Rule-based modulation of a sensorimotor transformation across cortical areas.

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes and uses rule information to guide behavior. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task where they switched between two rules: licking in response to tactile stimuli while rejecting visual stimuli, or vice versa. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, single-neuron activity distinguished between the two rules both prior to and in response to the tactile stimulus. We hypothesized that neural populations in these areas would show rule-dependent preparatory states, which would shape the subsequent sensory processing and behavior. This hypothesis was supported for the motor cortical areas (MM and ALM) by findings that (1) the current task rule could be decoded from pre-stimulus population activity; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states impaired task performance. Our findings indicate that flexible action selection in response to sensory input can occur via configuration of preparatory states in the motor cortex.

Tactile processing in mouse cortex depends on action context.

The brain receives constant tactile input, but only a subset guides ongoing behavior. Actions associated with tactile stimuli thus endow them with behavioral relevance. It remains unclear how the relevance of tactile stimuli affects processing in the somatosensory (S1) cortex. We developed a cross-modal selection task in which head-fixed mice switched between responding to tactile stimuli in the presence of visual distractors or to visual stimuli in the presence of tactile distractors using licking movements to the left or right side in different blocks of trials. S1 spiking encoded tactile stimuli, licking actions, and direction of licking in response to tactile but not visual stimuli. Bidirectional optogenetic manipulations showed that sensory-motor activity in S1 guided behavior when touch but not vision was relevant. Our results show that S1 activity and its impact on behavior depend on the actions associated with a tactile stimulus.

Erector spinae plane block reduces opioid consumption and improves incentive spirometry volume after cardiac surgery: A retrospective cohort study.

BACKGROUND: Effective postoperative pain management is vital in cardiac surgery to prevent opioid dependency and respiratory complications. Previous studies on the erector spinae plane (ESP) block have focused on single-shot applications or immediate postoperative outcomes. This study evaluates the efficacy of continuous ESP block vs conventional care in reducing opioid consumption and enhancing respiratory function recovery postcardiac surgery over 72 hours. METHODS: A retrospective study at a tertiary hospital (January 2021-July 2022) included 262 elective cardiac surgery patients. Fifty-three received a preoperative ESP block, matched 1:1 with a control group (n = 53). The ESP group received 0.5% ropivacaine intraoperatively and 0.16% ropivacaine every 4 hours postoperatively. Outcomes measured were cumulative oral morphine equivalent (OME) dose within 72 hours postextubation, daily maximum numerical rating scale (NRS) ≥3, incentive spirometry volume, and %baseline performance, stratified by surgery type (sternotomy or thoracotomy). RESULTS: Significant OME reduction was observed in the ESP group (sternotomy: median decrease of 113 mg, 95% CI: 60-157.5 mg, p < 0.001; thoracotomy: 172.5 mg, 95% CI: 45-285 mg, p = 0.010). The ESP group also had a lower risk of daily maximum NRS ≥3 (adjusted OR sternotomy: 0.22, p < 0.001; thoracotomy: 0.07, p < 0.001), a higher incentive spirometry volumes (sternotomy: mean increase of 149 mL, p = 0.019; thoracotomy: 521 mL, p = 0.017), and enhanced spirometry %baseline (sternotomy: mean increase of 11.5%, p = 0.014; thoracotomy: 26.5%, p < 0.001). CONCLUSION: Continuous ESP block was associated with a reduction of postoperative opioid requirements, lower instances of pain scores ≥3, and improve incentive spirometry performance following cardiac surgery. These benefits appear particularly prominent in thoracotomy patients. Further prospective studies with larger sample size are required to validate these findings.

Case report: Malignant transformation of ovarian endometrioma during long term use of dienogest in a young lady.

Endometriosis is a benign disease, which is also regarded as a precursor to ovarian malignancy. Dienogest is a progestin treatment for endometriosis with efficacy and tolerability. A 35-year-old Taiwanese lady with ovarian endometrioma had taken dienogest for the last 5 years. During sonographic follow-up, surgery was suggested owing to suspicious of malignant transformation of ovarian endometrioma. While she hesitated and turned to receive two cycles of oocyte retrieval because of nulliparity. Meanwhile, more papillary growth in the ovarian endometrioma with intratumor flow was found during follow-up. Laparoscopic enucleation was performed later, and pathology revealed clear cell carcinoma with peritoneal involvement, at least FIGO stage IIB. She then underwent debulking surgery to grossly no residual tumor and received adjuvant chemotherapy with no tumor recurrence in post-operative 17-months follow-up. Considering fertility preservation, conservative treatment of ovarian endometrioma is typically indicated for those women who have not yet completed childbearing. However, malignant transformation may still occur despite long-term progestin treatment. Therefore, careful image follow-up is still indispensable.

