Groundwater is a hidden global keystone ecosystem.

Groundwater is a vital ecosystem of the global water cycle, hosting unique biodiversity and providing essential services to societies. Despite being the largest unfrozen freshwater resource, in a period of depletion by extraction and pollution, groundwater environments have been repeatedly overlooked in global biodiversity conservation agendas. Disregarding the importance of groundwater as an ecosystem ignores its critical role in preserving surface biomes. To foster timely global conservation of groundwater, we propose elevating the concept of keystone species into the realm of ecosystems, claiming groundwater as a keystone ecosystem that influences the integrity of many dependent ecosystems. Our global analysis shows that over half of land surface areas (52.6%) has a medium-to-high interaction with groundwater, reaching up to 74.9% when deserts and high mountains are excluded. We postulate that the intrinsic transboundary features of groundwater are critical for shifting perspectives towards more holistic approaches in aquatic ecology and beyond. Furthermore, we propose eight key themes to develop a science-policy integrated groundwater conservation agenda. Given ecosystems above and below the ground intersect at many levels, considering groundwater as an essential component of planetary health is pivotal to reduce biodiversity loss and buffer against climate change.

Potential Benefit of Vitamin D Supplementation in COVID-19.

Vitamin D is an important nutrient in the body that plays a vital role in immune system function. Several epidemiologic studies have shown that low vitamin D levels are found in a large percentage of COVID-19 patients with acute respiratory failure and that vitamin D levels may predict mortality in COVID-19 infection. Based on these findings, vitamin D supplementation may be an effective approach to preventing and/or treating COVID-19. Potential underlying mechanisms and clinical trial data evaluating the impact of supplementation in humans are described below.

Correction: Application of a Mixed Methods Multi-Criteria Decision Analysis Framework in Integrated Health Care.

[This corrects the article DOI: 10.5334/ijic.5997.].

Application of a Mixed Methods Multi-Criteria Decision Analysis Framework in Integrated Health Care.

Background: Evaluating integrated care programs is complex. Integration benefits may not become apparent within short evaluation timeframes, and many programs provide a wide variety of health and non-health benefits. To address these challenges, we illustrate a mixed methods approach for evaluating multiple integrated care programs using multi-criteria decision analysis. Methods: We adapted a decision support tool used by local decision makers to compare data extracted from 17 different integrated care evaluations. Criteria included impact on health services capacity, patient outcomes, integration of care, workforce development and implementation risk, weighted based on stakeholder preferences. Program benefits were compared to their implementation costs, and assessed using cost-effectiveness methods. Sensitivity analysis examined the impact of different criteria weights. Results and discussion: This method captured a diverse range of benefits provided by integrated care programs and provided an accessible heuristic to compare many projects simultaneously. However, this approach may not be sensitive to the appropriateness of each criterion to the health system, the magnitude of difference in individual criteria, equity considerations or socio-political factors. Internal and external validation, especially for subjective criteria such as implementation risk, are needed. Conclusions: This work offers a feasible, flexible and pragmatic approach for evaluating integrated care programs.

Preliminary insights into associations between C-reactive protein and social network dynamics.

Recent social psychoneuroimmunology models suggest bidirectional associations between social experiences and the immune system. This work posits that social relationships and networks may influence the functioning of the immune system, but we know little about the role that the immune system plays in how social networks are created and maintained. We examine how salivary C-reactive protein (CRP), as an inflammatory protein, is associated with making new and keeping existing friendship and conflicted relationships among young adult members of a social group. Participants (n = 37; 67.6% female; M age = 18.18 years, 56.81% white/non-Hispanic) provided nominations of friends and individuals with whom they have conflict at wave 1 and two months later at wave 2. At wave 1, in a group setting, participants donated saliva, later assayed for CRP. Stochastic actor-based models revealed that CRP levels were negatively associated with keeping existing friends and positively associated with developing new friendships. We also found that CRP levels were negatively associated with creating new conflicted relationships and predicted an increased likelihood that group members continue conflicted relationships with the focal individual. These preliminary results support the premises of recent social psychoneuroimmunology models by suggesting that inflammation can also serve as a signal to seek new supportive relationships such as friendships and avoid creating new relationships characterized by threat and/or conflict. Findings provide new insights into the theorized function of the immune system for social approach and withdrawal patterns through which our social connections are constructed.

New light in the dark - a proposed multidisciplinary framework for studying functional ecology of groundwater fauna.

