Quantitation of genetic differences between Trypanosoma brucei gambiense, rhodesiense and brucei by restriction enzyme analysis of kinetoplast DNA

We have compared a total of 44 recognition sites for 12 restriction endonucleases on the 20 kilobase pair maxi-circle of kinetoplast DNA from nine Trypanosoma brucei stocks, four which are known to be infective to man (tow 'gambiense' and two 'rhodesiense' variants). In addition to five polymorphic sites, these DNAs differ in the size of a 5 kilo-base pair region which is cleaved only by one of the restriction enzymes tested and which varies in size over 1.5 kilo-base pairs. Our analysis shows that the maxi-circle sequences of these stocks are very similar, the maximal calculated difference between any two being 3%. A relatively large difference was found between a rhodesiense stock from uganda and one from Zambia, confirming the distinction between northern and southern East African rhodesiense stocks found by analysis of enzyme polymorphisms (Gibson et al. (1980) Adv. Parasitol. 18, 175-246). The gambiense variants could not be identified by unique restriction site polymorphisms, but contained the smallest maxi-circle found thus far in T. Brucei. Our results indicate that T. brucei stocks infective and not infective to man are so closely related as to preclude their differentiation by analysis of kinetoplast DNA. This analysis is useful, however, in providing quantitative information about relatedness of stocks.     

Asia Pacific Society of Human Genetics (APSHG) from conception to 2019: 13 years of collaboration to tackle congenital malformation and genetic disorders in Asia

Putting together the reports in this issue that come from a representation of the different countries in Asia presents an opportunity to share the unique story of the Asia Pacific Society of Human Genetics (APSHG), which has provided the authors of many of these articles. This paper, authored by the Past Presidents of the Society, shares glimpses of how medical genetics activities were first organized in the Asia Pacific region and provides interesting corollaries on how under‐developed and developing countries in this part of the world had developed a unique network for exchange and sharing of expertise and resources. Although APSHG was formally registered as a Society in Singapore in 2006, the Society has its origins as far back as in the 1990s with members from different countries meeting informally, exchanging ideas, and collaborating. This treatise documents the story of the experiences of the Society and hopes it will provide inspiration on how members of a genetics community can foster and build a thriving environment to promote this field.     

Impact of Weather Conditions on Atopic Dermatitis Prevalence in Abuja,Nigeria

Background

Climatic conditions may trigger subclinical disease in predisposed individuals and also exacerbate eczematous symptoms resulting in persistence or increased frequency of atopic dermatitis (AD) flares. The aim of this study is to assess the impact of tropical weather conditions on the frequency at which atopic dermatitis patients present at the dermatology clinic of a tertiary hospital in Abuja, Nigeria; and, to find out which component of these conditions exerts the most significant effects.

COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury

Patients with coronavirus disease 2019 (COVID-19) who are critically ill develop vascular complications characterized by thrombosis of small, medium, and large vessels. Dysfunction of the vascular endothelium due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated in the pathogenesis of the COVID-19 vasculopathy. Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express angiotensin-converting enzyme 2, the receptor that SARS-CoV-2 uses to gain entry into cells, or express it at low levels and are resistant to the infection. These new findings, together with the observation that COVID-19 triggers a cytokine storm capable of injuring the endothelium and disrupting its antithrombogenic properties, favor an indirect mechanism of endothelial injury mediated locally by an augmented inflammatory reaction to infected nonendothelial cells, such as the bronchial and alveolar epithelium, and systemically by the excessive immune response to infection. Herein we review the vascular pathology of COVID-19 and critically discuss the potential mechanisms of endothelial injury in this disease.

Following an initial outbreak of pneumonia in Wuhan, China, in December 2019,¹ coronavirus disease 19 (COVID-19) has spread rapidly worldwide, infecting more than 186 million people (Johns Hopkins Coronavirus Resource Center, https://coronavirus.jhu.edu, last accessed July 12, 2021). Caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),² the COVID-19 pandemic has put a major strain on the healthcare systems, causing a global health crisis of unparalleled proportions in modern times.³ Although most patients have recovered from the infection, many experienced a severe form of the disease that requires hospitalization and intensive care, and >3.2 million people have died. Individuals at greatest risk for the fatal complications of COVID-19 have been the elderly and those with underlying conditions, such as lung disease, hypertension, obesity, and diabetes.⁴Clinical manifestations of COVID-19 in severely ill patients are adult respiratory distress syndrome and multiorgan system failure.^4,5 The clinical course of the disease can be complicated by vascular events, including thrombosis of small, medium, and large blood vessels and thromboembolism.^6,7 Although the primary target of SARS-CoV-2 is the respiratory and alveolar epithelium,⁸ the frequent occurrence of vascular complications in COVID-19 has led to the hypothesis that dysfunction of the endothelium, the inner lining of blood vessels, plays an important role in the progression of this disease into a debilitating and lethal condition.⁹ Two potential mechanisms have been hypothesized to explain how SARS-CoV-2 causes endothelial dysfunction and thrombosis. In the first scenario, SARS-CoV-2 directly infects the endothelium, disrupting its antithrombogenic and barrier properties. The second scenario invokes an indirect mechanism of endothelial injury mediated by the local and systemic inflammatory response to the viral infection.^10,11 In this article, we briefly review the vascular pathology of COVID-19 and critically discuss the proposed mechanisms by which SARS-CoV-2 damages blood vessels, including recent studies that challenge the viral infection of endothelium hypothesis and strongly favor an indirect, inflammation-driven mechanism of endothelial injury.     