Rule-based modulation of a sensorimotor transformation across cortical areas.

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes rule information and uses this information to guide behavioral responses to sensory stimuli. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task in which they switched between two rules in different blocks of trials: licking in response to tactile stimuli applied to a whisker while rejecting visual stimuli, or licking to visual stimuli while rejecting the tactile stimuli. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, the single-trial activity of individual neurons distinguished between the two rules both prior to and in response to the tactile stimulus. Variable rule-dependent responses to identical stimuli could in principle occur via appropriate configuration of pre-stimulus preparatory states of a neural population, which would shape the subsequent response. We hypothesized that neural populations in S1, S2, MM and ALM would show preparatory activity states that were set in a rule-dependent manner to cause processing of sensory information according to the current rule. This hypothesis was supported for the motor cortical areas by findings that (1) the current task rule could be decoded from pre-stimulus population activity in ALM and MM; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states within ALM and MM impaired task performance. Our findings indicate that flexible selection of an appropriate action in response to a sensory input can occur via configuration of preparatory states in the motor cortex.

The Effectiveness of Parenting Programs in Preventing Abusive Head Trauma: A Systematic Review and Meta-Analysis.

Parenting programs are the most common intervention for preventing the lethal form of child maltreatment, abusive head trauma (AHT). However, certain results of the effects of these programs have not yet been compared across studies. A systematic review with meta-analysis is warranted to quantitively synthesize the available evidence to identify effective elements and strategies of the programs for preventing AHT. This review aims to estimate AHT preventive parenting programs' pooled effect on the reduction of AHT incidence, the improvement of parental knowledge, and the increased use of safe strategies in response to infants' inconsolable crying. Studies published in English and Mandarin were searched and retained if they were randomized control trials (RCTs) or with a quasi-experimental design, included an AHT preventive parenting program, and provided data that quantified targeted outcomes. Eighteen studies were included in this review. AHT preventive parenting programs had a pooled effect on improving parents' knowledge and increasing the use of safe coping strategies in response to inconsolable crying but not on the incidence of AHT and parents' emotional self-regulation. Subgroup analyses showed that the intervention effects were mostly present across study designs or measurements and emerged in the reduction of AHT incidence compared with historical controls. The findings suggest that AHT preventive parenting programs enhance parenting knowledge and skills to provide safe care for infants. Further efforts to evaluate AHT parenting programs on the reduction of AHT incidence are necessary for decision-making on allocating and disseminating interventions.

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes.

Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis. We conducted a two-part, randomized phase 2a trial in men and women with overweight or obesity diagnosed with T2DM to evaluate the efficacy and safety of cotadutide compared with placebo and liraglutide. The primary endpoints were change from baseline to day 28 of treatment in postprandial hepatic glycogen (part A) and to day 35 of treatment in fasting hepatic glycogen (part B) with cotadutide versus placebo. Secondary endpoints in part B were changes in fasting hepatic glycogen with cotadutide versus the mono glucagon-like peptide 1 receptor agonist, liraglutide, and change in hepatic fat fraction. The trial met its primary endpoint. We showed that cotadutide promotes greater reductions in liver glycogen and fat compared with placebo and liraglutide. Safety and tolerability findings with cotadutide were comparable to those of previous reports. Thus, this work provides evidence of additional benefits of cotadutide that could be attributed to glucagon receptor engagement. Our results suggest that cotadutide acts on the glucagon receptor in the human liver to promote glycogenolysis and improve the metabolic health of the liver. ClinicalTrials.gov registration: NCT03555994 .

Gut microbiota of Pacific white shrimp (Litopenaeus vannamei) exhibits distinct responses to pathogenic and non-pathogenic Vibrio parahaemolyticus.

