Risk profiles of personality traits for suicidality among mood disorder patients and community controls.

OBJECTIVE: To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls. METHOD: We recruited 365 bipolar, 296 major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self-reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups. RESULTS: All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients. CONCLUSION: Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high-risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.

The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity.

OBJECTIVES: Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity. METHODS: We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways. RESULTS: A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation. CONCLUSION: Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.

Predictive role of imaging in sentinel lymph node dissection for melanoma.

A retrospective study of 67 patients with metastatic melanoma was performed to evaluate if imaging from lymphoscintigraphy could predict a higher miss rate if only the most radioactive node were removed. Following protocol for sentinel node biopsy, the surgeon resected all lymph nodes containing radioactivity > 10% of the most radioactive node. A correlation was performed between the radioactive counts of the lymph nodes and the presence of metastases. The percentage of cases in which the most radioactive node was negative for metastasis on pathology was calculated. Two nuclear medicine physicians read the images from lymphoscintigraphy specifically to determine if the first lymph node visualized became less intense than other nodes on later images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. In 13 of 67 (19%) patients, the most radioactive lymph node was negative for metastasis while a less radioactive node contained metastatic disease. Consensus reading by the nuclear medicine physicians determined that in 9 cases, the first lymph node visualized became less intense than another lymph node on later images. Of the 9 cases, 4 were true positive and 5 were false positive when correlated with intraoperative count rate and pathology. Of the cases where the most radioactive node was not positive on histopathology (n = 13), the consensus reading by the nuclear medicine physicians reported 4 of them (31%). Imaging by lymphoscintigram had a sensitivity 31%, specificity 91%, positive predictive value 44%, and negative predictive value 85% for predicting whether the most radioactive lymph node at surgery would be negative for metastasis at pathology. We conclude that in patients with melanoma, lymphoscintigraphy has high specificity and negative predictive value but modest sensitivity and positive predictive value for detecting when the sentinel node will not be the most radioactive lymph node during sentinel lymph node dissection. These findings support that dynamic imaging by lymphoscintigraphy has a role in surgical planning but that the imaging protocol could benefit from further optimization.

Cleaning the brain through turbulent glymphatic flow: The washing machine hypothesis.

In a thought experiment, a "washing machine" model is proposed based on turbulent flow from complex multi-dimensional forces to characterize fluid dynamics in the brain. The glymphatic system's hypothetical role in this system is illustrated in a series of diagrams. Implications of this model are discussed in terms of normal physiology and a variety of pathologic conditions such as brain atrophy and Alzheimer disease.

Imaging of lymphatic dysplasia in Noonan syndrome: Case studies and historical atlas.

To determine the historical use and utility of various lymphatic imaging modalities in Noonan syndrome (NS) patients, we performed a comprehensive literature review by collecting the published medical imaging of NS lymphatic dysplasias. We correlated imaging findings with clinical phenotypes and treatment. Our analysis of lymphatic imaging modalities provides an algorithmic approach to imaging and patient care across the spectrum of NS developmental defects. A total of 54 NS cases have been published since 1975. Using the observations reported in 15 reviewed publications, an association was made between disruptions in central lymphatic flow and poor clinical presentations/outcomes in NS patients.

Effect of temperature on race times on a synthetic surface.

REASONS FOR PERFORMING STUDY: Differences in racing times have been noted on synthetic track surfaces that appear to depend on the temperature of the track. No published study to date has considered this effect in a systematic manner. OBJECTIVES: To investigate the relationship between temperature of track and speed of horses racing on a synthetic surface. Potential changes in the wax component of the synthetic track were investigated as one possible cause of changes in the track speed at the temperatures observed. METHODS: At Del Mar racetrack (California, USA), the air, surface and subsurface temperatures at 4 depths in the synthetic race surface were measured periodically throughout the day over a 42 day period. The 6 furlong (1.2 km) race (afternoon) and fast training 'work' (morning) times were also compiled. Samples of the track were obtained and the wax separated using a solvent separation technique. Differential scanning calorimetry was used to determine the range of temperatures at which the wax from the track underwent softening and other material changes. Transformation temperatures were compared to temperatures acquired from the track to evaluate the likelihood of changes in the wax properties during racing. RESULTS: Average air, surface and subsurface temperatures changed significantly throughout the day. Temperatures were higher during the afternoon race sessions and race times were significantly slower compared to morning work times. Temperatures at which some of the components of the wax began to soften were found to be within the range of temperature measured during track operation. CONCLUSIONS: A correlation was found between temperature of the synthetic track and speed of horse. Wax separated from the track showed that the temperatures experienced in the surface during normal operation exceed the temperatures at which the wax begins to experience thermal transformation. It is therefore hypothesised that the wax may be a cause of the observed changes in the track performance. POTENTIAL RELEVANCE: Future work should include a study of components of the synthetic track responsible for the change and epidemiological association of risk of injury.

