Unexplained severe portal hypertension in HIV-infected patients: a new clinical entity?

Cases of non-cirrhotic portal hypertension have been reported in HIV-negative patients as a result from exposure to adenosine analogues (e.g. azathioprine), bacterial infections, trace metals and chemicals, genetic coagulation disorders and/or autoimmune diseases. More recently, reports of similar cases in HIV-positive individuals have attracted much attention

Functional Divergence of the Arabidopsis Florigen-Interacting bZIP Transcription Factors FD and FDP.

Flowering of many plant species depends on interactions between basic leucine zipper (bZIP) transcription factors and systemically transported florigen proteins. Members of the genus Arabidopsis contain two of these bZIPs, FD and FDP, which we show have largely complementary expression patterns in shoot apices before and during flowering. CRISPR-Cas9-induced null mutants for FDP flower slightly earlier than wild-type, whereas fd mutants are late flowering. Identical G-box sequences are enriched at FD and FDP binding sites, but only FD binds to genes involved in flowering and only fd alters their transcription. However, both proteins bind to genes involved in responses to the phytohormone abscisic acid (ABA), which controls developmental and stress responses. Many of these genes are differentially expressed in both fd and fdp mutant seedlings, which also show reduced ABA sensitivity. Thus, florigen-interacting bZIPs have distinct functions in flowering dependent on their expression patterns and, at earlier stages in development, play common roles in phytohormone signaling

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Prognosis: the “missing link” within the CanMEDS competency framework

Abstract Background The concept of prognosis dates back to antiquity. Quantum advances in diagnostics and therapeutics have relegated this once highly valued core competency to an almost negligible role in modern medical practice. Medical curricula are devoid of teaching opportunities focused on prognosis. This void is driven by a corresponding relative dearth within physician competency frameworks. This study aims to assess the level of content related to prognosis within CanMEDS (Canadian Medical Education Directives for Specialists), a leading and prototypical physician competency framework. Methods A quantitative content analysis of CanMEDS competency framework was carried out to measure the extent of this deficiency. Foxit Reader 5.1 (Foxit Corporation), a keyword scanning software, was used to assess the CanMEDS 2005 framework documents of 29 physician specialties and 37 subspecialties across the seven physician roles (medical expert, communicator, collaborator, manager, health advocate, scholar, and professional). The keywords used in the search included prognosis, prognostic, prognosticate, and prognostication. Results Of the 29 specialties six (20.7%) contained at least one citation of the keyword “prognosis”, and one (3.4%) contained one citation of the keyword “prognostic”. Of the 37 subspecialties, sixteen (43.2%) contained at least one citation of the keyword “prognosis”, and three (8.1%) contained at least one citation of the keyword “prognostic”. The terms “prognosticate” and “prognostication” were completely absent from all CanMEDS 2005 documents. Overall, the combined citations for “prognosis” and “prognostic” were linked with the following competency roles: Medical Expert (80.3%), Scholar (11.5%), and Communicator (8.2%). Conclusions Given the fundamental and foundational importance of prognosis within medical practice, it is recommended that physicians develop appropriate attitudes, skills and knowledge related to the formulation and communication of prognosis. The deficiencies within CanMEDS, demonstrated by this study, should be addressed in advance of the launch of its updated version in 2015

Preferences for Active and Aggressive Intervention among Patients with Advanced Cancer

BACKGROUND: Intrinsic to Patient-Centered Care is being respectful and responsive to individual patient preferences, expressed needs, and personal values. Establishing a patient\u27s preferences for active and aggressive intervention is imperative and foundational to the development of advance care planning. With the increasing awareness and acceptance of palliative philosophies of care, patients with advanced cancer are increasingly transitioning from active and aggressive medical management (AAMM) to conservative palliative management (CPM). METHODS: A cross-sectional study based on a prospective and sequential case series of patients referred to a regional palliative medicine consultative program was assembled between May 1, 2005 and June 30, 2006. Patients and/or their substitute decision makers (SDM) completed a questionnaire, at baseline, that assessed their preferences for AAMM en route to their eventual deaths. Seven common interventions constituting AAMM were surveyed: cardiopulmonary resuscitation (CPR) & mechanical ventilation (MV), chemotherapy, antibiotics, anticoagulants, blood transfusions, feeding tubes, and artificial hydration. Multivariable analyses were conducted on the seven interventions individually as well as on the composite score that summed preferences for the seven interventions. RESULTS: 380 patients with advanced cancer agreed to participate in the study. A trend to desire a mostly conservative palliative approach was noted as 42% of patients desired one or fewer interventions. At baseline, most patients and their SDM\u27s were relatively secure about decisions pertaining to the seven interventions as the rates of being undecided ranged from a high of 23.4% for chemotherapy to a low of 3.9% for feeding tubes. Multivariable modeling showed that more AAMM was preferred by younger patients (P \u3c 0.0001), non-Caucasians (P = 0.042), patients with higher baseline Palliative Performance Scale scores (P = 0.0002) and where a SDM was involved in the decision process (p = 0.027). Non-statistically significant trends to prefer more AAMM was observed with male gender (p = 0.077) and higher levels of the Charlson Comorbidity index (p = 0.059). There was no association between treatment preferences and cancer class. CONCLUSIONS: Although the majority of patients with advanced cancer in this study expressed preferences for CPM, younger age, higher baseline PPSv2, and involvement of SDMs in the decision process were significantly associated with preferences for AAMM

A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting

Mark A Ware1, Paul Daeninck2, Vincent Maida31Pain Center, McGill University Health Center, Montréal, Quebec, Canada; 2Pain and Symptom Clinic, CancerCare Manitoba, Winnipeg, Manitoba, Canada; 3University of Toronto, Toronto, Ontario, CanadaAbstract: Chemotherapy-induced nausea and vomiting (CINV) in cancer patients places a significant burden on patients’ function and quality of life, their families and caregivers, and healthcare providers. Despite the advances in preventing CINV, a substantial proportion of patients experience persistent nausea and vomiting. Nabilone, a cannabinoid, recently received Food and Drug Administration approval for the treatment of the nausea and vomiting in patients receiving cancer chemotherapy who fail to achieve adequate relief from conventional treatments. The cannabinoids exert antiemetic effects via agonism of cannabinoid receptors (CB1 and CB2). Clinical trials have demonstrated the benefits of nabilone in cancer chemotherapy patients. Use of the agent is optimized with judicious dosing and selection of patients.Keywords: nabilone, chemotherapy-induced nausea/vomiting, pai

A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting. Ther Clin Risk Manag. 2008 February; 4(1): 99–107 2

Abstract: Chemotherapy-induced nausea and vomiting (CINV) in cancer patients places a signifi cant burden on patients' function and quality of life, their families and caregivers, and healthcare providers. Despite the advances in preventing CINV, a substantial proportion of patients experience persistent nausea and vomiting. Nabilone, a cannabinoid, recently received Food and Drug Administration approval for the treatment of the nausea and vomiting in patients receiving cancer chemotherapy who fail to achieve adequate relief from conventional treatments. The cannabinoids exert antiemetic effects via agonism of cannabinoid receptors (CB1 and CB2). Clinical trials have demonstrated the benefi ts of nabilone in cancer chemotherapy patients. Use of the agent is optimized with judicious dosing and selection of patients