Acute hepatopancreatic necrosis disease (AHPND), a high-mortality-rate shrimp disease, is caused by specific Vibrio parahaemolyticus (Vp) strains with a plasmid encoding the PirABVp toxins. As a bacterial pathogen, the invasion of AHPND-causing Vp might impose pressure on commensal microbiota in the shrimp gut, while the relationship between the pathogenesis of AHPND and the dysbiosis of gut bacterial communities remains unclear. Here we explored the temporal changes of shrimp gut microbiota in response to AHPND-causing and non-AHPND-causing Vp strains, with the non-infected controls as a baseline of the shrimp gut microbiota. The diversity and composition of bacterial communities from 168 gut samples (covering three treatments at seven time points with eight individuals per set) were investigated using 16S rRNA gene metabarcoding with high-throughput sequencing. The results showed that (i) species diversity of gut bacterial communities declined in Vp-infected shrimp, independent of the strain pathogenicity; (ii) taxonomic compositions of gut bacterial communities were significantly different between shrimp infected by AHPND-causing and non-AHPND-causing Vp strains; (iii) short-term (within 6 hours) compositional shifts in the gut microbiota were found only in AHPND-causing Vp-infected shrimp; (iv) the gut microbiota of AHPND-causing Vp-infected shrimp was enriched with genera Photobacterium and Vibrio, with a decline in Candidatus Bacilliplasma; and (v) functional predictions suggested the loss of normal metabolism due to compositional shifts in the gut microbiota. Our work reveals distinct features of community dynamics in shrimp gut microbiota, associated with pathogenic versus non-pathogenic Vibrio infections, providing a new perspective of the pathogenesis of AHPND. IMPORTANCE Shrimp production is continually threatened by newly emerging diseases, such as AHPND, which is caused by specific Vp strains. Previous studies on the pathogenesis of AHPND have mainly focused on the histopathology and immune responses of the host. However, more attention needs to be paid to the gut microbiota, which acts as the first barrier to pathogen colonization. In this study, we revealed that shrimp gut microbiota responded differently to pathogenic and non-pathogenic Vp strains, with bacterial genera Photobacterium and Vibrio enriched in pathogenic Vp-infected shrimp, and Candidatus Bacilliplasma enriched in non-pathogenic Vp-infected shrimp. Moreover, functional predictions suggested that changes in taxonomic compositions would further affect normal metabolic functions, emphasizing the importance of sustaining an equilibrium in the gut microbiota. Several biomarkers associated with specific microbial taxa and functional pathways were identified in our data sets, which help predict the incidence of disease outcomes.

Update on Regulation of Regenerative Medicine in Taiwan.

Due to rapid development of biotechnology in recent years, the field of regenerative medicine has attracted considerable attention. Regenerative medicine-related regulations have been established in several countries to ensure the quality, safety, and efficacy of innovative treatments. Considering the diversity of regenerative medicine, the regulatory framework in Taiwan has been adjusted in response to global trend and local demand. Before 2010, cell and gene therapies were regarded as "new medical practice" under the "Medical Care Act." Along with the establishment of Taiwan Food and Drug Administration (TFDA) in 2010, regenerative medicine was regulated as "medicinal products" under the "Pharmaceutical Affairs Act." Then, the Ministry of Health and Welfare (MOHW) established a new dual-track regulatory pathway for regenerative medicine in 2016. The dual-track pathway divided regenerative medicine into medical practices and medicinal products, aiming to improve the accessibility of new treatments to patients and maintain the flexibility for clinical operations. In order to refine the regulation, the MOHW proposed two draft Acts for regenerative medicine in 2022. The two draft Acts are currently under legislative process. It is expected that the research and development of regenerative medicine can be further accelerated, thus providing early access to innovative therapies for patients in the future.

Kernel-wise difference minimization for convolutional neural network compression in metaverse.

Convolutional neural networks have achieved remarkable success in computer vision research. However, to further improve their performance, network models have become increasingly complex and require more memory and computational resources. As a result, model compression has become an essential area of research in recent years. In this study, we focus on the best-case scenario for Huffman coding, which involves data with lower entropy. Building on this concept, we formulate a compression with a filter-wise difference minimization problem and propose a novel algorithm to solve it. Our approach involves filter-level pruning, followed by minimizing the difference between filters. Additionally, we perform filter permutation to further enhance compression. Our proposed algorithm achieves a compression rate of 94× on Lenet-5 and 50× on VGG16. The results demonstrate the effectiveness of our method in significantly reducing the size of deep neural networks while maintaining a high level of accuracy. We believe that our approach holds great promise in advancing the field of model compression and can benefit various applications that require efficient neural network models. Overall, this study provides important insights and contributions toward addressing the challenges of model compression in deep neural networks.

Workplace Deceptions During the Pandemic: Differences in Conspiracy Beliefs, Psychological Functioning, and Covid-19 Experiences.