Plasma calcitonin gene-related peptide in diagnosing and predicting paediatric migraine.

To investigate the role of plasma calcitonin gene-related peptide (CGRP) in paediatric migraine, we prospectively collected 134 blood samples during or between attacks from 66 migraine, 33 non-migraine headache (non-migraine) and 22 non-headache patients, aged 4-18 years. Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment (PedMIDAS) questionnaire. Migraineurs had higher plasma CGRP levels than non-migraine patients (P = 0.007). The attack level was higher than the non-attack level in migraine (P = 0.036), but not in non-migraine, patients. This was also revealed in paired comparison (n = 9, P = 0.015 vs. n = 4, P = 0.47). Using a threshold of 55.1 pg/ml, the sensitivity of the attack level in predicting migraine was 0.81, and specificity 0.75. The PedMIDAS score tended to be higher in the high CGRP (> 200 pg/ml, n = 7) group than in the low (< 200 pg/ml, n = 33) group (26.07 vs. 19.32, P = 0.16) using Mann-Whitney test. Plasma CGRP is useful for diagnosis in paediatric migraine.

Whole-body lymphangioscintigraphy and SPECT/CT in children with lymphatic complications after surgery for complex congenital heart disease.

The number of patients surviving repair of complex congenital heart disease (CCHD) has increased due to improved surgical techniques, post operative management and outpatient care. Likewise, this growing patient population has demonstrated an increasing number and complexity of complications involving the lymphatic system. To evaluate the peripheral and central lymphatic system, whole-body lymphangioscintigraphy (LAS) is considered as the initial imaging evaluation of choice. To date, very few publications exist on the value of lymphatic imaging techniques in infants and small children with lymphatic complications following surgery for congenital heart disease. A retrospective review of medical records from 2008 to 2018 was performed for pediatric patients referred for lymphatic complications after CCHD surgery at an academic medical center. LAS and SPECT/CT was performed using intradermal bipedal injections of Tc 99m labeled filtered sulfur colloid, and in some patients also bilateral hand injections, followed by dynamic imaging and whole- body planar imaging typically up to 180 minutes post injection. Clinical decision making and outcomes were recorded. LAS and SPECT/CT were performed without complication in pediatric patients with prior surgery for CCHD. LAS successfully localized various lymphatic abnormalities such as lymphatic obstruction, reflux, and leaks, which were further delineated by SPECT/CT. LAS findings directed further evaluation with more definitive studies, management and prognosis. Five of the ten patients had follow up outcome data - 2 years and up to 10 years. LAS and SPECT/CT are safe and effective techniques for the initial evaluation of lymphatic abnormalities in pediatric patients with CCHD. LAS, particularly with further 3D localization by SPECT/CT, provides functional imaging of peripheral and central lymphatic flow and thus provides guidance for medical therapy, non operative interventional management, and surgical therapy for these diverse, debilitating, and often life threatening disorders.

Neonatal Lymphedema from Thoracic Duct Obstruction Complicating Percutaneous Intravenous Central Catheterization.

Percutaneous intravenous central catheter (PICC) complications are not common and generalized edema and anasarca in neonates as a complication of PICC malposition is even rarer. Documentation of the pathomechanisms of lymphedema in cases of severe anasarca in neonates is not often done. Here we document thoracic duct obstruction as the cause of lymphedema in a neonate with severe nonpitting generalized edema. Most PICC procedures should ideally be guided by point-of-care bedside ultrasound (US), and this precaution may prevent malposition of PICC lines although it will not detect subsequent migration or extravasation.

Molecular mechanisms of rotational catalysis in the F(0)F(1) ATP synthase.

Rotation of the F(0)F(1) ATP synthase gamma subunit drives each of the three catalytic sites through their reaction pathways. The enzyme completes three cycles and synthesizes or hydrolyzes three ATP for each 360 degrees rotation of the gamma subunit. Mutagenesis studies have yielded considerable information on the roles of interactions between the rotor gamma subunit and the catalytic beta subunits. Amino acid substitutions, such as replacement of the conserved gammaMet-23 by Lys, cause altered interactions between gamma and beta subunits that have dramatic effects on the transition state of the steady state ATP synthesis and hydrolysis reactions. The mutations also perturb transmission of specific conformational information between subunits which is important for efficient conversion of energy between rotation and catalysis, and render the coupling between catalysis and transport inefficient. Amino acid replacements in the transport domain also affect the steady state catalytic transition state indicating that rotation is involved in coupling to transport.

Stability and functionality of cysteine-less F(0)F1 ATP synthase from Escherichia coli.

All 21 native cysteines in the Escherichia coli F(0)F1 ATP synthase were replaced by alanines. In isolated E. coli membranes, ATP-dependent proton pumping, turnover of ATP hydrolysis and steady-state transition state thermodynamic parameters of the cysteine-less enzyme were similar to wild-type. The cysteine-less enzyme was solubilized in n-octyl beta-D-glucopyranoside, purified by affinity chromatography, and reconstituted into pre-formed liposomes made from E. coli lipids. The properties of the reconstituted, purified enzyme were not significantly different from the membranous enzyme. These data demonstrate that cysteine-less F(0)F1 is biochemically stable and has functionality similar to wild-type.

Catamenial hemoptysis from tracheobronchial endometriosis: reappraisal of diagnostic value of bronchoscopy and bronchial brush cytology.

OBJECTIVES: To analyze the clinical data of four patients with a diagnosis of tracheobronchial endometriosis, and to reappraise the diagnostic value of bronchoscopy and bronchial brush cytology in these patients. METHODS: We conducted a retrospective study of four patients with documented tracheobronchial endometriosis treated at National Taiwan University Hospital from 1994 to 1998. The complete histories, diagnostic time interval, results of physical examinations, laboratory data, bronchoscopic findings, cytologic results, chest radiographs, and chest CT of these patients were analyzed. RESULTS: These patients tend to be younger and nonmultiparous as compared to other patients with thoracic endometriosis. Bronchoscopic examination performed within 1 day or 2 days of menses disclosed multiple purplish-red submucosal patches bilaterally that bled easily when touched. Cytologic evaluation of the brushing specimens demonstrated clusters of small cuboid cells consistent with an endometrial origin. Follow-up bronchoscopic examination in the middle of the menstrual cycle showed disappearance of the previous tracheobronchial lesions. The mean diagnostic interval was 3.25 months. All four patients were successfully treated with danazol therapy. CONCLUSIONS: Tracheobronchial endometriosis consists of a special subgroup of patients with thoracic endometriosis. Proper timing of bronchoscopic examination plays an important diagnostic role in these patients. Cytologic features as well as cyclic changes in bronchoscopic findings are sufficient to warrant the diagnosis. The results of treatment with danazol in these patients seemed favorable.

Severe immune hemolytic anemia in disseminated tuberculosis with response to antituberculosis therapy.

Severe hemolytic anemia in patients with disseminated tuberculosis is exceedingly rare. We report an episode of Coombs'-positive hemolytic anemia in a previously healthy young man with miliary tuberculosis, resulting in a hemoglobin level of 5 g/dL and an undetectable haptoglobin level. The patient responded well to treatment with antituberculosis drugs, and the results of the direct Coombs' test became negative without the need of blood transfusion or steroid therapy.

Serial analysis of fat-containing macrophages in bronchoalveolar lavage fluid in a patient with fat embolism syndrome.