Complex systems for evaluation of public health interventions: a critical review

Background

There has been a growth in interest in applying systems thinking to public health research, including greater consideration of the complex and changing nature of real-world environments where public health interventions take place. We aimed to assess how a systems approach could be applied in the context of public health evaluation.

Fungal infections in patients with acute leukemia

We reviewed the records of 32 patients with acute leukemia and proved invasive fungal infections to determine the clinical and pathologic characteristics of systemic mycosis in patients undergoing intensive induction chemotherapy. The incidence of invasive fungal infections among our patients was at least 27 percent, and Candida and Aspergillus accounted for the majority of these infections. Patients with systemic candidiasis generally had prolonged severe neutropenia, fever refractory to antibiotics, and evidence of mucosal colonization by fungi. At autopsy, Candida was always widely disseminated. Patients with aspergillosis generally had neutropenia, fever, and pulmonary infiltrates at the time of admission to the hospital and, at autopsy, their infections were primarily confined to the lungs. Patients infected with both Candida and Aspergillus had clinical and pathologic findings that were a combination of the features of each type of infection. A diagnosis of invasive fungal infection was established before death in only nine of the patients, all of whom had systemic candidiasis. Four of these patients were successfully treated and survived their hospitalization. The reasons for frequently misdiagnosing and unsuccessfully treating systemic mycosis in patients with acute leukemia are examined, and suggestions are made for improved management of patients at high risk for these infections. These suggestions are based upon recognition of the clinical settings in which fungal infections occur, the aggressive use of invasive diagnostic procedures, and the early empiric use of amphotericin B.     

Does genetic risk of obesity modify associations between the neighbourhood environment and body-mass index? A cross-sectional analysis of the UK Biobank dataset

Background

In studies of gene–environment interactions and obesity, the term environment usually refers to individual behavioural factors that influence energy balance. However, evidence suggests that the built environments in which individuals live, work, and play are associated with obesity and may therefore be environmental triggers of genetic risk. No studies have explored whether individual response to such environmental determinants of obesity varies with genetic risk. We aimed to examine whether genetic risk of obesity modifies associations between various neighbourhood characteristics and body-mass index (BMI).

Integrating Interprofessional Education and Cultural Competency Training to Address Health Disparities

Problem: Many U.S. medical schools have accreditation requirements for interprofessional education and training in cultural competency, yet few programs have developed programs to meet both of these requirements simultaneously. Furthermore, most training programs to address these requirements are broad in nature and do not focus on addressing health disparities. The lack of integration may reduce the students' ability to apply the knowledge learned. Innovative programs that combine these two learning objectives and focus on disenfranchised communities are needed to train the next generation of health professionals. Intervention: A unique interprofessional education program was developed at the University of Arkansas for Medical Sciences Northwest. The program includes experiential learning, cultural exposure, and competence-building activities for interprofessional teams of medicine, nursing, and pharmacy students. The activities include (a) educational seminars, (b) clinical experiential learning in a student-led clinic, and (c) community-based service-learning through health assessments and survey research events. Context: The program focuses on interprofessional collaboration to address the health disparities experienced by the Marshallese community in northwest Arkansas. The Marshallese are Pacific Islanders who suffer from significant health disparities related to chronic and infectious diseases. Outcome: Comparison tests revealed statistically significant changes in participants' retrospectively reported pre/posttest scores for Subscales 1 and 2 of the Readiness for Interpersonal Learning Scale and for the Caffrey Cultural Competence in Healthcare Scale. However, no significant change was found for Subscale 3 of the Readiness for Interpersonal Learning Scale. Qualitative findings demonstrated a change in students' knowledge, attitudes, and behavior toward working with other professions and the underserved population. Lessons Learned: The program had to be flexible enough to meet the educational requirements and class schedules of the different health professions' education programs. The target community spoke limited English, so providing interpretation services using bilingual Marshallese community health workers was integral to the program's success.     