The global pandemic has disrupted virtually all countries on health, psychological functioning, and economies, to name a few. Accurate information has also fallen victim to the pandemic, which has been rife with misinformation and conspiracy theories. The current study investigated Covid-19 deceptions related to employment. With complete anonymity via MTurk, 389 participants from the United States rated their likelihood of deception regarding hypothetical four workplace scenarios. The first set of analyses examined differences between high and low risk of deceptions for each scenario based on participants' self-appraisals. The largest differences were found for general conspiracy beliefs and affective disorders, specifically major depression and generalized anxiety. The second set of analyses focused across the workplace scenarios on two operationalized groups with Likely-Deceptive (n = 189) vastly outnumbering Likely-Genuine (n = 55). Personal experiences with Covid-19 dramatically increased deceptions. Testing positive for Covid-19 increased the odds of being in the Likely-Deceptive by twelve-fold. Two discriminant models examined cognitive misbeliefs and psychological functioning. When both were combined, depression and Covid-19 misinformation produced the strongest structure coefficients followed closely by general conspiracy beliefs and generalized anxiety. The far-ranging implications of these findings are discussed.

The role of vein grafts in reconstructive head and neck microsurgery

Abstract Objective: Free tissue transfer is widely used for head and neck reconstruction. In certain circumstances, vein grafting is required to elongate free flap pedicles to connect them to appropriate recipient vessels. Because of controversy regarding the use of interposition vein grafts in free tissue reconstruction, this paper reports vein graft indications, techniques, safety, and outcomes for head and neck microvascular surgery. Methods: Twenty-six patients (23 men and 3 women) who underwent interposition vein grafting concurrent with free tissue transfer were included in this study. The most common reason for head and neck reconstruction with vein graft was tumor recurrence, followed by flap salvage. The interposition vein grafts were applied in two manners as temporary arteriovenous (A-V) loop and conduit to extend the length of the free flap for venous drainage. Results: The most common reconstructions were anterolateral thigh flaps (15 cases), followed by vastus lateralis myocutaneous (3 cases) and radial forearm (2 cases) flaps. The common recipient vessels were superior thyroid artery, superficial temporal artery and external jugular vein. The free flap loss rate was 7.7% with vein grafts and 4.9 without vein grafts (p = 0.380). The free flap complication rate was 50.0% and 16.8% in patients with and without vein grafts, respectively (p < 0.001). Radiation therapy, chemotherapy, prior neck dissection, and prior free flap transfer were more common in the vein graft group (all p < 0.001). The hospital stay was significantly longer for the vein graft group than for the non-vein graft group (29.5 vs. 19.0 days; p = 0.001). Conclusion: Overall free flap survival rates of 92.3% and 95.1% in the vein and non-vein graft groups, respectively - indicating the reliability of the vein grafts in challenging head and neck reconstructions, particularly in salvage cases and patients with multiple reconstructions. Level of evidence: Level 3.

Effect of Total Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Microvascular Reconstruction for Head and Neck Cancer: A Randomized Clinical Trial.

Importance: Free flap surgery is a lengthy procedure with massive tissue destruction and reconstruction, which makes postoperative pulmonary complications (PPCs) a noticeable issue among patients with head and neck cancer. Propofol-based total intravenous anesthesia (TIVA) has better survival outcomes than inhalational anesthesia (INH) in several types of cancer surgery. A previous retrospective study found that patients in the TIVA group had a lower PPC rate, which may be correlated with a lower intraoperative fluid requirement. We hypothesize that the protective effect remains among patients undergoing free flap surgery for head and neck cancer in a prospective and goal-directed fluid therapy setting. Objective: To assess the effect of TIVA vs INH on PPCs in patients undergoing microvascular reconstruction for head and neck cancer. Design, Setting, and Participants: This prospective, 2-arm, randomized clinical trial was conducted at a tertiary hospital in Taiwan; a total of 78 patients 18 years and older with American Society of Anesthesiologists physical status classification 1 to 3 who were scheduled for elective free flap surgery under general anesthesia were included. The trial started in October 2017, completed in October 2019, and finished analysis in January 2022. Interventions: Patients were enrolled and randomized to the TIVA or INH group. All patients received goal-directed fluid therapy and hemodynamic management if they had a mean arterial pressure (MAP) below 75 mm Hg or a reduction of 10% from baseline MAP. Main Outcomes and Measures: The primary outcome was a composite of PPCs. The secondary outcomes were the differences in intraoperative hemodynamic values (mean arterial pressure, MAP; cardiac index, CI; systemic vascular resistance index, SVRI; and stroke volume variation, SVV). Results: A total of 70 patients (65 men [93%]; 5 women [7%]) completed the trial; median (IQR) age was 52.0 (48-59) years in the TIVA group and 57.0 (46-64) years in the INH group. The demographic characteristics were similar between the 2 groups, except that patients in the TIVA group had a slightly lower body mass index. Patients in the TIVA group had a lower risk of developing PPCs (unadjusted odds ratio, 0.25; 95% CI, 0.08-0.80). The TIVA group had significantly higher MAP, lower CI, and higher SVRI than the INH group after the third hour of monitoring. The TIVA group showed a relatively stable hourly MAP, CI, SVRI, and SVV across time points, while the INH group showed a more varying pattern. The generalized estimating equation showed no clinical differences in the trend of hemodynamic parameters across time between groups. Conclusions and Relevance: In this randomized clinical trial, using propofol-based TIVA reduced the incidence of PPCs in free flap surgery. This finding may be related to more stable hemodynamic manifestations and a lower total balance of fluid throughout the surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03263078.

