BPD Group Research Articles

Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma

BackgroundTriplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse.MethodsIn this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed.ResultsA total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group.ConclusionsAmong lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.)

“Esketamine” in Borderline Personality Disorder: focud on suicide ideation

IntroductionBorderline personality disorder is often associated with comorbid conditions such as eating disorders, mood disorders, and substance use disorders. The prevalence of BPD and major depressive disorder (MDD) are about 5.9% and 8%, respectively, but up to 80% of patients with BPD experience one or more episodes of MDD in their lifetime. BPD is associated with suicidal behaviors and self-harm, thei are also fifty times more likely than the general population to attempt or die by suicide, Up to 10% of BPD patients will die by suicideObjectivesOur aim is to verify if Esketamine could be effectiveness in treating patterns of behavior that have proven to be socially disruptive like self harm, suicidal attempts in patients with BPD. Suicidal ideation is a major risk factor for suicide in patients with TRD and BPD. The interval between the onset of suicidal ideation and suicide attempt is often very short, highlighting the need for urgent intervention and the development of new rapid-onset antidepressant therapies.MethodsWe recruited 25 adult subjects referred to the outpatient clinics of Pavia suffering from TRD with current Moderate-Severe Depressive Episode (scoring ≥ 22 on the MADRS). Of them 9/25 patients has a BPD. Study duration was 8 weeks.The following evaluation scales were administered before the first drug administration (T0) and repeated after one week (T1), four weeks (T2) and eight weeks (T3) of treatment: Montgomery Asberg Depression Rating Scale (MADRS), Columbia-Suicide Severity Rating Scale (CSSRS), and The Zanarini Rating Scale for BPD subgroup patients. We also collected sociodemographic and clinical information. Dosages and frequency of esketamine administration during the study period, adverse events and reasons for discontinuation were also recorded.ResultsA significant reduction of depressive symptoms was found at T1 and T2 compared to T0. Suicidal ideation disappeared as early as T1 and was maintained at T2, expecially in the BPD group. In the subgroup with borderline disorder we saw more improvement in impulsive (Self-mutilation and/or suicidal efforts; two other forms of impulsivity) and affective categories ( Inappropriate anger / frequent angry acts; chronic feelings of emptiness; mood instability) in Zanarini Rating Scale.ConclusionsOur findings support the safety and tolerability of esketamine in TRD and BPD comorbidity sample. It is noteworthy that esketamine has an action on various pathways that are considered defective in borderline patients. Glutamate plays a key role in personality traits such as impulsivity, aggression, and suicidal behavior. Treatment with esketamine could reduce the number of suicide attempts and help reduce the self-harm of BPD.Disclosure of InterestNone Declared

Machine learning predictive models for grading bronchopulmonary dysplasia: umbilical cord blood IL-6 as a biomarker.

This study aimed to analyze the predictive value of umbilical cord blood Interleukin-6 (UCB IL-6) for the severity-graded BPD and to establish machine learning (ML) predictive models in a Chinese population based on the 2019 NRN evidence-based guidelines. In this retrospective analysis, we included infants born with gestational age <32 weeks, who underwent UCB IL-6 testing within 24 h of admission to our NICU between 2020 and 2022. We collected their medical information encompassing the maternal, perinatal, and early neonatal phases. Furthermore, we classified the grade of BPD according to the 2019 NRN evidence-based guidelines. The correlation between UCB IL-6 and the grades of BPD was analyzed. Univariate analysis and ordinal logistic regression were employed to identify risk factors, followed by the development of ML predictive models based on XGBoost, CatBoost, LightGBM, and Random Forest. The AUROC was used to evaluate the diagnostic value of each model. Besides, we generated feature importance distribution plots based on SHAP values to emphasize the significance of UCB IL-6 in the models. The study ultimately enrolled 414 preterm infants, with No BPD group (n = 309), Grade 1 BPD group (n = 73), and Grade 2-3 BPD group (n = 32). The levels of UCB IL-6 increased with the grades of BPD. UCB IL-6 demonstrated clinical significance in predicting various grades of BPD, particularly in distinguishing Grade 2-3 BPD patients, with an AUROC of 0.815 (95% CI: 0.753-0.877). All four ML models, XGBoost, CatBoost, LightGBM, and Random Forest, exhibited Micro-average AUROC values of 0.841, 0.870, 0.851, and 0.878, respectively. Notably, UCB IL-6 consistently appeared as the most prominent feature across the feature importance distribution plots in all four models. UCB IL-6 significantly contributes to predicting severity-graded BPD, especially in grade 2-3 BPD. Through the development of four ML predictive models, we highlighted UCB IL-6's importance.

