconstruction, the radial forearm flap (RFF) is commonly used. In the last decade, the medial sural artery perforator (MSAP) flap has been successfully used with reportedly superior donor-site outcomes. Our study is the first to compare the RFF and MSAP for reconstruction of partial glossectomy defects (<50% of tongue). METHODS: We conducted a retrospective review of 20 patients with partial glossectomy defects reconstructed at a tertiary referral center. Patient demographics, perioperative data, and postoperative complications were analyzed. Objective measures of speech, swallowing, and subjective patient satisfaction with their donor site were recorded. RESULTS: Ten RFF and MSAP were each used, with a mean partial glossectomy defect size of 40.5 and 43.5%, respectively. The MSAP was significantly thicker (7.8 vs. 4.3 mm, p < 0.05) with a longer harvest time (122.5 vs. 75.0 minutes, p < 0.05). There were no cases of free flap failure. Donor-site healing times were comparable, but the MSAP group experienced significantly less donor-site complications (n = 1 vs. n = 7, p < 0.05). Functional outcomes were comparable with 13 patients achieving normal speech and diet after 3 months (MSAP = 6 vs. RFF = 7, p = 1.00). All patients were satisfied with their donor-site outcome with the MSAP group having a marginally higher score. CONCLUSION: Both flaps are good options for partial glossectomy reconstruction. Though more challenging to harvest, the MSAP gives comparable functional results and has become our first reconstructive option given its superior donor-site outcomes.

Associations of Affect, Action Readiness, and Sexual Functioning.

INTRODUCTION: Emotions are theorized to contain the components of affect and action readiness. Affect guides behavior by causing an approach or withdrawal orientation. Action readiness is the individual's degree of willingness to interact with the environment. Emotions contribute to changes in behavior and physiological responses. AIM: The present study applied these notions to sexuality and examined the associations between affect, action readiness, and sexual functioning. METHODS: Participants were male patients with urologic condition (N = 70) with and without sexual problems. MAIN OUTCOME MEASURE: Affect and action readiness were jointly assessed using the latent factor of affective polarity of the Positive and Negative Affect Schedule. Trait affective polarity was assessed questioning generally experienced feelings. State affective polarity was assessed after exposure to an erotic stimulus and questioning momentaneously experienced feelings. Sexual functioning was assessed using the International Index of Erectile Functioning questionnaire. RESULTS: A significant increase of approach-oriented action readiness was found after erotic stimulation, relative to trait levels. In addition, significant associations were found between state approach-oriented action readiness and various aspects of sexual functioning. Interventions based on principles of positive psychology might be developed to reinforce action readiness in men with erectile dysfunction. The strength of the current research concerns the introduction of action readiness as a potential psychological factor implied in sexual functioning. Limitations pertain to the use of the algorithm used to calculate state approach-oriented action readiness and the use of the current sample of patients with urological conditions, limiting generalizability of findings. CONCLUSION: Action readiness was found to correlate positively with all aspects of sexual functioning. Further research into the role of action readiness in sexuality is recommended. Henckens MJMJ, de Vries P, Janssen E, et al. Associations of Affect, Action Readiness, and Sexual Functioning. Sex Med 2020;8:691-698.

Gender Differences in Developing Biomarker-Based Major Depressive Disorder Diagnostics.

The identification of biomarkers associated with major depressive disorder (MDD) holds great promise to develop an objective laboratory test. However, current biomarkers lack discriminative power due to the complex biological background, and not much is known about the influence of potential modifiers such as gender. We first performed a cross-sectional study on the discriminative power of biomarkers for MDD by investigating gender differences in biomarker levels. Out of 28 biomarkers, 21 biomarkers were significantly different between genders. Second, a novel statistical approach was applied to investigate the effect of gender on MDD disease classification using a panel of biomarkers. Eleven biomarkers were identified in men and eight in women, three of which were active in both genders. Gender stratification caused a (non-significant) increase of Area Under Curve (AUC) for men (AUC = 0.806) and women (AUC = 0.807) compared to non-stratification (AUC = 0.739). In conclusion, we have shown that there are differences in biomarker levels between men and women which may impact accurate disease classification of MDD when gender is not taken into account.

Methylation of geometrically constrained lysine analogues by histone lysine methyltransferases.

We report synthesis and enzymatic assays on human histone lysine methyltransferase catalysed methylation of histones that possess lysine and its geometrically constrained analogues containing rigid (E)-alkene (KE), (Z)-alkene (KZ) and alkyne (Kyne) moieties. Methyltransferases G9a and GLP do have a capacity to catalyse methylation in the order K ≫ KE > KZ ∼ Kyne, whereas monomethyltransferase SETD8 catalyses only methylation of K and KE.

Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers.

Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the "bio depression score"). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P < .001), in serum (P = .02) and in the combined serum plus urine result (P < .001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.

Perioperative Vasopressor Use in Free Flap Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of vasopressors in free flap surgery has traditionally been avoided due to the presumed risk of pedicle vasospasm leading to flap failure. However, there is a lack of strong clinical evidence to suggest that their administration during microvascular surgery is absolutely contraindicated. The aim of this study is to clarify the impact of perioperative vasopressor use on free flap outcomes. METHODS: A systematic review was performed of all English-language articles that have compared free flap outcomes between patients who received vasopressors and those who did not. The outcome measures were total flap failure, pedicle thrombosis, and overall flap complications. Meta-analysis was performed using Mantel-Haenszel fixed-effects and DerSimonian and Laird random-effects models. RESULTS: From a total of 130 citations, 14 studies representing 8,653 cases were analyzed. Majority of these did not find any negative effects of vasopressor use irrespective of dose, timing of administration, and method of delivery. Meta-analysis demonstrated that vasopressors were associated with less total flap failure overall (odds ratio, [OR]: 0.71, p = 0.05) and less pedicle thrombosis in head and neck reconstruction specifically (OR: 0.58, p = 0.02). Flap complication rates were similar across all defect types (OR: 0.97, p = 0.81) but appeared to be increased in breast reconstruction (OR: 1.46, p = 0.01). CONCLUSION: Perioperative vasopressor administration does not appear to be as detrimental to free flap survival as has been previously feared. Their role in optimizing hemodynamic stability may have a more beneficial effect on overall flap perfusion and in minimizing the complications of iatrogenic fluid overload.

Assessing adequacy of informed consent for elective surgery by student-administered interview.

BACKGROUND: Studies show that patients often sign consent documents without fully comprehending the risks, benefits and potential complications. There is currently no Asian study performed analysing adequacy of informed consent. This study aims to assess adequacy of informed consent by evaluating patient understanding and retention of key information and complications pertaining to surgery via medical student-administered interview. METHODS: A prospective study was performed on 48 patients undergoing groin hernia surgery, laparoscopic cholecystectomy and total thyroidectomy from 2017 to 2018 in a teaching hospital. Standardized assessment forms including major common complications and key details of the surgery were prepared. Structured one-to-one interviews between students and patients were performed and recorded on the morning of surgery. RESULTS: Although 93.8% of the patients claimed to have understood the information regarding their surgery, only 19.4%, 44.4% and 62.5% of the patients could actually recall the serious complications of groin hernia surgery, laparoscopic cholecystectomy and thyroidectomy, respectively. Elderly patients (>65 years) had poorer understanding of surgical procedure compared to the young (80% versus 100%, respectively, P = 0.008) with 26.7% of elderly patients claiming that they did not understand the indication for surgery. High satisfaction rates with this preoperative interview were reported by both patients and students (95.8% and 97.9%, respectively). Time interval from informed consent to surgery did not make any difference. CONCLUSION: Understanding of information and key complications was generally low, especially in the elderly population. The structured preoperative interview achieved the dual goal of reinforcing patient gaps in knowledge and improving student communication skills.

Automatic Sex-Liking and Sex-Failure Associations in Men With Sexual Dysfunction.