Peri-Implant Marginal Bone Changes around Dental Implants with Platform-Switched and Platform-Matched Abutments: A Retrospective 5-Year Radiographic Evaluation.

Preserving the marginal bone level (MBL) is essential for the long-term success of dental implant therapy, and bone remodeling around dental implants is considered to vary with time. Numerous studies comparing the platform-switching (PS) and platform-matching (PM) dental implants have indicated that PS dental implants showed a lesser reduction for the MBL, and the majority of them had a relatively short period. This study aimed to evaluate vertical and horizontal bone defects by using digital periapical radiographs to examine the changes in MBL around PM and PS dental implants over 5 years after functional loading. The vertical MBL (vMBL) was measured from the implant-abutment junction to the first bone-to-implant contact. The horizontal MBL (hMBL) was measured from the implant-abutment junction to the bone crest. All data were presented as means ± standard errors. Paired and independent t-tests with Welch's correction were used to analyze the data. A total of 61 dental implants in 38 patients after 5 years of functional loading were evaluated. Over time, PS dental implants were more likely to gain bone; by contrast, PM dental implants were more likely to lose bone during the observation time. Changes in vMBL for PS dental implants were significantly less than those for PM dental implants at 1-year (p = 0.045), 3-year (p = 0.021), and 5-year (p = 0.010) loading. Likewise, changes in hMBL for PS dental implants were significantly smaller than in those for PM dental implants at 3-year (p = 0.021) and 5-year (p = 0.006) loading; however, the changes were minimal in both approaches. PS dental implants had a significant increment in the percentage of bone integration, whereas that for PM dental implants dropped over time, with no significance. In PS dental implants that occlude with natural teeth, vertical and horizontal bone gain was observed, and it was significant at 3 years (p = 0.023). A significant horizontal bone gain was observed in the opposing natural teeth at 3-year (p = 0.002) and 5-year loading (p = 0.002). The PS concept appears to preserve more MBL around dental implants by stabilizing the vMBL and hMBL over a 5-year period. A minimal marginal bone change was detected in both concepts. The opposing natural teeth at PS dental implants showed a favorable effect on marginal bone tissues.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Time-dependent effects of storage at -80 °C on the stability of butyrylcholinesterase activity in human serum.

Objectives: Butyrylcholinesterase (BChE) is an important biomarker in serum, and aberrant BChE activity indicates onset and progression of human diseases. The duration of serum storage at -80 °C may introduce variability into and compromise the reproducibility of BChE activity measurements. Design and Methods: We collected serum samples from eight healthy volunteers and determined serum BChE activity in these samples using a sensitive fluorescence assay at various time points during a six-month storage period at -80 °C. Changes in averaged BChE activity over storage time were assessed by repeated measures analysis of variance (ANOVA). Sidak multiple comparisons test was also used to perform post-hoc analysis. Results: Almost all determined BChE activity values lay within the normal physiological range of BChE activity. However, repeated measures ANOVA using mean BChE activity vs. storage time showed that BChE activity values from two time points were significantly different. Analysis by Sidak multiple comparisons test provided no substantial change of BChE activity during the first 90 days of storage, but BChE activity noticeably decreased after 90 days. Conclusions: Serum samples stored in -80 °C for up to 90 days can be exploited to accurately determine BChE activity.