Intranasal Oxytocin as an adjunct treatment in patients with major depression with and without comorbid borderline personality disorder

Introduction The mechanisms leading to Oxytocin’s differential effects among patients with borderline personality disorder have thus far been elusive. Objectives This study was aimed to explore the differential effect of OT administration among depressive patients with or without comorbid borderline personality disorder, and to explore the mediating role of attachment in these differential patterns. Methods Patients treated with psychotherapy in an inpatient settings (N=58) were randomized and double-blindly allocated to receive oxytocin or placebo for a period of four weeks. The effect of OT on therapy process and outcome was examined among patients with (n=35) and without (n=23) borderline personality disorder. Moderated mediational models were estimated to explore whether attachment differentially affected the association between oxytocin and treatment outcomes. Results patients without BPD showed significantly larger improvements following OT administration (B=-8.32, p=.001) as compared to placebo in OQ-45. On the other hand, patients with BPD showed no significant improvement following OT (B=0.61, p=.76). The same pattern was observed in the HSCL, where patients without BPD demonstrated significantly larger improvements following OT administration (B=-0.29 ,p=.0009) as compared to placebo, while patients with BPD demonstrated no significant improvement (B=-0.04 ,p=.55). Moderated mediational models indicated no significant moderated indirect effect, however, a significant trend of indirect effect only in the BPD group was observed, whereby the no-BPD group showed a stronger direct effect (β=-0.19, t=-1.30, p=.20), whereas the BPD group showed a stronger indirect effect (β=-0.72, SE=0.45, CI= -1,71, -0.00). Conclusions Patients with depression and comorbid BPD benefit less from OT administration as compared depressive patients without such comorbidity. It is possible that the involvement of the attachment system may be associated with the attenuation of OT’s effect. Disclosure of Interest None Declared

The value of plasma insulin-like growth factor 1 and interleukin-18 in the diagnosis of bronchopulmonary dysplasia in premature infants.

ObjectiveTo explore the diagnostic value of IGF-1 and IL-18 in premature infants with BPD.MethodsThrough a prospective observational study, the serum samples of infants in the BPD group and the non-BPD group were collected at different targeted time points, and the serum IGF-1 and IL-18 concentrations were dynamically monitored by ELISA. The Student t-test and one-way analysis of variance were adopted to analyze data, and the receiver operating characteristic (ROC) curve was used to test the diagnostic value.ResultA total of 90 VLBW premature infants admitted to NICU between January 2020 and 2021 were finally included. Compared with the non-BPD group, infants diagnosed with BPD had a significantly lower serum concentration of IGF-1 (P < 0.05) but a higher level of IL-18 (P < 0.05) on days 1, 7, 14, and 28 after birth. With the ROC curve analysis, the serum concentration IGF-1 on day 14 and IL-18 on day 28 reported high sensitivity and specificity to predict the risk of BPD (IGF-1: sensitivity: 89.29%, specificity: 77.78%, AUC: 0.8710; IL-18: sensitivity: 53.57%, specificity: 83.33%, AUC: 0.7887). And more substantial predictive power was found in combined analysis of IGF-1 and serum IL-18 on day 14: the sensitivity was 91.07% and the specificity was 83.33%, with the AUC of 0.9142.ConclusionIGF-1 and IL-18 might be closely involved in the occurrence and development of BPD. The serum concentration of IGF-1 combined with IL-18 could be potentially sensitive markers for the early diagnosis and severity of BPD.

Increased cytotoxic T-cells in the airways of adults with former bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) in preterm-born infants is a risk factor for chronic airway obstruction in adulthood. Cytotoxic T-cells are implicated in COPD, but their involvement in BPD is not known. To characterise the distribution of airway T-cell subsets in adults with a history of BPD. Young adults with former BPD (n=22; median age 19.6 years), age-matched adults born preterm (n=22), patients with allergic asthma born at term (n=22) and healthy control subjects born at term (n=24) underwent bronchoalveolar lavage (BAL). T-cell subsets in BAL were analysed using flow cytometry. The total number of cells and the differential cell counts in BAL were similar among the study groups. The percentage of CD3+CD8+ T-cells was higher (p=0.005) and the proportion of CD3+CD4+ T-cells was reduced (p=0.01) in the BPD group, resulting in a lower CD4/CD8 ratio (p=0.007) compared to the healthy controls (median 2.2 versus 5.3). In BPD and preterm-born study subjects, both CD3+CD4+ T-cells (rs=0.38, p=0.03) and CD4/CD8 ratio (rs=0.44, p=0.01) correlated positively with forced expiratory volume in 1 s (FEV1). Furthermore, CD3+CD8+ T-cells were negatively correlated with both FEV1 and FEV1/forced vital capacity (rs= -0.44, p=0.09 and rs= -0.41, p=0.01, respectively). Young adults with former BPD have a T-cell subset pattern in the airways resembling features of COPD. Our findings are compatible with the hypothesis that CD3+CD8+ T-cells are involved in mechanisms behind chronic airway obstruction in these patients.

Dynamic Changes of NCR\u2212 Type 3 Innate Lymphoid Cells and Their Role in Mice with Bronchopulmonary Dysplasia

—Inflammation is one of the important pathogenesis of bronchopulmonary dysplasia (BPD). Type 3 innate lymphoid cells (ILC3) play a role in a variety of inflammatory lung diseases. In this study, we established the BPD model by injecting lipopolysaccharide into the amniotic cavity of pregnant mice. Here, we investigated the dynamic changes of ILC3 and NKP46− ILC3 population in lung tissues of mice from BPD and the control groups. Results showed that the proportion of ILC3 and NKP46−ILC3 in the BPD group was higher than those of the control group. In addition, the cytokines interleukin-17 (IL-17) and interleukin-22 (IL-22) secreted by ILC3 in this model had also changed that their expression was significantly increased compared with that of the control group. Flow cytometry demonstrated that ILC3 were a rapid source of IL-17. In the anti-CD90 knockdown experiment, we confirmed the alleviation of BPD inflammation in the absence of ILC3. In addition, we injected mice with anti-IL-17 neutralizing antibody, and the results showed that IL-17 could aggravate BPD inflammation. Taken together, ILC3 may play a pro-inflammatory role in BPD by secreting IL-17.

Diabetes Resolution at 10 Years After Biliopancreatic Diversion in Overweight and Class 1 Obese Patients with Type 2 Diabetes

BackgroundLong-term anti-diabetic effects of BPD in overweight or class 1 obese T2DM patients were investigated reporting the results at 10 years after BPD performed in severely non-obese T2DM patients.Material and MethodsThirty T2DM patients with BMI lower than 35 kg/m2 were investigated at 1, 5, and 10 years after BPD, and the results are compared with those of 30 T2DM patients followed for 10 years on pharmacological and/or behavioral conventional therapy.ResultsMean levels of fasting blood glucose (FBG) and serum glycated hemoglobin (HbA1C) showed a marked reduction 1 year after BPD, values remaining slightly above the diabetic range throughout the entire follow-up. T2DM remission was observed in about 50% of the cases at 5 and 10 years after the operation. In 16 patients (53%), severe BPD-related complications developed, in ten cases requiring a surgical revision of the operation. In the BPD group, one patient died for malignant lymphoma and two patients after surgical revision. Within the control group, during the 10-year follow-up, no changes in the diabetic status were observed, being the FBG and HbA1C mean values higher than those recorded in the BPD patients at any follow-up time. All T2DM subjects of the control group were alive at the end of the 10-year follow-up.ConclusionDespite satisfactory long-term metabolic outcomes, these data indicate that BPD should be used with caution as a metabolic procedure in the treatment of T2DM in overweight or class 1obese patients.Graphical abstract

The Correlation Between Bronchopulmonary Dysplasia and Platelet Metabolism in Preterm Infants.