Recent studies suggest that an increase in fat-containing macrophages in bronchoalveolar lavage (BAL) fluid may be helpful in the diagnosis of fat embolism syndrome (FES). Nevertheless, none of these studies have explored the sequential findings of BAL fluid. We report the case of a 19-year-old man admitted to our intensive care unit because of dyspnea with radiographic evidence of bilateral alveolar infiltrate after traumatic fracture. Analysis of BAL fluid on the third hospital day revealed 8.3% fat-containing macrophages and a lipid-laden macrophages (LLM) index of 23. Pathologic examination of lung biopsy showed numerous fat globules within arterioles. For comparison, the BAL fluid from four other patients with acute respiratory distress syndrome (ARDS) but without FES was also analyzed. The underlying diseases leading to ARDS included Wegener's granulomatosis in one case, pneumonia in two cases, and alveolar proteinosis in one case. The percentages of fat-containing macrophages in these specimens were 1.3%, 52%, 2.3%, and 74%, respectively. The LLM indexes were 1, 133, 3, and 243, respectively. As the patient's condition improved, the percentage of fat-containing macrophages in the BAL fluid decreased to 4.7% on the eighth hospital day and the LLM index also decreased to 6. These findings suggest that the presence of fat-containing macrophages in BAL fluid is not specific for the diagnosis of FES, but serial changes in the percentage of these cells and the LLM index may be helpful in the follow-up of disease severity.

Anaphylaxis after propofol infusion for Port-A-Cath insertion in a 35-year old man.

Anaphylaxis to propofol is rare and has not been previously reported in Asia. We describe a 35-year-old man with nasopharyngeal carcinoma who developed acute respiratory distress and hypotension after propofol infusion for parenteral anesthesia for Port-A-Cath insertion. Chest roentgenogram showed bilateral diffuse alveolar infiltrates. Respiratory failure ensued, and vocal cord swelling was found during endotracheal intubation. Hemodynamic data included a low cardiac index, a low systemic vascular resistance, and a high pulmonary vascular resistance. His condition and the shadows on the chest roentgenogram improved quickly after fluid challenge and the use of vasopressors, antihistamine, and intravenous steroids. Early awareness and appropriate management are necessary to prevent a fatal outcome in patients with propofol anaphylaxis.

Clinical spectrum of acute respiratory distress syndrome in a tertiary referral hospital: etiology, severity, clinical course, and hospital outcome.

BACKGROUND AND PURPOSE: The clinical picture of patients with acute respiratory distress syndrome (ARDS) in Taiwan has seldom been reported, although new definitions of ARDS have been introduced over the past years. The purpose of this study was to investigate the clinical characteristics, modalities of management, and outcomes in patients with ARDS treated in a tertiary referral hospital. METHODS: Case records were selected through a computerized search of diagnosis codified at discharge during the period from January 1995 to June 1997. Patients who met the criteria of the American-European Consensus Conference definition of ARDS were included and their medical records were retrospectively reviewed. RESULTS: A total of 145 patients (91 men, 54 women; mean age, 58 years) who fulfilled the criteria for ARDS were identified. Malignancy (n = 53) and diabetes mellitus (n = 23) were the most common co-morbid conditions. Pneumonia (n = 90), including community-acquired pneumonia in 45 (31%) patients, was the most common risk factor. The lung injury score at the time of ARDS diagnosis was 2.89 +/- 0.40 (mean +/- standard error, SE). The worst value of PaO2/FIO2 was 86.8 +/- 3.8 mm Hg (mean +/- SE). Among the 145 patients, 130 (90%) received mechanical ventilation and 118 (81%) were treated in the intensive care unit. In-hospital mortality was 87%. Seventy (48%) patients received intensive treatment for ARDS, among whom 52 (74%) died; the most common causes of death were multiple organ failure (54%) and respiratory failure (23%). CONCLUSIONS: The mortality in patients with ARDS was high in this tertiary referral institution. Our findings suggest that aggressive ventilatory, pharmacologic, and supportive therapy may be important to achieve a higher survival rate.

Ultrasound-guided percutaneous transthoracic needle aspiration biopsy for diagnosis of pulmonary lesions in advanced HIV infection.

