Because of their selectivity, biologicals are crucial therapeutic agents in oncological, immunological, and inflammatory diseases and their use in clinical practice is broadening. Biologicals are among the most common drugs that can cause hypersensitivity reactions (HSRs), and this is primarily attributed to an explosion in new treatment options that has developed through personalized and precision medicine. Patients can develop HSRs to these agents during the first lifetime exposure or after repeated exposure. Despite its relatively high prevalence, the underlying mechanisms and optimal management of HSRs to biologicals remain incompletely explained. In this position paper, the authors provided evidence-based recommendations for the diagnosis and management of HSRs to biologicals. Additionally, the document defines unmet needs, which should be topics of future studies.

A document by Lara Lemon. Click on the document to view its contents.

Adaptations to anthropogenic domestic habitats contribute to the success of mosquito Aedes aegypti as a major global vector of several arboviral diseases. The species inhabited African forests before expanding into domestic habitats and spreading to the rest of the world. Despite a well-studied evolutionary history, how this species initially moved into human settlements in Africa remains unclear. During this initial habitat transition, Ae. aegypti switched from using natural containers like tree holes as larval breeding sites to using artificial containers like clay pots. Little is known about how these natural versus artificial containers differ in their environments, or whether Ae. aegypti in forest versus domestic habitats evolved any corresponding incipient behavioral divergence, such as in oviposition. To address these gaps, we first characterized physical characteristics, larval density, microbial density, bacterial composition, and volatile profiles of natural versus artificial containers used as mosquito larval breeding sites. We focused on two localities in Africa, La Lopé, Gabon and Rabai, Kenya. In both localities, our data showed that the two habitat-specific container types had significantly different characteristics. We then examined whether such containers differed in their attractiveness for oviposition, a key behavior affecting larval distribution. Forest Ae. aegypti readily accepted artificial containers in our field experiments, and laboratory choice experiments did not find distinct oviposition preference between forest and village Ae. aegypti colonies. These results suggested that African Ae. aegypti were likely generalists in their oviposition site choice. This flexibility to accept different containers might play a vital role during the initial domestication of Ae. aegypti, allowing the mosquitoes to use human-stored water as fallback breeding sites during dry seasons. Although ovipositional changes were not present initially, after longer domestic habitat breeding, the mosquitoes did evolve divergence oviposition preference, as suggested by previous comparisons of African Ae. aegypti and human-specialized non-African Ae. aegypti.

Abstract Introduction The COVID-19 pandemic has resulted in a significant burden on healthcare systems causing disruption to medical and surgical training of doctors globally. Aims and objectives This is the first international survey assessing the perceived impact of the COVID-19 pandemic on training of doctors of all grades and specialties. Methods An online global survey was disseminated using Survey Monkey® between 4th August 2020 and 17th November 2020. A global network of collaborators facilitated participant recruitment. Data was collated anonymously with informed consent and analysed using univariate and adjusted multivariable analysis. Results 743 doctors of median age 27 (IQR: 25-30) were included with the majority (56.8%, n=422) being male. Two-thirds of doctors were in a training post (66.5%, n=494), 52.9% (n=393) in a surgical specialty and 53.0% (n= 394) in low- and middle-income countries. 69.2% (n=514) reported an overall perceived negative impact of the COVID-19 pandemic on their training. A significant decline was noted among non-virtual teaching methods such as face-to-face lectures, tutorials, ward-based teaching, theatre sessions, conferences, simulation sessions and morbidity and mortality meetings (p≤0.05). Doctors from low or middle-income countries were associated with perceived inadequate supervision while performing invasive procedures under general, local or regional anaesthetic. (p≤0.05) Conclusion In addition to the detrimental impact of the COVID-19 pandemic on healthcare infrastructure, there has been an indirect consequence of disrupted training within medical and surgical subspecialties. A focus on reconfiguration of training programs through a variety of additional resources will become imperative to reduce the long-term sequalae of COVID-19 on doctors’ training.

Background: Quantifying age trends in healthcare costs of pediatric asthma leads to better understanding of the natural history of the disease and informed decision-making on the allocation of healthcare resources. Methods: We identified children with incident asthma from the health administrative data of British Columbia, Canada (Jan 1998 to Dec 2015), and followed them from their first diagnosis of asthma or wheezing until age 18. We estimated direct medical costs (in 2016 Canadian dollars [$]), including inpatient and outpatient encounters and pharmacy costs, attributed to asthma (primary outcome) and other respiratory diseases (secondary outcome). We assessed the impact of sex and socioeconomic status on age trends, adjusting for calendar effect. Results: The final analysis included 44,552 children with asthma (62% boys). From age 0 to 18, costs of asthma/wheezing and other respiratory conditions decreased from $1,036 to $29/child-year, and from $1,145 to $31/child-year, respectively. Children under 3 years of age incurred 4–fold higher costs for asthma/wheezing and other respiratory conditions. In particular, costs of asthma hospitalizations were 10 times higher in this age group compared to older children. Age trends were generally similar between sex groups and across socioeconomic status. However, medication costs for asthma/wheezing decreased in boys, whereas those in girls declined during childhood but increased during adolescence. Conclusions: The highest costs of pediatric asthma are concentrated in children younger than 3. Age trends were generally consistent between sex and across socioeconomic status.

We herein report first Iranian families with spastic paraplegia 35 and 49 and claim that TECPR2 gene causes complicated spastic paraplegia 49 with or without sensory autonomic neuropathy. In addition, we show how coexistence of SPG49 and griscelli syndrome can lead to misdiagnosis.

We report a rare case of a large prolapsed pedunculated uterine myoma measuring 15cm in its greater diameter. In order to make a surgical procedure safe and feasible, appropriate clinical predictors should be taken into account and pre- and intraoperative preparations be available to the surgeon's armamentarium.

Monoclonal gammopathy of undetermined significance (MGUS) may be associated with pathologies with severe neuromuscular manifestations such as sporadic late-onset nemaline myopathy (SLONM). We describe a difficult to diagnose case of SLNOM with marked clinical improvement after achieving gammopathy complete hematologic response.

Metronidazole may rarely cause encephalopathy and neuropathy. In this study we report a 30-year-old post-partum, ex-addicted female with leukoencephalopathy due to metronidazole.

Rereading Popper’s “The Logic of scientific discovery”, at his 120th anniversary, brings some thoughts regarding the diagnostic process and decision making in medicine from the viewpoint of the classical scientific method. In recent years physicians are increasingly becoming technical experts who base their decision-making on uniform criteria, guidelines and classifications but unfortunately have moved away from understanding the basic concepts in the philosophy of science. This raises an ethically and philosophically important issue; what does a medical diagnosis mean? Is this an absolute or a relative truth? The implications of this question are enormous in terms of prognosis and treatment. Both patients and physicians should be educated about the nature of the diagnostic process.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID19), is associated with flares of psoriasis in patients with well-documented disease. Both viral infection and medications used for treatment, like hydroxychloroquine, were incriminated. Herein, we report the case of a 25-year-old patient who presented a first-onset guttate psoriasis following COVID19.

We are presenting a newborn with a very rare and most severe form of congenital ichthyosis that is characterized by a thick, heavily keratinized and scaly skin.

The coronavirus 2019 disease (COVID-19) affected 125 million people worldwide and caused 2.7 million deaths. Some comorbidities are associated with worse prognosis and left ventricular assist device (LVAD) recipients are probably part of this high-risk population. We report a 31-year-old male patient who developed COVID-19 during LVAD implantation. His postoperative period was complicated by severe pneumonia and mechanical ventilation leading to right ventricular failure (RVF) and inotrope necessity. He experienced multiple complications, but eventually recovered. We present a systematic review of LVAD recipients and COVID-19. Among 14 patients, the mean age was 62.7 years, 78.5% were male. Five patients (35.7%) required mechanical ventilation and 3 patients (21.4%) died. Two patients (14.2%) had thromboembolic events. This case and systematic review suggest LVAD recipients are at particular risk of unfavorable outcomes and they may be more susceptible to RVF in the setting of COVID-19, particularly during perioperative period.

Phosphate (Pi) and jasmonic acid (JA) play critical roles in plant growth and development. In particular, crosstalk between JA and Pi starvation signaling has been reported to mediate insect herbivory resistance in dicot plants. However, its roles and mechanism in monocot-bacterial defense systems remain obscure. Here, we report that Pi starvation in rice activates the JA signaling and enhances resistance to Xanthomonas oryzae pv. oryzae (Xoo) infection. The direct regulation of OsPHR2 on the OsMYC2 promoter was confirmed by yeast one-hybrid, electrophoretic mobility shift, dual-luciferase, and chromatin immunoprecipitation assays. Molecular analyses and infection studies using OsPHR2-Ov1 and phr2 mutants further demonstrated that OsPHR2 enhances JA response and antibacterial resistance via transcriptional regulation of OsMYC2 expression, indicating a positive role of OsPHR2-OsMYC2 crosstalk in modulating the JA response and Xoo infection. Genetic analysis and infection assays using myc2 mutants revealed that Pi starvation-induced JA signaling activation and consequent Xoo resistance depends on the regulation of OsMYC2. Together, these results reveal a clear interlink between Pi starvation signaling and the JA signaling in monocot plants, and provide new insight into how plants balance growth and defense by integrating nutrient deficiency and phytohormone signaling.

Pneumomediastinum is a rare complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that has increased in incidence with the novel coronavirus disease 2019 pandemic. Although traditionally managed with conservative measures, we present the indications and methods for the first operative management of tension pneumomediastinum with concomitant SARS-CoV-2 infection.

Mountain regions are an important regulator in the global water cycle through their disproportionate water contribution. Often referred to as the “Water Towers of the World”, mountains contribute 40 to 60% of the world’s annual surface flow. Shade is a common feature in mountains, where complex terrain cycles land surfaces in and out of shadows over daily and seasonal scales. This study investigated turbulent water and carbon dioxide fluxes over the snow-free period in a subalpine wetland in the Canadian Rocky Mountains, from June 7th to September 10th, 2018. Shading had a significant and substantial effect on water and carbon fluxes at our site. Each hourly increase of shade per day reduced evapotranspiration (ET) and gross primary production (GPP) by 0.42 mm and 0.77 gCm-2, equivalent to 17% and 15% per day, respectively, over the entire study period. However, during only peak growing season, when leaves were fully out and mature, shade caused by the local complex terrain, reduced ET and increased GPP, likely due to enhanced diffuse radiation. The overall result was increased water use efficiency at the site during periods of increased shading during the peak growing season. In addition to incoming solar radiation (Rg), temporal variability in ET was found to relate to temporal variability in soil temperature, moisture and vapour pressure deficit. Shade impacted the curvature and intercept of the nonlinear ET-Rg relationship at our site. In contrast, temporal variability in GPP at our site was dependent largely on Rg only. Our findings suggest that shaded subalpine wetlands can store large volumes of water for late season runoff and are productive through short growing seasons.

Using an Accelerated Junctional Rhythm to Predict the Success and Safety of Slow AV Nodal Pathway Ablation G. Neal Kay MD

A document by Jana Eckert. Click on the document to view its contents.