Background: Platelets play an important role in the formation of pulmonary blood vessels, and thrombocytopenia is common in patients with pulmonary diseases. However, a few studies have reported on the role of platelets in bronchopulmonary dysplasia.Objective: The objective of the study was to explore the relationship between platelet metabolism and bronchopulmonary dysplasia in premature infants.Methods: A prospective case-control study was performed in a cohort of premature infants (born with a gestational age <32 weeks and a birth weight <1,500 g) from June 1, 2017 to June 1, 2018. Subjects were stratified into two groups according to the diagnostic of bronchopulmonary dysplasia: with bronchopulmonary dysplasia (BPD group) and without bronchopulmonary dysplasia (control group). Platelet count, circulating megakaryocyte count (MK), platelet-activating markers (CD62P and CD63), and thrombopoietin (TPO) were recorded and compared in two groups 28 days after birth; then serial thrombopoietin levels and concomitant platelet counts were measured in infants with BPD.Results: A total of 252 premature infants were included in this study. Forty-eight premature infants developed BPD, 48 premature infants without BPD in the control group who were matched against the study infants for gestational age, birth weight, and admission diagnosis at the age of postnatal day 28. Compared with the controls, infants with BPD had significantly lower peripheral platelet count [BPD vs. controls: 180.3 (24.2) × 109/L vs. 345.6 (28.5) × 109/L, p = 0.001]. Circulating MK count in the BPD group was significantly more abundant than that in the control group [BPD vs. controls: 30.7 (4.5)/ml vs. 13.3 (2.6)/ml, p = 0.025]. The level of CD62p, CD63, and TPO in BPD group was significantly higher than the control group [29.7 (3.1%) vs. 14.5 (2.5%), 15.4 (2.0%) vs. 5.8 (1.7%), 301.4 (25.9) pg/ml vs. 120.4 (14.2) pg/ml, all p < 0.05]. Furthermore, the concentration of TPO was negatively correlated with platelet count in BPD group with thrombocytopenia.Conclusions: Our findings suggest that platelet metabolism is involved in the development of BPD in preterm infants. The possible mechanism might be through increased platelet activation and promoted TPO production by feedback.

'Rich' and 'poor' in mentalizing: Do expert mentalizers exist?

Mentalization theory is concerned with the capacity to notice, and make sense of, thoughts and feelings in self and others. This development may be healthy or impaired and therefore, by extension, it may be theorized that expertise in mentalizing can exist. Furthermore, a continuum from impairment to expertise should exist within separate dimensions of mentalizing: of self and of others. This study hypothesized that three groups would be distinguishable on the basis of their mentalizing capacities. In a cross-sectional design, Psychological Therapists (‘expert’ mentalizers; n = 51), individuals with a diagnosis of Borderline Personality Disorder (‘poor’ mentalizers; n = 43) and members of the general population (‘non-clinical controls’; n = 35) completed a battery of self-report measures. These assessed the mentalizing of self and of others (using an extended version of the Reflective Function Questionnaire (RFQ18)), alexithymia and cognitive empathy. As hypothesized, Psychological Therapists’ scores were higher than controls on self-mentalizing and control group scores were higher than those with BPD. Cognitive empathy scores in the BPD group indicated markedly lower capacities than the other two groups. Contrary to predictions, no significant differences were found between groups on mentalizing others in RFQ18 scores. The Psychological Therapist and BPD profiles were characterized by differential impairment with regards to mentalizing self and others but in opposing directions. Results suggest that the RFQ18 can identify groups with expertise in mentalizing. Implications of these results for the effectiveness of psychological therapy and of Psychological Therapists are discussed.

Encouraging outcomes of using a small-donor single graft in pediatric kidney transplantation.

