Types of childhood maltreatment as predictors of posttraumatic stress disorder severity and complex posttraumatic stress disorder in patients with substance use disorders.

Background: Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is associated with (Complex)Posttraumatic stress disorder (PTSD/CPTSD) and substance use disorder (SUD).Objective: This cross-sectional study examined the relationships between CM-subtypes with PTSD-severity and CPTSD in patients with SUD-PTSD.Method: Participants (N = 209) were treatment-seeking SUD-PTSD patients who completed the Childhood Trauma Questionnaire-short form, the Clinician-Administered PTSD Scale for DSM-5 and the International Trauma Questionnaire. Regression analyses and a model selection procedure to select an optimal model were used to examine CM-subtypes as predictors of (C)PTSD, adjusted for sex and age.Results: Total CM and all CM-types significantly predicted PTSD-severity in the univariate regression analysis, with EA begin the strongest predictor. In the multiple regression only SA predicted PTSD-severity. Subsequently, model selection indicated that the optimal model to predict PTSD-severity included EA and SA. In the univariate analyses total CM, EA, and PN significantly predicted CPTSD-classification, and total CM and all CM-types significantly predicted CPTSD-severity. In the multiple regression for CPTSD-classification only EA and PA were significant predictors and for CPTSD-severity EA, PA and SA were significant predictors. In post-hoc multiple regression analyses, only EA was a significant predictor of CPTSD-classification and CPTSD-severity. Finally, in the model selection the most parsimonious model only included EA for both CPTSD-classification and CPTSD-severity. Sex was not a moderator in the relationship between CM and PTSD, nor in CM and CPTSD.Conclusions: These findings indicate that for SUD-PTSD patients, several CM-types have predictive value for (C)PTSD-severity, however SA and especially EA appear to contribute to these complaints. Since EA does not constitute an A-criterion, it is generally more overlooked in PTSD treatment. Its impact should therefore be underlined, and clinicians should be attentive to EA in their treatment.

All types of Childhood Maltreatment are associated with PTSD severity.Emotional Abuse and Sexual Abuse are most predictive for PTSD severity.Emotional Abuse is most predictive for CPTSD classification and symptom severity.

Structure-guided approach to modify the substrate specificity of the protein human deglycase-1 (hDJ-1).

Glycation is a non-enzymatic reaction wherein sugars or dicarbonyls such as methylglyoxal (MGO) and glyoxal (GO) react with proteins, leading to protein inactivation. The hydrolysing enzyme human deglycase-1 (hDJ-1) is reported to decrease glycative stress by deglycating the modified proteins, specifically at cysteine, lysine, and arginine sites. This specificity of hDJ-1 is thought to be regulated by its active site cysteine residue (Cys106). Structural analysis of hDJ-1 by molecular docking and simulation studies, however, indicates a possible role of glutamate (Glu18) in determining its substrate specificity. To elucidate this, Glu18 present at the catalytic site of hDJ-1 was modified to aspartate (Asp18) by SDM, and the resultant mutant was termed mutant DJ-1 (mDJ-1). Both hDJ-1 and mDJ-1 were heterologously expressed in Escherichia coli BL21 (DE3) strain and purified to homogeneity. The hDJ-1 showed kcat values of 1.45 × 103 s-1, 3.6 × 102 s-1, and 3.1 × 102 s-1, and Km values 0.181 mM, 18.18 mM, and 12.5 mM for N-acetylcysteine (NacCys), N-acetyllysine (NacLys), and N-acetylarginine (NacArg), respectively. The mDJ-1 showed altered kcat values (8 × 102 s-1, 3.8 × 102 s-1, 4.9 × 102 s-1) and Km values of 0.14 mM, 6.25 mM, 5.88 mM for NacCys, NacLys and NacArg, respectively. A single amino acid change (Glu18 to Asp18) improved the substrate specificity of mDJ-1 toward NacLys and NacArg. Understanding hDJ-1's structure and enhanced functionality will facilitate further exploration of its therapeutic potential for the treatment of glycation-induced diabetic complications.

