Exploration of a cognitive model to predict post-traumatic stress symptoms following childbirth

Women can suffer from post-traumatic stress disorder (PTSD) following childbirth. This study investigated the application of a cognitive model to PTS symptoms following childbirth and explored the addition of social support to the model. Methods: Women (N=138) completed questionnaires in pregnancy, three-weeks and three-months after birth, measuring prior trauma, beliefs, and coping in pregnancy; and birth interventions, social support, post-traumatic cognitions, and PTS symptoms post-birth. Results: Using structural equation modeling, a cognitive model explained 23% of the variance in PTS symptoms three-weeks postpartum. Three-months postpartum, the model explained only 9% of the variance in PTS symptoms. The addition of social support, partially mediated by post-traumatic cognitions, increased the variance to 16%. Discussion: Results suggest that a cognitive model accounts for early PTS symptoms after birth. Social support after birth increases the explanatory power of the model at three months. A test of the model on a larger sample is warranted

Differences between Mycobacterium chimaera and tuberculosis Using Ocular Multimodal Imaging: A Systematic Review

Due to their non-specific diagnostic patterns of ocular infection, differential diagnosis between Mycobacterium (M.) chimaera and tuberculosis can be challenging. In both disorders, ocular manifestation can be the first sign of a systemic infection, and a delayed diagnosis might reduce the response to treatment leading to negative outcomes. Thus, it becomes imperative to distinguish chorioretinal lesions associated with M. chimaera, from lesions due to M. tuberculosis and other infectious disorders. To date, multimodal non-invasive imaging modalities that include ultra-wide field fundus photography, fluorescein and indocyanine green angiography, optical coherence tomography and optical coherence tomography angiography, facilitate in vivo examination of retinal and choroidal tissues, enabling early diagnosis, monitoring treatment response, and relapse detection. This approach is crucial to differentiate between active and inactive ocular disease, and guides clinicians in their decisional-tree during the patients' follow-up. In this review, we summarized and compared the available literature on multimodal imaging data of M. chimaera infection and tuberculosis, emphasizing similarities and differences in imaging patterns between these two entities and highlighting the relevance of multimodal imaging in the management of the infections

TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons

<p>Abstract</p> <p>Background</p> <p>Familial amyloidotic polyneuropathy (FAP) is a peripheral neuropathy caused by the extracellular accumulation and deposition of insoluble transthyretin (TTR) aggregates. However the molecular mechanism that underlies TTR toxicity in peripheral nerves is unclear. Previous studies have suggested that amyloidogenic proteins can aggregate into oligomers which disrupt intracellular calcium homeostasis by increasing the permeability of the plasma membrane to extracellular calcium. The aim of the present study was to examine the effect of TTR on calcium influx in dorsal root ganglion neurons.</p> <p>Results</p> <p>Levels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Na_v1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.</p> <p>Conclusions</p> <p>These data suggest that activation of TRPM8 channels triggers the activation of Na_v1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of Alzheimer's disease.</p

Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARS-CoV-2 Infection (COVID-19) Compared with Healthy Young Controls

Purpose: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Methods: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l’Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant’s eyes. Results: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group. Conclusion: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02–0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues

A new method for targeted and sustained induction of type 2 diabetes in rodents

Type 2 diabetes is a chronic metabolic disorder that is becoming a leading cause of morbidity and mortality. The prolonged time-course of human type 2 diabetes makes modelling of the disease difficult and additional animal models and methodologies are needed. The goal of this study was to develop and characterise a new method that allows controlled, targeted and sustained induction of discrete stages of type 2 diabetes in rodents. Using adult, male rats, we employed a three-week high fat-diet regimen and confirmed development of obesity-associated glucose intolerance, a key feature of human type 2 diabetes. Next, we utilised osmotic mini-pumps to infuse streptozotocin (STZ; doses ranging 80-200&thinsp;mg/kg) over the course of 14-days to decrease insulin-producing capacity thus promoting hyperglycemia. Using this new approach, we demonstrate a dose-dependent effect of STZ on circulating glucose and insulin levels as well as glucose tolerance, while retaining a state of obesity. Importantly, we found that insulin secretion in response to a glucose load was present, but reduced in a dose-dependent manner by increasing STZ. In conclusion, we demonstrate a novel method that enables induction of discrete stages of type 2 diabetes in rodents that closely mirrors the different stages of type 2 diabetes in humans

Psychological trauma and evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among West Nile refugees

BACKGROUND: Political instability and the civil war in Southern Sudan have resulted in numerous atrocities, mass violence, and forced migration for vast parts of the civilian population in the West Nile region. High exposure to traumatic experiences has been particularly prominent in the Ugandan and Sudanese of the West Nile Region, representing an indication of the psychological strain posed by years of armed conflict. METHODS: In this study the impact of traumatic events on the prevalence and severity of posttraumatic stress disorder (PTSD) in a random sample of 3.339 Ugandan nationals, Sudanese nationals, and Sudanese refugees (1.831 households) of the West Nile region is assessed. RESULTS: Results show a positive correlation between the number of traumatic events and the number of endorsed PTSD symptoms. Of the 58 respondents who experienced the greatest number of traumatizing experiences, all reported symptoms which met the DSM-IV criteria for PTSD. CONCLUSIONS: There is a clear dose-effect relationship between traumatic exposure and PTSD in the studied populations with high levels of traumatic events. In this context, it is probable that any individual could develop PTSD regardless of other risk-factors once the trauma load reaches a certain threshold

Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Re-examination of the Controversial Coexistence of Traumatic Brain Injury and Posttraumatic Stress Disorder: Misdiagnosis and Self-Report Measures

The coexistence of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) remains a controversial issue in the literature. To address this controversy, we focused primarily on the civilian-related literature of TBI and PTSD. Some investigators have argued that individuals who had been rendered unconscious or suffered amnesia due to a TBI are unable to develop PTSD because they would be unable to consciously experience the symptoms of fear, helplessness, and horror associated with the development of PTSD. Other investigators have reported that individuals who sustain TBI, regardless of its severity, can develop PTSD even in the context of prolonged unconsciousness. A careful review of the methodologies employed in these studies reveals that investigators who relied on clinical interviews of TBI patients to diagnose PTSD found little or no evidence of PTSD. In contrast, investigators who relied on PTSD questionnaires to diagnose PTSD found considerable evidence of PTSD. Further analysis revealed that many of the TBI patients who were initially diagnosed with PTSD according to self-report questionnaires did not meet the diagnostic criteria for PTSD upon completion of a clinical interview. In particular, patients with severe TBI were often misdiagnosed with PTSD. A number of investigators found that many of the severe TBI patients failed to follow the questionnaire instructions and erroneously endorsed PTSD symptoms because of their cognitive difficulties. Because PTSD questionnaires are not designed to discriminate between PTSD and TBI symptoms or determine whether a patient's responses are accurate or exaggerated, studies that rely on self-report questionnaires to evaluate PTSD in TBI patients are at risk of misdiagnosing PTSD. Further research should evaluate the degree to which misdiagnosis of PTSD occurs in individuals who have sustained mild TBI

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe