To the best of our knowledge, this study describes the first successful isolation of LSDV in India, besides providing insights into the life cycle Vero cell-adapted LSDV.
  Carfilzomib is a second-generation irreversible proteasome inhibitor that is efficacious in the treatment of myeloma and carries less risk of peripheral neuropathy than first-generation proteasome inhibitors, making it more amenable to combination therapy.
 
  The Myeloma XI+ trial recruited patients from 88 sites across the UK between 5 December 2013 and 20 April 2016. Patients with newly diagnosed multiple myeloma eligible for transplantation were randomly assigned to receive the combination carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) or a triplet of lenalidomide, dexamethasone, and cyclophosphamide (Rdc) or thalidomide, dexamethasone, and cyclophosphamide (Tdc). All patients were planned to receive an autologous stem cell transplantation (ASCT) prior to a randomisation between lenalidomide maintenance and observation. Eligible patients were aged over 18 years and had symptomatic myeloma. The co-primary endpoints for the study were progression-free survival (PFS) and overall survivisease negativity (cutoff 4 × 10-5 bone marrow leucocytes) was achieved in 55% of patients tested in the KRdc group at the end of induction, increasing to 75% of those tested after ASCT. The most common adverse events were haematological, with a low incidence of cardiac events. The trial continues to follow up patients to the co-primary endpoint of OS and for planned long-term follow-up analysis. Limitations of the study include a lack of blinding to treatment regimen and that the triplet control regimen did not include a proteasome inhibitor for all patients, which would be considered a current standard of care in many parts of the world.
 
  The KRdc combination was well tolerated and was associated with both an increased percentage of patients achieving at least a very good partial response and a significant PFS benefit compared to immunomodulatory-agent-based triplet therapy.
 
  ClinicalTrials.gov ISRCTN49407852.
 ClinicalTrials.gov ISRCTN49407852.
  Chronic idiopathic constipation (CIC) is a prevalent functional gastrointestinal disorder diagnosed based on patient-reported symptoms and the absence of structural gastrointestinal abnormalities. Individuals with CIC typically institute dietary changes and use stool softeners or over-the-counter (OTC) laxatives, possibly at the direction of a healthcare provider, before prescription medications for CIC are initiated. Although highly prevalent, there is limited information regarding CIC patient experiences with OTC medications.
 
  This post-hoc analysis used patient-reported data from a questionnaire administered during patient screening for a prospective linaclotide Phase 3b clinical trial in patients with CIC (N = 1482 screened). The questionnaire asked patients to report their experiences with OTC CIC medications over the preceding 6 months.
 
  Among patients with screening responses (N = 1423), most were female (85%) and white (66%), with a mean age of 48.9 years. A high proportion of patients had used one or more OTC medications (70% had ≥1 OTC; 19% had ≥3 OTCs), with the majority being bisacodyl (33%) and polyethylene glycol (30%). The most commonly cited reason for stopping an OTC medication was insufficient symptom relief (17-40%). The majority of patients taking OTC medications reported no or little satisfaction with the medication's effect on their constipation (62%) and CIC-specific abdominal symptoms (78%). Many patients had little to no confidence in bowel movement (BM) frequency after taking OTC medications and their confidence in their ability to predict BM timing was also low (49-81% not at all confident).
 
  Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC.
 
  NCT01642914.
 NCT01642914.The COVID-19 pandemic does not fit into prevailing Post-traumatic Stress Disorder (PTSD) models, or diagnostic criteria, yet emerging research shows traumatic stress symptoms as a result of this ongoing global stressor. Current pathogenic event models focus on past, and largely direct, trauma exposure to certain kinds of life-threatening events. Yet, traumatic stress reactions to future, indirect trauma exposure, and non-Criterion A events exist, suggesting COVID-19 is also a traumatic stressor which could lead to PTSD symptomology. To examine this idea, we asked a sample of online participants (N = 1,040), in five western countries, to indicate the COVID-19 events they had been directly exposed to, events they anticipated would happen in the future, and other forms of indirect exposure such as through media coverage. We then asked participants to complete the Posttraumatic Stress Disorder Checklist-5, adapted to measure pre/peri/post-traumatic reactions in relation to COVID-19. We also measured general emotional reactions (e.g., angry, anxious, helpless), well-being, psychosocial functioning, and depression, anxiety, and stress symptoms. We found participants had PTSD-like symptoms for events that had not happened and when participants had been directly (e.g., contact with virus) or indirectly exposed to COVID-19 (e.g., via media). Moreover, 13.2% of our sample were likely PTSD-positive, despite types of COVID-19 "exposure" (e.g., lockdown) not fitting DSM-5 criteria. The emotional impact of "worst" experienced/anticipated events best predicted PTSD-like symptoms. Taken together, our findings support emerging research that COVID-19 can be understood as a traumatic stressor event capable of eliciting PTSD-like responses and exacerbating other related mental health problems (e.g., anxiety, depression, psychosocial functioning, etc.). Our findings add to existing literature supporting a pathogenic event memory model of traumatic stress.
  Psoriasis is a chronic immune-mediated disease and psoriatic arthritis is a common coexisting condition. Cardiorespiratory fitness is the overall capacity to perform exertion exercise. Low levels of cardiorespiratory fitness are associated with negative health outcomes. Individuals with psoriasis have lower cardiorespiratory fitness compared with individuals without psoriasis. There are no previous studies exploring the association between cardiorespiratory fitness and new-onset psoriasis and psoriatic arthritis.
 
  With the objective to investigate whether low cardiorespiratory fitness in late adolescence increases the risk for onset of psoriasis and psoriatic arthritis, a cohort of Swedish men in compulsory military service between 1968 and 2005 was created using data from the Swedish Military Service Conscription Register.  https://www.selleckchem.com/products/z-ietd-fmk.html  Cardiorespiratory fitness, estimated by maximum capacity cycle ergometer testing at conscription, was divided into three groups high, medium, and low. Diagnoses were obtained using the Swedish National Patient Register and cohort members were followed from conscription until an event, new-onset psoriasis or psoriatic arthritis, occurred, or at the latest until 31 December 2016.