Treating posttraumatic stress disorder in substance use disorder patients with co-occurring posttraumatic stress disorder: study protocol for a randomized controlled trial to compare the effectiveness of different types and timings of treatment.

BACKGROUND: Posttraumatic stress disorder (PTSD) and substance use disorder (SUD) have high comorbidity. Although prior research indicated that PTSD can effectively be treated with Prolonged Exposure (PE) in these patients, reported effects are small and treatment dropout rates high. Eye Movement Desensitization and Reprocessing (EMDR) and Imagery Rescripting (ImRs) are other promising treatment options for PTSD, that have not yet been examined in this patient group. Furthermore, it is unclear whether PTSD treatment is most effective when offered simultaneous to or after SUD treatment. METHODS: In this article, the Treatment Of PTSD and Addiction (TOPA) study is described: a Dutch randomized controlled trial (RCT) that studies the effectiveness of PTSD treatment as an add-on to regular SUD treatment in patients with SUD and co-occurring PTSD. Effects of PE, EMDR, ImRs, and a 3-month SUD treatment only condition will be compared, as well as simultaneous SUD/PTSD treatment to sequential SUD/PTSD treatment. The primary outcome measure is PTSD symptoms. Secondary outcomes are: treatment completion, psychological distress, substance use, interpersonal problems, emotion dysregulation, and trauma-related emotions guilt, shame, and anger. DISCUSSION: This study is the first to compare effects of PE, EMDR, and ImRs in one study and to compare simultaneous SUD/PTSD treatment to sequential SUD/PTSD treatment as well. This RCT will provide more knowledge about the effectiveness of different treatment strategies for PTSD in patients with co-occurring SUD and will ultimately improve treatment outcomes for patients with this common co-morbidity worldwide. TRIAL REGISTRATION: Netherlands Trial Register (NTR), Identifier: NL7885 . Registered 22 July 2019.

Neutrophil fluorescence in clozapine users is attributable to a 14kDa secretable protein.

Clozapine is the only antipsychotic agent with demonstrated efficacy in refractory schizophrenia. However, use of clozapine is hampered by its adverse effects, including potentially fatal agranulocytosis. Recently, we showed an association between neutrophil autofluorescence and clozapine use. In this study, we evaluated the subcellular localization of clozapine-associated fluorescence and tried to elucidate its source. Neutrophils of clozapine users were analyzed with fluorescence microscopy to determine the emission spectrum and localization of the fluorescence signal. Next, these neutrophils were stimulated with different degranulation agents to determine the localization of fluorescence. Lastly, isolated neutrophil lysates of clozapine users were separated by SDS-PAGE and evaluated. Clozapine-associated fluorescence ranged from 420 nm to 720 nm, peaking at 500-550 nm. Fluorescence was localized in a large number of small loci, suggesting granular localization of the signal. Neutrophil degranulation induced by Cytochalasin B/fMLF reduced fluorescence, whereas platelet-activating factor (PAF)/fMLF induced degranulation did not, indicating that the fluorescence originates from a secretable substance in azurophilic granules. SDS-PAGE of isolated neutrophil lysates revealed a fluorescent 14kDa band, suggesting that neutrophil fluorescence is likely to be originated from a 14kDa protein/peptide fragment. We conclude that clozapine-associated fluorescence in neutrophils is originating from a 14kDa soluble protein (fragment) present in azurophilic granules of neutrophils. This protein could be an autofluorescent protein already present in the cell and upregulated by clozapine, or a protein altered by clozapine to express fluorescence. Future studies should further explore the identity of this protein and its potential role in the pathophysiology of clozapine-induced agranulocytosis.

Resetting the bar: Statistical significance in whole-genome sequencing-based association studies of global populations.

Genome-wide association studies (GWAS) of common disease have been hugely successful in implicating loci that modify disease risk. The bulk of these associations have proven robust and reproducible, in part due to community adoption of statistical criteria for claiming significant genotype-phenotype associations. As the cost of sequencing continues to drop, assembling large samples in global populations is becoming increasingly feasible. Sequencing studies interrogate not only common variants, as was true for genotyping-based GWAS, but variation across the full allele frequency spectrum, yielding many more (independent) statistical tests. We sought to empirically determine genome-wide significance thresholds for various analysis scenarios. Using whole-genome sequence data, we simulated sequencing-based disease studies of varying sample size and ancestry. We determined that future sequencing efforts in >2,000 samples of European, Asian, or admixed ancestry should set genome-wide significance at approximately P = 5 × 10-9 , and studies of African samples should apply a more stringent genome-wide significance threshold of P = 1 × 10-9 . Adoption of a revised multiple test correction will be crucial in avoiding irreproducible claims of association.

[Perforation of the superior vena cava and hemothorax caused by insertion of a pulmonary artery catheter].

A 70-year-old woman with aortic regurgitation was scheduled for aortic valve replacement. After induction of anesthesia resistance was encountered when attempting to remove the guide wire with a sheath dilator prior to insertion of a pulmonary artery (PA) catheter through the right internal jugular vein. Ten hours after catheter insertion, chest X-ray examination in ICU showed poorly delineated right lung field, and hemothorax was suspected, as a large amount of fluid was also seen draining from the chest drain tube. Twenty two hours after catheter insertion, we opened her chest and found that the superior vena cava (SVC) had been perforated. After surgical closure of the hole on the SVC, the hemodynamics because stabilized and active bleeding was controlled. The patient was subsequently discharged from the hospital without any further complications. This perforation was thought to be caused by carelessness during insertion of the PA catheter. To prevent serious complications, such as perforation of the great vessels or heart by a catheter, the results of the present case suggest that careful attention is required during catheterization, especially when resistance is encountered.

The volume limit in fluid resuscitation to prevent respiratory failure in massively burned children without inhalation injury.

We evaluated the accurate fluid requirement to prevent respiratory failure during the postresuscitation period in the resuscitation of massively burned children without inhalation injury. Forty-nine children were treated by similar fluid resuscitation and physiologic support protocols. Using a retrospective chart review, the children were divided into three groups as follows: Group N (no lung injury, n = 33, 41.4+/-18.7%TBSA burned), Group M (mild-to-moderate lung injury, n = 11, 73.7+/-17.1%TBSA burned) and Group S (severe lung injury, n = 5, 67.2+/-16.6%TBSA burned). Information about fluid resuscitation during the first 24 hr post-injury was collected and compared among the three groups. There was no significant difference in the hourly urine output and the resuscitation volume estimated by body weight and burn size among the groups. The volumes estimated by ml/kg/%TBSA burned were 7.0 ml/kg/%TBSA burned, 8.0 ml/kg/%TBSA burned, and 9.4 ml/kg/%TBSA burned in Groups N, M, and S, respectively. According to the fluid volume estimated by the burn index (BI; 1/2 of % second-degree burns plus % third-degree burns), the volumes were 13.8+/-4.0 ml/kg/BI, 14.4+/-4.4 ml/kg/BI, 18.8+/-3.7ml/kg/BI in Groups N, M, and S, respectively (Group N < Group S, p < 0.05). There was a significant positive correlation between the maximum respiratory index (AaDO2/PaO2) during the first week and the initial total volume administered (ml/kg/BI). These findings indicated that the fluid requirements to prevent postresuscitation respiratory failure in massively burned children might be estimated according to the depth of burned area in addition to body weight and burn size.

Parasympathetic activity in brain death: effect of apnea on heart rate variability.