Current models of sexual functioning imply an important role for both automatic and controlled appraisals. Accordingly, it can be hypothesized that erectile dysfunction may be due to the automatic activation of negative appraisals at the prospect of sexual intercourse. However, previous research showed that men with sexual dysfunction exhibited relatively strong automatic sex-positive instead of sex-negative associations. This study tested the robustness of this unexpected finding and, additionally, examined the hypothesis that perhaps more specific sex-failure versus sex-success associations are relevant in explaining sexual dysfunction and distress. Male urological patients (N = 70), varying in level of sexual functioning and distress, performed two Single-Target Implicit Association Tests (ST-IATs) to assess automatic associations of visual erotic stimuli with attributes representing affective valence ("liking"; positive versus negative) and sexual success versus sexual failure. Consistent with the earlier findings, the lower the scores on sexual functioning, the stronger the automatic sex-positive associations. This association was independent of explicit associations and most prominent in the younger age group. Automatic sex-positive and sex-failure associations showed independent relationships with sexual distress. The relationship between sexual distress and sex-failure associations is consistent with the view that automatic associations with failure may contribute to sexual distress.

Colour pattern homology and evolution in Vanessa butterflies (Nymphalidae: Nymphalini): eyespot characters.

Ocelli are serially repeated colour patterns on the wings of many butterflies. Eyespots are elaborate ocelli that function in predator avoidance and deterrence as well as in mate choice. A phylogenetic approach was used to study ocelli and eyespot evolution in Vanessa butterflies, a genus exhibiting diverse phenotypes among these serial homologs. Forty-four morphological characters based on eyespot number, arrangement, shape and the number of elements in each eyespot were defined and scored. Ocelli from eight wing cells on the dorsal and ventral surfaces of the forewing and hindwing were evaluated. The evolution of these characters was traced over a phylogeny of Vanessa based on 7750 DNA base pairs from 10 genes. Our reconstruction predicts that the ancestral Vanessa had 5 serially arranged ocelli on all four wing surfaces. The ancestral state on the dorsal forewing and ventral hindwing was ocelli arranged in two heterogeneous groups. On the dorsal hindwing, the ancestral state was either homogenous or ocelli arranged in two heterogeneous groups. On the ventral forewing, we determined that the ancestral state was organized into three heterogeneous groups. In Vanessa, almost all ocelli are individuated and capable of independent evolution relative to other colour patterns except for the ocelli in cells -1 and 0 on the dorsal and ventral forewings, which appear to be constrained to evolve in parallel. The genus Vanessa is a good model system for the study of serial homology and the interaction of selective forces with developmental architecture to produce diversity in butterfly colour patterns.

The development and evolution of crossveins in insect wings.

The formation of crossveins in Drosophila was an important early case study in understanding the role of the environment in the development and evolution of morphological structures. More recent work has shown that signalling processes play a crucial role in the formation of crossveins in Drosophila and that the interaction of a heat shock factor, Hsp90, with components of signal transduction pathways may account for the sensitivity of these structures to environmental perturbations. A new model for the development of crossveins is presented that divides the formation of crossveins into 3 separate stages. First, the number and placement of the crossveins is determined by signalling along the proximal-distal axis of the wing. This signal may involve the cdc42 gene product and the Jun-N-terminal Kinase signal transduction pathway. Then, during the second stage, an inductive signal from the dorsal wing epithelium is sent to the ventral wing epithelium at locations specified by the first signal. The second signal appears to involve the BMP-like signalling pathway. Finally, in the third stage, a domain of vein competent cells is defined by the signalling from the EGF-receptor-Map Kinase signal transduction pathway, and the exact location of the veins is eventually determined within that domain by Notch-Delta signalling interactions. By altering components of these 3 stages, insects can independently regulate the presence or absence, the number and placement, and the thickness and flexibility of the crossveins. This capacity for the modulation of crossvein structure in many different ways may have contributed to the evolution of different modes of insect flight.