A systematic review and evaluation of post-stroke depression clinical practice guidelines.

OBJECTIVE: Post-stroke depression is a depressive mood disorder that follows a cerebrovascular accident and is a burden on stroke patients. Its management is included in clinical practice guidelines focused on stroke, and the recommended treatment is selective serotonin reuptake inhibitors in conjunction with psychotherapy. Clinical practice guidelines are recommendations used to standardize best medical practice, but there is no current evaluation of guidelines containing post stroke depression recommendations. Thus, the objective is to appraise the selected guidelines manner of development and quality. MATERIALS AND METHODS: A systematic literature review across three databases and a manual google search was performed to collect guidelines that included recommendations on the management of post-stroke depression. 1236 guidelines were screened, and 27 were considered for inclusion. Considered guidelines were manually reviewed by the authors, and ultimately, 7 met inclusion criteria. The appraisal of guidelines for research and evaluation was used to evaluate these guidelines' recommendations around post-stroke depression. RESULTS: Three guidelines met the threshold considered "High", with all of them having five or more quality domains eclipse the cutoff score of 70%. Across all guidelines, the highest scoring domains were "Scope and Purpose", "Clarity of Presentation", and "Editorial Independence" with scores of 76.98%, 73.81%, and 91.36% respectively. The lowest scoring domains were "Applicability", "Rigor of Development", and "Stakeholder Involvement" with respective scores of 58.73%, 54.02%, and 43.90%. CONCLUSIONS: The domains "Applicability", "Rigor of Development," and "Stakeholder Involvement" were the lowest scoring domains. These specific domains represent areas in which future guidelines could be more developed.

Different behaviors of cyclic dipeptide prenyltransferases toward the tripeptide derivative ardeemin fumiquinazoline and its enantiomer.

In nature, cyclic dipeptide prenyltransferases catalyze regioselective Friedel-Crafts alkylations of tryptophan-containing cyclic dipeptides. This enzyme class, belonging to the dimethylallyl tryptophan synthase superfamily, is known to be flexible toward aromatic prenyl acceptors, while mostly retaining its typical regioselectivity. Ardeemin fumiquinazoline (FQ) (1), a tryptophan-containing cyclic tripeptide derivative, is assembled in Aspergillus fischeri by the non-ribosomal peptide synthetase ArdA and modified by the prenyltransferase ArdB, leading to the pharmaceutically active hexacyclic ardeemin. Therefore, 1 and its enantiomer ent-ardeemin FQ (2) constitute potential substrates for aromatic prenyltransferases. In this study, we investigated the acceptance of both enantiomers by two cyclic dipeptide C2-prenyltransferases BrePT and FtmPT1 and three C3-prenyltransferases CdpNPT, CdpC3PT, and AnaPT. LC-MS analysis of the incubation mixtures and NMR analysis of the isolated products revealed that the stereochemistry at C11 and C14 in 1 and 2 has a strong influence on their acceptance by these enzymes and the regioselectivity of the prenylation reactions. 1 was very well accepted by BrePT, FtmPT1, and CdpNPT, with C2- or C3-prenylated derivatives as predominant products, which fills the prenylation gaps by tryptophan prenyltransferases reported in a previous study. 2 was a poor substrate for all the enzymes and converted with low regioselectivity and mainly prenylated at C6 and C7 of the indole moiety.

Theoretical Basis for Virtual Skull Orientation According to Three-Dimensional Frankfort Horizontal Plane for Computer-Aided Surgical Simulation.

PURPOSE: Computer-aided surgical simulation (CASS) is an evolving technology which has significantly affected surgical correction of dentofacial deformities, a key step of which is orientation of the virtual skull model to allow for analysis and treatment planning. Explored in this study is the coplanarity of a 3-dimensional Frankfort horizontal plane (3D FHP). MATERIALS AND METHODS: The 122 17.0 cm field-of-view cone-beam computed-tomogram (CBCT) scans were oriented to a 3D FHP using right porion, right orbitale, and left orbitale. The distance between the 3D FHP and left porion was then measured. The 18 CBCT scans were found to have external fiducial markers which were used for orientation into natural head position (NHP). The distance between left porion and a true horizontal plan coincidental with the right porion was measured. Concordance reliability measures were calculated to compare NHP to 3D FHP. RESULTS: The average distance of left porion to 3D FHP was found to be -0.107 mm (SD = 1.148), and the average distance from the coincidental left porion in NHP was found to be 0.846 mm (SD = 2.611). Concordance reliability calculations shows little consistency between the 2 methods of orientation (P = 0.838). CONCLUSIONS: The data shows coincidence between left porion and 3D FHP. Orientation of the virtual skull model according to 3D FHP offers a quick and easy method for this important step in CASS. Further study is needed for evaluation of this method in vivo.

Structure-based protein engineering enables prenyl donor switching of a fungal aromatic prenyltransferase.

Microorganisms provide valuable enzyme machinery to assemble complex molecules. Fungal prenyltransferases (PTs) typically catalyse highly regiospecific prenylation reactions that are of significant pharmaceutical interest. While the majority of PTs accepts dimethylallyl diphosphate (DMAPP), very few such enzymes can use geranyl diphosphate (GPP) or farnesyl diphosphate (FPP) as donors. This catalytic gap prohibits the wide application of PTs for structural diversification. Structure-guided molecular modelling and site-directed mutagenesis of FgaPT2 from Aspergillus fumigatus led to the identification of the gatekeeping residue Met328 responsible for the prenyl selectivity and sets the basis for creation of GPP- and FPP-accepting enzymes. Site-saturation mutagenesis of the gatekeeping residue at position 328 in FgaPT2 revealed that the size of this side chain is the determining factor for prenyl selectivity, while its hydrophobicity is crucial for allowing DMAPP and GPP to bind.

Switching a regular tryptophan C4-prenyltransferase to a reverse tryptophan-containing cyclic dipeptide C3-prenyltransferase by sequential site-directed mutagenesis.

FgaPT2 from Aspergillus fumigatus catalyzes a regular C4- and its mutant K174A a reverse C3-prenylation of l-tryptophan in the presence of dimethylallyl diphosphate. FgaPT2 also uses tryptophan-containing cyclic dipeptides for C4-prenylation, while FgaPT2_K174A showed almost no activity toward these substrates. In contrast, Arg244 mutants of FgaPT2 accept very well cyclic dipeptides for regular C4-prenylation. In this study, we demonstrate that FgaPT2_K174F, which catalyzes a regular C3-prenylation on tyrosine, can also use cyclo-l-Trp-l-Ala, cyclo-l-Trp-l-Trp, cyclo-l-Trp-Gly, cyclo-l-Trp-l-Phe, cyclo-l-Trp-l-Pro, and cyclo-l-Trp-l-Tyr as substrates, but only with low activity. Combinational mutation on Lys174 and Arg244 increases significantly the acceptance of these cyclic dipeptides. With the exception of cyclo-l-Trp-l-Trp, the tested dipeptides were much better accepted by FgaPT2_K174F_R244X (X = L, N, Q, Y) than FgaPT2, with an increase of two- to six-fold activity. In comparison to FgaPT2_K174F, even two- to ten-fold conversion yields were calculated for the double mutants. Isolation and structural elucidation of the enzyme products revealed stereospecific reverse C3-prenylation on the indole ring, resulting in the formation of syn-cis configured hexahydropyrroloindole derivatives. The results presented in this study highlight the convenience of site-directed mutagenesis for creating new biocatalysts.

Bifid Mandibular Canal: A Case Review and Retrospective Review of CBCTs.

PURPOSE: This case presentation and retrospective review of cone-beam computed tomograms is to evaluate prevalence, classification, and demographics of bifid mandibular canals (BMC) to inform practitioners on this variation and avoid untoward complications due to failure to diagnose. MATERIALS AND METHODS: Two thousand one hundred thirty scans were evaluated by 2 oral and maxillofacial radiologists. BMCs were noted and classified according to Naitoh. Demographic data were also collected and analyzed. RESULTS: Twenty-eight patients were noted to have bifid mandibular canal, with an average age of 39 years (± 19.5), with no strong sex predilection. Patients (1.31%) were noted to have bifid canals. A greater percentage of patients were shown to have bilateral bifid canals (42.9%) versus either unilateral side (25% left, 32.1% right), but is statistically insignificant. Prevalence was greatest in types 1 and 3 (35.9% and 51.3%, respectively, P = 0.000011). Types 2 and 4 were much less common. CONCLUSION: BMCs are an important anatomic variation that has implications on any mandibular surgery, including implant surgery. Just more than 1% of patients have this variation, but failure to recognize this in a patient can result in poor outcome, as illustrated in the case presented.