Pulmonary diseases remain the most common complication associated with high morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. Invasive diagnostic procedures are often needed to establish a specific diagnosis of pulmonary disease. We report our experience with ultrasound (US)-guided percutaneous transthoracic needle aspiration (PTNA) biopsy in 20 consecutive patients with advanced HIV infection who presented with a variety of pulmonary lesions with or without pleural effusion. A specific diagnosis was established in 16 patients (80%), with infection being the most common etiology. Sputum culture yielded the same causative pathogen in three patients (15%) and all had more than one bacterial or fungal isolates. Mild pneumothorax, the only complication, was observed in two patients (10%) following the procedure. Neither patient required chest tube drainage. Our findings suggest that US-guided PTNA can be a useful and safe alternative to fluoroscopy-guided PTNA in selected HIV-infected patients with focal pulmonary lesions and pleural effusion.

Factors associated with adherence to low-tidal volume strategy for acute lung injury and acute respiratory distress syndrome and their impacts on outcomes: an observational study and propensity analysis.

BACKGROUND: The purpose of this study was to investigate the factors affecting adherence to the low-tidal volume (LTV) strategy in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and their impacts on outcomes. METHODS: This prospective observational study included 111 patients with ALI/ARDS admitted to six intensive care units between March 2010 and February 2011. The patients were divided into the LTV group, which received a TV ≤7.5 mL/kg predicted body weight (PBW), and the non-LTV group, which received a TV >7.5 mL/kg PBW. We studied the association of selected clinical factors and adherence to the LTV strategy, and evaluated their impacts on 28-day mortality and 1-year mortality by the propensity-match process. RESULTS: Adherence to the LTV strategy was only 44%, which was related to lung injury severity (odds ratio [OR]: 3.15, P=0.038), muscle relaxant use (OR: 3.28, P=0.031), and depth of sedation (OR: 0.65, P=0.008). Propensity score-based analysis showed that the LTV group had modestly better 28-day survival (P=0.081) and 1-year survival (P=0.067) than the non-LTV group. Moreover, muscle relaxant use was strongly associated with reducing the risk of death at both 28 days (hazard ratio [HR]: 0.122, 95% confidence interval [CI]: 0.027-0.542, P=0.006) and 1 year ([HR]: 0.111, 95% [CI]: 0.030-0.408, P=0.001). CONCLUSION: Adherence to the LTV strategy was strongly associated with the lung injury score, muscle relaxant use, and depth of sedation. Propensity score-based analysis showed that the use of LTV ventilation and muscle relaxants reduced 28-day and 1-year mortality in ALI/ARDS patients.

The relationship of family characteristics and bipolar disorder using causal-pie models.

Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.

Identification of novel loci for bipolar I disorder in a multi-stage genome-wide association study.

OBJECTIVE: Identification of genetic variants that influence bipolar I disorder (BPD-I) through genome-wide association (GWA) studies is limited in Asian populations. The current study aimed to identify novel common variants for BPD-I in an ethnically homogeneous Taiwanese sample using a multi-stage GWA study design. METHOD: At the discovery stage, 200 BPD-I patients and 200 controls that combined to form 16 pools were genotyped with 1 million markers. Utilizing a newly developed rank-based method, top-ranked markers were selected. After validation with individual genotyping, a fine-mapping association study was conducted to identify associated loci using 240 patients and 240 controls. At the last stage, independent samples were collected (351 cases and 341 controls) for replication. RESULTS: Among the top-ranked markers from the discovery stage, eight genes and 15 individual SNPs were evaluated in the fine-mapping stage. At this stage, rs7619173, which is not in a gene coding region, showed the most significant association (P = 2 ∗ 10(-5)) with BPD-I. Four genes had empirical P-values<0.05, including KCNH7 (P = 0.0047), MYST4 (P = 0.0047), NRXN3 (P = 0.0095), and SEMA3D (P = 0.037). For markers genotyped in replication samples, rs7619173 exhibited a significant association (P(combined) = 2 ∗ 10(-4)) after multiple testing correction, while markers rs11001178 (MYST4) and rs2217887 (NRXN3) showed weak associations (P(combined) = 0.02) with BPD-I. CONCLUSION: A multi-stage GWA design has the potential to uncover the underlying pathogenesis of a complex trait. Findings in the present study highlight three loci that warrant further investigation for bipolar.