From the Cover: Changing central Pacific El Ni?os reduce stability of North American salmon survival rates

Pacific salmon are a dominant component of the northeast Pacific ecosystem. Their status is of concern because salmon abundance is highly variable—including protected stocks, a recently closed fishery, and actively managed fisheries that provide substantial ecosystem services. Variable ocean conditions, such as the Pacific Decadal Oscillation (PDO), have influenced these fisheries, while diminished diversity of freshwater habitats have increased variability via the portfolio effect. We address the question of how recent changes in ocean conditions will affect populations of two salmon species. Since the 1980s, El Niño Southern Oscillation (ENSO) events have been more frequently associated with central tropical Pacific warming (CPW) rather than the canonical eastern Pacific warming ENSO (EPW). CPW is linked to the North Pacific Gyre Oscillation (NPGO), whereas EPW is linked to the PDO, different indicators of northeast Pacific Ocean ecosystem productivity. Here we show that both coho and Chinook salmon survival rates along western North America indicate that the NPGO, rather than the PDO, explains salmon survival since the 1980s. The observed increase in NPGO variance in recent decades was accompanied by an increase in coherence of local survival rates of these two species, increasing salmon variability via the portfolio effect. Such increases in coherence among salmon stocks are usually attributed to controllable freshwater influences such as hatcheries and habitat degradation, but the unknown mechanism underlying the ocean climate effect identified here is not directly subject to management actions.Understanding the influence of nonstationary climatic shifts on the productivity and persistence of populations is a key challenge to successful management of harvested marine and anadromous resources (1). Management of Pacific salmon fisheries in the United States and Canada exemplifies the challenges posed by climatic shifts; managers must set harvests for some stocks while protecting stocks at risk. The influence of variable survival of juvenile salmon after ocean entry complicates decision making, with increasing variability generally increasing population risk. As an example of this variability, poor ocean productivity was largely responsible for an unprecedented complete closure of the Chinook salmon fisheries in California and southern Oregon when extremely low numbers returned to spawn in 2008 and 2009 (2).Salmon management is unique in that it focuses on stocks comprising identifiable separate populations in individual spawning streams. Recent studies show that increased covariability in abundance among separate populations of Chinook salmon has increased coherence of salmon stocks, thus increasing aggregate variability of the stocks through the portfolio effect (3–5). These effects of declining diversity among salmon subpopulations are an example of the general global concern for the loss of biodiversity in many forms (e.g., loss of genes, species, within-species variability) and its effects on ecosystem services (6–10). The portfolio effect has been a useful way of quantifying the effects on aggregate population variability in salmon stocks in terms of the loss of diversity among populations spawning in different streams (3, 4, 11). The recently detected increased coherence of salmon populations, and associated increases in aggregate population variability, and, thus, increased risk, have generally been attributed to declining biocomplexity of freshwater habitats due to the increase in hatcheries, dams, and stream habitat homogenization (3–5, 12, 13). However, the extent to which responses to physical oceanographic conditions in the marine phase of salmon life limit the scope for reducing population variability through the portfolio effect has not been considered. We analyzed early ocean survival of hatchery coho salmon from 72 hatcheries and Chinook salmon from 104 hatcheries along western North America from central California to southeast Alaska between 1980 and 2006 using coded wire tag (CWT) data (14, 15) to show how a climatic shift has influenced the coherence in survival rates of two important salmon species in the northeast Pacific Ocean (Fig. S1).Open in a separate windowFig. S1.Locations of the 72 coho (Oncorhynchus kisutch, red diamonds) and 104 Chinook salmon (O. tshawytscha, blue circles) hatcheries and the geographical regions used in this study; note that some hatcheries release both species (black squares). Geographic regions with survival time series data used in this study: A, northern southeast Alaska; B, southern southeast Alaska; C, west coast of Vancouver Island; D, Strait of Georgia and Puget Sound; E, north coastal Washington; F, south coastal Washington; G, Columbia River; H, north coastal Oregon; I, south coastal Oregon; J, north coastal California; K, central California. Geographic regions with insufficient time series data to include in this study: L, northern British Columbia; M, Fraser River.In recent decades, El Niño events have been characterized by central Pacific warming (CPW) events more frequently than eastern Pacific warming (EPW) events typically associated with El Niño (16, 17). El Niño events drive a large fraction of both interannual and decadal variability in the northern Pacific Ocean (18), but CPW and EPW events excite different teleconnections to the northern Pacific Ocean. EPW events drive fluctuations in the North Pacific Ocean by intensifying the variance of the wintertime Aleutian Low pressure cell (19), which, in turn, drives the Pacific Decadal Oscillation (PDO). CPW events, however, influence northern Pacific Ocean climate differently by influencing the North Pacific Oscillation (NPO), which, in turn, modulates the strength of the North Pacific Current indexed by the North Pacific Gyre Oscillation (NPGO) (17). This shift in El Niño signals influences teleconnections to the northern Pacific Ocean, with less variability ascribed to PDO, which is the dominant mode of northern Pacific Ocean low-frequency variability, and an increasing fraction to the second mode of low-frequency variability, the NPGO (17, 20, 21). Because the PDO explained important shifts in salmon productivity in the past (22), the increased variability related to the NPGO raises the question of how it affects salmon productivity.