The use of small pediatric kidneys as single graftsfor transplantation is controversial, due to the potential risk for graft thrombosis and insufficient nephron mass. Aiming to test the benefits of transplanting these kidneys, 375 children who underwent kidney transplantation in a single center were evaluated: 49 (13.1%) received a single graft from a small pediatric donor (≤ 15kg, SPD group), 244 (65.1%) from a bigger pediatric donor (> 15kg, BPD group), and 82 (21.9%) from adult living donors (group ALD). Groups had similar baseline main characteristics. After 5years of follow-up, children from the SPD group were comparable to children from BPD and ALD in patient survival (94%, 96%, and 98%, respectively, p = 0.423); graft survival (89%, 88%, and 93%, respectively, p = 0.426); the frequency of acute rejection (p = 0.998); the incidence of post-transplant lymphoproliferative disease (p = 0.671); the odds ratio for severely increased proteinuria (p = 0.357); the rates of vascular thrombosis (p = 0.846); and the necessity for post-transplant surgical intervention prior to discharge (p = 0.905). The longitudinal evolution of eGFR was not uniform among groups. The three groups presented a decrease in eGFR, but the slope of the curve was steeper in ALD children. At 5years, the eGFR of the ALD group was 10ml/min/1.73m2 inferior to the others. At that time, the eGFR from the SPD group was statistically similar to the BPD group (p = 0.952). In a specialized transplant center, the use of a single small pediatric donor kidney for transplantation is as successful as bigger pediatric or adult living donors, after 5years of follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impaired impulse inhibition of emotional stimuli in patients with borderline personality disorder

This study was aimed to investigate whether BPD patients showed impaired impulse inhibition of emotional and non-emotional stimuli and to explore relevant neuroelectrophysiological mechanisms. A total of 32 BPD patients and 32 matched healthy controls were recruited. Self-reported scales were used to measure psychiatric symptoms. The event-related potentials (ERPs) were recorded when subjects were performing neutral and emotional Stop Signal Task (SST). Group differences in self-reported scores, behavioral variables and ERPs were compared. The BPD group scored significantly higher on impulsivity, severity of BPD symptoms, levels of depression and anxiety than the control group. In neutral SST, no significant group differences were detected in the amplitude and latency of ERPs components induced. In emotional SST, the P2 amplitude of negative emotion was significantly larger than that of neutral emotion in Go trials. In Stop trials, the P2 amplitude of BPD group was significantly smaller than that of control group, and the N2 amplitude of BPD group was significantly greater than that of control group. BPD patients showed impaired inhibition of emotional stimuli rather than non-emotional stimuli. The deficits of emotional impulse control mainly exhibit at the early attention, stimulus evaluation and conflict detection stages.

EVALUASI IMPLEMENTASI PROGRAM PEMBANGUNAN DAN PEMBERDAYAAN MASYARAKAT DESA (P3MD) DALAM MEWUJUDKAN DESA MANDIRI DI DESA KUALU NENAS KECAMATAN TAMBANG KABUPATEN KAMPAR

The Village Community Development and Empowerment Program (P3MD) is a strategic government program. The implementation of the program in Kualu Nenas Village has not had a significant impact on changing the status of the village, from a developing village to a developed and independent village. The research objective was to determine program implementation and to determine the impact of the program in Kualu Nenas Village. The research method used a qualitative approach, with evaluative research type. Sources of data obtained through observations at the target location of program activities, in-depth interviews, with key informants; Village Head, Village Officials, BPD, LKMD, community leaders and community group representatives, village assistants. Data was also obtained through distributing questionnaires to 30 informants who were selected by purposive sampling. Research result. The implementation of the Program covers 4 (four) areas of activity, namely activities of village administration, village development, village community empowerment, village communities. The implementation of activities has not been fully carried out properly, not all program activities are carried out in accordance with the activity items, according to the program implementation instructions and the specific objectives of the program. There has been no innovation (change) that has led to the achievement of a change in the status of the village from being left behind to becoming a developed and independent village. The programs that have been implemented have not been fully felt by the community, especially in the aspect of developing community productive economic facilities in the agricultural and plantation sectors, and increasing community capacity.

Chronic Inflammatory Placental Lesions Correlate With Bronchopulmonary Dysplasia Severity in Extremely Preterm Infants.

Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH). Eligible infants were 230/7-276/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined. Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P = .003), chronic chorioamnionitis (23% vs 12%, P = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P = .047). The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.