Daily positive affect and nocturnal cardiac activation.

BACKGROUND: Positive affect (PA) has been suggested to benefit health via psychobiological pathways. Studies found higher cardiac vagal tone in individuals who exhibit a positive emotional style. PURPOSE: This study aimed to examine the relationship between momentary-assessed PA and nocturnal heart rate (HR) and heart rate variability (HRV) in everyday life. METHODS: Participants were 60 healthy adults who provided multiple ratings of activated (e.g., dynamic, activated) and deactivated PA (e.g., relaxed, even-tempered) and negative affect (NA) throughout one day. HR and HRV were recorded the subsequent night. RESULTS: Aggregated deactivated PA throughout the day was associated with higher nocturnal HRV and lower HR. Activated PA and NA were unrelated with both cardiac variables. Findings were independent of other demographic and behavioral confounds. CONCLUSIONS: Feeling relaxed, calm, content, and even-tempered throughout the day might have beneficial effects on the heart during sleep, although the causality of this effect remains speculative because of the correlational design of this study.

Immune-Mediated Small Fiber Neuropathy With Trisulfated Heparin Disaccharide, Fibroblast Growth Factor Receptor 3, or Plexin D1 Antibodies: Presentation and Treatment With Intravenous Immunoglobulin.

OBJECTIVES: Up to 50% of small fiber neuropathy (SFN) cases are idiopathic, but novel antibodies to Trisulfated Heparin Disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) have been implicated in half of these cases; the role of anti-Plexin D1 is less clear. We aimed to clarify presentation and management of these patients. METHODS: An 18-month retrospective analysis revealed 54 cases of cryptogenic SFN who had testing for the 3 autoantibodies. Demographics, clinical features, epidermal nerve fiber density, and Quantitative Sudomotor Axon Reflex Test results were analyzed. Intravenous immunoglobulin (IVIG) treatment response was assessed. RESULTS: In total, 44.4% of patients had antibodies (62.5% TS-HDS, 29.2% FGFR-3, and 20.8% Plexin D1). Male patients were more likely to be FGFR-3 positive (P = 0.014). Facial involvement was more common in seropositive patients (P = 0.034), and patients with a higher Utah Early Neuropathy Scale score had a higher TS-HDS titer (P = 0.0469), but other clinical features were not significantly different. Seropositive patients trended toward a higher SFN screening list score (P = 0.16), abnormal Quantitative Sudomotor Axon Reflex Test (P = 0.052), and prior erroneous diagnosis (P = 0.19). In patients who completed IVIG, examinations and questionnaires improved and mean epidermal nerve fiber density increased by 297%. CONCLUSIONS: TS-HDS, FGFR-3, and Plexin D1 antibodies are present in a high proportion of cryptogenic SFN cases with more facial involvement, and greater disease severity is associated with higher antibody titers. They are often misdiagnosed but may respond subjectively and objectively to IVIG.

Social interaction moderates the relationship between depressive mood and heart rate variability: evidence from an ambulatory monitoring study.

OBJECTIVE: There is considerable evidence that depressive mood is related to lower parasympathetic control of the heart, thus increasing cardiovascular risk. However, little is known about social factors (e.g., social affiliation) that might moderate this relationship. DESIGN: The authors examined whether cardiac autonomic control in healthy individuals with depressive symptoms could be altered by social interaction. Therefore, the authors conducted a 22-hr ambulatory monitoring study with a sample of 63 adults. MAIN OUTCOME MEASURES: Depression was assessed by questionnaire. Heart rate, heart rate variability (HRV), physical activity, and negative affect were recorded throughout one day via portable monitoring devices. RESULTS AND CONCLUSION: Multilevel analyses revealed that depression was related to elevated negative affect and higher heart rate throughout the day. Moreover, there was a tendency toward lower HRV in individuals with higher depression scores. This association, however, was moderated by social context. When depressive participants were alone they evidenced lower HRV and higher negative affect, but not when they were engaged in social interactions with a partner, family members, or friends. These findings suggest that the relation between depression and cardiac autonomic control could be altered by social interaction, thus possibly buffering adverse health effects.