BACKGROUND: Power spectral analysis of heart rate variability is a useful monitoring of brain-damaged patients. However, the effect of artificial ventilation is not clearly demonstrated in assessing vagal activity because the locus of its activity is originated close to the respiratory center in the brain stem. We studied heart rate variability during artificial ventilation and apnea test as part of an assessment of brain death. METHODS: Ten adult patients with severe brain damage were studied. Power spectral analysis of heart rate variability from electrocardiographic R-R intervals was integrated to compare spectral components before, during and after the apnea test. Before the test, circulatory and blood gas variables and electrocardiographic recording were obtained under controlled mechanical ventilation at a rate of 12 and 18 (/min), each for 5 min. Measurements were made for 10 min during the apnea test, and repeated thereafter as before the test. Power spectral analysis based on fast Fourier transformation was made by integrating each low- (LF: 0.04-0.15 Hz) and high- (HF: 0.15-0.40 Hz) frequency band areas. LF was assessed as sympathetic and parasympathetic nervous activity, and HF as respiratory-related parasympathetic vagal activity. The HF/LF ratio showed sympathovagal balance. RESULTS: All patients were assessed as brain dead. During apnea, PaCO2 (P<0.01) and LF (P<0.05) increased, and pH (P<0.01) and HF/LF ratio (P<0.05) decreased. Heart rate, mean arterial pressure, PaO2 and HF remained consistent throughout. CONCLUSION: It was shown that sympathovagal balance was inclined to be sympathotonic during apnea, and that there were no changes in the respiratory-related vagal activity in spite of stopping artificial ventilation.

Alterations of fibrinolytic activity in human during and after hyperbaric oxygen exposure.

To clarify the stage of fibrinolytic activation by hyperbaric oxygen (HBO) exposure, we examined its alterations in human during and after the HBO exposure. Eight healthy female volunteers breathed oxygen at 284 kPa (2.8 atmospheres absolute). Blood samples were collected before compression, shortly after compression to the pressure 284 kPa, shortly before the start of decompression, shortly after decompression, and then again 3 hours after decompression. We estimated the euglobulin fibrinolytic activity (EFA) and, the activities and antigens of both tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). The PAI-1 activity and PAI-1 antigen showed significant decrease after compression to a pressure 284 kPa, before the start of decompression, and after decompression. The EFA level and t-PA activity rose significantly shortly after decompression, and 3 hours later returned on baseline. These findings suggest that fibrinolytic activity is elicited after HBO rather than during HBO.

[Health check on divers and compressed air workers].

We have conducted the health check of 3,554 compressed air workers and 1,821 divers, and also examined the incidence and severity of aseptic bone necrosis by using Roentgen pictures. We could classify 4,859 of 5,375 persons into four groups (A-D), based on our classification. We could also classify 4,205 of 5,375 persons that had had a bone X ray examination on the basis of the criteria described by Ota and Matsunaga (A-C). 4,859 persons belonged to four groups: class A (persons who can work, no limitations): 4,099 (84.4%), class B (persons who can work under conditions below 1.0 kg/cm2): 357 (7.3%), class C (persons who had better quit work under hyperbaric conditions, though they are not prohibited by regulations): 183 (3.8%), class D (persons who must be prohibited from working in a hyperbaric environment by laws of the Ministry of Labor): 88 (1.8%). About 90% of compressed air workers and divers (classes A and B) were permitted to work under hyperbaric conditions. Most of those belonging to classes C and D suffered from hypertension, cardiovascular disease and liver dysfunction. The incidence of aseptic bone necrosis was 11.1% (465 out of 4,205 persons). Eight persons (2.2%) belonged to criteria A which means poor prognosis. They were classified into class D. There is no differences between compressed air workers and divers in the incidence of aseptic bone necrosis.

[Saturation diving system at high altitude].

Practical saturation diving was firstly performed at high altitude in Japan in 1987. Its work was to change the screen which had covered the pipeline of a hydroelectric dam located 850 meters above sea level, the same operation had been conducted in 1992 and in 1993, 2 times each year (Total = 5 operations) after the work. The saturation dives have lasted from six to eight days on 4 occasions and 13 days (Total duration = 4075 minutes) on 1 occasion, since the initial pressurization until the end of the last decompression. In each operation, there had always been involved 3 divers. They have been compressed to an equivalent depth of 45-73m in the deck decompression chamber (DDC), briefed for work and transferred to the submersible decompression chamber (SDC), which was then submersed to 53-78m of depth. Wearing heated suit and breathing Heliox (both at the same temperature as the inside of the SDC), the divers have been locked out to perform their tasks, all monitored and supervised by the use of a remotely operated vehicle (ROV). The works have run uneventful and successfully until the end. The water temperature had been higher than the expected, i.e. 9-13 degrees C in all occasions. The inside conditions of the chamber had been the following: partial pressure of nitrogen was from 0.78 ATA; partial pressure of oxygen was from 0.35 to 0.40 ATA; partial pressure of carbon dioxide was less than 0.005 ATA; the inside temperature of the SDC was from 26 to 30 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulatory stability and plasma lidocaine levels during continuous and intermittent thoracic epidural analgesia.