Assessment of Malingering among Servicemembers with a Focused Examination of Explanatory Models.

Umbrasas briefly mentioned established models of malingering that sought to understand the driving motivations for feigning mental disorders. He used these models as a point of departure to consider the unique experiences and enduring challenges of active and retired servicemembers. For military malingering, he identified acute distress malingering and disability malingering with the former occurring within the first five years and the latter after a military career had been established. To provide a strong foundation, this commentary revisits three explanatory models of malingering (i.e., pathogenic, criminological, and adaptational) that have been empirically tested. Of these, the adaptational model appears the best suited in the military context to explain nongenuine responding because most mandatory evaluations carry highly negative consequences, such as seriously damaging future careers in the armed forces. Most examinees would be seen as denying and defensive, however, the polar opposite of malingering. When symptoms are eventually reported, Umbrasas acknowledges the temptation to consider this atypical presentation as possible evidence of malingering. We concur with Umbrasas's conclusion that such an extrapolation would be generally unwarranted. In summary, the overriding goal of this commentary is to understand Umbrasas's thought-provoking contributions to military malingering in the larger landscape of explanatory models of malingering.

Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease.

AIM: To assess the efficacy, safety and tolerability of cotadutide in patients with type 2 diabetes mellitus and chronic kidney disease. MATERIALS AND METHODS: In this phase 2a study (NCT03550378), patients with body mass index 25-45 kg/m2 , estimated glomerular filtration rate 30-59 ml/min/1.73 m2 and type 2 diabetes [glycated haemoglobin 6.5-10.5% (48-91 mmol/mol)] controlled with insulin and/or oral therapy combination, were randomized 1:1 to once-daily subcutaneous cotadutide (50-300 µg) or placebo for 32 days. The primary endpoint was plasma glucose concentration assessed using a mixed-meal tolerance test. RESULTS: Participants receiving cotadutide (n = 21) had significant reductions in the mixed-meal tolerance test area under the glucose concentration-time curve (-26.71% vs. +3.68%, p < .001), more time in target glucose range on continuous glucose monitoring (+14.79% vs. -21.23%, p = .001) and significant reductions in absolute bodyweight (-3.41 kg vs. -0.13 kg, p < .001) versus placebo (n = 20). In patients with baseline micro- or macroalbuminuria (n = 18), urinary albumin-to-creatinine ratios decreased by 51% at day 32 with cotadutide versus placebo (p = .0504). No statistically significant difference was observed in mean change in estimated glomerular filtration rate between treatments. Mild/moderate adverse events occurred in 71.4% of participants receiving cotadutide and 35.0% receiving placebo. CONCLUSIONS: We established the efficacy of cotadutide in this patient population, with significantly improved postprandial glucose control and reduced bodyweight versus placebo. Reductions in urinary albumin-to-creatinine ratios suggest potential benefits of cotadutide on kidney function, supporting further evaluation in larger, longer-term clinical trials.

Health services utilization and cost of abusive head trauma in Taiwan: A population-based retrospective matched cohort study.

BACKGROUND: Abusive head trauma (AHT) is a serious health problem that results the highest mortality among children who are maltreated. Many AHT survivors suffer from long-term sequelae and require medical treatment. However, the knowledge of AHT-attributable health services utilization and costs at national level are limited. OBJECTIVE: To estimate health services utilization and costs attributable to AHT among children aged 0-4 years in Taiwan. PARTICIPANTS AND SETTING: Sixty-three fatal and 664 survival AHT cases were identified using Taiwan national population database between 2003 and 2015. A total of 2656 non-AHT children were exactly 4:1 matched to the survival cases based on their birth year, gender, the calendar year of the index date, insured location, and health insurance premium (social economic status indicator). METHODS: Health services utilization and costs were calculated on an annual basis for 3 years after the index date. AHT-attributable health services utilization and costs during 3-year follow-up period was evaluated by regression models. RESULTS: AHT diagnosis was positively associated with inpatient admissions, length of stay, emergency room (ER) visits, and outpatient visits. AHT-attributable medical costs were 1.64-17.27 times, 1.25-5.22 times, and 1.77-2.36 times greater for inpatient, ER, and outpatient during 3-year period than matched controls, respectively. Fatal AHT cases had higher inpatient utilization and greater medical costs than AHT survivors. CONCLUSIONS: Children with AHT had greater health services utilization and higher costs for years. Strategies to reduce the burden of AHT on health care system are imperative.