Complete Decoration of the Indolyl Residue in cyclo-l-Trp-l-Trp with Geranyl Moieties by Using Engineered Dimethylallyl Transferases.

Mutation of the gatekeeping residues for prenyl donor selectivity in six dimethylallyl transferases significantly increased their activities toward geranyl diphosphate. Forty-two geranylated derivatives were obtained from 15 cyclic dipeptides by using the engineered enzymes. Taking cyclo-l-Trp-l-Trp as an example, the geranyl moiety can be attached to all seven possible positions of the indole nucleus. This study demonstrates a convenient way to increase the structural diversity of geranylated products by structure-based engineering of the available dimethylallyl transferases.

Psychosocial Care Needs of Melanoma Survivors: Are They Being Met?

Patients who have survived malignant melanoma for more than five years may lack the opportunity to talk about their burden. As a consequence their psychosocial care needs remain undetected and available supportive interventions may not be utilised. Therefore, the psychosocial burden of this patient group needs to be assessed using specific screening instruments. The aim of this study was to investigate the psychosocial burden of long-term melanoma survivors, their psychosocial care needs and the determinants of these needs. We wanted to find out if the use of professional support corresponds to the care needs defined by experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients diagnosed at least 5 years before the survey were contacted by physicians. N = 689 former patients completed the Hornheide Questionnaire (short form HQ-S) to identify psychosocial support need (scale cut off ≥ 16 or item-based cut-off score) and the potential psychosocial determinants of these needs. Additionally, they were asked about their utilisation of the professional support system. More than one third (36%) of them was in need for professional psychosocial support. The highest burden scores concerned worry about tumour progression. Younger age (< 50), higher general fatigue, higher symptom burden, lower general health, negative social interactions and unfulfilled information needs were significant predictors of the need for psychosocial intervention. Related to the percentage of survivors identified as 'in need', the professional support system was underused. Further studies should investigate whether using the HQ-S to routinely identify burdened melanoma patients could lead to better fulfilment of their intervention needs, ultimately enhancing health-related quality of life.

Depression, anxiety and quality of life in long-term survivors of malignant melanoma: a register-based cohort study.

AIM: The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma. METHODS: In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2%) completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7) and depression (PHQ-9) and the EORTC Quality of Life Questionnaire (EORTC QLQ 30). Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population. RESULTS: An average of 8.4 (5.7 to 12.2) years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients). Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women), but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases. CONCLUSION: Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.

Negative pressure wound therapy for the treatment of the open abdomen and incidence of enteral fistulas: a retrospective bicentre analysis.

Introduction. The open abdomen (OA) is often associated with complications. It has been hypothesized that negative pressure wound therapy (NPWT) in the treatment of OA may provoke enteral fistulas. Therefore, we analyzed patients with OA and NPWT with special regard to the occurrence of intestinal fistulas. Methods. The present study included all consecutive patients with OA treated with NWPT from April 2010 to August 2011 in two hospitals. Patients' demographics, indications for OA, risk factors, complications, outcome and incidence of fistulas before, during and after NPWT were recorded. Results. Of 81 patients with OA, 26 had pre-existing fistulas and 55 were free from a fistula at the beginning of NPWT. Nine of the 55 patients developed fistulas during (n = 5) or after NPWT (n = 4). Seventy-five patients received ABThera therapy, 6 patients other temporary abdominal closure devices. Only diverticulitis seemed to be a significant predisposing factor for fistulas. Mortality was slightly lower for patients without fistulas. Conclusion. The present study revealed no correlation between occurrence of fistulas before, during, and after NWPT, with diverticulitis being the only risk factor. Fistula formation during NPWT was comparable to reports from literature. Prospective studies are mandatory to clarify the impact of NPWT on fistula formation.