Cerebral Oxygenation and Perfusion when Positioning Preterm Infants: Clinical Implications

To evaluate cerebral tissue oxygenation (cTOI) and cerebral perfusion in preterm infants in supine vs prone positions. Sixty preterm infants, born before 32weeks of gestation, were enrolled; 30 had bronchopulmonary dysplasia (BPD, defined as the need for respiratory support and/or supplemental oxygen at 36weeks of postmenstrual age). Cerebral perfusion, cTOI, and polysomnography were measured in both the supine and prone position with the initial position being randomized. Infants with a major intraventricular hemorrhage or major congenital abnormality were excluded. Cerebral perfusion was unaffected by position or BPD status. In the BPD group, the mean cTOI was higher in the prone position compared with the supine position by a difference of 3.27% (P=.03; 95% CI 6.28-0.25) with no difference seen in the no-BPD group. For the BPD group, the burden of cerebral hypoxemia (cumulative time spent with cTOI <55%) was significantly lower in the prone position (23%) compared with the supine position (29%) (P<.001). In those without BPD, position had no effect on cTOI. In preterm infants with BPD, the prone position improved cerebral oxygenation and reduced cerebral hypoxemia. These findings may have implications for positioning practices. Further research will establish the impact of position on short- and long-term developmental outcomes.

Functional respiratory imaging provides novel insights into the long-term respiratory sequelae of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Lung function and imaging are classically used to assess BPD. Functional respiratory imaging (FRI) combines a structural and functional assessment of the airways and their vasculature. We aimed to assess BPD using FRI and to correlate these findings with the clinical presentation. We included 37 adolescents with a history of preterm birth (22 BPD cases and 15 preterm controls). The study protocol included a detailed history, lung function testing and computed tomography (CT) (at total lung capacity (TLC) and functional residual capacity (FRC)) with FRI. CT images were also assessed using the Aukland scoring system. BPD patients had lower forced expiratory volume in 1 s to forced vital capacity ratio (p=0.02) and impaired diffusion capacity (p=0.02). Aukland CT scores were not different between the two groups. FRI analysis showed higher lobar volumes in BPD patients at FRC (p<0.01), but not at TLC. Airway resistance was significantly higher in the BPD group, especially in the distal airways. Additionally, FRI showed more air trapping in BPD patients, in contrast to findings on conventional CT images. This study is the first to use FRI in research for BPD. FRI analysis showed higher lobar volumes in BPD patients, indicating air trapping and reduced inspiratory capacity. In contrast to Aukland CT scores, FRI showed more air trapping in the BPD group, suggesting that FRI might be a more sensitive detection method. Importantly, we also showed increased distal airway resistance in BPD patients. By combining structural and functional assessment, FRI may help to better understand the long-term sequelae of BPD.

Validation of computerized reflective function: A replication study

Objective: The Reflective Function (RF) Scale is the original validated measure of mentalizing, applied to Adult Attachment Interview (AAI) transcripts. This study aimed to replicate the preliminary validation of Computerized RF (CRF), a computerized text analysis measure of RF. Methods: 49 women with borderline personality disorder (BPD; n = 20) and without (n = 29) completed diagnostic interviews and the AAI. AAIs were scored by certified coders using the RF Scale, and by computerized text analysis software using CRF dictionaries. Results: CRF significantly correlated with RF. The frequency of High CRF words had moderate-to-strong correlations with RF in the total sample (rs = .47), BPD group (rs = .61), and non-BPD group (rs = .41). Adding the frequency of Low CRF words to create a proportion of High and Low CRF words, and applying CRF to AAIs trimmed to include only items that “demand” RF, both produced significant, but not stronger, correlations with RF. Conclusion: CRF is an efficient alternative to the RF Scale that can estimate mentalization. Near average levels, neither RF nor CRF significantly differentiated between groups, indicating mentalizing deficits may not always be present, detectable, or defining in BPD samples. While more research is needed, CRF is a valid assessment of RF when codable text is available.

Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in bipolar disorder with current major depressive episode patients

BackgroundThe microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). MethodsWe performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. ResultsCompared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LimitationsThe features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. ConclusionsThe present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.