Groundwaters provide the vast majority of unfrozen freshwater resources on the planet, but our knowledge of subsurface ecosystems is surprisingly limited. Stygofauna, or stygobionts -subterranean obligate aquatic animals - provide ecosystem services such as grazing biofilms and maintaining water quality, but we know little about how their ecosystems function. The cryptic nature of groundwaters, together with the high degree of local endemism and stygofaunal site-specific adaptations, represent major obstacles for the field. To overcome these challenges, and integrate biodiversity and ecosystem function, requires a holistic design drawing on classical ecology, taxonomy, molecular ecology and geochemistry. This study presents an approach based on the integration of existing concepts in groundwater ecology with three more novel scientific techniques: compound specific stable isotope analysis (CSIA) of amino acids, radiocarbon analysis (14C) and DNA analyses of environmental samples, stygofauna and gut contents. The combination of these techniques allows elucidation of aspects of ecosystem function that are often obscured in small invertebrates and cryptic systems. Carbon (δ13C) and nitrogen (δ15N) CSIA provides a linkage between biogeochemical patterns and ecological dynamics. It allows the identification of stygofaunal food web structures and energy flows based on the metabolic pathway of specific amino groups. Concurrently, 14C provides complementary data on the carbon recycling and incorporation within the stygobiotic trophic webs. Changes in groundwater environmental conditions (e.g. aquifer recharge), and subsequent community adaptations, can be pinpointed via the measurementof the radiocarbon fingerprint of water, sediment and specimens. DNA analyses are a rapidly expanding approach in ecology. eDNA is mainly employed as a biomonitoring tool, while metabarcoding of individuals and/or gut contents provides insight into diet regimes. In all cases, the application of the approaches in combination provides more powerful data than any one alone. By combining quantitative (CSIA and 14C) and qualitative (eDNA and DNA metabarcoding) approaches via Bayesian Mixing Models (BMM), linkages can be made between community composition, energy and nutrient sources in the system, and trophic function. This suggested multidisciplinary design will contribute to a more thorough comprehension of the biogeochemical and ecological patterns within these undervalued but essential ecosystems.

Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species.

1. Antiretroviral concentrations in cerebrospinal fluid (CSF) are used as surrogate for brain tissue, although sparse data support this. We quantified antiretrovirals in brain tissue across preclinical models, compared them to CSF, and calculated 90% inhibitory quotients (IQ90) for nonhuman primate (NHP) brain tissue. Spatial distribution of efavirenz was performed by mass-spectrometry imaging (MSI). 2. HIV or RT-SHIV-infected and uninfected animals from two humanized mouse models (hemopoietic-stem cell/RAG2-, n = 36; bone marrow-liver-thymus/BLT, n =13) and an NHP model (rhesus macaque, n =18) were dosed with six antiretrovirals. Brain tissue, CSF (NHPs), and plasma were collected at necropsy. Drug concentrations were measured by LC-MS/MS. Rapid equilibrium dialysis determined protein binding in NHP brain. 3. Brain tissue penetration of most antiretrovirals were >10-fold lower (p < 0.02) in humanized mice than NHPs. NHP CSF concentrations were >13-fold lower (p <0.02) than brain tissue with poor agreement except for efavirenz (r = 0.91, p = 0.001). Despite 97% brain tissue protein binding, efavirenz achieved IQ90>1 in all animals and 2-fold greater white versus gray matter concentration. 4. Brain tissue penetration varied across animal models for all antiretrovirals except raltegravir, and extrapolating brain tissue concentrations between models should be avoided. With the exception of efavirenz, CSF is not a surrogate for brain tissue concentrations.

Implicit Mental Motor Imagery Task Demonstrates a Distortion of the Body Schema in Patients With Eating Disorders.

OBJECTIVES: A rich body of literature has established the role of body image distortion and dissatisfaction in the development and maintenance of eating disorders. However, many of the currently used techniques require explicit comparison of the person's body to an external stimulus. As the body schema is a largely unconscious construct, explicit comparison tasks may reflect a proxy, rather than the body schema itself. METHODS: Here we use an implicit mental motor imagery (MMI) task to interrogate the body schema in healthy control participants (N=40) and participants at a residential eating disorder treatment center (N=42). By comparing the time it takes to imagine making a movement along a part of the body to the time it takes to actually make the same movement, we were able to assess participants' mental image of their body (i.e., body schema). RESULTS: We found that participants with eating disorders, but not healthy controls, exhibited distortions of the body schema such that they believed their abdomen, buttocks, and thighs to be larger than they really are. Additionally, the MMI task used here provided information above and beyond traditional self-report measures (i.e., Body Shape Questionnaire). Together the MMI task and traditional measures provide the most information. CONCLUSIONS: Findings using the novel MMI task are in line with the literature; participants with eating disorders consider themselves to be larger than they truly are. Taken together, results of this study suggest that MMI tasks provide complementary information to traditional self-report measures. (JINS, 2018, 24, 715-723).