Circulatory stability and plasma levels of lidocaine were investigated in 20 patients who received thoracic epidural analgesia with plain lidocaine during elective abdominal surgery under general anesthesia. In one group, bolus injection of 8 ml of 2% lidocaine was followed by volumetric continuous pump-driven infusion (CPI) of 8 ml of 1.5% lidocaine per hour. In the other group, the same initial bolus injection was followed by repetitive intermittent bolus infusions (RII) of 6 ml of 1.5% lidocaine at a 45 min-interval. Circulatory stability was evaluated by a discriminant function. The results showed that epidural analgesia produced smaller circulatory fluctuations with CPI than with RII. Venous plasma lidocaine levels were consistently higher with CPI than with RII. Plasma levels increased stepwise with RII and kept constant with CPI. Differences in plasma levels were significant from 20 min after the initial injection to 135 min. We therefore conclude that epidural analgesia with CPI is superior to that with RII. However, it must be remembered that higher plasma levels may occur with CPI than with RII.

[Conversion to 2nd degree from 1st degree atrioventricular (AV) block by the reversal of neuromuscular blockade].

A case of intraoperative conversion to 2nd degree from 1st degree AV block by the reversal of neuromuscular blockade was reported. A 78 year old male, who originally suffered from 1st degree AV block, underwent choledocholithotomy and T-tube drainage for choledocholithiasis. He was administered 4 mg of pancuronium at the time of intubation. The operation lasted for 160 minutes under epidural anesthesia, NLA and nitrous oxide-oxygen. The patient started spontaneous breathing and the recovery was confirmed after the operation which finished without any problem. Neuromuscular blockade was reversed with atropine 0.5 mg and neostigmine 1.0 mg that were administered simultaneously taking 3 minutes. Then he was extubated without any troublesome stimulation. Suddenly, however, he suffered from the worse condition of bradycardia with the 2nd degree AV block. It took about 45 minutes until he recovered to the original 1st degree AV block despite atropine treatment. We believe that this accident was induced by a vasovagal reflex which was triggered by extubation under the effect of neostigmine which acts longer than that of atropine. We should be careful in reversing the effect of the non-depolarizing neuromuscular blockade. A short acting neuromuscular blockade, i.e. vecuronium, is preferable so as to avoid neostigmine reversal, and extubation should be performed when the effect of neuromuscular blockade is confirmed to be exhausted.

[Perioperative management of patients with dilated cardiomyopathy].

Dilated cardiomyopathy (DCM) is defined as a syndrome of dilated ventricles with gross impairment of ventricular systolic function. However, few reports on perioperative management of DCM were obtainable. This paper describes perioperative management of two patients with DCM. A 72-year-old man, whose DCM had been treated with medication, was planned for gastrectomy. His cardiac signs indicated NYHA class II. Cardiac function, evaluated prior to the surgery with echocardiography to determine an operative indication, turned out to be well compensated. Minimal cardiac derangements were anticipated perioperatively. The procedure was carried out under general anesthesia with neuroleptanalgesia utilizing butorphanol and vasoactive agents. No circulatory complications were observed throughout the surgery. A 66-year-old man, who had long-standing heart disease, hemiplegia and hydronephrosis due to ureteral stone, was planned for percutaneous nephrolithotomy. However, the planned surgery was withdrawn because he had DCM with minimal compensatory function and perioperative cardiac derangements were anticipated according to the categorized data classified with echocardiography. We conclude that preoperative assessment of cardiac function is essential to minimize perioperative cardiac derangements in patients with DCM.