EVALUASI PROGRAM PEMBERDAYAAN MASYARAKAT MENURUT UNDANG-UNDANG NOMOR 6 TAHUN 2014 (STUDI KASUS PROGRAM DESA MAJU INHIL JAYA DI DESA DANAU PULAI INDAH DAN DESA KARYA TANI KECAMATAN KEMPAS (KABUPATEN INDRAGIRI HILIR)

The Integrated Village of Inhil Jaya (DMIJ) Plus Program, is the flagship program of the Government of Indragiri Hilir Regency. This research is to find out the implementation of the Integrated Maju Inhil Jaya Plus Village (DMIJ) program, the impact of the implementation and the constraints of the Integrated DMIJ Plus program in Danau Pulai Indah Village and Karya Tani Village. The research method used a qualitative research approach, with evaluative research types by case studies. Sources of data obtained through observation, documents, and in-depth interviews (indepth interview), with key informants; Village Heads, Village Officials, BPD, LKMD, community leaders and community group representatives. The results of the study, showed that the implementation of the Maju Inhil Jaya Village program in Danau Pulai Indah Village and Karya Tani Village covered 4 (four) fields of activities that were not fully implemented, the program implementation was still conservative-involutive. The integrated DMIJ Plus program has a positive impact on the field of village governance, the field of village development, and the field of village community development can also be said to be good. while the field of village community empowerment, the desired results have not been good or less than the maximum. The impact of the DMIJ program has not been fully felt by the community, the contribution of the program is still minimal in the field of community empowerment. The constraints are the still limited quality of the human resources of the program implementers, and the program target communities.

Outcome of revisional bariatric surgery for insufficient weight loss after laparoscopic Roux-en-Y gastric bypass: an observational study.

Insufficient weight loss or secondary weight regain with or without recurrence of comorbidity can occur years after laparoscopic Roux en Y gastric bypass (LRYGB). In selected patients, increasing restriction or adding malabsorption may be a surgical option after conservative measures failed. Evaluation of short and long term results of revisional surgery for insufficient weight loss or weight regain after LRYGB. Tertiary hospital. Retrospective analysis of prospectively collected data from a cohort of 1150 LRYGB patients. Included were patients, who underwent revisional bariatric surgery after LRYGB for insufficient weight loss with a follow-up of minimal 1 year. Fifty-four patients were included in the analysis. After an interdisciplinary evaluation, patients with insufficient weight loss, signs of dumping syndrome, and lacking restriction were offered a nonadjustable band around the pouch (banded group, n = 34) and patients with sufficient restriction, excellent compliance, and adherence were offered a revision to laparoscopic biliopancreatic diversion (BPD group, n = 20). The revisional procedure was performed 3.3 ± 2.3 years after LRYGB in the banded-group and after 6.4 ± 4.3 years in the BPD group (P = .001). Mean body mass index at the time of the primary bariatric procedure was 41.7 ± 6.2 kg/m2 in the banded group and 45.2 ± 8.2 kg/m2 in the BPD group (P = .08); minimal body mass index between both operations was 29.1 ± 4.7 kg/m2 in the banded group and 36.5 ± 9.4 kg/m2 in the BPD group, and, at the time of revisional surgery, 31.4 ± 5.5 kg/m2 in the banded group and 40.8 ± 6.7 kg/m2 in the BPD group (P = .0001). The mean body mass index difference 1 year after revisional surgery was 1.3 ± 3.0 kg/m2 in the banded group and 6.7 ± 4.5 kg/m2 in the BPD group (P = .01). In the banded group, 11 patients (32.4%) needed removal of the band, 4 patients (11.8%) needed an adjustment, and 4 patients (11.8%) were later converted to BPD. In the BPD group, 2 (10.0%) patients needed revision for severe protein malabsorption. Insufficient weight loss or secondary weight regain after LRYGB is a rare indication for revisional surgery. Banded bypass has modest results for additional weight loss but can help patients suffering from dumping. In very carefully selected cases, BPD can achieve additional weight loss with acceptable complication rate but higher risk for reoperation. Future "adjuvant medical treatments," such as glucagon-like peptide 1 analogues and other pharmacologic treatment options could be an alternative for achievingadditional weight loss and better metabolic response.