Changes in ectomycorrhizal fungal community composition and declining diversity along a 2-million-year soil chronosequence.

Ectomycorrhizal (ECM) fungal communities covary with host plant communities along soil fertility gradients, yet it is unclear whether this reflects changes in host composition, fungal edaphic specialization or priority effects during fungal community establishment. We grew two co-occurring ECM plant species (to control for host identity) in soils collected along a 2-million-year chronosequence representing a strong soil fertility gradient and used soil manipulations to disentangle the effects of edaphic properties from those due to fungal inoculum. Ectomycorrhizal fungal community composition changed and richness declined with increasing soil age; these changes were linked to pedogenesis-driven shifts in edaphic properties, particularly pH and resin-exchangeable and organic phosphorus. However, when differences in inoculum potential or soil abiotic properties among soil ages were removed while host identity was held constant, differences in ECM fungal communities and richness among chronosequence stages disappeared. Our results show that ECM fungal communities strongly vary during long-term ecosystem development, even within the same hosts. However, these changes could not be attributed to short-term fungal edaphic specialization or differences in fungal inoculum (i.e. density and composition) alone. Rather, they must reflect longer-term ecosystem-level feedback between soil, vegetation and ECM fungi during pedogenesis.

Vitamin C in the Prevention and Treatment of the Common Cold.

During the winter months, absenteeism or decreased productivity at work or school can often be attributed to symptoms of the common cold. Many people seek over-the-counter (OTC) products for their symptoms, and some of the commonly purchased products are those with high-dose supplements of vitamin C (ascorbic acid). The common cold causes enormous morbidity worldwide, and it is important to know the effects of vitamin C for both preventive and therapeutic purposes to correctly recommend the proper OTC product for these symptoms. The purpose of this article is to review the current data on the relationship between vitamin C and immune function, specifically, the utility of vitamin C supplementation in the prevention and treatment of the common cold.

Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM).

Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines.

Pneumatosis intestinalis with a focus on hyperbaric oxygen therapy.

Pneumatosis intestinalis is a rare condition of air in the bowel wall. Pneumatosis intestinalis is most often secondary to another medical condition. The diagnosis is most often made radiologically with a computed tomography scan. The disease severity ranges from benign to life-threatening. Predictors of poor outcomes include pH less than 7.3, bicarbonate level of less than 20 mEq/L, lactate level of more than 2 mmol/L, amylase level of more than 200 U/L, and portal venous gas on imaging. Early recognition of life-threatening signs and symptoms is critical. Treatment options include bowel rest, antibiotics, surgery, and, more recently, the use of hyperbaric oxygen therapy. Hyperbaric oxygen therapy is extremely safe, with no reported complications in the literature when used for pneumatosis intestinalis. When surgery is not emergently needed, symptomatic pneumatosis intestinalis can be safely treated with hyperbaric oxygen with a high likelihood of success without any considerable adverse effects.

Deep sequencing of plant and animal DNA contained within traditional Chinese medicines reveals legality issues and health safety concerns.

Traditional Chinese medicine (TCM) has been practiced for thousands of years, but only within the last few decades has its use become more widespread outside of Asia. Concerns continue to be raised about the efficacy, legality, and safety of many popular complementary alternative medicines, including TCMs. Ingredients of some TCMs are known to include derivatives of endangered, trade-restricted species of plants and animals, and therefore contravene the Convention on International Trade in Endangered Species (CITES) legislation. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCMs, and there are numerous cases of adverse reactions. It is in the interests of both biodiversity conservation and public safety that techniques are developed to screen medicinals like TCMs. Targeting both the p-loop region of the plastid trnL gene and the mitochondrial 16S ribosomal RNA gene, over 49,000 amplicon sequence reads were generated from 15 TCM samples presented in the form of powders, tablets, capsules, bile flakes, and herbal teas. Here we show that second-generation, high-throughput sequencing (HTS) of DNA represents an effective means to genetically audit organic ingredients within complex TCMs. Comparison of DNA sequence data to reference databases revealed the presence of 68 different plant families and included genera, such as Ephedra and Asarum, that are potentially toxic. Similarly, animal families were identified that include genera that are classified as vulnerable, endangered, or critically endangered, including Asiatic black bear (Ursus thibetanus) and Saiga antelope (Saiga tatarica). Bovidae, Cervidae, and Bufonidae DNA were also detected in many of the TCM samples and were rarely declared on the product packaging. This study demonstrates that deep sequencing via HTS is an efficient and cost-effective way to audit highly processed TCM products and will assist in monitoring their legality and safety especially when plant reference databases become better established.